21 CFR Part 866 — Immunology and Microbiology Devices

PART 866—IMMUNOLOGY AND MICROBIOLOGY DEVICES Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360 l, Source: 47 FR 50823, Nov. 9, 1982, unless otherwise noted. Editorial Note: Nomenclature changes to part 866 appear at 73 FR 35341, June 23, 2008. Subpart A—General Provisions § 866.1 Scope. (a) This part sets forth the classification of immunology and microbiology devices intended for human use that are in commercial distribution. (b) The indentification of a device in a regulation in this part is not a precise description of every device that is, or will be, subject to the regulation. A manufacturer who submits a premarket notification submission for a device under part 807 may not show merely that the device is accurately described by the section title and identification provisions of a regulation in this part, but shall state why the device is substantially equivalent to other devices, as required by § 807.87. (c) To avoid duplicative listings, an immunology and microbiology device that has two or more types of uses (e.g., used both as a diagnostic device and as a microbiology device) is listed only in one subpart. (d) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted. (e) Guidance documents referenced in this part are available on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. [52 FR 17733, May 11, 1987, as amended at 68 FR 5827, Feb. 5, 2003; 79 FR 50552, Aug. 25, 2014] § 866.3 Effective dates of requirement for premarket approval. A device included in this part that is classified into class III (Premarket approval) shall not be commercially distributed after the date shown in the regulation classifying the device unless the manufacturer has an approval under section 515 of the act (unless an exemption has been granted under section 520(g)(2) of the act). An approval under section 515 of the act consists of FDA's issuance of an order approving an application for premarket approval (PMA) for the device or declaring completed a product development protocol (PDP) for the device. (a) Before FDA requires that a device commercially distributed before the enactment date of the amendments, or a device that has been found substantially equivalent to such a device, has an approval under section 515 of the act FDA must promulgate a regulation under section 515(b) of the act requiring such approval, except as provided in paragraphs (b) and (c) of this section. Such a regulation under section 515(b) of the act shall not be effective during the grace period ending on the 90th day after its promulgation or on the last day of the 30th full calendar month after the regulation that classifies the device into class III is effective, whichever is later. See section 501(f)(2)(B) of the act. Accordingly, unless an effective date of the requirement for premarket approval is shown in the regulation for a device classified into class III in this part, the device may be commercially distributed without FDA's issuance of an order approving a PMA or declaring completed a PDP for the device. If FDA promulgates a regulation under section 515(b) of the act requiring premarket approval for a device, section 501(f)(1)(A) of the act applies to the device. (b) Any new, not substantially equivalent, device introduced into commercial distribution on or after May 28, 1976, including a device formerly marketed that has been substantially altered, is classified by statute (section 513(f) of the act) into class III without any grace period and FDA must have issued an order approving a PMA or declaring completed a PDP for the device before the device is commercially distributed unless it is reclassified. If FDA knows that a device being commercially distributed may be a “new” device as defined in this section because of any new intended use or other reasons, FDA may codify the statutory classification of the device into class III for such new use. Accordingly, the regulation for such a class III device states that as of the enactment date of the amendments, May 28, 1976, the device must have an approval under section 515 of the act before commercial distribution. (c) A device identified in a regulation in this part that is classified into class III and that is subject to the transitional provisions of section 520(l) of the act is automatically classified by statute into class III and must have an approval under section 515 of the act before being commercially distributed. Accordingly, the regulation for such a class III transitional device states that as of the enactment date of the amendments, May 28, 1976, the device must have an approval under section 515 of the act before commercial distribution. [52 FR 17733, May 11, 1987; 52 FR 22577, June 12, 1987] § 866.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act (the act). The exemption from the requirement of premarket notification (section 510(k) of the act) for a generic type of class I or II device is only to the extent that the device has existing or reasonably foreseeable characteristics of commercially distributed devices within that generic type or, in the case of in vitro diagnostic devices, only to the extent that misdiagnosis as a result of using the device would not be associated with high morbidity or mortality. Accordingly, manufacturers of any commercially distributed class I or II device for which FDA has granted an exemption from the requirement of premarket notification must still submit a premarket notification to FDA before introducing or delivering for introduction into interstate commerce for commercial distribution the device when: (a) The device is intended for a use different from the intended use of a legally marketed device in that generic type of device; e.g., the device is intended for a different medical purpose, or the device is intended for lay use where the former intended use was by health care professionals only; (b) The modified device operates using a different fundamental scientific technology than a legally marketed device in that generic type of device; e.g., a surgical instrument cuts tissue with a laser beam rather than with a sharpened metal blade, or an in vitro diagnostic device detects or identifies infectious agents by using deoxyribonucleic acid (DNA) probe or nucleic acid hybridization technology rather than culture or immunoassay technology; or (c) The device is an in vitro device that is intended: (1) For use in the diagnosis, monitoring, or screening of neoplastic diseases with the exception of immunohistochemical devices; (2) For use in screening or diagnosis of familial or acquired genetic disorders, including inborn errors of metabolism; (3) For measuring an analyte that serves as a surrogate marker for screening, diagnosis, or monitoring life-threatening diseases such as acquired immune deficiency syndrome (AIDS), chronic or active hepatitis, tuberculosis, or myocardial infarction or to monitor therapy; (4) For assessing the risk of cardiovascular diseases; (5) For use in diabetes management; (6) For identifying or inferring the identity of a microorganism directly from clinical material; (7) For detection of antibodies to microorganisms other than immunoglobulin G (IgG) or IgG assays when the results are not qualitative, or are used to determine immunity, or the assay is intended for use in matrices other than serum or plasma; (8) For noninvasive testing as defined in § 812.3(k) of this chapter; and (9) For near patient testing (point of care). [65 FR 2311, Jan. 14, 2000] Subpart B—Diagnostic Devices § 866.1620 Antimicrobial susceptibility test disc. (a) Identification. (b) Classification. § 866.1640 Antimicrobial susceptibility test powder. (a) Identification. (b) Classification. § 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system. (a) Identification. (b) Classification. [68 FR 5827, Feb. 5, 2003] § 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) Detailed device description documentation, including the device components, ancillary reagents required but not provided, a detailed explanation of the methodology, including primer/probe sequence, design, rationale for sequence selection, and details of the antimicrobial agents, as applicable. (ii) Detailed documentation from the following analytical and clinical performance studies: limit of detection, inclusivity, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination, quality control and additional studies, as applicable to specimen type and assay intended use. (iii) Detailed documentation from an appropriate clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods. (iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software. (2) The labeling required under § 809.10(b) of this chapter must include: (i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable. (ii) A detailed explanation of the interpretation of results and acceptance criteria. (iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting. [90 FR 24963, June 13, 2025] § 866.1655 System for detection of microorganisms and antimicrobial resistance using reporter expression. (a) Identification. (b) Classification. (1) The intended use for the device in the labeling required under § 809.10 of this chapter must include a detailed description of the targets the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (2) Any device used for specimen collection and transport must be FDA-cleared, approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of the specimen types claimed by this device and for the maintenance of viability of the targeted microorganisms; alternatively, the specimen collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed description of the device, including reagents, instruments, ancillary materials, applicable specimen collection and transport device(s) and control elements, and a detailed explanation of the methodology, including all pre-analytical methods for handling and processing of specimens and controls to maintain organism viability; (ii) Detailed descriptions of the test procedure, including the preparation and maintenance of quality controls and the interpretation of test results; (iii) Detailed discussion of the performance characteristics of the device for all claimed organisms and specimen types based on analytical studies, including evaluation of analytical sensitivity, inclusivity, cross-reactivity, potentially interfering substances and microorganisms, contamination, specimen stability, precision, and reproducibility; (iv) Detailed discussion of the performance characteristics of the device observed in a clinical study performed on a population that is consistent with the intended use population in comparison to the results obtained by a reference or comparator method determined to be acceptable by FDA, for microbial detection, identification, and antimicrobial susceptibility testing; and (v) A limiting statement indicating that a negative test result does not preclude colonization or infection with organisms that do not express detectable levels of the reporter that is identified by the device. (4) Design verification and validation must include: (i) A detailed description of the device, including an explanation of the technology, hardware, software, and consumables, as well as an explanation of the result algorithms and method(s) of data processing from signal acquisition to result assignment; (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions; (iii) Detailed documentation of the analytical and clinical studies required in paragraphs (b)(3)(iii) and (iv) of this section, including the study protocols containing descriptions of the test methods, prescribed methods of data analysis and acceptance criteria, final study reports, and data line listings; (iv) Detailed documentation of quality control procedures, including an explanation of how quality control materials were selected, the recommended frequency of testing, methods of control preparation, acceptance criteria for performance and the results from quality control testing performed during the analytical and clinical studies required under paragraphs (b)(3)(iii) and (iv) of this section; (v) Detailed documentation of studies performed to establish onboard and in-use reagent stability, including the test method(s), data analysis plans, acceptance criteria, final study reports, and data line listings; (vi) Detailed documentation of studies to establish reagent shelf-life for the assay kit and each applicable specimen collection and transport device, including study protocols containing descriptions of the test method(s), data analysis plans, and acceptance criteria; and (vii) Documentation of an appropriate end user device training program that will be offered as part of efforts to assure appropriate conduct of the assay and to mitigate the risk associated with false results, including failure to use the device correctly or correctly interpret results. [87 FR 6417, Feb. 4, 2022] § 866.1700 Culture medium for antimicrobial susceptibility tests. (a) Identification. (b) Classification. Subpart C—Microbiology Devices § 866.2050 Staphylococcal typing bacteriophage. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 866.2120 Anaerobic chamber. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38790, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 866.2160 Coagulase plasma. (a) Identification. Staphylococcus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38790, July 25, 2001] § 866.2170 Automated colony counter. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 866.2180 Manual colony counter. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38790, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 866.2190 Automated image assessment system for microbial colonies on solid culture media. (a) Identification. (b) Classification. (1) Premarket notification submissions must include a detailed description of the device, including the technology employed, components and software modules, as well as a detailed explanation of the result algorithms and any expert rules that are used to assess colony characteristics and enumerate colonies from image capture through end result. (2) Premarket notification submissions must include detailed documentation of the analytical studies performed to characterize device performance to support the intended use, as appropriate. (3) Premarket notification submissions must include detailed documentation from clinical studies performed on a population that is consistent with the intended use population. (i) The clinical studies must establish the device performance based on comparison to results obtained by an acceptable reference method, as appropriate. (ii) The clinical study documentation must include the study protocol with a predefined statistical analysis plan and the final report documenting support for the Indications for Use and the results of the statistical analysis, as appropriate. (4) Premarket notification submissions must include detailed documentation for device software, including but not limited to software applications and hardware based components that incorporate software, and any decision-making thresholds used to generate results for the device. If a part of a Total Laboratory Automation System, the premarket notification submission must include detailed documentation addressing the instrument and software system integration. (5) Premarket notification submissions must include detailed documentation of appropriate instructions for use regarding the intended user's device quality control procedures for the instrument system and components, as appropriate. (6) The 21 CFR 809.10 compliant device labeling must include: (i) Detailed user instructions to mitigate the risk of failure to operate the instrument correctly. (ii) A detailed explanation of the interpretation of results and limitations regarding the need for review of culture plates by a qualified microbiologist, as appropriate. (iii) A summary of performance data obtained from the analytical studies used to support device performance, as appropriate. (iv) A summary of performance data obtained from clinical studies performed on a population that is consistent with the intended use population, as appropriate. (7) Under 21 CFR 820.10(c) design and development, device manufacturers must, as appropriate: (i) Conduct human factors/usability validation testing with the final version of the labeling and related materials to adequately mitigate the risk of failure to operate the instrument correctly. (ii) Document a device training program that will be offered to the end user to adequately mitigate the risk of failure to operate the instrument correctly. [82 FR 47969, Oct. 16, 2017, as amended at 90 FR 55982, Dec. 4, 2025] § 866.2300 Multipurpose culture medium. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001] § 866.2320 Differential culture medium. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38790, July 25, 2001] § 866.2330 Enriched culture medium. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2350 Microbiological assay culture medium. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2360 Selective culture medium. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2390 Transport culture medium. (a) Identification. (b) Classification. § 866.2410 Culture medium for pathogenic Neisseria (a) Identification. Neisseria Neisseria Neisseria, (b) Classification. § 866.2420 Oxidase screening test for gonorrhea. (a) Identification. Neisseria gonorrhoeae. Neisseria gonorrhoeae (b) Classification. (c) Date PMA or notice of completion of a PDP is required. [47 FR 50823, Nov. 9, 1982, as amended at 52 FR 17734, May 11, 1987] § 866.2440 Automated medium dispensing and stacking device. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025] § 866.2450 Supplement for culture media. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2480 Quality control kit for culture media. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2500 Microtiter diluting and dispensing device. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2540 Microbiological incubator. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025] § 866.2560 Microbial growth monitor. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 60 FR 38482, July 27, 1995] § 866.2580 Gas-generating device. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.2600 Wood's fluorescent lamp. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38791, July 25, 2001; 90 FR 55982, Dec. 4, 2025] § 866.2660 Microorganism differentiation and identification device. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.2680 Streptococcus spp. (a) Identification. Streptococcus spp. Streptococcus spp. Streptococcus (b) Classification. (1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection. (2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination. (3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods. (4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software. (5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate. (6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate. (7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate. [82 FR 50074, Oct. 30, 2017] § 866.2850 Automated zone reader. (a) Identification. (b) Classification. § 866.2900 Microbiological specimen collection and transport device. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019; 85 FR 18445, Apr. 2, 2020] § 866.2950 Microbial nucleic acid storage and stabilization device. (a) Identification. (b) Classification. (1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of microorganisms and types of human specimens intended to be preserved. (2) The labeling required under § 809.10(b) of this chapter must include the following: (i) A detailed device description, including all device components; (ii) Performance characteristics from applicable analytical studies, including nucleic acid stability and microorganism inactivation; (iii) A limiting statement that erroneous results may occur when the transport device is not compatible with molecular testing; and (iv) A limiting statement that the device has only been validated to preserve the representative microorganisms used in the analytical studies. (3) Design verification and validation must include the following: (i) Overall device design, including all device components and all control elements incorporated into the analytical validation procedures; (ii) Thorough description of the microorganisms and methodology used in the validation of the device including, extraction platforms and assays used for the detection of preserved nucleic acids; and (iii) The limit of detection (LoD) of the molecular test used to establish microorganism nucleic acid stability. [90 FR 19645, May 9, 2025] § 866.2952 Device to preserve and stabilize relative abundances of microbial nucleic acids in clinical samples. (a) Identification. i.e., (b) Classification. (1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include a detailed description of the type(s) of human specimens intended for collection and preservation, and the characteristics of the microbial population intended for subsequent analysis. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, ancillary reagents required but not provided, and all other parts that make up the device. (ii) A warning statement that the device is not for the detection of specific microbial pathogens. (iii) A warning statement that the device should only be used with legally marketed assays that are indicated for use with the device, including, as appropriate, indicated for the relevant storage and transport conditions. (iv) Description of the microorganisms used for studies, including the results and performance summaries, required under paragraph (b)(3)(i) of this section. (3) Design verification and validation must include: (i) Detailed documentation and results from studies used for device validation. This detailed documentation must include a detailed identification of each of the following (which must be representative of the spectrum of situations in which the device might be used that are within the scope of the device's intended use): the panel of microorganisms, the extraction platforms, the assay protocols used to measure the stabilization of relative ratios (relative abundance) of the microorganisms in the sample, and the bioinformatic pipelines used in the validation studies for the determination of relative abundances of preserved nucleic acids. (ii) For devices intended for the collection of samples, detailed documentation and results from studies that demonstrate the device's usability, including user collection studies that demonstrate that the user instructions are appropriate for the intended collection methods ( e.g., [91 FR 24342, May 6, 2026] Subpart D—Serological Reagents § 866.3010 Acinetobacter calcoaceticus (a) Identification. Acinetobacter calcoaceticus Acinetobacter calcoaceticus Acinetobacter calcoaceticus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3020 Adenovirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3035 Arizona (a) Identification. Arizona Arizona Arizona Arizona (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3040 Aspergillus (a) Identification. Aspergillus Aspergillus Aspergillus. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3045 In vitro diagnostic device for Bacillus (a) Identification. Bacillus Bacillus B. anthracis Bacillus Bacillus Bacillus B. anthracis Bacillus B. anthracis B. anthracis, B. cereus. (b) Classification. Bacillus (c) Restriction on Distribution. (d) Restriction on Use. (1) The device must be in the possession of: (i)(A) A person, or his agents or employees, regularly and lawfully engaged in the manufacture, transportation, storage, or wholesale or retail distribution of such device; or (B) A practitioner, such as a physician, licensed by law to use or order the use of such device; and (ii) The device must be sold only to or on the prescription or other order of such practitioner for use in the course of his professional practice. (2) The label of the device shall bear the statement “Caution: Federal law restricts this device to sale by or on the order of a ____”, the blank to be filled with the word “physician” or with the descriptive designation of any other practitioner licensed by the law of the State in which he practices to use or order the use of the device. (3) Any labeling, as defined in section 201(m) of the Federal Food, Drug, and Cosmetic Act, whether or not it is on or within a package from which the device is to be dispensed, distributed by, or on behalf of the manufacturer, packer, or distributor of the device, that furnishes or purports to furnish information for use of the device contains adequate information for such use, including indications, effects, routes, methods, and frequency and duration of administration and any relevant hazards, contraindications, side effects, and precautions, under which practitioners licensed by law to employ the device can use the device safely and for the purposes for which it is intended, including all purposes for which it is advertised or represented. This information will not be required on so-called reminder-piece labeling which calls attention to the name of the device but does not include indications or other use information. (4) All labeling, except labels and cartons, bearing information for use of the device also bears the date of the issuance or the date of the latest revision of such labeling. [84 FR 12088, Apr. 1, 2019] § 866.3046 Simple in vitro diagnostic device for the detection of secreted proteins from Bacillus (a) Identification. in vitro Bacillus in vitro B. anthracis Bacillus Bacillus Bacillus B. anthracis, B. cereus. (b) Classification. (1) The distribution of these devices is limited to laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of the sample types with which this device is intended to be used; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under 21 CFR 809.10(b) of this chapter must include: (i) An intended use statement that includes the following: (A) A detailed description of targets the device detects and measures; (B) The results provided to the user ( i.e., (C) The clinical indications appropriate for test use ( e.g., (D) Sample types with which it is intended for use; (E) The specific population(s) with which the device is intended to be used; (F) The testing location(s) where the device is to be used (if not intended for all locations); (G) A statement that the device results are for the presumptive identification of Bacillus (H) A statement that negative results do not preclude infection with Bacillus (I) A statement that testing is to be performed and reported in accordance with current guidelines provided by the appropriate public health authorities. (ii) Detailed instructions for minimizing the risk of user exposure to Bacillus (iii) Detailed instructions for minimizing the risk of generating false positive test results due to contamination from positive test samples and/or positive control materials. (iv) A prominent and conspicuous precaution that interpretation of test results is intended to be performed by experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and the expertise to report results. (v) A prominent and conspicuous warning statement that the test results alone do not conclusively establish infection and that additional testing and confirmation procedures may be necessary in consultation with the appropriate public health or other authorities to whom reporting is required. (vi) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of samples. (vii) Detailed descriptions of the performance characteristics of the device for all claimed sample types as shown by the analytical and clinical studies required under paragraphs (b)(4)(ii) and (b)(4)(iii) of this section, except sample stability performance characteristics. (viii) For any devices intended for use in a near-patient setting, a brief reference sheet for healthcare professionals that accompanies the device and that includes the name and intended use of the test, step-by-step instructions of all control and sample testing procedures for the claimed sample types, the result(s) interpretation, warning and limitation statements, and information for troubleshooting or technical assistance with the device. (ix) A statement that a nationally notifiable disease caused by a biothreat microbial agent must be reported to public health authorities in accordance with local, state, and federal law. (x) Limiting statements indicating, as applicable: (A) Situations where the device has been demonstrated to fail or may not perform at its expected performance level ( e.g., (B) Any specific circumstances that pose significant risk to public health, and for which the device has not been validated. For example: ( 1 ( 2 (4) Design verification and validation must include: (i) A detailed device description, including all device parts, control elements incorporated into the test procedure, reagents required but not provided, the principle of device operation and test methodology, and the computational path from collected raw data to reported result ( e.g., (ii) Detailed documentation of analytical studies, as applicable, including those demonstrating limit of detection, inclusivity, cross-reactivity, microbial interference, interfering substances, carryover/cross contamination, sample stability, within lab precision, hook effect, reproducibility, and other studies relevant to the technology ( e.g., (iii) Detailed documentation and results from either a clinical study or, when determined to be acceptable by FDA, a study with an equivalent data set. Documentation from this study must include study reports, testing results, and results of all statistical analyses, including line data of all test samples, and an appropriate justification describing how the sample set is representative of the intended use population. This study must compare the device performance to results obtained from a reference or comparator method that FDA has determined to be appropriate. This study must include prospective (sequentially collected) samples for each intended sample type that are representative of the intended use populations and may, when determined to be acceptable by FDA, include additional characterized clinical samples; or, as an alternative, when determined to be acceptable by FDA, an equivalent sample set. This study must include samples spanning all relevant analyte concentrations for all of the indicated sample type(s) and the targeted analyte(s). (iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions, as applicable. (v) For any devices that detect the presence of an analyte directly from sample, detailed documentation and results from a shelf-life assessment that includes samples formulated in the most complex clinical matrix identified in the device's intended use. (vi) As part of the risk management activities, if the labeling includes hyperlinks to documents from public health authorities regarding sampling, sample shipment, sample testing, or clinical management of patients suspected of being infected; or if the labeling includes direct contact information for any such public health authority, then the hyperlinks and contact information must be reviewed at least annually and updated to reflect any changes to those hyperlinks or contact information. [91 FR 36978, June 22, 2026] § 866.3050 Beta-glucan serological assays. (a) Identification. (b) Classification. [69 FR 56936, Sept. 23, 2004] § 866.3060 Blastomyces dermatitidis (a) Identification. Blastomyces dermatitidis Blastomyces determatitidis Blastomyces dermatitidis. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3065 Bordetella (a) Identification. Bordetella Bordetella Bordetella Bordetella Bordetella pertussis (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3085 Brucella (a) Identification. Brucella Brucella Brucella Brucella Brucella (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3110 Campylobacter fetus (a) Identification. Campylobacter fetus Campylobacter fetus Campylobacter fetus (b) Classification. § 866.3120 Chlamydia serological reagents. (a) Identification. Chlamydia (b) Classification. § 866.3125 Citrobacter (a) Identification. Citrobacter Citrobacter Citrobacter Citrobacter (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3130 Clostridium difficile toxin gene amplification assay. (a) Identification. Clostridium difficile Clostridium difficile Clostridium difficile Clostridium difficile. (b) Classification. Clostridium difficile; [80 FR 51939, Aug. 27, 2015] § 866.3135 Coccidioides immitis (a) Identification. Coccidioides immitis Coccidioides immitis Coccidioides Coccidioides immitis (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3140 Corynebacterium (a) Identification. Corynebacterium Corynebacterium Corynebacterium Corynebacterium diphtheriae, (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3145 Coxsackievirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3165 Cryptococcus neoformans (a) Identification. Cryptococcus neoformans Cryptococcus neoformans Cryptococcus neoformans (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3169 Hepatitis C virus antibody tests. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors. (ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: (A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected. (B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results. (D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test. (iii) A detailed explanation of the principles of operation and procedures for performing the test. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and nature of all primary, secondary, and subsequent standards used for calibration. (ii) Documentation and characterization ( e.g., (iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (iv) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) Final release test results for each lot used in clinical studies. (viii) Multisite reproducibility study that includes the testing of three independent production lots. (ix) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (x) Analytical sensitivity of the test is the same or better than that of other cleared or approved tests. (xi) Detailed documentation of clinical performance testing from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved HCV antibody test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an acceptable number of HCV positive and negative samples in applicable risk categories. Additional relevant patient groups must be validated as appropriate. The samples may be a combination of fresh and repository samples, sourced from geographically diverse areas. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (A) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (B) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (3) For any HCV antibody test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment. [86 FR 66176, Nov. 22, 2021] § 866.3170 Nucleic acid-based hepatitis C virus ribonucleic acid tests. (a) Identification. (b) Classification. (1) For all nucleic acid-based HCV RNA tests, the labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for use as a donor screening test for the presence of HCV RNA from human cells, tissues, and cellular and tissue-based products. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. These limitations must include, but are not limited to, statements that indicate: (A) The specimen types for which the device has been cleared and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results. (B) When applicable, that assay performance characteristics have not been established in populations of immunocompromised or immunosuppressed patients or, other populations where test performance may be affected. (C) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (2) For all nucleic acid-based HCV RNA tests, the design verification and validation must include: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included such as design of primers and probes, rationale for the selected gene targets, specifications for amplicon size, and degree of nucleic acid sequence conservation. (ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., (iii) Documentation and characterization ( e.g., (iv) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of detection (LoD), upper and lower limits of quantitation (ULoQ and LLoQ, respectively), linearity, precision, endogenous and exogenous interferences, cross reactivity, carryover, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies must include samples from HCV RNA negative subjects with other causes of liver disease, including autoimmune hepatitis, alcoholic liver disease, chronic hepatitis B virus, primary biliary cirrhosis, and nonalcoholic steatohepatitis, when applicable. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated. (v) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (vi) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Multisite reproducibility study that includes the testing of three independent production lots. (viii) All stability protocols, including acceptance criteria. (ix) Final release test results for each lot used in clinical studies. (x) Analytical sensitivity and specificity of the test must be the same or better than that of other cleared or approved tests. (xi) Lot-to-lot precision studies, as appropriate. (3) For devices intended for the qualitative detection of HCV RNA, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, the design verification and validation must include detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved qualitative HCV RNA test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with appropriate numbers of HCV positive and negative samples in applicable risk categories. Additional genotypes must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (i) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (ii) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (4) For devices intended for the quantitative detection of HCV RNA, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Labeling required under § 809.10(b) of this chapter must include a prominent statement that the test is not intended as a diagnostic test to confirm the presence of active HCV infection, when applicable. (ii) Design verification and validation must include the following: (A) Detailed documentation of the following analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including but not limited to: LoD, ULoQ and LLoQ. LoD, LLoQ, and linearity studies must demonstrate acceptable device performance with all HCV genotypes detected by the device. (B) Detailed documentation of clinical performance testing from either: ( 1 ( 2 (C) Detailed documentation of a qualitative analysis near the lower end of the measuring range demonstrating acceptable performance when used as an aid in diagnosis. (5) For devices intended for HCV RNA genotyping, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, design verification and validation must include the following: (i) Detailed documentation of an analytical performance study demonstrating the LoD for all HCV genotypes detected by the device. (ii) Detailed documentation, including results, of a multisite clinical study that assesses genotyping accuracy ( i.e., i.e., (6) For any nucleic acid-based HCV RNA test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment. [86 FR 66172, Nov. 22, 2021] § 866.3172 Qualitative hepatitis B virus antigen assays. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate: (A) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (B) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other populations where assay performance may be affected. (C) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures. (D) Detection of HBV antigens indicates a current infection with hepatitis B virus but does not differentiate between acute or chronic infection. False reactive HbsAg result may occur for up to 2 weeks after vaccination with HbsAg containing vaccine. (E) Current methods for the detection of hepatitis B antigens may not detect all potentially infected individuals. A non-reactive assay result does not exclude the possibility of exposure to or infection with hepatitis B virus. A non-reactive assay result in individuals with prior exposure to hepatitis B may be due to but not limited to antigen levels below the detection limit of this assay or lack of antigen reactivity to the antibodies in this assay. HBV mutants lacking the ability to produce antigens have been reported. These may occur as “escape” mutants in the presence of anti-HBV antibodies and such patients may be infectious. (F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, design of the capture antibody(ies), external controls, and computational path from collected raw data to reported result ( e.g., (ii) For devices with assay calibrators, the design and composition of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., (iii) Documentation and characterization ( e.g., (iv) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (v) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specifications will meet the identified analytical and clinical performance characteristics as well as stability. (vi) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vii) All stability protocols, including acceptance criteria. (viii) Final release assay results for each lot used in clinical studies. (ix) Reproducibility study data that includes the testing of three independent production lots. (x) Detailed documentation of analytical performance studies conducted, as appropriate to the technology, specimen types tested, and intended use of the device, including, the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, prominent mutants/variants detection ( e.g., (xi) Analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (xii) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xiii) Detailed documentation and results from a clinical study. Performance must be analyzed relative to an FDA cleared or approved HBV antigen assay or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an appropriate number of HBV reactive and non-reactive samples in applicable risk and disease categories, and any applicable confirmatory testing. Additional relevant patient groups must be validated as appropriate. The samples must include prospective (sequential) samples for each identified specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas. This study must be conducted in the appropriate settings by the intended users to demonstrate clinical performance. [90 FR 44975, Sept. 18, 2025] § 866.3173 Hepatitis B virus antibody assays. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for the screening of blood, plasma, cells, or tissue donors. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include statements that indicate: (A) When appropriate, performance characteristics of the assay have not been established in populations of immunocompromised or immunosuppressed patients or other special populations where assay performance may be affected. (B) Detection of HBV antibodies to a single viral antigen indicates a present or past infection with hepatitis B virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (D) Diagnosis of hepatitis B infection should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures. (E) A non-reactive assay result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the assay. (F) Results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (v) For devices intended for the quantitative detection of HBV antibodies (anti-HBs), in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, labeling required under § 809.10(b) of this chapter must include: (A) The assay calibrators' traceability to a standardized reference material that FDA has determined is appropriate ( e.g., (B) Performance results of the analytical sensitivity study testing a standardized reference material that FDA has determined is appropriate ( e.g., (2) Design verification and validation must include the following: (i) Detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and composition of all primary, secondary and subsequent standards used for calibration. (ii) Documentation and characterization ( e.g., (iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (iv) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specifications will meet the identified analytical and clinical performance characteristics as well as stability. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) When applicable, analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (viii) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility), including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (ix) For devices intended for the detection of antibodies for which a standardized reference material (that FDA has determined is appropriate) is available, the analytical sensitivity study and results testing the standardized reference material. Detailed documentation of that study and its results must be provided, including the study protocol, study report, testing results, and all statistical analyses. (x) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xi) Detailed documentation of clinical performance testing from a clinical study with an appropriate number of HBV reactive and non-reactive samples in applicable risk categories and conducted in the appropriate settings by the intended users. Performance must be analyzed relative to an FDA cleared or approved HBV antibody assay or a comparator that FDA has determined is appropriate. Additional relevant patient groups must be validated as appropriate. The samples must include prospective (sequential) samples for each identified specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas. (3) For any HBV antibody assay intended for quantitative detection of anti-HBV antibodies, the following special controls, in addition to those special controls listed in paragraphs (b)(1) and (2) of this section, also apply: (i) Detailed documentation of the metrological calibration traceability hierarchy to a standardized reference material that FDA has determined is appropriate. (ii) Detailed documentation of the following analytical performance studies conducted, as appropriate to the technology, specimen types tested, and intended use of the device, including upper and lower limits of quantitation (UloQ and LloQ, respectively), linearity using clinical samples, and an accuracy study using the recognized international standard material. [90 FR 44976, Sept. 18, 2025] § 866.3174 Hepatitis B virus nucleic acid-based assays. (a) Identification. (b) Classification. (1) Labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the assay is not intended for use as a screening assay for the presence of HBV DNA in blood or blood products, plasma, cells, or tissue donors, or as a diagnostic assay to confirm the presence of HBV infection. (ii) A detailed explanation of the principles of operation and procedures for performing the assay. (iii) A detailed explanation of the interpretation of results. (iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and/or management. These limitations must include statements that indicate: (A) Management of patients undergoing HBV treatment should not be established on the basis of a single assay result but should be determined by a licensed healthcare professional in conjunction with the clinical presentation, history, and other diagnostic procedures, e.g., (B) The specimen types for which the device has been cleared, and that use of this assay with specimen types other than those specifically cleared for this device may result in inaccurate assay results. (C) The results obtained with this assay may not be used interchangeably with results obtained with a different manufacturer's assay. (2) Design verification and validation must include the following: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included such as design of primers and probes, rationale for the selected gene targets, specifications for amplicon size, and degree of nucleic acid sequence conservation. (ii) For devices with assay calibrators, the design and composition of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate ( e.g., (iii) Documentation and characterization ( e.g., (iv) Risk analysis and management strategies demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on assay performance. (v) Final release criteria to be used for manufactured assay lots with appropriate evidence that lots released at the extremes of the specification will meet the identified analytical and clinical performance characteristics as well as stability. (vi) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vii) All stability protocols, including acceptance criteria. (viii) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including limit of detection (LoD), linearity, precision, endogenous and exogenous interferences, cross-reactivity, carryover, matrix equivalency, sample and reagents stability, and as applicable, upper and lower limits of quantitation (ULoQ and LLoQ, respectively). Samples selected for use must be from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies must include samples from HBV nucleic acid negative subjects with other viral or non-viral causes of liver disease, including autoimmune hepatitis, alcoholic liver disease, chronic hepatitis C virus, primary biliary cirrhosis, and nonalcoholic steatohepatitis, when applicable. The effect of each identified nucleic-acid isolation and purification procedure on detection must be evaluated. (ix) Analytical sensitivity of the assay that is the same or better than that of other cleared or approved assays. (x) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (xi) Detailed documentation of performance from a clinical study with a design and number of clinical samples (appropriately statistically powered) that is appropriate for the intended use of the device as well as conducted in the appropriate settings by the intended users. The samples must include prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. Samples must be sourced from geographically diverse areas. [90 FR 44977, Sept. 18, 2025] § 866.3175 Cytomegalovirus serological reagents. (a) Identification. (b) Classification. § 866.3180 Quantitative cytomegalovirus nucleic acid tests for transplant patient management. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the device is not intended for use as a donor screening test for the presence of CMV DNA in blood or blood products. (ii) Limitations, which must be updated to reflect current clinical practice. The limitations must include, but are not limited to, statements that indicate: (A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; (B) Negative test results do not preclude CMV infection or tissue invasive CMV disease, and that CMV test results must not be the sole basis for patient management decisions. (iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in CMV viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in CMV viral load measurements across different CMV assays, it is recommended that the same device be used for the quantitation of CMV viral load when managing CMV infection in individual patients.” (iv) A detailed explanation of the principles of operation and procedures for assay performance. (2) Design verification and validation must include the following: (i) Detailed documentation of the device description, including all parts that make up the device, reagents required for use with the CMV assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary, and tertiary quantitation standards used for calibration must also be described. (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's function. (iii) Documentation and characterization of all critical reagents ( e.g., (iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life. (v) All stability protocols, including acceptance criteria. (vi) Final lot release criteria, along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel CMV stains ( e.g., (viii) Analytical performance testing that includes: (A) Detailed documentation of the following analytical performance studies: Limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device. (B) Identification of the CMV strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains. (C) Inclusivity study results obtained with a variety of CMV genotypes as applicable to the specific assay target and supplemented by in silico analysis. (D) Reproducibility studies that include the testing of three independent production lots. (E) Documentation of calibration to a standardized reference material that FDA has determined is appropriate for the quantification of CMV DNA ( e.g., (F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material. (ix) Clinical performance testing that includes: (A) Detailed documentation of device performance data from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device. (B) Data from patient samples, with an acceptable number of the CMV positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. (C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol. (D) The final release test results for each lot used in the clinical study. [89 FR 77450, Sept. 23, 2024] § 866.3181 Cytomegalovirus nucleic acid detection device for congenital cytomegalovirus infection. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use with a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) to be tested. (ii) A detailed device description, including all device components, instrument requirements, ancillary reagents required but not provided, and an explanation of the methodology, including all pre-analytical methods for specimen processing. (iii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section. (iv) A detailed explanation of the interpretation of results and criteria for validity of results. (v) A limiting statement that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. (vi) As applicable, a limiting statement and specific sample collection recommendations to indicate that breast milk can result in false positive results for saliva samples if samples are collected less than 1 hour after breastfeeding. Sample collection a minimum of 1 hour from breastfeeding must be recommended. (vii) Detailed instructions for use that minimize the risk of generating a false result. (2) Design verification and validation must include: (i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for sequence selection, and computational path from collected raw data to reported result ( e.g., (ii) Detailed documentation of analytical studies including characterization of the cutoff, analytical sensitivity (limit of detection), inclusivity, reproducibility, interference, cross reactivity, instrument and method carryover/cross contamination, and sample stability and handling. (iii) Detailed documentation from a clinical study documenting sensitivity and specificity of the device; if the number of positive samples in the clinical study is insufficient to properly estimate device sensitivity, additional pre-selected positive samples must be evaluated to supplement the study. Clinical study subjects must be consistent with the intended use population ( i.e., (iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software. [90 FR 19636, May 9, 2025] § 866.3183 Quantitative viral nucleic acid test for transplant patient management. (a) Identification. (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the device is not intended for use as a donor screening test for the presence of viral nucleic acid in blood or blood products. (ii) Limitations which must be updated to reflect current clinical practice. These limitations must include, but are not limited to, statements that indicate: (A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; and (B) Negative test results do not preclude viral infection or tissue invasive viral disease and that test results must not be the sole basis for patient management decisions. (iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in [analyte] measurements across different [analyte] assays, it is recommended that the same device be used for the quantitation of [analyte] when managing individual patients.” (iv) A detailed explanation of the principles of operation and procedures for assay performance. (2) Design verification and validation must include the following: (i) Detailed documentation of the device description, including all parts that make up the device, ancillary reagents required for use with the assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary and tertiary quantitation standards used for calibration must also be described. (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions; (iii) Documentation and characterization ( e.g., (iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life. (v) All stability protocols, including acceptance criteria. (vi) Final lot release criteria along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Mode Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel viral stains ( e.g., (viii) Analytical performance testing that includes: (A) Detailed documentation of the following analytical performance studies: limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device; (B) Identification of the viral strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains; (C) Inclusivity study results obtained with a variety of viral genotypes as applicable to the specific assay target and supplemented by in silico analysis; (D) Reproducibility studies that include the testing of three independent production lots; (E) Documentation of calibration to a reference standard that FDA has determined is appropriate for the quantification of viral DNA or RNA ( e.g., (F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material. (ix) Clinical performance testing that includes: (A) Detailed documentation from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device; (B) Data from patient samples, with an acceptable number of the virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. If an acceptable number of virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision cannot be obtained, contrived samples may be used to supplement sample numbers when appropriate, as determined by FDA; (C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol; and (D) The final release test results for each lot used in the clinical study. [89 FR 75954, Sept. 17, 2024] § 866.3200 Echinococcus (a) Identification. Echinococcus Echinococcus Echinococcus Echinococcus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3205 Echovirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3210 Endotoxin assay. (a) Identification. (b) Classification. [68 FR 62008, Oct. 31, 2003. Redesignated at 70 FR 53069, Sept. 7, 2005] § 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended. (2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection. (3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability. (4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information: (i) Results must demonstrate adequate device performance relative to a well-accepted comparator. (ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population. (iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses. (5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics ( e.g., (6) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples ( e.g., [82 FR 49099, Oct. 24, 2017, as amended at 90 FR 55982, Dec. 4, 2025] § 866.3220 Entamoeba histolytica (a) Identification. Entamoeba histolytica Entamoeba histolytica Entamoeba histolytica Entamoeba histolytica (b) Classification. [47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3225 Enterovirus nucleic acid assay. (a) Identification. (b) Classification. [74 FR 8, Jan. 2, 2009] § 866.3230 Device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections. (a) Identification. (b) Classification. (1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use with a detailed description of what the device detects and measures, the type of results provided to the user, the sample type, whether the measure is qualitative and/or quantitative, the clinical indications for the test use, and the specific population(s) for which the device is intended. (ii) A detailed description of the performance characteristics of the device for all intended specimen types from the analytical and clinical studies (as applicable) required under paragraphs (b)(3)(ii) and (iii) of this section. (iii) A detailed explanation of the interpretation of results, including acceptance criteria for evaluating the validity of individual runs ( e.g., (iv) The following limiting statements: (A) A statement that a negative test result does not preclude the possibility of infection; (B) A statement that the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) A statement that consistent device performance is dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (D) A statement that details any limitations associated with the samples, as appropriate ( e.g., (3) Design verification and validation must include the following: (i) A detailed device description, including as appropriate, all device parts; control elements incorporated into the test procedure; instrument requirements; reagents required but not provided; and the principle of device operation and test methodology, including all preanalytical methods for the processing of specimens and the methodology from obtaining a sample to the result; design of primer/probe sequences; rationale for target analyte selection; and computational path from collected raw data to reported result ( e.g., (ii) Detailed documentation of analytical studies including analytical sensitivity (Limit of Detection, Limit of Quantitation, and Limit of Blank), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross-contamination, specimen stability, within-lab precision, reproducibility, and linearity, as applicable. (iii) Detailed documentation and results either from a clinical study, that includes prospective (sequentially collected) samples for each intended specimen type that are representative of the intended use populations and, when determined to be acceptable by FDA, additional characterized clinical samples; or, when determined to be acceptable by FDA, an equivalent sample set. The clinical study must compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol ( e.g., (iv) An evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics ( e.g., (v) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risks of false results, failure to operate the device correctly, and failure to interpret test results correctly. (vi) An appropriate risk mitigation strategy to ensure that the device does not prevent any other device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use ( e.g., (vii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions. [90 FR 19643, May 9, 2025] § 866.3231 Device to detect bacterial protease activity in chronic wound fluid. (a) Identification. (b) Classification. (1) Any swab used to collect a patient specimen must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of wound fluid specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that includes the following statements: (A) A statement that the device detects and measures bacterial proteases from a swab saturated with wound fluid. (B) A statement that the device provides a qualitative output to aid the user in assessing the risk for non-healing of wounds ( e.g., (C) A description of the clinical indications for test use. (D) The specific population(s) for which the device is intended. (E) A description of the recommended training ( e.g., (ii) A detailed description of the performance characteristics of the device from the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section. (iii) A detailed explanation of the interpretation of results. (iv) A warning statement describing situations where the device has not been validated or may not perform as identified in the labeling ( e.g., 2 (v) The following limiting statements: (A) That the device is not intended to provide a risk assessment of chronic wound infection status or aid in the diagnosis of infection in chronic wounds, nor is the device intended for monitoring the effectiveness of anti-infective therapy. (B) That a negative result does not exclude the presence of bacterial proteases. Therefore, the results should be used in conjunction with clinical findings to make an accurate assessment of risk of nonhealing. The test result should be interpreted in conjunction with other risk factors, along with clinical and laboratory data available to the clinician. (C) That the device has been validated using wound fluid samples only. Other sample types ( e.g., (D) That skin flora may secrete bacterial proteases therefore, swab contact with intact skin should be avoided as this may yield false positive results. (vi) Labeling must include a brief reference sheet for healthcare professionals that includes the intended use, summary of clinical performance, results from analytical testing on normal skin and human proteases, and warning and limiting statements. (3) Design verification and validation must include the following: (i) A detailed device description ( e.g., (ii) Detailed documentation and results from analytical studies, including the limit of detection, inclusivity, cross-reactivity, microbial interference, analytical sensitivity for normal skin flora and human proteases, interfering substances, specimen stability, within-lab precision, and reproducibility. (iii) Detailed documentation and results from a clinical study that includes prospective (sequentially collected) samples for the intended specimen type that are representative of the intended use population(s). The clinical study must compare the device performance to results obtained from a reference or comparator method that FDA has determined is appropriate. [90 FR 23282, June 2, 2025] § 866.3235 Epstein-Barr virus serological reagents. (a) Identification. (b) Classification. § 866.3236 Device to detect or measure nucleic acid from viruses associated with head and neck cancers. (a) Identification. (b) Classification. (1) Any device used for specimen collection and transport must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include, as determined to be appropriate by FDA: (i) An intended use statement that includes the following: (A) The analyte(s) detected by the device; (B) Data output of the device (qualitative, semiquantitative, or quantitative); (C) The specimen types with which the device is intended for use; (D) The clinical indications appropriate for test use ( e.g., (E) The intended use populations ( e.g., (F) The intended use location(s) ( e.g., (ii) A detailed device description, including reagents, instruments, ancillary materials, specimen collection and transport devices, controls, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (iii) A detailed explanation of the interpretation of results. (iv) Limiting statements indicating: (A) The device is not intended for use in screening for head and neck cancer in asymptomatic populations. (B) Results of the device are not predictive of a patient's future risk of head and neck cancer. (C) Patients who test negative for the virus should be managed in accordance with the standard of care, based on the assessment of endoscopy and/or other clinical information by a licensed healthcare professional. (D) Results of the device are not intended to be used as the sole basis for determining the need for biopsy or for any other patient management decision. (3) Design verification and validation must include the following: (i) A detailed device description including pre-analytical specimen processing, assay technology, target region, primer/probe sequences, reagents, controls, instrument requirements, and the computational path from collected raw data to reported result. (ii) Detailed documentation and results from analytical performance studies, including characterization of the cutoff(s), limit of detection, limit of quantitation, precision (including multisite reproducibility, if applicable), inclusivity, cross-reactivity, interference, carryover/cross-contamination, reagent stability, and specimen/sample stability, as determined to be appropriate by FDA. (iii) Detailed documentation of a clinical performance study that includes patients from the intended use population, including the clinical study protocol, with a predefined statistical analysis plan, and a clinical study report with testing results and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and software incorporated in hardware-based devices, on the device's functions. [89 FR 75493, Sept. 16, 2024] § 866.3240 Equine encephalomyelitis virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3250 Erysipelothrix rhusiopathiae (a) Identification. Erysipelothrix rhusiopathiae Erysipelothrix rhusiopathiae Erysipelothrix. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3255 Escherichia coli (a) Identification. Escherichia coli Escherichia coli Escherichia coli Escherichia coli Escherichia, Escherichia coli (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001] § 866.3270 Flavobacterium (a) Identification. Flavobacterium Flavobacteriuim Flavobacterium Flavobacterium meningosepticum (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3280 Francisella tularensis (a) Identification. Francisella tularensis Francisella tularensis Francisella tularensis Francisella tularensis Francisella tularensis (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3290 Gonococcal antibody test (GAT). (a) Identification. Neisseria gonorrhoeae Neisseria gonorrhoeae. (b) Classification. (c) Date PMA or notice of completion of a PDP is required. [47 FR 50823, Nov. 9, 1982, as amended at 52 FR 17734, May 11, 1987] § 866.3300 Haemophilus (a) Identification. Haemophilus Haemophilus Haemophilus Haemophilus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998] § 866.3305 Herpes simplex virus serological assays. (a) Identification. (b) Classification. [72 FR 15830, Apr. 3, 2007, as amended at 74 FR 42775, Aug. 25, 2009; 76 FR 48717, Aug. 9, 2011] § 866.3307 Herpes simplex virus nucleic acid-based assay for central nervous system infections. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) Detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer design and selection. (ii) Detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination. Documentation must include reagent and sample stability recommendations. (iii) Detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to the results of two polymerase chain reaction methods followed by bidirectional sequencing. (iv) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument. (v) Quality assurance protocols and detailed documentation for device software, including standalone software applications and hardware-based devices that incorporate software. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed explanation of the interpretation of results and acceptance criteria. (ii) A limiting statement indicating that negative results do not preclude HSV-1 or HSV-2 infection and should not be used as the sole basis for treatment or other patient management decisions. [90 FR 27235, June 26, 2025] § 866.3309 Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel. (a) Identification. (b) Classification. (1) Premarket notification submissions must include detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer design and selection. (2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination. (3) Premarket notification submissions must include detailed documentation of a clinical study using lesion samples in which Herpes Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA detection was requested. The study must compare the device performance to an appropriate well established reference method. (4) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (5) The device labeling must include a limitation statement that reads: “The device is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS).” (6) Premarket notification submissions must include quality assurance protocols and a detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (7) The risk management activities performed as part of the manufacturer's 21 CFR 820.10(c) design and development activities must document an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument. [83 FR 52314, Oct. 17, 2018, as amended at 90 FR 55982, Dec. 4, 2025] § 866.3310 Hepatitis A virus (HAV) serological assays. (a) Identification. (b) Classification. [71 FR 6679, Feb. 9, 2006] § 866.3320 Histoplasma capsulatum (a) Identification. Histoplasma capsulatum Histoplasma capsulatum Histoplasma capsulatum Histoplasma capsulatum Histoplasma (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3328 Influenza virus antigen detection test system. (a) Identification. (b) Classification. (1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria: (i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method: (A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method: (A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent. (B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent. (2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies. (3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. (4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. [82 FR 3618, Jan. 12, 2017] § 866.3330 Influenza virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3332 Reagents for detection of specific novel influenza A viruses. (a) Identification. (b) Classification. (1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document. (2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment. [71 FR 14379, Mar. 22, 2006] § 866.3336 John Cunningham Virus serological reagents. (a) Identification. (b) Classification. [79 FR 3740, Jan. 23, 2014] § 866.3340 Klebsiella (a) Identification. Klebsiella Klebsiella Klebsiella (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3350 Leptospira (a) Identification. Leptospira Leptospira Leptospira Leptospira Leptospira Leptospira (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3355 Listeria (a) Identification. Listeria Listeria Listeria Listeria Listeria, Listeria monocytogenes, (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3360 Lymphocytic choriomeningitis virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3361 Mass spectrometer system for clinical use for the identification of microorganisms. (a) Identification. (b) Classification. (1) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (2) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols. (3) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (4) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (5) Premarket notification submissions must include details on the appropriate end user device training program that will be offered while marketing the device. [82 FR 49101, Oct. 24, 2017, as amended at 90 FR 55982, Dec. 4, 2025] § 866.3365 Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures. (a) Identification. (b) Classification. [80 FR 30154, May 27, 2015] § 866.3367 Device to detect and identify microbial nucleic acids by FISH in clinical specimens. (a) Identification. (b) Classification. (1) Design verification and validation must include the following: (i) Detailed device description documentation, including the device components, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens, probe sequences, and rationale for probe sequence selection; (ii) Detailed description of the fluorophores, signal source, detection mechanism, and method of result interpretation; (iii) Detailed documentation from the following analytical studies: analytical sensitivity (Limit of Detection), inclusivity, reproducibility, interference, cross reactivity, and specimen stability; and (iv) Detailed documentation from a clinical study that includes prospective (sequential) samples. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from appropriate and well-accepted comparator methods. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A statement that the device is intended to be used in conjunction with clinical history, signs, symptoms, and the results of other diagnostic testing; (ii) A detailed explanation of the interpretation of results and acceptance criteria for any quality control testing; and (iii) A limitation that negative results do not preclude the possibility of infection. [90 FR 19638, May 9, 2025] § 866.3370 Mycobacterium tuberculosis (a) Identification. Mycobacterium tuberculosis Mycobacterium tuberculosis Mycobacterium tuberculosis (b) Classification. § 866.3372 Nucleic acid-based in vitro diagnostic devices for the detection of Mycobacterium tuberculosis complex in respiratory specimens. (a) Identification. Mycobacterium tuberculosis Mycobacterium tuberculosis (b) Classification. Mycobacterium tuberculosis [79 FR 31027, May 30, 2014] § 866.3373 Nucleic acid-based in vitro diagnostic devices for the detection of Mycobacterium tuberculosis complex (MTB-complex) and the genetic mutations associated with MTB-complex antibiotic resistance in respiratory specimens. (a) Identification. Mycobacterium tuberculosis (b) Classification. (1) The FDA document entitled “Class II Special Controls Guideline: Nucleic Acid-Based In Vitro Diagnostic Devices for the Detection of Mycobacterium tuberculosis (2) The following items, which address the mitigation of risks specific to the detection of the genetic mutations associated with antibiotic resistance of MTB-complex: (i) The device must include an external positive assay control as appropriate. Acceptable positive assay controls include MTB-complex isolates containing one or more antibiotic-resistance associated target sequences detected by the device. (ii) The device must include internal controls as appropriate. An acceptable internal control may include human nucleic acid co-extracted with MTB-complex containing nucleic acid sequences associated with antibiotic resistance and primers amplifying human housekeeping genes (e.g., RNaseP, β-actin). (iii) The device's intended use must include a description of the scope of antibiotic resistance targeted by the assay, i.e., the specific drugs and/or drug classes. (iv) The specific performance characteristics section of the device's labeling must include information regarding the specificity of the assay oligonucleotides for detecting mutations associated with antibiotic resistance of MTB-complex, and any information indicating the potential for non-specific binding (e.g., BLAST search). (v) In demonstrating device performance you must perform: (A) Pre-analytical studies that evaluate: ( 1 Frozen samples. ( 2 Nucleic acid extraction methods. (B) Analytical studies that analyze: ( 1 Limit of Detection. ( 2 Analytical Reactivity (Inclusivity). ( 3 Within-Laboratory (Repeatability) Precision Testing. ( 4) Between Laboratory Reproducibility Testing. (C) Clinical Studies. Clinical performance of the device must be established by conducting prospective clinical studies that include subjects with culture confirmed active tuberculosis. Studies must attempt to enroll subjects at risk for antibiotic-resistant MTB-complex; however, it may be necessary to include supplemental antibiotic resistant retrospective and contrived samples. Clinical studies must compare device results to both phenotypic drug susceptibility testing and genotypic reference methods. The genotypic reference method must be a polymerase chain reaction based method that uses primers different from those in the experimental device and confirmed by bidirectional sequencing. [79 FR 63036, Oct. 22, 2014] § 866.3375 Mycoplasma (a) Identification. Mycoplasma Mycoplasma Mycoplasma Mycoplasma Mycoplasma Mycoplasma Mycoplasma pneumoniae (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3376 Device to detect and identify fungal nucleic acids directly in respiratory specimens. (a) Identification. (b) Classification. (1) The intended use must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) and testing location(s) for which the device is intended. (2) The labeling required under 21 CFR 809.10(b) must include: (i) A detailed device description, including the parts that make up the device, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology including all pre-analytical methods for processing of specimens. (ii) Performance characteristics from analytical studies, including analytical sensitivity (Limit of Detection), inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, and specimen stability. (iii) A statement that the device is intended to be used in conjunction with clinical history, signs and symptoms and the results of other diagnostic tests. (iv) A detailed explanation of the interpretation of test results and acceptance criteria for any quality control testing. (v) A limiting statement that negative results do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (3) Design verification and validation activities must include: (i) Performance characteristics from clinical studies that include prospective (sequential) samples and, if appropriate, additional characterized samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from comparator methods. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan), clinical study report, and results of all statistical analyses. (ii) A detailed device description of the following: (A) Overall device design including all parts that make up the device and all control elements incorporated into the testing procedure. (B) Thorough description of the methodology including, primer/probe sequences, primer/probe design and rationale for target sequence selection. (C) Computational path from collected raw data to reported result ( e.g., (iii) A detailed documentation for device software, including, software applications and hardware-based devices that incorporate software. [90 FR 24968, June 13, 2025] § 866.3378 Clinical mass spectrometry microorganism identification and differentiation system. (a) Identification. (b) Classification. (1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable. (ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples. (iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable. (iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing. (4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate. (5) Design verification and validation must include: (i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses. (ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate: (A) Bacteria, (B) Yeasts, (C) Molds, (D) Mycobacteria, (E) Nocardia, (F) Direct sample testing ( e.g., (G) Antibiotic resistance markers, and (H) Select agents ( e.g., (iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use ( e.g., (iv) A detailed device description, including the following: (A) Overall device design, including all device components and all control elements incorporated into the testing procedure. (B) Algorithm used to generate a final result from raw data ( e.g., (C) A detailed description of device software, including validation activities and outcomes. (D) Acquisition parameters ( e.g., (E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device. (F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed. (G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced. (H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error. [90 FR 24965, June 13, 2025] § 866.3380 Mumps virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2311, Jan. 14, 2000] § 866.3390 Neisseria (a) Identification. Neisseria Neisseria Neisseria Neisseria Neisseria, (b) Classification. § 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s). (a) Identification. (b) Classification. (1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate; (iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) Limiting statements indicating that: (A) A negative test result does not preclude the possibility of infection; (B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (D) If appropriate ( e.g., (v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that: (A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present; (B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora; (C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and (D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy. (4) Design verification and validation must include: (i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result ( e.g., (ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions. [90 FR 19633, May 9, 2025] § 866.3395 Norovirus serological reagents. (a) Identification. (b) Classification. [76 FR 14274, Mar. 9, 2012, as amended at 84 FR 71800, Dec. 30, 2019] § 866.3400 Parainfluenza virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3402 Plasmodium species antigen detection assays. (a) Identification. Plasmodium Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium falciparum Plasmodium (b) Classification. Plasmodium [73 FR 29054, May 20, 2008] § 866.3405 Poliovirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3410 Proteus (a) Identification. Proteus Proteus vulgaris Rickettsiae (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3415 Pseudomonas (a) Identification. Pseudomonas Pseudomonas Pseudomonas. Pseudomonas aeruginosa Pseudomonas pseudomallei (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3460 Rabiesvirus immunofluorescent reagents. (a) Identification. (b) Classification. § 866.3470 Reovirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3480 Respiratory syncytial virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3490 Rhinovirus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3500 Rickettsia serological reagents. (a) Identification. Rickettsiae (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3510 Rubella virus serological reagents. (a) Identification. (b) Classification. (1) National Committee for Clinical Laboratory Standards': (i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,” (ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,” (iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,” (iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and (v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,” (2) Centers for Disease Control's: (i) Low Titer Rubella Standard, (ii) Reference Panel of Well Characterized Rubella Sera, and (3) World Health Organization's International Rubella Standard. [47 FR 50823, Nov. 9, 1982, as amended at 52 FR 17734, May 11, 1987; 65 FR 17144, Mar. 31, 2000] § 866.3520 Rubeola (measles) virus serological reagents. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3550 Salmonella (a) Identification. Salmonella Salmonella Salmonella Salmonella (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3600 Schistosoma (a) Identification. Schistosoma Schistosoma Schistosoma. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3630 Serratia (a) Identification. Serratia Serratia Serratia Serratia (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3660 Shigella (a) Identification. Shigella Shigella Shigella (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3680 Sporothrix schenckii (a) Identification. Sporothrix schenckii Sporothrix schenckii Sporothrix (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3700 Staphylococcus aureus (a) Identification. Staphylococcus aureus Staphylococcus Staphylococcus aureus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.3720 Streptococcus (a) Identification. Streptococcus Streptococcus Streptococcus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38792, July 25, 2001] § 866.3740 Streptococcus (a) Identification. Streptococcus Streptococcus Streptococcus (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3780 Toxoplasma gondii (a) Identification. Toxoplasma gondii Toxoplasma gondii Toxoplasma gondii Toxoplasma gondii (b) Classification. § 866.3820 Treponema pallidum (a) Identification. Treponema pallidum Treponema (b) Classification. § 866.3830 Treponema pallidum (a) Identification. Treponema pallidum Treponema pallidum Treponema pallidum Treponema (b) Classification. § 866.3850 Trichinella spiralis (a) Identification. Trichinella spiralis Trichinella spiralis Trichinella (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.3860 Trichomonas vaginalis (a) Identification. Trichomonas vaginalis Trichomonas vaginalis (b) Classification. Trichomonas vaginalis; [80 FR 46192, Aug. 4, 2015] § 866.3870 Trypanosoma (a) Identification. Trypanosoma Trypanosoma Trypanosoma. (b) Classification. § 866.3900 Varicella-zoster virus serological reagents. (a) Identification. (b) Classification. § 866.3920 Assayed quality control material for clinical microbiology assays. (a) Identification. (b) Classification. (1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate: (i) Analyte concentration; (ii) Expected values; (iii) Analyte source; (iv) Base matrix; (v) Added components; (vi) Safety and handling information; and (vii) Detailed instructions for use. (2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including: (i) Description of the process for value assignment and validation. (ii) Description of the protocol(s) used to establish stability. (iii) Line data establishing precision/reproducibility. (iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance. (v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method. (vi) Where applicable, detailed documentation related to studies for surrogate controls. (3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling. (4) Your 21 CFR 809.10 compliant labeling must include the following: (i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following: (A) Assayed control material analyte(s); (B) Whether the material is intended for quantitative or qualitative assays; (C) Stating if the material is a surrogate control; and (D) The system(s), instrument(s), or test(s) for which the quality control material is intended. (ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.” (iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.” [82 FR 34850, July 27, 2017] § 866.3930 Vibrio cholerae (a) Identification. Vibrio cholerae Vibrio cholerae Vibrio cholerae (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.3935 Zika virus serological reagents. (a) Identification. in vitro (b) Classification. (1) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use with a detailed description of what the device detects (Zika IgM antibodies, other Zika antibodies, or Zika antigens), the type of results provided to the user, the specimen type for which testing is indicated ( e.g., (ii) Performance characteristics from analytical and clinical studies required under paragraphs (b)(2)(ii) and (iii) of this section. (iii) A detailed explanation of the interpretation of results and criteria for validity of results ( e.g., (iv) Limiting statements indicating that: (A) Results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. The test results should be interpreted in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence. (B) Device results are intended to be followed up according to the latest professional guidelines ( e.g., (C) Negative test results do not preclude the possibility of Zika virus infection, past or present. (D) Specimens can result in false negative results on the device if collected outside of the appropriate response window for specific Zika virus antigens or antibodies, as determined by scientific evidence ( e.g., (v) Detailed instructions for use that minimize the risk of generating a false positive or false negative result ( e.g., (2) Design verification and validation must include: (i) A detailed device description, including all device parts ( e.g., (ii) Detailed documentation and results from analytical performance studies including: characterization of the cut-off(s), analytical sensitivity to a standardized reference material that FDA has determined is appropriate ( e.g., e.g., (iii) Detailed documentation and results from clinical studies, including the clinical study protocol (with a description of the testing algorithm and results interpretation table), detailed clinical study report, including line data of the clinical study results, and other appropriate statistical analysis. The samples used in the clinical study must be collected from subjects representative of the full spectrum of the intended use population ( e.g., [90 FR 22633, May 29, 2025] § 866.3940 West Nile virus serological reagents. (a) Identification. (b) Classification. [68 FR 61745, Oct. 30, 2003] § 866.3945 Dengue virus serological reagents. (a) Identification. (b) Classification. [79 FR 31023, May 30, 2014] § 866.3946 Dengue virus nucleic acid amplification test reagents. (a) Identification. (b) Classification. [79 FR 53609, Sept. 10, 2014] § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. (b) Classification. [72 FR 44382, Aug. 8, 2007] § 866.3955 Human immunodeficiency virus (HIV) drug resistance genotyping assay using next generation sequencing technology. (a) Identification. (b) Classification. (1) The intended use of the device must: (i) Specify the analyte (RNA or DNA), the genes in which mutations are detected, the clinical indications appropriate for test use, the sample type, and the specific population(s) for which the device in intended. (ii) State that the device in not intended for use as an aid in the diagnosis of infection with HIV or to confirm the presence of HIV infection, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products. (2) The labeling must include: (i) A detailed device description, including but not limited to, all procedures from collection of the patient sample to reporting the final result, all device components, the control elements incorporated into the test procedure, instrument requirements, and reagents required for use but not provided as part of the device. (ii) Performance characteristics from analytical studies and all intended specimen types. (iii) A list of specific mutations detected. (iv) The name and version of the standardized database used for sequence comparison and results derivation. (v) A detailed explanation of the interpretation of test results, including acceptance criteria for evaluating the validity of a test run. (vi) A limitation statement that the device is intended to be used in conjunction with clinical history and other laboratory findings. Results of this test are intended to be interpreted by a physician or equivalent. (vii) A limitation statement that lack of detection of drug resistance mutations does not preclude the possibility of genetic mutation. (viii) A limitation statement indicating the relevant genetic mutations that are included in the standardized database of HIV genomic sequences used for comparison and results derivation but that are not detected by the test. (ix) A limitation statement that detection of a genomic drug resistance mutation may not correlate with phenotypic gene expression. (x) A limitation statement that the test does not detect all genetic mutations associated with antiviral drugs. (xi) A limitation statement listing the HIV types for which the test is not intended, if any. (3) Device verification and validation must include: (i) Design of primer sequences and rationale for sequence selection. (ii) Computational path from collected raw data to reported result. (iii) Detailed documentation of analytical studies including, but not limited to, characterization of the cutoff, analytical sensitivity, inclusivity, reproducibility, interference, cross reactivity, instrument and method carryover/cross contamination, sample stability, and handling for all genomic mutations claimed in the intended use. (iv) Precision studies that include all genomic mutations claimed in the intended use. (v) Detailed documentation of a multisite clinical study evaluating the sensitivity and specificity of the device. Clinical study subjects must represent the intended use population and device results for all targets claimed in the intended use must be compared to Sanger sequencing or other methods found acceptable by FDA. Drug resistance-associated mutations at or above the 20 percent frequency level must detect the mutations in greater than 90 percent of at least 10 replicates, for each of drug class evaluated. (vi) Documentation that variant calling is performed at a level of coverage that supports positive detection of all genomic mutations claimed in the intended use. (vii) Detailed documentation of limit of detection (LoD) studies in which device performance is evaluated by testing a minimum of 100 HIV-positive clinical samples including samples with analyte concentrations near the clinical decision points and near the LoD. (A) The LoD for the device must be determined using a minimum of 10 HIV-1 group M genotypes if applicable. A detection rate at 1 × LoD greater than or equal to 95 percent must be demonstrated for mutations with a frequency greater than 20 percent. (B) The LoD of genetic mutations at frequency levels less than 20 percent must be established. (viii) A predefined HIV genotyping bioinformatics analysis pipeline (BAP). The BAP must adequately describe the bioinformatic analysis of the sequencing data, including but not limited to read alignment, variant calling, assembly, genotyping, quality control, and final result reporting. (ix) A clear description of the selection and use of the standardized database that is used for sequence comparison and results derivation. (4) Premarket notification submissions must include the information in paragraphs (b)(3)(i) through (ix) of this section. [85 FR 7217, Feb. 7, 2020] § 866.3956 Human immunodeficiency virus (HIV) serological diagnostic and/or supplemental test. (a) Identification. (b) Classification. (1) For all HIV serological diagnostic and supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( 1 ( 2 ( 3 ( 4 ( 5 (ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as the amino acid sequence of antigen(s) and design of capture antibodies. (B) For devices with assay calibrators, the design of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA-cleared or approved comparator. This study must be conducted using patient samples, with an appropriate number of HIV positive and HIV negative samples in applicable risk categories. Additional subgroups or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ( 2 (G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determines when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint if available: The type of event ( e.g., (2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation of performance from a multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( 1 2 ( 1 ( 2 (B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a different confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results from a diagnostic test and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the HIV types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information. [87 FR 29665, May 16, 2022] § 866.3957 Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and/or supplemental test. (a) Identification. (b) Classification. (1) For all HIV NAT diagnostic and/or supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products, or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( 1 ( 2 ( 3 ( 4 ( 5 (ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as design of primers and probes. (B) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be as the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using appropriate patient samples, with appropriate numbers of HIV positive and negative samples in applicable risk categories. Additional subtype, strain, or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ( 2 (G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determine when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint, if available: The type of event ( e.g., (2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section, apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation from a well-conducted multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( 1 2 ( 1 ( 2 (B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information. [87 FR 29667, May 16, 2022] § 866.3958 Human immunodeficiency virus (HIV) viral load monitoring test. (a) Identification. (b) Classification. (1) The labeling must include: (i) An intended use that states that the device is not intended for use as an aid in diagnosis or for use in screening donors of blood or blood products, or HCT/Ps. (ii) A detailed explanation of the principles of operation and procedures used for assay performance. (iii) A detailed explanation of the interpretation of results and that recommended actions should be based on current clinical guidelines. (iv) Limitations, which must be updated to reflect current clinical practice and patient management. The limitations must include, but are not limited to, statements that indicate: (A) The matrices and sample types with which the device has been cleared and that use of this test with specimen types other than those specifically cleared for this device may cause inaccurate test results. (B) Mutations in highly conserved regions may affect binding of primers and/or probes resulting in the under-quantitation of virus or failure to detect the presence of virus. (C) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results. (2) Device verification and validation must include: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included, such as detailed information on the design of primers and probes. (ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (iii) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including but not limited to, limit of blank, limit of detection, limit of quantitation, cutoff determination, precision, linearity, endogenous and exogenous interferences, cross-reactivity, carry-over, quality control, matrix equivalency, sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant genotypes circulating in the United States. (iv) Multisite reproducibility study that includes the testing of three independent production lots. (v) Analytical sensitivity of the device must demonstrate acceptable performance at current clinically relevant medical decision points. Samples tested to demonstrate analytical sensitivity must include appropriate numbers and types of samples, including real clinical samples near the lower limit of quantitation and any clinically relevant medical decision points. Analytical specificity of the device must demonstrate acceptable performance. Samples tested to demonstrate analytical specificity must include appropriate numbers and types of samples from patients with different underlying illnesses and infection and from patients with potential interfering substances. (vi) Detailed documentation of performance from a multisite clinical study or a multisite analytical method comparison study. (A) For devices evaluated in a multisite clinical study, the study must use specimens from individuals living with HIV being monitored for changes in viral load, and the test results must be compared to the clinical status of the patients. (B) For tests evaluated in a multisite analytical method comparison study, the performance of the test must be compared to an FDA-cleared or approved comparator. The multisite method comparison study must include appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The multisite method comparison study design, including number of samples tested, must be sufficient to meet the following criteria: ( 1 ( 2 (vii) Detailed documentation of a single-site analytical method comparison study between the device and an FDA-cleared or approved comparator if a multisite clinical study is performed under paragraph(b)(2)(vi) of this section. The analytical method comparison study must use appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The results must meet the criteria in paragraphs (b)(2)(vi)(B)( 1 2 (viii) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (ix) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (x) Final release criteria to be used for manufactured device lots with an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (xi) All stability protocols, including acceptance criteria. (xii) Appropriate and acceptable procedure(s) for addressing complaints and other device information that determines when to submit a medical device report. (xiii) Premarket notification submissions must include the information contained in paragraphs (b)(2)(i) through (xii) of this section. [87 FR 66548, Nov. 4, 2022] § 866.3960 Nucleic acid-based device for the amplification, detection, and identification of microbial pathogens directly from whole blood specimens. (a) Identification. (b) Classification. (1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer/probe sequence, design, and rationale for sequence selection. (2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (limit of detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, and cross contamination. (3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods. (4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software. (5) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate. (6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (7) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate. (8) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. [82 FR 47967, Oct. 16, 2017, as amended at 90 FR 55982, Dec. 4, 2025] § 866.3966 Device to detect and identify selected microbial agents that cause acute febrile illness. (a) Identification. (b) Classification. (1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (ii) Limiting statements indicating: (A) Not all pathogens that cause febrile illness are detected by this test and negative results do not rule out the presence of other infections; (B) Evaluation of more common causes of acute febrile illness should be considered prior to evaluation with this test; (C) Test results are to be interpreted in conjunction with other clinical, epidemiologic, and laboratory data available to the clinician; and (D) When using this test, consider patient travel history and exposure risk, as some pathogens are more common in certain geographical locations. (iii) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (iv) Detailed discussion of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section, except specimen stability performance characteristics. (v) A statement that nationally notifiable results are to be reported to public health authorities in accordance with local, state, and federal law. (3) Design verification and validation must include: (i) A detailed device description ( e.g., e.g., (ii) Detailed documentation of analytical studies, including those demonstrating Limit of Detection (LoD), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iii) Detailed documentation and performance results from a clinical study that includes prospective (sequentially collected) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA-accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. (iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions. [89 FR 66558, Aug. 16, 2024] § 866.3970 Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid. (a) Identification. (b) Classification. (1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including primer/probe sequence, design, and rationale for sequence selection. (2) Premarket notification submissions must include detailed documentation from the following analytical studies: Analytical sensitivity (limit of detection), inclusivity, reproducibility, interference, cross reactivity, and specimen stability. (3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted comparator methods. (4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software. (5) The Intended Use statement in the device labeling must include a statement that the device is intended to be used in conjunction with standard of care culture. (6) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (7) The device labeling must include a limitation stating that the negative results do not preclude the possibility of central nervous system infection. (8) The device labeling must include a limitation stating that device results are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. (9) The device labeling must include a limitation stating that positive results do not mean that the organism detected is infectious or is the causative agent for clinical symptoms. (10) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. [82 FR 48763, Oct. 20, 2017, as amended at 90 FR 55982, Dec. 4, 2025] § 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection. (ii) Documentation with information that demonstrates the performance characteristics of the device, including: (A) Limit of Detection; (B) Precision (reproductivity); (C) Analytical specificity; (D) Analytical reactivity (inclusivity); (E) Specimen stability; and (F) Effects of interfering substances. (iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator methods. (iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed explanation of the interpretation of results and acceptance criteria; (ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status. (iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population. (iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that Candida [90 FR 40728, Aug. 21, 2025] § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. (1) Influenza A and Influenza B; (2) Influenza A subtype H1 and Influenza A subtype H3; (3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B; (4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus; (5) Human Metapneumovirus; (6) Rhinovirus; and (7) Adenovirus. (b) Classification. (1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;” (2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and (3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents. [74 FR 52138, Oct. 9, 2009] § 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test. (a) Identification. (b) Classification. (1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies; (iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety ( e.g., (v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population ( e.g., (vi) Limiting statements that indicate that: (A) A negative test result does not preclude the possibility of infection; (B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician; (C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens; (D) That positive and negative predictive values are highly dependent on prevalence; (E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and (F) When applicable ( e.g., (4) Design verification and validation must include: (i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. (ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains ( e.g., (iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection. (iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( e.g., e.g., (v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review. (vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter. (6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. (ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to State or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( i.e., (7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access. [89 FR 66554, Aug. 16, 2024] § 866.3982 Simple point-of-care device to directly detect SARS-CoV-2 viral targets from clinical specimens in near-patient settings. (a) Identification. e.g., (b) Classification. (1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: analytes the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) The intended use of the device must only include indications for testing of respiratory specimens. (3) If sample collection devices are used, any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (4) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed and comprehensive device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: limit of detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, hook-effect, carryover/cross contamination, specimen stability, precision, reproducibility, human factors analysis, flex studies, and clinical studies; (iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) A statement in the intended use that positive results do not preclude co-infection with bacteria or other viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions; (v) Detailed instructions for minimizing the risk of user's exposure to infectious microbial agents that may be present in test specimens and those used as control materials; (vi) Detailed instructions for minimizing the risk of generating false positive test results due to carry-over contamination from positive test specimens and/or positive control materials, as applicable to the design of the test device; (vii) A brief reference sheet (Quick Reference Instructions) for the intended user(s) that includes, at a minimum, the name and intended use of the test, easy to follow step-by-step instructions of all control and sample testing procedures for the claimed sample types, including graphic illustrations targeted towards lay users (as applicable), the result(s) interpretation guidance, warnings and limitation statements, toxicology information and safety considerations for any hazardous materials, information for troubleshooting ( e.g., e.g., (viii) Limiting statements indicating that: (A) For those devices intended for testing in symptomatic subjects, a statement that specifies the number of days post symptom onset validated for use of the device and/or a range in which the performance of the test is known; (B) A negative test result does not preclude the possibility of infection with other bacteria or viruses; (C) The test results should be interpreted in conjunction with other clinical and laboratory data available to the healthcare provider (as applicable); (D) There is a risk of erroneous results ( i.e., e.g., (E) False positive test results are more likely when prevalence of upper respiratory infection is low in the community; (F) Accurate results are dependent on adequate specimen collection, transport, storage, and processing (as applicable). Failure to observe proper procedures in any one of these steps can lead to incorrect results; (G) This test should not be used beyond the expiration date listed on the packaging. Use of expired tests can lead to incorrect results; and (H) The performance characteristics for that analyte were established when [insert predominant strain, subtype, or variant] was prevalent and that due to the propensity of the virus to mutate, new strains emerge over time which may affect the performance of this device and have serious public health implications. Additional testing with a molecular test and/or sequencing should be considered in situations where a new virus strain or variant is suspected. (5) Design verification and validation must include: (i) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including viral target(s), identification of target detection reagents ( e.g., e.g., (ii) Detailed documentation of data from a prospective multisite clinical study with a design and performance that is appropriate for the intended use of the device, including performance estimates derived from a sufficient number of samples from the intended use population for each claimed specimen type. Results must be obtained from a geographically diverse population, such that the performance of the test device is appropriately representative of all present, circulating strains of the target respiratory virus, at the time of the study and submission. The clinical study must be consistent with and support the intended use population and intended operators (as applicable) and must be conducted in a representative intended use setting. The clinical study must compare the results of the candidate device to results obtained using an FDA accepted molecular comparator method. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses; (iii) The clinical study designs, including number of samples tested, must be sufficient to meet either of the following criteria: (A) The lower bound of the two-sided 95 percent confidence interval of the positive percent agreement must be greater than or equal to 80 percent and appropriate risk mitigation measures are established ( e.g., (B) The lower bound of the two-sided 95 percent confidence interval of the positive percent agreement must be greater than or equal to 70 percent and additional and appropriate risk mitigations measures are established ( e.g., (iv) Detailed documentation of analytical studies, including those demonstrating the limit of detection, inclusivity (including relevant variants), cross-reactivity, microbial interference, interfering substances, competitive inhibition, specimen stability, within-lab precision, hook effect, carryover, cross contamination, and site-to-site reproducibility, as applicable; (v) Detailed documentation and characterization ( e.g., i.e., (vi) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims; (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. (A) This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel isolates or strains ( e.g., (B) This must include detailed documentation that demonstrates the effectiveness of risk control measures and device robustness, including the entire testing procedure from sampling to result interpretation, based on results from the following studies, as applicable per the intended use of the test device: human factors engineering ( e.g., (viii) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review; and (ix) For devices intended for the detection and identification of an analyte for which an FDA recommended reference material is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference material. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (6) If one of the actions listed in section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to one or more of the analytes claimed in the intended use, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to one or more of the analytes claimed in the intended use: (i) Within 30 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation, the manufacturer must have testing performed on the device with those samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate; and (ii) Within 60 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation and continuing until 3 years from that date, the results of the emergency analytical reactivity testing, including the detailed information for the samples tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format. [91 FR 35389, June 11, 2026] § 866.3983 SARS-CoV-2 serology test. (a) Identification. (b) Classification. (1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes the device detects, the specimen types tested, the results provided to the end user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use, as appropriate. (2) If sample collection devices are used, any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (3) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens; (ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies, including the following, as applicable: Assay cutoff or limit of detection expressed in international standard units, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover and cross contamination, matrix equivalency, hook effect, specimen stability, precision, reproducibility, and clinical studies, including the time period in which the clinical performance was established and the variant(s) prevalent in the United States at the time of performance validation; (iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing; (iv) When applicable, performance results of the analytical study testing of a standardized reference material that FDA has determined is appropriate; (v) Limiting statements that indicate: (A) A negative test result does not preclude the possibility of infection; (B) A negative result can occur if the quantity of the anti-SARS-CoV-2 antibodies present in the specimen is below the detection limits of the assay, or the antibodies that are detected are not present during the stage of disease in which a sample is collected; (C) There is a risk of erroneous results ( i.e., (D) The performance characteristics for that analyte were established when [insert predominant strain, subtype, or variant] was prevalent and that due to the propensity of the virus to mutate, new strains emerge over time which may affect the performance of this device and have serious public health implications; (E) The test results should be interpreted in conjunction with other clinical and laboratory data available to the healthcare provider (as applicable); (F) Positive and negative predictive values are highly dependent on prevalence; (G) Accurate results are dependent on adequate specimen collection, transport, storage, and processing (as applicable). Failure to observe proper procedures in any one of these steps can lead to incorrect results; (H) The test is not intended for donor screening; and (I) The test is not intended to diagnose acute SARS-CoV-2 infection. An assay that directly detects the virus should be used to evaluate individuals for acute COVID-19, particularly those who have been in contact with the virus. (vi) For devices intended for the quantitative detection of SARS-CoV-2 antibodies, labeling must include a prominent statement that includes the following: the test calibrators' traceability to a standardized reference material that FDA has determined is appropriate and the limit of blank, limit of detection, and limit of quantitation, with the defined analytical measuring interval. (4) Design verification and validation must include: (i) Detailed documentation of performance from a multisite clinical study with an appropriate number of clinical samples ( i.e., (ii) For any SARS-CoV-2 antibody test intended for use in near-patient settings, detailed documentation that demonstrates the effectiveness of risk control measures and device robustness, including flex studies, and performance with weakly-reactive samples when used by the intended operators; (iii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as failure modes effects analysis and hazard analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains ( e.g., (iv) Documentation of the specific amino acid sequence of the SARS-CoV-2 target protein(s) that the device utilizes to detect specific antibodies to SARS-CoV-2; (v) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including protein sequence target(s) for each analyte, design of target detection reagents, internal and external controls, and computational path from collected raw data to reported result ( e.g., (vi) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users and patients as part of cybersecurity review; (vii) For devices intended for the detection of SARS-CoV-2 antibodies for which a standardized reference material (that FDA has determined is appropriate) is available, the performance results of an analytical study testing this standardized reference material. Detailed documentation of that study and its results must be provided, including the study protocol, study report, testing results, and all statistical analyses; (viii) Detailed documentation of analytical studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including precision, endogenous interferences, cross reactivity, carryover, matrix equivalency, class specificity, hook effect, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare contrived samples for use in analytical studies must be from subjects with clinically relevant circulating antibodies to SARS-CoV-2 in the United States. Cross-reactivity studies must include samples from SARS-CoV-2 antibody negative subjects with antibodies to viruses, high prevalence disease agents, and normal or pathogenic flora. Endogenous interference studies must include SARS-CoV-2 antibody negative and low positive samples with endogenous interference substances, including antibodies present in autoimmune diseases that are reasonably likely to be encountered in clinical specimens under actual use conditions. In addition, for devices intended for the quantitative detection of SARS-CoV-2 antibodies, the information provided must also include the metrological calibration traceability hierarchy to a standardized reference material that FDA has determined is appropriate. As appropriate to the technology and specimen types tested, the information provided to support quantitative tests must also include studies to support the analytical measuring interval, including a limit of blank study, a limit of detection study, an upper and lower limits of quantitation study, a precision study, and a linearity study using clinical samples, and, using a standardized reference material that FDA has determined is appropriate, an accuracy study; (ix) Detailed documentation of data and protocols, including acceptance criteria, from a real-time reagent stability study must include testing of samples with adequately challenging analyte concentrations and must include shelf-life stability and shipping stability, and, as applicable, in-use and open-kit stability and freeze-thaw stability. The shelf-life stability assessment must include a minimum of three lots; (x) Detailed documentation of a multisite reproducibility study with testing conducted at a minimum of three sites; (xi) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims; and (xii) Lot-to-lot precision studies, as appropriate. (5) For any SARS-CoV-2 antibody test intended for use in near-patient settings, labeling must also include a brief reference sheet (quick reference instructions) for the intended user(s) that includes, at a minimum, the name and intended use of the test, easy to follow step-by-step instructions of all control and sample testing procedures for the claimed sample types, including graphic illustrations targeted towards lay users (as applicable), the result(s) interpretation guidance, warnings and limitation statements, toxicology information and safety considerations for any hazardous materials, information for troubleshooting ( e.g., e.g., (6) If one of the actions listed in section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to one or more of the analytes claimed in the intended use, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to one or more of the analytes claimed in the intended use: (i) Within 30 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation, the manufacturer must have testing performed on the device with those samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate; and (ii) Within 60 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation and continuing until 3 years from that date, the results of the emergency analytical reactivity testing, including the detailed information for the samples tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format. [91 FR 38500, June 26, 2026] § 866.3984 Over-the-counter test to detect SARS-CoV-2 from clinical specimens. (a) Identification. (b) Classification. (1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: analytes the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), and other conditions of use as appropriate. (2) The intended use of the device must only include indications for testing of respiratory specimens that are appropriate for collection by lay users for which there are performance data that demonstrate lay users can collect specimens without health care provider supervision in home settings or similar environments. (3) The labeling required under § 809.10(b) of this chapter must include the following: (i) A statement in the intended use that positive results do not rule out co-infection with other respiratory pathogens; (ii) Summary instructions and information written in appropriate language for the intended user that includes easy to follow step-by-step instructions for sample testing, explanation of test results, any warnings and precautions relevant to testing, and frequently asked questions (FAQs), as required by paragraph (b)(5)(iii) of this section; (iii) Limiting statements including the following, as applicable: (A) For those devices intended for testing in symptomatic subjects, a specification of the number of days post symptom onset validated for use of the device and/or a range in which the performance of the test is known, where applicable; (B) Statements that a negative test result does not preclude the possibility of infection with other pathogens, and that a positive test result does not preclude the possibility of co-infection with additional pathogens; (C) A statement that persons with risk factors for severe disease from respiratory pathogens ( e.g., (D) A statement that the test is not a substitute for consultation with a health care provider and should not be used to determine any treatments without provider supervision. A statement that the healthcare provider will consider additional information such as the patient's personal medical history and symptoms, current disease prevalence in the community, and additional test results if applicable, to help determine what steps are best for diagnosis and treatment if needed; (E) A statement that it is especially important to discuss any test results with a healthcare provider if any of the following occur: ( 1 ( 2 ( 3 e.g., ( 4 (F) A statement that accurate results are dependent on adequate product storage and adherence to the specimen collection and testing procedures. A statement that failure to follow test procedures can lead to incorrect results; (G) A statement that the test must not be used beyond the expiration date listed on the packaging. A statement that use of expired tests can lead to incorrect results; (H) A statement that false positive test results are more likely when prevalence of SARS-CoV-2 is low in the community; and (I) A statement that includes all of the following: The performance characteristics for SARS-CoV-2 were established when [insert predominant strain, subtype, or variant and timeframe] was dominant. Test accuracy may change as new SARS-CoV-2 viruses emerge. Additional testing with a lab-based molecular test ( e.g., (4) The outer box label required under § 809.10(a) of this chapter must include the following: (i) A description of who may use the test, including the presence of symptoms, the days post symptom onset and age restrictions (as applicable); (ii) A list of the components included with the test; (iii) A list of the components required to run the test, but not provided; (iv) A statement that persons with risk factors for severe disease from respiratory pathogens should consult and follow-up with a healthcare provider. (5) The device's labeling must include a prominent hyperlink to the manufacturer's public website where the manufacturer must make the information, identified in this section, publicly and prominently available. The information must include, written in language appropriate for the intended user: (i) A brief summary of the purpose of the test; (ii) Instructions that describe how to appropriately perform the test, interpret the results, and, if applicable, perform follow-up testing. The instructions must include the name and intended use of the test, detailed step-by-step instructions of the sample testing procedures, the result(s) interpretation guidance, warnings and limitation statements, information for troubleshooting, and technical assistance with the device ( e.g., (iii) FAQ: This document must provide technical and educational information ( e.g., (iv) Information that demonstrates the performance characteristics established in the studies required under paragraph (b)(6) of this section. (6) Design verification and validation must include: (i) A detailed device description, including, but not limited to, device components, and a detailed explanation of the methodology, including viral target(s), identification of target detection reagents ( e.g., e.g., (ii) Detailed documentation of data from a prospective multisite clinical study with a design and performance that is appropriate for the intended use of the device, including performance estimates derived from a sufficient number of samples from the intended use population for each claimed specimen type. Results must be obtained from geographically diverse locations, such that the performance of the test device is appropriately representative of all present, circulating strains of the claimed viral analyte(s) at the time of the study and submission. Additionally, the clinical study must include participants that are representative of the intended use population and across the clinical range of the claimed viral analyte. The clinical study must be performed in the intended use setting ( e.g., (iii) The clinical study designs, including number of samples tested, must be sufficient such that the lower bound of the two-sided 95 percent confidence interval of the positive percent agreement with the comparator must be greater than 70 percent and additional and appropriate risk mitigation measures are established ( e.g., (iv) Detailed documentation of analytical studies, including those demonstrating the limit of detection, inclusivity (including relevant variants), cross-reactivity, microbial interference, interfering substances, competitive inhibition, specimen stability, within-lab precision, hook effect, carryover, and cross-contamination, as applicable; (v) Detailed documentation and characterization ( e.g., i.e., (vi) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as failure modes effects analysis and/or hazard analysis. (A) This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel isolates or strains ( e.g., (B) This must include detailed documentation that demonstrates the effectiveness of risk control measures and device robustness, including the entire testing procedure from sampling to result interpretation, based on results from the following studies, as applicable per the intended use of the test device: usability studies, user label comprehension, and flex studies; (vii) For devices with associated software or instrumentation, documentation must include a detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users and patients as part of cybersecurity review; and (viii) For devices intended for the detection of SARS-CoV-2 for which an FDA recommended reference material and/or test panel is available, the performance results of an analytical study testing the FDA recommended reference material. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (7) If one of the actions listed in section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to one or more of the analytes claimed in the intended use, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to SARS-CoV-2: (i) Within 30 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation, the manufacturer must have testing performed on the device with those samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate; and (ii) Within 60 days from the date that FDA notifies manufacturers that characterized samples are available for test evaluation and continuing until 3 years from that date, the results of the emergency analytical reactivity testing, including the detailed information for the samples tested as described in the certificate of authentication, must be included in a tabular format on the hyperlink the manufacturer's public website as described in paragraph (b)(5) of this section. [91 FR 46717, July 24, 2026] § 866.3985 Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens. (a) Identification. (b) Classification. (1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (2) The 21 CFR 809.10(b) labeling must include: (i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (ii) Performance characteristics from analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, and linearity, as applicable. (iii) A limiting statement that the device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing. (iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing. (v) A limiting statement that negative results for microorganisms do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (vi) If applicable, a limiting statement that detected microorganisms may not be the cause of lower respiratory tract infection and may be indicative of colonizing or normal respiratory flora. (vii) If applicable, a limiting statement that detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora. (viii) If applicable, a limiting statement that detection of antibiotic resistance markers may not correlate with phenotypic gene expression. (3) The 21 CFR 809.10(b) labeling and any test report generated by the device must include a limiting statement that negative results for resistance markers do not indicate susceptibility of detected microorganisms. (4) Design verification and validation must include: (i) Performance characteristics from clinical studies that include prospective (sequential) samples and, if appropriate, additional characterized samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from an FDA accepted reference method and/or FDA accepted comparator method, as appropriate. Results from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses. (ii) A detailed device description including the following: (A) Thorough description of the assay methodology including, but not limited to, primer/probe sequences, primer/probe design, and rationale for target sequence selection, as applicable. (B) Algorithm used to generate a final result from raw data (e.g., how raw signals are converted into a reported result). (iii) A detailed description of device software, including, but not limited to, validation activities and outcomes. (iv) As part of the risk management activities, an appropriate end user device training program must be offered as an effort to mitigate the risk of failure from user error. [84 FR 9228, Mar. 14, 2019] § 866.3988 Device to detect and identify microorganism nucleic acids and resistance markers from patients with suspected orthopedic infection. (a) Identification. (b) Classification. (1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended. (ii) Limiting statements, when applicable, indicating: (A) The device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing; (B) Detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay; and (C) Antimicrobial resistance can occur via multiple mechanisms. A not detected result for the antimicrobial resistance gene assays does not indicate antimicrobial susceptibility. Culturing and susceptibility testing of isolates is needed to determine antimicrobial susceptibility. (iii) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens. (iv) Detailed descriptions of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(iii) and (b)(3)(iv) of this section except specimen stability performance characteristics. (3) Design verification and validation must include: (i) A detailed device description, including all device parts, control elements incorporated into the test procedure, reagents required but not provided, the principle of device operation and test methodology, and the computational path from collected raw data to reported result ( e.g., (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions. (iii) Detailed documentation of analytical studies, including those demonstrating Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate. (iv) Detailed documentation and performance results from a clinical study that includes prospective (sequentially collected) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator method that FDA has determined to be appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses. [91 FR 25785, May 12, 2026] § 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay. (a) Identification. in vitro (b) Classification. [80 FR 67314, Nov. 2, 2015] § 866.4001 A multiplex respiratory panel to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens. (a) Identification. (b) Classification. (1) The intended use for the labeling required under § 809.10 of this chapter must include a description of what the device detects and measures, the specimen types, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) The labeling required under § 809.10 of this chapter must include: (i) A device description, including the parts that make up the device, ancillary reagents required but not provided, and an explanation of the methodology. (ii) Performance characteristics from analytical studies, including cut-off (if applicable), analytical sensitivity ( i.e., (iii) Detailed instructions for minimizing the risk of potential users' exposure to the emerging respiratory pathogen(s) that may be present in test specimens and those used as control materials. (iv) Detailed instructions for minimizing the risk of generating false positive test results due to carry-over contamination from positive test specimens and/or positive control materials. (v) A warning statement that the interpretation of test results requires experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and reporting of results, in conjunction with the patient's medical history, clinical signs and symptoms, and the results of other diagnostic tests. (vi) A warning statement that culture should not be attempted in cases of positive results for an emerging respiratory pathogen unless a facility with an appropriate level of laboratory biosafety ( e.g., (vii) A warning statement that device positive results for one or more common respiratory pathogens do not rule out bacterial infection, or co-infection with other common respiratory pathogens. (viii) A warning statement that respiratory pathogen(s) detected may not be the definite cause of disease. (ix) A warning statement that the use of additional laboratory testing ( e.g. (x) A limiting statement that device negative results for the common respiratory pathogens do not preclude infection of a respiratory pathogen and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (xi) A limiting statement that analyte targets ( e.g., (xii) A limiting statement that detection of pathogen nucleic acid sequences or other molecular signatures is dependent upon proper specimen collection, handling, transportation, storage and preparation. Failure to observe proper procedures in any one of these steps can lead to incorrect results. There is a risk of false negative values resulting from improperly collected, transported, or handled specimens. (xiii) A limiting statement that there is a risk of false positive values resulting from cross-contamination by target organisms, their nucleic acids or amplified product, or from non-specific signals in the assay. (xiv) A limiting statement that there is a risk of false negative results due to the presence of nucleic acid sequence variants in the pathogen targets of the device. (xv) A limiting statement that device performance was not established in immunocompromised patients. (xvi) A limiting statement that positive and negative predictive values are highly dependent on prevalence. The device performance was established during one or more specific respiratory seasons. The performance for some respiratory pathogens may vary depending on the prevalence and patient population tested. False positive test results are likely when prevalence of disease due to a particular respiratory pathogen is low or non-existent in a community. (xvii) In situations where the performance of the device was estimated based largely on testing pre-selected banked retrospective clinical specimens and/or contrived clinical specimen, a limiting statement that the estimated device performance of that specific pathogen or pathogen subtype may not reflect the performance or prevalence in the intended use population. (xviii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that testing with the device should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected specimens of the emerging respiratory pathogen. (xix) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that positive results obtained with the device for the emerging respiratory pathogen are for the presumptive identification of that pathogen and that the definitive identification of the emerging respiratory pathogen requires additional testing and confirmation procedures in consultation with the appropriate public health authorities ( e.g., (xx) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen, even in the context of device positive results for one or more of the common respiratory pathogens, do not preclude infection with the emerging respiratory pathogen and should not be used as the sole basis for patient management decisions. (xxi) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen may be due to infection of the emerging respiratory pathogen at a specific respiratory tract location that may not be detected by a particular clinical specimen type. A negative result for the emerging respiratory pathogen in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious. (xxii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that a nationally notifiable Rare Disease of Public Health Significance caused by an emerging respiratory pathogen must be reported, as appropriate, to public health authorities in accordance with local, state, and federal law. (3) Design verification and validation must include: (i) Performance results of an appropriate clinical study ( e.g., (ii) For devices with an intended use that includes detection of emerging respiratory pathogen(s) for which an FDA recommended panel is available, design verification and validation must include the performance results of an analytical study testing an FDA recommended reference panel of characterized samples that contain the emerging respiratory pathogen. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (iii) An appropriate risk mitigation strategy, including a detailed description of all procedures and methods, for the post-market identification of genetic mutations and/or novel respiratory pathogen isolates or strains ( e.g., (iv) For devices with an intended use that includes detection of multiple common respiratory pathogens, in addition to detecting emerging respiratory pathogen(s) in human clinical specimens, a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the common respiratory pathogens that the device is designed to detect is addressed. Also, address in detail how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory diagnosis of respiratory tract infection. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (v) A detailed device description, including the parts that make up the device, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( e.g., e.g., (vi) A detailed description of the device software, including software applications and hardware-based devices that incorporate software. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (4) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), the labeling required under § 809.10 of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. (ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling required under § 809.10(b)(9) of this chapter must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required follow up actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( e.g., (5) The manufacturer must perform annual analytical reactivity testing of the device with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access. (6) If one of the actions listed at section 564(b)(1)(A)-(D) of the FD&C Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access. [90 FR 40711, Aug. 21, 2025] Subpart E—Immunology Laboratory Equipment and Reagents § 866.4070 RNA Preanalytical Systems. (a) Identification. (b) Classification. [70 FR 49863, Aug. 25, 2005] § 866.4100 Complement reagent. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 2001, as amended at 66 FR 38792, July 25, 2001] § 866.4500 Immunoelectrophoresis equipment. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.4520 Immunofluorometer equipment. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.4540 Immunonephelometer equipment. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.4600 Ouchterlony agar plate. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.4700 Automated fluorescence in situ (a) Identification. (b) Classification. in situ [70 FR 14534, Mar. 23, 2005] § 866.4750 Automated indirect immunofluorescence microscope and software-assisted system. (a) Identification. (b) Classification. (1) The labeling for the device must reference legally marketed assays intended for use with the device. (2) Premarket notification submissions must include the following information: (i) A detailed description of the device that includes: (A) A detailed description of instrumentation and equipment, and illustrations or photographs of non-standard equipment or methods, if applicable; (B) Detailed documentation of the software, including, but not limited to, stand-alone software applications and hardware-based devices that incorporate software, if applicable; (C) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the recommended testing procedures; (D) Detailed description and specifications for sample preparation, processing, and storage, if applicable; (E) Methodology and protocols for detecting fluorescence and visualizing results; and (F) Detailed specification of the criteria for test results interpretation and reporting. (ii) Data demonstrating the performance characteristics of the device, which must include: (A) A comparison study of the results obtained with the conventional manual method ( i.e., (B) Device clinical performance established by comparing device results at multiple U.S. sites to the clinical diagnostic standard used in the United States, using patient samples from the assay-specific intended use population and the differential diagnosis population. For all samples, the diagnostic clinical criteria and the demographic information must be collected and provided. Clinical validation must be based on the determination of clinical sensitivity and clinical specificity using the test results ( e.g., (C) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-operator, between-instruments, between-site, and total precision for multiple nonconsecutive days (as applicable) using multiple operators, multiple instruments and at multiple sites. A well-characterized panel of patient samples or pools from the associated assay specific intended use population must be used; (D) Device linearity data generated from patient samples covering the assay measuring range, if applicable; (E) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation, if applicable; (F) Device assay specific cutoff, if applicable; (G) Device analytical specificity data, including interference by endogenous and exogenous substances, if applicable; (H) Device instrument carryover data, if applicable; (I) Device stability data including real-time stability under various storage times and temperatures, if applicable; and (J) Information on traceability to a reference material and description of value assignment of calibrators and controls, if applicable. (iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices, incorporated into the directions for use that mitigate risks associated with testing. (3) Your 21 CFR 809.10 compliant labeling must include: (i) A warning statement that reads “The device is for use by a trained operator in a clinical laboratory setting”; (ii) A warning statement that reads “All software-aided results must be confirmed by the trained operator”; (iii) A warning statement that reads “This device is only for use with reagents that are indicated for use with the device”; and (iv) A description of the protocol and performance studies performed in accordance with paragraph (b)(2)(ii) of this section and a summary of the results, if applicable. [82 FR 52648, Nov. 14, 2017, as amended at 86 FR 20283, Apr. 19, 2021] § 866.4800 Radial immunodiffusion plate. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 66 FR 38792, July 25, 2001] § 866.4830 Rocket immunoelectrophoresis equipment. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] § 866.4900 Support gel. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25047, June 12, 1989; 66 FR 38792, July 25, 2001] Subpart F—Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.5060 Prealbumin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5065 Human allotypic marker immunological test system. (a) Identification. 2 (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5080 Alpha (a) Identification. alpha alpha Alpha (b) Classification. § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. (b) Classification. § 866.5100 Antinuclear antibody immunological test system. (a) Identification. (b) Classification. § 866.5110 Antiparietal antibody immunological test system. (a) Identification. 12 12 (b) Classification. § 866.5120 Antismooth muscle antibody immunological test system. (a) Identification. (b) Classification § 866.5130 Alpha (a) Identification. alpha alpha alpha (b) Classification. § 866.5150 Bence-Jones proteins immunological test system. (a) Identification. (b) Classification. § 866.5160 Beta (a) Identification. beta Beta beta (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5170 Breast milk immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5180 Fecal calprotectin immunological test system. (a) Identification. in vitro in vitro (b) Classification. [71 FR 42598, July 27, 2006] § 866.5200 Carbonic anhydrase B and C immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5210 Ceruloplasmin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019] § 866.5220 Cohn fraction II immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5230 Colostrum immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5240 Complement components immunological test system. (a) Identification. 1q 1r 1s 2 3 4 5 6 7 8 9 (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 53 FR 11253, Apr. 6, 1988] § 866.5250 Complement C 1 (a) Identification. 1 1 1 1 1 (b) Classification. § 866.5260 Complement C 3b (a) Identification. 3b 3b 3b (b) Classification. § 866.5270 C-reactive protein immunological test system. (a) Identification. (b) Classification. § 866.5320 Properdin factor B immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.5330 Factor XIII, A, S, immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5340 Ferritin immunological test system. (a) Identification. (b) Classification. § 866.5350 Fibrinopeptide A immunological test system. (a) Identification. (b) Classification. § 866.5360 Cohn fraction IV immunological test system. (a) Identification. alpha- beta- alpha- beta- alpha- beta- alpha- (b) Classification. [47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5370 Cohn fraction V immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5380 Free secretory component immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.5400 Alpha (a) Identification. alpha- alpha- alpha- (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5420 Alpha (a) Identification. alpha- alpha- alpha- alpha- (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5425 Alpha (a) Identification. alpha alpha alpha- alpha (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5430 Beta (a) Identification. beta beta beta (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5440 Beta (a) Identification. beta beta beta (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5460 Haptoglobin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.5470 Hemoglobin immunological test system. (a) Indentification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019] § 866.5490 Hemopexin immunological test system. (a) Indentification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59227, Nov. 3, 1998] § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. (b) Classification. § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. (b) Classification. § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001] § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001] § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5550 Immunoglobulin (light chain specific) immunological test system. (a) Identification. (b) Classification. § 866.5560 Lactic dehydrogenase immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5570 Lactoferrin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2312, Jan. 14, 2000] § 866.5580 Alpha (a) Identification. alpha alpha- alpha- (b) Classification. § 866.5590 Lipoprotein X immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2313, Jan. 14, 2000] § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. (b) Classification. § 866.5620 Alpha (a) Identification. alpha alpha alpha (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019] § 866.5630 Beta (a) Identification. beta beta beta (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019] § 866.5640 Infectious mononucleosis immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, 1982] § 866.5660 Multiple autoantibodies immunological test system. (a) Identification. (b) Classification. § 866.5665 Aquaporin-4 autoantibody immunological test system. (a) Identification. e.g., (b) Classification. (1) Premarket notification submissions must include the following information: (i) A detailed device description including: (A) A detailed description of all components including all required ancillary reagents in the test; (B) If applicable, a detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals; (C) If applicable, detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software; (D) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the specified testing procedures; (E) Detailed specifications for sample collection, processing, and storage; (F) A detailed description of methodology and assay procedure; (G) A description of how the assay cutoff (the medical decision point between positive and negative) was established and validated as well as supporting data; and (H) Detailed specification of the criteria for test results interpretation and reporting. (ii) Detailed information demonstrating the performance characteristics of the device, including: (A) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-site, and total precision for multiple nonconsecutive days, as applicable. A well characterized panel of patient samples or pools from the indicated population that covers the device measuring range must be used. (B) Device linearity data generated from samples covering the device measuring range, if applicable. (C) Information on traceability to a reference material and description of value assignment of calibrators and controls, if applicable. (D) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation, if applicable. (E) Device analytical specificity data, including interference by endogenous and exogenous substances, as well as cross-reactivity with samples derived from patients with other autoimmune diseases or conditions. (F) Device instrument carryover data, when applicable. (G) Device stability data, including real-time stability under various storage times and temperatures. (H) Specimen stability data, including stability under various storage times, temperatures, freeze-thaw, and transport conditions, where appropriate. (I) Method comparison data generated by comparison of the results obtained with the device to those obtained with a legally marketed predicate device with similar indications of use. A well-characterized panel of patient samples from the indicated population covering the device measuring range must be used. (J) Specimen matrix comparison data, if more than one specimen type or anticoagulant can be tested with the device. Samples used for comparison must be from well-characterized patient samples covering the device measuring range. (K) Clinical performance must be established by comparing data generated by testing samples from the indicated population and the differential diagnosis or non-target disease groups with the device to the clinical diagnostic standard. ( 1 e.g., e.g., ( 2 ( 3 ( 4 ( 5 ( 6 (L) Expected/reference values generated by testing an adequate number of samples from apparently healthy normal individuals. (iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) The device's 21 CFR 809.10(b) compliant labeling must include warnings relevant to the device including: (i) A warning statement that reads “The device is for use by laboratory professionals in a clinical laboratory setting”; and (ii) A warning statement that reads “The device is not to be used as a stand-alone device but as an adjunct to other clinical information. A diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD) should not be made on a single test result. The clinical symptoms, results from physical examination, laboratory tests ( e.g., e.g. (3) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol and performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results. [82 FR 50076, Oct. 30, 2017] § 866.5670 Zinc transporter 8 autoantibody immunological test system. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) A detailed description of the device that includes: (A) A detailed description of all components in the test system, including a description of the assay components in the kit and all required ancillary reagents; (B) A detailed description of instrumentation and equipment, and illustrations or photographs of non-standard equipment or methods if applicable; (C) Detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software where applicable; (D) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the recommended testing procedures; (E) Detailed specifications for sample collection, processing, and storage; (F) A detailed description of methodology and assay procedure; and (G) Detailed specification of the criteria for test results interpretation and reporting. (ii) Information that demonstrates the performance characteristics of the device, including: (A) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-operator, between-instruments, between-site, and total precision for multiple nonconsecutive days as applicable. A well characterized panel of patient samples or pools from the intended use population that covers the device measuring range must be used; (B) Device linearity data generated from patient samples covering the assay measuring range if applicable; (C) Information on traceability to a reference material and description of value assignment of calibrators and controls if applicable; (D) Device analytical sensitivity data, including limit of blank, limit of detection and limit of quantitation if applicable; (E) Device analytical specificity data, including interference by endogenous and exogenous substances, as well as cross-reactivity with samples derived from patients with other autoimmune diseases or conditions; (F) Device instrument carryover data when applicable; (G) Device stability data including real-time stability under various storage times and temperatures; (H) Specimen stability data, including stability under various storage times, temperatures, freeze-thaw, and transport conditions where appropriate; (I) Method comparison data generated by comparison of the results obtained with the device to those obtained with a legally marketed predicate device with similar indication of use. Patient samples from the intended use population covering the device measuring range must be used; (J) Specimen matrix comparison data if more than one specimen type or anticoagulant can be tested with the device. Samples used for comparison must be from patient samples covering the device measuring range; (K) A description of how the assay cut-off (the medical decision point between positive and negative) was established and validated as well as supporting data; (L) Clinical performance must be established by comparing data generated by testing samples from the intended use population and the differential diagnosis groups with the device to the clinical diagnostic standard. The diagnosis of Type 1 diabetes mellitus must be based on clinical history, physical examination, and laboratory tests, such as one or more pancreatic or insulin autoantibody test. Because the intended use population for Type 1 diabetes mellitus includes subjects less than 18 years old, samples from representative numbers of these subjects must be included. Representative numbers of samples from all age strata must also be included. The differential diagnosis groups must include, but not be limited to the following: Type 2 diabetes mellitus; metabolic syndrome; latent autoimmune diabetes in adults; other autoimmune diseases such as celiac disease (without a concomitant diagnosis of Type 1 diabetes mellitus), systemic lupus erythematosus, rheumatoid arthritis, and Hashimoto's thyroiditis; infection; renal disease; and testicular cancer. Diseases for the differential groups must be based on established diagnostic criteria and clinical evaluation. For all samples, the diagnostic clinical criteria and the demographic information must be collected and provided. The clinical validation results must demonstrate clinical sensitivity and clinical specificity for the test values based on the presence or absence of Type 1 diabetes mellitus. The data must be summarized in tabular format comparing the interpretation of results to the disease status; and (M) Expected/reference values generated by testing an adequate number of samples from apparently healthy normal individuals. (iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) Your 21 CFR 809.10(a) compliant label and 21 CFR 809.10(b) compliant labeling must include warnings relevant to the assay including: (i) A warning statement that reads, “The device is for use by laboratory professionals in a clinical laboratory setting”; (ii) A warning statement that reads, “The test is not a stand-alone test but an adjunct to other clinical information. A diagnosis of Type 1 diabetes mellitus should not be made on a single test result. The clinical symptoms, results on physical examination, and laboratory tests ( e.g., (iii) A warning statement that reads, “Absence of Zinc T8 autoantibody does not rule out a diagnosis of Type 1 diabetes mellitus”; and (iv) A warning statement that reads, “The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment.” (3) Your 21 CFR 809.10(b) compliant labeling must include a description of the protocol and performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results. [82 FR 49103, Oct. 20, 2017] § 866.5680 Myoglobin immunological test system. (a) Identification. (b) Classification. § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, 2001] § 866.5715 Plasminogen immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2313, Jan. 14, 2000] § 866.5735 Prothrombin immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2313, Jan. 14, 2000] § 866.5750 Radioallergosorbent (RAST) immunological test system. (a) Identification. (b) Classification. Table 1—Class II Exempt Allergens Under § 866.5750—Radioallergosorbent (RAST) Immunological Test Systems Allergen code Allergen product Source Grass Pollens g1 Sweet vernal grass Anthoxanthum odoratum. g3 Cocksfoot grass, Orchard grass Dactylis glomerata. g4 Meadow fescue Festuca elatior. g5 Rye-grass (perennial rye grass) Lolium perenne. g7 Common reed (common reed grass) Phragmites communis. g8 Meadow grass, Kentucky blue (June grass) Poa pratensis. g9 Redtop, Bentgrass Agrostis stolonifera Agrostis gigantea Agrostis alba g11 Brome grass Bromus inermis. g12 Cultivated rye (cultivated rye grass) Secale cereale. g13 Velvet grass Holcus lanatus. g14 Cultivated oat (cultivated oat grass) Avena sativa. g15 Cultivated wheat (cultivated wheat grass) Triticum aestivum Triticum g16 Meadow foxtail (meadow foxtail grass) Alopecurus pratensis. g17 Bahia grass Paspalum notatum. g24 Wheat grass, Western Agropyron smithii Elymus smithii g30 Bluegrass, annual Poa annua. g70 Wild rye grass Elymus triticoides Elymus condensatus. g71 Canary grass Phalaris arundinacea. g201 Barley, cultivated Hordeum vulgare. g202 Maize, corn (cultivated corn) Zea mays. g203 Salt grass Distichlis spicata. g204 False oat-grass Arrhenatherum elatius. g216 Cyn d 1 Cynodon dactylon. g701 Phl p 1.0102, Phl p 5.0101 Phleum pratense. g702 Phl p 7.0101 Phleum pratense. g703 Phl p 12.0101 Phleum pratense. Weed Pollens w2 Western ragweed Ambrosia psilostachya. w4 False ragweed Ambrosia acanthicarpa Franseria acanthicarpa w5 Wormwood Artemisia absinthium Artemisia annua. w6 Mugwort Artemisia vulgaris. w7 Marguerite, ox-eye daisy Chrysanthemum leucanthemum. w8 Dandelion Taraxacum vulgare Taraxacum officinale. w9 Plantain (English), Ribwort Plantago lanceolata. w10 Goosefoot, lamb's quarters Chenopodium album. w11 Saltwort (prickly), Russian thistle Salsola kali Salsola pestifer w12 Goldenrod Solidago virgaurea Solidago w13 Cocklebur, common Xanthium commune. w14 Common pigweed (rough pigweed) Amaranthus retroflexus. w15 Scale, Lenscale Atriplex lentiformis. w16 Rough marsh elder Iva ciliate Iva annua. w17 Firebush (Kochia) Kochia scoparia. w18 Sheep sorrel Rumex acetosella. w19 Wall pellitory Parietaria officinalis. w20 Nettle (Common stinging nettle) Urtica dioica. w21 Wall pellitory Parietaria judaica. w22 Japanese hop (careless weed) Humulus japonicas Humulus scandens w23 Yellow dock, Yellow dockweed Rumex crispus. w24 Spiny pigweed Amaranthus spinosus. w27 Carnation Dianthus w28 Rose Rosa rugosa. w33 Clover Trifolium pratense. w35 Mexican tea Chenopodium ambrosioides. w36 Rabbit bush Ambrosia deltoidea Franseria deltoides w37 Salt bush, annual Atriplex wrightii. w39 Water hemp, Western Amaranthus rudis Acnida tamariscina w41 Burrobrush Hymenoclea salsola. w42 Poverty weed Baccharis neglecta. w43 Common sagebrush Artemisia tridentata. w45 Alfalfa Medicago sativa. w46 Dog fennel Eupatorium capillifolium. w53 Geranium Geranium w67 Groundsel bush Baccharis halimifolia. w69 Iodine bush Allenrolfea occidentalis. w70 Ragweed, slender Ambrosia confertiflora. w75 Wing scale (wingscale) Atriplex canescens. w82 Careless weed Amaranthus palmeri Amaranthus hybridus. w90 Japanese hop Humulus japonicas Humulus scandens w203 Rape (rape pollen) Brassica napus. w204 Sunflower Helianthus annuus. w206 Camomile Matricaria chamomilla. w207 Lupin Lupinus w210 Sugar-beet Beta vulgaris. w211 Par j 2.0101 Parietaria judaica. w231 Art v 1 Artemisia vulgaris w232 Sal k 1 Salsola kali. w233 Art v 3 Artemisa vulgaris w234 Pla l 1 Plantago lanceolata. w235 Che a 1.0101 Chenopodium album. w236 Mer a 1.0101 Mercurialis annua. a753 Art v 1 Artemisia vulgaris Tree Pollens t1 Box-elder (Maple) Acer negundo Acer saccharum. t2 Gray alder, speckled alder (alder) Alnus incana. t4 Hazel, hazelnut Corylus avellana Corylus americana. t5 American beech (beech) Fagus grandifolia Fagus americana t6 Mountain juniper, Mountain cedar Juniperus ashei Juniperus sabinoides t8 Elm Ulmus americana. t9 Olive Olea europaea. t10 Walnut Juglans californica Juglans nigra. t11 Maple leaf sycamore, London plane, Plane tree Platanus acerifolia. t61 Sycamore Platanus occidentalis. t12 Willow Salix caprea Salix nigra. t14 Cottonwood (Eastern Cottonwood/Black Cottonwood) Populus deltoides. t15 White ash Fraxinus americana. t16 White pine Pinus strobus. t18 Eucalyptus, gum-tree Eucalyptus globulus Eucalyptus t19/t26 Acacia Acacia longifolia Acacia t20 Mesquite Prosopis glandulosa/ Prosopis juliflora. t21 Melaleuca, cajeput tree Melaleuca quinquenervia Melaleuca leucadendron t22 Pecan, hickory Carya illinoinensis Carya pecan t23 Italian/Mediterranean/funeral cypress Cupressus sempervirens. t24 Japanese cypress Chamaecyparis obtusa Chamaecyparis t25 Ash Fraxinus excelsior. t27 Maple, red Acer rubrum. t29 Acacia Acacia t30 Birch, white Betula populifolia. t32 Willow, black Salix nigra. t33 Ash, Arizona Fraxinus velutina. t35 Cedar, salt Tamarix gallica. t37 Bald cypress (white bald cypress) Taxodium distichum. t38 Elm, Chinese/Siberian Ulmus pumila. t40 Hazelnut tree Corylus americana. t41 White hickory Carya alba Carya tomentosa t42 Oak, red Quercus rubra. t43 Loblolly pine Pinus taeda. t44 Hackberry Celtis occidentalis. t45 Cedar elm Ulmus crassifolia. t47 Juniper, one seed Juniperus monosperma. t48 Pine, lodgepole Pinus contorta. t49 Pine, ponderosa Pinus ponderosa. t50 Beech, European Fagus sylvatica. t51 Tree of Heaven Ailanthus altissima. t52 Western white pine Pinus monticola. t54 Russian olive Elaeagnus angustifolia. t55 Scotch broom Cytisus scoparius. t56 Bayberry Myrica cerifera. t57 Red cedar Juniperus virginiana. t60 Western juniper Juniperus occidentalis. t61 Sycamore Platanus occidentalis. t70 Mulberry (white mulberry) Morus alba. t71 Red mulberry Morus rubra. t72 Queen palm Arecastrum romanzoffiamon. t73 Australian pine Casuarina equisetifolia. t77 Oak mix (red, white, black) Quercus t80 Japanese cypress Chamaecyparis obtusa. t81 Japanese alder Alnus japonica. t83 Mango tree Mangifera indica. t90 Walnut, black Juglans nigra. t96 Poplar, white (poplar) Populus alba. t103/t218 Virginia live oak (live oak) Quercus virginiana. t105 Pepper tree Schinus molle. t110 Orange tree Citrus sinensis. t201 Spruce, Norway spruce Picea abies Picea excelsa t202 Alder, smooth Alnus incana Rugosa Alnus rugosa t203 Horse chestnut Aesculus hippocastanum. t205 Elder Sambucus nigra. t206 Chestnut Castanea sativa. t207 Douglas fir Pseudotsuga menziesii Pseudotsuga taxifolia t208 Linden Tilia cordata. t209 Horn beam Carpinus betulus. t210 Privet Ligustrum vulgare. t211 Sweet gum Liquidambar styraciflua. t212 Cedar Libocedrus decurrens. t213 Pine Pinus radiata. t214 Date palm Phoenix canariensis. t215 Lilac Syringa vulgaris. t217 Pepper tree Schinus molle. t217 Red alder Alnus rubra. t218 Virginia live oak Quercus virginiana. t218 Bayberry (bayberry/sweet gale) Myrica gale. t219 Palo verde Cercidium floridum. t219 Red cedar Juniperus virginiana. t220 Bet v 4 Betula verrucosa t221 Bet v 2.0101, Bet v 4 Betula verrucosa t222 Cypress (Arizona cypress) Cupressus arizonica. t223 Oil palm Elaeis guineensis. t224 Ole e 1 Olea europaea. t225 Bet v 6 Betula verrucosa t226 Cup a 1 Cupressus arizonica. t227 Ole e 7 Olea Europaea. t228 Aspen, quaking Populus tremuloides. t229 Eastern hemlock Tsuga canadensis. t230 Redwood (sequoia) Sequoia sempervirens. t232 Pussy willow Salix discolor. t240 Ole e 9.0101 Olea Europaea. t241 Pla a 1.0101 Platanus acerifolia. t242 Pla a 2 Platanus acerifolia. t243 Pla a 3.0101 Platanus acerifolia. t244 Cor a 1.0103 Corylus avellana. t245 Aln g 1.0101 Alnus glutinosa. t246 Cry j 1 Cryptomeria japonica. t280 Locust tree Robinia pseudoacacia. t401 Brazilian peppertree Schinus terebinthifolius. t402 Mastic tree Pistacia lentiscus. t404 Tree of heaven Ailanthus altissima. t406 Date palm Phoenix dactylifera. a482 Ole e 1 Olea europaea Mites d207 Blo t 5.0101 Blomia tropicalis. d208 Lep d 2.0101 Lepidoglyphus destructor. Microorganisms, Molds, Yeast m1 Penicillium chrysogenum Penicillium notatum Penicillium chrysogenum Penicillium notatum m2 Cladosporium herbarum Hormodendrum Cladosporium herbarum Hormodendrum m3 Aspergillus fumigatus Aspergillus fumigatus. m4 Mucor racemosus Mucor racemosus. m5 Candida albicans Candida albicans. m7 Botrytis cinerea Botrytis cinerea. m8 Drechslera halodes Setomelanomma rostrata, Helminthosporium halodes, Helminthosporium interseminatum Drechslera halodes Setomelanomma rostrata, Helminthosporium halodes. m9 Fusarium moniliforme Fusarium proliferatum Fusarium moniliforme Fusarium proliferatum m10 Stemphylium botryosum Stemphylium herbarum Stemphylium botryosum m11 Rhizopus nigricans Rhizopus nigricans. m12 Aureobasidium pullulans Aureobasidium pullulans. m13 Phoma betae Phoma betae. m14 Epicoccum purpurascens Epicoccum purpurascens Epicoccum nigrum m15 Trichoderma viride Trichoderma viride. m16 Curvularia lunata Curvularia lunata Curvularia specifera K923044 m17 Cladosporium fulvum Cladosporium fulvum. m18 Fusarium culmorum Fusarium culmorum. m19 Aspergillus versicolor Aspergillus versicolor. m20 Mucor mucedo Mucor mucedo. m21 Aspergillus clavatus Aspergillus clavatus. m22 Micropolyspora faeni Saccharopolyspora rectivirgula Micropolyspora faeni m23 Thermoactinomyces vulgaris Thermoactinomyces vulgaris. m24 Stachybotrys atra Stachybotrys chartarum Stachybotrys atra m24 Paecilomyces Paecilomyces m25 Aspergillus versicolor Aspergillus versicolor. m25 Penicillium brevicompactum Penicillium brevicompactum. m26 Cladosporium cladosporioides Cladosporium cladosporioides. m26 Penicillium citrinum Penicillium citrinum. m27 Penicillium Penicillium m29 Aspergillus repens Aspergillus repens. m30 Penicillium roqueforti Penicillium roqueforti. m32 Cladosporium cladosporioides Cladosporium cladosporioides. m34 Serpula lacrymans Serpula lacrymans. m36 Aspergillus terreus Aspergillus terreus. m37 Trichophyton mentagrophytes Trichophyton mentagrophytes. m40 Aspergillus amstelodami Aspergillus amstelodami. m43 Saccharomyces Carlsberg Saccharomyces carlsbergensis. m44 Saccharomyces cerevisiae Saccharomyces cerevisiae. m45 Hormodendrum hordei Hormodendrum hordei. m46 Bipolaris spicifera Bipolaris spicifera. m47 Aspergillus nidulans Aspergillus nidulans. m48 Aspergillus oryzae Aspergillus oryzae. m49 Fusarium oxysporum Fusarium oxysporum. m50 Micropolyspora faeni Saccharopolyspora rectivirgula Micropolyspora faeni m51 Thermoactinomyces vulgaris Thermoactinomyces vulgaris. m53 Microspora canis Microsporum canis Microspora canis m54 Aspergillus flavus Aspergillus flavus. m63 Helminthosporium intersemin Helminthosporium intersemin. m66 Mucor plumbeus Mucor plumbeus. m67 Mycogone Mycogone perniciosa. m68 Nigrospora oryzae Nigrospora oryzae. m69 Rhodotorula Rhodotorula rubra Rhodotorula mucilaginosa m70 Malassezia furfur Pityrosporum orbiculare Malassezia furfur Pityrosporum orbiculare m71 Spondylocladium Spondylocladium m72 Epidermophyton Epidermophyton floccosum. m73 Epicoccum nigrum Epicoccum purpurascens Epicoccum nigrum m80 Staphylococcal enterotoxin A Sta a SEA Staphylococcus aureus. m80 Helminthosporium Helminthosporium m81 Staphylococcal enterotoxin B Sta a SEB Staphylococcus aureus. m88 Stemphylium solani Stemphylium solani. m93 Gliocladium fimbriatum Gliocladium fimbriatum. m94 Phycomyces blakesleeanus Phycomyces blakesleeanus. m201 Tilletia tritici Ustilago nuda, Ustilago tritici Tilletia tritici Ustilago nuda, Ustilago tritici m202 Acremonium kiliense Cephalosporium acremonium Acremonium kiliense Cephalosporium acremonium m203 Trichosporon pullulans Trichosporon pullulans. m204 Ulocladium chartarum Ulocladium chartarum. m205 Trichophyton rubrum Trichophyton rubrum. m207 Aspergillus niger Aspergillus niger. m208 Chaetomium globosum Chaetomium globosum. m209 Penicillium frequentans Penicillium glabrum Penicillium frequentans m209 Stachybotrys chartarum Stachybotrys chartarum Stachybotrys atra m210 Trichophyton mentagrophytes var. goetzii Trichophyton mentagrophytes var. goetzii. m211 Trichophyton mentagrophytes var. interdigitale Trichophyton mentagrophytes var. interdigitale. m211 Oat smut Ustilago avenae. m212 Micropolyspora faeni Saccharopolyspora rectivirgula Micropolyspora faeni m212 Geotrichum candidum Geotrichum candidum. m213 Bermuda grass smut Ustilago cynodontis. m214 Johnson grass smut Sphacelotheca cruenta. m215 Corn smut Ustilago maydis. m218 Asp f 1.0101 Aspergillus fumigatus. a3050 Asp r 1 Aspergillus restrictus. m219 Asp f 2 Aspergillus fumigatus. m220 Asp f 3.0101 Aspergillus fumigatus. m221 Asp f 4 Aspergillus fumigatus. m222 Asp f 6.0101 Aspergillus fumigatus. m223 Staphylococcal enterotoxin C Sta a SEC Staphylococcus aureus. m224 Staphylococcal enterotoxin D Sta a SED Staphylococcus aureus. m226 Staphylococcal enterotoxin TSST Sta a TSST Staphylococcus aureus. m227 Malassezia Pityrosporum Malassezia Pityrosporum m228 Aspergillus flavus. m229 Alt a 1.0101 Alternaria alternata Alternaria tenuis m230 Alt a 6.0101 Alternaria alternata Alternaria tenuis m231 Cla h 8.0101 Cladosporium herbarum Hormodendrum m300 Eurotium Eurotium m304 Aspergillus oryzae Aspergillus oryzae. m305 Penicillium brevicompactum Penicillium brevicompactum. m309 Aspergillus terreus Aspergillus terreus. m310 Aspergillus nidulans Aspergillus nidulans. m311 Aspergillus flavus Aspergillus flavus. m312 Aspergillus clavatus Aspergillus clavatus. Epidermal & Animal e6 Guinea pig epithelium Cavia porcellus. e7 Pigeon droppings Columba palumbus Columba livia. e25 Chicken serum Gallus domesticus Gallus gallus domesticus; Gallus e26 Parrot serum Psittacoidea e62 Camel Camelus dromedaries. e70 Goose feathers Anser anser. e71 Mouse epithelium Mus musculus Mus e73 Rat epithelium Rattus norvegicus. e74 Rat urine proteins Rattus norvegicus Rattus rattus. e75 Rat serum proteins Rattus norvegicus Rattus rattus. e76 Mouse serum proteins Mus musculus Mus e77 Budgerigar droppings Melopsittacus undulatus. e78 Budgerigar feathers Melopsittacus undulatus. e79 Budgerigar serum proteins Melopsittacus undulatus. e80 Goat epithelium Capra hircus. e81 Sheep epithelium Ovis aries Ovis e82 Rabbit epithelium Oryctolagus cuniculus Oryctolagus e83 Swine epithelium Sus scrofa Sus scrofa domesticus; Sus e84 Hamster epithelium Cricetus cricetus, Mesocricetus auratus, and Phodopus sungorus. e85 Chicken feathers Gallus domesticus Gallus gallus domesticus; Gallus e86 Duck feathers Anas platyrhynchos. e87 Rat epithelium, serum proteins, and urine proteins Rattus norvegicus Rattus rattus. e88 Mouse epithelium, serum proteins, and urine proteins (mouse) Mus musculus Mus e89 Turkey feathers Meleagris gallopavo. e90 Budgerigar serum proteins, feathers, and droppings Melopsittacus undulatus. e91 Pigeon serum proteins, feathers, and droppings Streptopelia roseogrisea Psittacidae e92 Parrot serum proteins, feathers, and droppings Ara e93 Pigeon serum proteins Streptopelia roseogrisea. e94 Fel d 1.0101 Felis domesticus. a345 Fel d 1 Felis domesticus. e98 Parrot droppings Psittacoidea e101 Can f 1.0101 Canis familiaris Canis domesticus a174 Can f 1 Canis familiaris Canis domesticus e102 Can f 2.0101 Canis familiaris Canis domesticus e196 Parakeet feathers Nymphicus hollandicus. e197 Parakeet droppings Nymphicus hollandicus. e198 Parakeet serum Nymphicus hollandicus. e199 Canary bird serum Serinus canarius. e200 Canary bird droppings Serinus canarius. e201 Canary bird feathers (Canary feathers) Serinus canarius. e202 Reindeer epithelium Rangifer tarandus. e203 Mink epithelium Mustela e204 Bos d 6 Bos domesticus Bos taurus; Bos e205 Horse, serum proteins Equus caballus Equus e206 Rabbit, serum proteins Oryctolagus cuniculus Oryctolagus e208 Chinchilla epithelium Chinchilla laniger. e209 Gerbil epithelium Meriones unguiculatus. e210 Fox epithelium Vulpes vulpes. e211 Rabbit, urine proteins Oryctolagus cuniculus Oryctolagus e212 Swine, urine proteins Sus scrofa Sus scrofa domesticus; Sus e213 Parrot feathers Ara e214 Finch feathers Lonchura domestica. e215 Pigeon feathers Streptopelia roseogrisea Streptopelia Columbia e216 Deer epithelium Dama dama. e217 Ferret epithelium Mustela putorius. e218 Chicken droppings Gallus domesticus Gallus gallus domesticus; Gallus e219 Chicken, serum proteins Gallus domesticus Gallus gallus domesticus; Gallus e220 Fel d 2, Cat serum albumin Felis domesticus. e221 Can f 3 Canis familiaris Canis domesticus Dog serum albumin e222 Swine serum albumin (Sus s PSA) Sus scrofa Sus scrofa domesticus; Sus e225 Lovebird feathers Psittacoidea agapomis. e226 Can f 5.0101 Canis familiaris. e227 Equ c 1.0101 Equus caballus. e228 Fel d 4.0101 Felis domesticus. e230 Equ c 3 Equus caballus. e231 Mus m 1 Mus musculus. Food f9 Rice Oryza sativa. f12 Pea (green pea) Pisum sativum. f15 White bean Phaseolus vulgaris. f19 Cayenne pepper Capsicum frutescens Capsicum annum f21 Sugar cane Saccharum officinarum. f22 Raspberry Rubus idaeus. f26 Pork Sus scrofa Sus scrofa domesticus; Sus f29 Watermelon Citrullus lanatus Citrullus vulgaris f31 Carrot Daucus carota. f32 Oyster mushroom Pleurotus ostreatus. f33 Orange Citrus sinensis. f35 Potato Solanum tuberosum. f43 Mother's milk Homo sapiens. f44 Strawberry Fragaria vesca Fragaria f45 Yeast, baker's Saccharomyces cerevisiae. f46 Pepper, Red Capsicum annuum. f47 Garlic Allium sativum. f48 Onion Allium cepa. f49 Apple Malus x domestica Malus f51 Bamboo shoot Phyllostachys pubescens. f52 Cacao/chocolate Theobroma cacao. f54 Sweet potato Ipomoea batatas. f55 Common millet Panicum miliaceum. f56 Foxtail millet Setaria italica. f57 Japanese millet Echinochloa crus-galli. f58 Pacific squid Todarodes pacificus. f59 Octopus Octopus vulgaris Octopus f63 Kefir NA. f67 Parmesan cheese NA. f81 Cheese, cheddar type NA. f82 Cheese, mold type NA. f83 Chicken Gallus domesticus Gallus gallus domesticus; Gallus f86 Parsley Petroselinum crispum. f87 Melon Cucumis melo Cucumis melo + Citrullus lanatus. f88 Mutton (lamb) Ovis aries Ovis f90 Malt Hordeum vulgare. f92 Banana Musa f93 Cacao Theobroma cacao. f94 Pear Pyrus communis Pyrus f97 Yam Dioscorea Dioscorea opposita. f97 Chamomile tea Matricaria chamomilla. f98 Gliadin Triticum aestivum Triticum f102 Cantaloupe Cucumis melo var. cantalupensis. f105 Chocolate Theobroma cacao. f109 Cottonseed Gossypium hirsutum. f110 Giant radish Raphanus sativus. f118 Zucchini Cucurbita pepo. f119 Radish Raphanus sativus. f120 Venison Capreolus capeolus. f121 Pinto bean Phaseolus vulgaris. f122 Cheese, American NA. f127 Black-eyed pea Vigna unguiculata. f131 Black Olive Olea europaea. f136 Red beet Beta vulgaris var. conditiva. f139 Goat's Cheese Capra aegagrus. f140 Bran NA. f141 Corn (vegetables) Zea mays. f152 Green bell pepper Capsicum annuum. f155 Brewer's yeast Saccharomyces carlsbergensis. f157 Duck Anas domesticus. f158 Goose Anser anser. f160 Camembert cheese NA. f162 Nectarine Prunus persica var. nucipersica. f163 Kohlrabi Brassica oleracea var. gongylodes. f65 Perch f166 Leek Allium porrum. f170 Cheese (Switzerland) (Swiss cheese) NA. f174 Fig Ficus carica. f177 Cranberry Vaccinium macrocarpon. f179 Raisin Vitis f182 Lima bean Phaseolus lunatus. f198 Flaxseed (bruised grain) Linum usitatissimum. f199 Untreated native milk Bos domesticus Bos taurus; Bos f208 Lemon Citrus limon. f209 Grapefruit Citrus paradisi. f210 Pineapple Ananas comosus. f211 Blackberry Rubus fruticosus. f212 Mushroom (champignon) Agaricus hortensis Agaricus f213 Rabbit Oryctolagus cuniculus Oryctolagus f214 Spinach Spinacia oleracea. f215 Lettuce Lactuca sativa. f216 Cabbage Brassica oleracea var. capitata. f217 Brussels sprouts Brassica oleracea var. gem. f218 Paprika, sweet pepper Capsicum annuum. f219 Fennel seed Foeniculum vulgare. f219 Sage Salvia officinalis. f220 Cinnamon Cinnamomum f221 Coffee Coffea f222 Tea Camellia sinensis. f223 Green olive Olea europaea. f225 Summer squash, pumpkin Cucurbita pepo. f225 Pumpkin Cucurbita maxima. f226 Pumpkin seed Cucurbita pepo. f227 Sugar-beet seed Beta vulgaris. f229 Safflower Seed Carthamus tinctorius. f231 Milk, boiled Bos domesticus Bos taurus; Bos f234 Vanilla Vanilla planifolia. f237 Apricot Prunus armeniaca. f241 Gouda cheese NA. f242 Cherry Prunus avium. f244 Cucumber Cucumis sativus. f246 Guar, guar gum Cyamopsis tetragonoloba. f247 Honey NA. f248 Rosemary Rosmarinus officinalis. f254 Plaice Pleuronectes platessa. f255 Plum Prunus domestica Prunus americana. f258 Squid Loligo f259 Grape Vitis vinifera Vitis f260 Broccoli Brassica oleracea var. italica Brassica oleracea var. cultivar f261 Asparagus Asparagus officinalis. f262 Aubergine, eggplant Solanum melongena. f263 Green pepper Piper nigrum Capsicum annuum. f264 Eel Anguilla anguilla. f265 Caraway Carum carvi. f265 Cumin Cuminum cyminum. f266 Mace Myristica fragrans. f267 Cardamon Elettaria cardamomum. f268 Clove Syzygium aromaticum. f269 Basil Ocimum basilicum. f270 Ginger Zingiber officinale. f271 Anise Pimpinella anisum. f272 Tarragon Artemisia dracunculus. f273 Thyme Thymus vulgaris. f274 Marjoram Origanum majorana. f275 Lovage Levisticum officinale. f276 Fennel, fresh Foeniculum vulgare. f277 Dill Anethum graveolens. f278 Bay leaf Laurus nobilis. f279 Chili pepper Capsicum frutescens. f280 Black pepper Piper nigrum. f281 Curry (Santa Maria) NA. f282 Nutmeg Myristica fragrans. f283 Oregano Origanum vulgare. f284 Turkey meat Meleagris gallopavo. f285 Elk/moose meat Alces f286 Mare's milk Equus caballus Equus f287 Red kidney bean Phaseolus vulgaris. f288 Blueberry Vaccinium myrtillus Vaccinium f289 Date Phoenix dactylifera. f291 Cauliflower Brassica oleracea var. botrytis. f292 Guava Psidium guajava. f293 Papaya Carica papaya. f294 Passion fruit, Maracuja Passiflora edulis Passiflora f295 Carambola Averrhoa carambola. f296 Carob Ceratonia siliqua. f297 Gum Arabic Acacia senegal Acacia f298 Tragacanth Astragalus f299 Sweet chestnut (chestnut) Castanea sativa. f300 Pinto bean Phaseolus f301 Persimmon (kaki fruit, sharon) Diospyros kaki. f302 Mandarin (tangerine, clementine, satsumas) Citrus reticulata. f305 Fenugreek Trigonella foenum-graecum. f306 Lime Citrus aurantifolia. f307 Hake Merluccius merluccius. f308 Sardine (pilchard) Sardina pilchardus. f310 Blue vetch Lathyrus sativus. f311 Megrim Lepidorhombus whiffiagonis. f315 Green bean Phaseolus vulgaris. f316 Rape seed Brassica napus. f317 Coriander Coriandrum sativum. f318 Jack fruit Artocarpus heterophyllus. f319 Beetroot Beta vulgaris. f320 Crayfish Astacus astacus. f321 Horse meat Equus caballus Equus f322 Red currant Ribes sylvestre. f324 Hop (fruit cone) Humulus lupulus. f325 Saffron Colchicum autumnale. f328 Fig Ficus carica. f329 Watermelon Citrullus lanatus. f330 Rose hip Rosa f331 Saffron Crocus sativus. f332 Mint Mentha piperita. f333 Linseed Linum usitatissimum. f336 Jujube Ziziphus jujuba. f336 Wine vinegar Vitis vinifera Vitis f337 Sole Solea solea. f337 English sole Parophrys vetulus. f338 Wine, white Vitis vinifera Vitis f339 Allspice Pimenta dioica. f339 Wine, red Vitis vinifera Vitis f341 Cranberry Vaccinium oxycoccus Vaccinium macrocarpon. f342 Olive (black, fresh) Olea europaea. f343 Raspberry Rubus idaeus. f344 Sage Salvia officinalis. f346 Chives Allium schoenoprasum. f347 Quinoa Chenopodium quinoa. f348 Litchi Litchi chinensis. f349 Chum salmon roe Oncorhynchus keta. f358 Artichoke Cynara scolymus. f360 Yogurt NA. f368 Black bass Micropterus dolomieu Micropterus dolomieui f374 Karaya gum Sterculia urens. f375 Horseradish Armoracia rusticana. f377 Maple syrup NA. f379 Okra Abelmoschus esculentus. f382 Beet, sugar Beta vulgaris var. altissima. f401 Loquat Eriobotrya japonica. f402 Fig Ficus carica. f403 Brewer's yeast Saccharomyces cerevisiae. f405 Mint Mentha f406 Arugula Eruca vesicaria. House Dust h1 Greer Labs., Inc NA. h2 Hollister-Stier Labs NA. h6 Japan NA. Venoms & Insects i7 Midge Chironomus yoshimatsui. i8 Moth Bombyx mori Heterocera i47 Water flea Daphnia i49 Deer fly Chrysops i51 Black ant Camponotus pennsylvanicus. i54 Flea mix (dog/cat), common flea Ctenocephalides i71 Mosquito Aedes communis Aedes and Culex i72 Green nimitti Cladotanytarsus lewisi. i73 Blood worm Chironomus thummi Chironomusri parius Chironomus i75 European hornet Vespa crabro. i76 Berlin beetle Trogoderma angustum. i77 European paper wasp Polistes dominulus. i78 Fly Musca domestica. i80 Bumblebee Bombus pennsylvanicus. i201 Horse bot fly Gasterophilus intestinalis. i202 Grain weevil Sitophilus granarius. i203 Mediterranean flour moth Ephestia kuehniella Anagasta kuehniella i204 Horse fly Tabanus i205 Bumblebee Bombus terrestris. i208 Api m 1.0101 Apis mellifera. a45 Api m 1 Apis mellifera. i209 Ves v 5.0101 Vespula vulgaris. a670 Ves v 5 Vespula vulgaris. i210 Pol d 5.0101 Polistes dominulus. i211 Ves v 1.0101 Vespula vulgaris. i213 Api m 4 Apis mellifera. i214 Api m 2 Apis mellifera. i215 Api m 3 Apis mellifera. i216 Api m 5 Apis mellifera. i217 Api m 10 Apis mellifera. i220 Bla g 1.0101 Blattella germanica. i221 Bla g 2.0101 Blattella germanica. i222 Bla g 5.0101 Blattella germanica. i223 Bla g 7 Blattella germanica. a46 Api m 2 Apis mellifera. Miscellaneous o1 Cotton, crude fibers Gossypium o3 Cotton (treated) Gossypium o70 Seminal fluid Homo sapiens. o71 Staphylococcus aureus Staphylococcus aureus. o72 Pichia pastoris Pichia pastoris. o72 Sperm-sediment Homo sapiens. o73 Pichia pastoris Pichia pastoris. o74 Pichia pastoris Pichia pastoris. o201 Tobacco leaf, tobacco dust Nicotiana tabacum. o202 Artemia salina, fish feed Artemia salina. o203 Tetramin, fish feed NA. o207 Daphnia, fish feed Daphnia o211 Mealworm Tenebrio molitor. o212 Streptavidin Streptomyces avidini. o213 MBP (maltose binding protein) Escherichia coli. o214 CCD; MUXF3 from bromelain Ananas comosus. o72 Enterotoxin A (Sta a SEA) Staphylococcus aureus. o73 Enterotoxin B (Sta a SEB) Staphylococcus aureus. Parasites p1 Ascaris Ascaris suum. p2 Echinococcus Echinococcus granulosus. p3 Schistosoma Schistosoma mansoni. p4 Anisakis (Herring Worm) Anisakis simplex Anisakis p5 Toxocara canis Toxocara canis. p10 Ani s 3.0101 Anisakis simplex Anisakis p11 Ani s 1 Anisakis simplex Anisakis Occupational k4 Threshing dust NA. k5 Flax NA. k7 Hay Dust NA. k8 Hop (hops) Humulus lupulus. k12 Grain mill dust NA. k14 Kapok NA. k20 Sheep's wool (treated) (wool) Ovis aries Ovis k21 Sheep's wool (Untreated) Ovis aries Ovis k23 Straw Dust NA. k33 Oak NA. k70 Green coffee bean Coffea k71 Castor bean Ricinus communis. k72 Ispaghula Plantago psyllium/Plantago ovata. k73 Silk waste NA. k74 Silk Bombyx mori. k75 Isocyanate TDI (Toluene diisocyanate) NA. k76 Isocyanate MDI (Diphenylmethane diisocyanate) NA. k77 Isocyanate HDI (Hexamethylen diisocyanate) NA. k78 Ethylene oxide NA. k79 Phthalic anhydride NA. k80 Formaldehyde/Formalin NA. k81 Ficus Ficus benjamina Ficus k83 Cotton seed Gossypium hirsutum. k84 Sunflower seed Helianthus annuus. k85 Chloramin T NA. k86 Trimellitic anhydride, TMA NA. k87 Asp o 21, alpha-amylase Aspergillus oryzae. k89 Orris root Iris florentina. k99 HSA (Human Serum Albumin) (Hom s HSA) Homo sapiens. k201 Car p 1, Papain Carica papaya. k202 Ana c 2, Bromelain Ananas comosus. k204 Maxatase Bacillus licheniformis. k205 Alcalase Bacillus k206 Savinase, Protease 1 (Bac l Subtilisin) Bacillus k208 Gal d 4, Lysozyme Gallus domesticus Gallus gallus domesticus; Gallus k209 Hexahydrophtalic anhydrid NA. k210 Maleic anhydride NA. k211 Methyltetrahydrophtalic anhydrid NA. k212 Abachi wood dust Triplochiton scleroxylon. k213 Pepsin (Sus s Pepsin) Sus scrofa Sus scrofa domesticus; Sus k213 TCPA NA. k214 Bougainvillea Bougainvillea k225 Horse radish peroxidase (Arm r HRP) Armoracia rusticana. k226 Ascorbate oxidase (Cuc p ascorbate oxidase) Cucurbita pepo. k301 Flour dust Triticum k501 Savinase customer specific Proprietary knowledge of customer. k502 Lipolase customer specific Proprietary knowledge of customer. k503 Termamyl customer specific Proprietary knowledge of customer. k504 Clazinase customer specific Proprietary knowledge of customer. [47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019] § 866.5760 Tryptase test system. (a) Identification. (b) Classification. [79 FR 56010, Sept. 18, 2014] § 866.5765 Retinol-binding protein immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 65 FR 2313, Jan. 14, 2000] § 866.5775 Rheumatoid factor immunological test system. (a) Identification. (b) Classification. § 866.5780 Anti-phospholipase A2 receptor immunological test system. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) A detailed description of the device that includes: (A) A detailed description of all parts of the test system, including a description of the assay parts in the kit and all required ancillary reagents; (B) A detailed description of instrumentation and equipment, and illustrations or photographs of non-standard equipment or methods if applicable; (C) Detailed documentation of the device software, including standalone software applications and hardware-based devices that incorporate software where applicable; (D) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the recommended testing procedures; (E) Detailed specifications for sample collection, processing, and storage; (F) A detailed description of methodology and assay procedure; and (G) Detailed specification of the criteria for test results interpretation and reporting. (ii) Information that demonstrates the performance characteristics of the device, including: (A) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-operator, between-instruments, between-site, and total precision for multiple nonconsecutive days as applicable. A well-characterized panel of patient samples or pools from the intended use population that covers the device measuring range must be used; (B) Device linearity data generated from patient samples covering the assay measuring range if applicable; (C) Information on traceability to a reference material and description of value assignment of calibrators and controls if applicable; (D) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation if applicable; (E) Device analytical specificity data, including interference by endogenous and exogenous substances, as well as cross-reactivity with samples derived from patients with other autoimmune diseases or conditions; (F) Device instrument carryover data when applicable; (G) Device stability data including real-time stability under various storage times and temperatures; (H) Specimen stability data including stability under various storage times, temperatures, freeze-thaw, and transport conditions where appropriate; (I) Method comparison data generated by comparison of the results obtained with the device to those obtained with a legally marketed predicate device with similar indication of use. Patient samples from the intended use population covering the device measuring range must be used; (J) Specimen matrix comparison data if more than one specimen type or anticoagulant can be tested with the device. Samples used for comparison must be from patient samples covering the device measuring range; (K) A description of how the assay cut-off (the medical decision point between positive and negative) was established and validated as well as supporting data; (L) A clinical performance assessment established by comparing data generated by testing samples from the intended use population and differential diagnosis groups with the device to the clinical diagnostic standard. Diagnosis of pMGN must be based primarily on clinical history, physical examination, laboratory tests (including urinalysis), and renal biopsy. Membranous glomerulonephritis is considered to be idiopathic/primary when no secondary cause can be elucidated on the basis of clinical and laboratory criteria. The differential diagnosis groups must include secondary membranous glomerulonephritis, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, IgA nephritis, diabetic nephropathy, systemic lupus erythematosus, systemic sclerosis, and Goodpasture syndrome. Diagnosis of autoimmune and immune-mediated diseases that are associated with membranous glomerulonephritis must be based on established diagnostic criteria and clinical evaluation. For all samples, clinical criteria, including demographic information, must be considered in the differentiation between pMGN and secondary membranous glomerulonephritis. The clinical validation results must demonstrate correlation clinical sensitivity and clinical specificity between the test values and the presence or absence of pMGN. The data must be summarized in tabular format comparing the interpretation of results to the disease status; and (M) Expected/reference values generated by testing an adequate number of samples from apparently healthy normal individuals. (iii) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) The label required under § 809.10(a) and labeling required under § 809.10(b) of this chapter must include warnings relevant to the assay including: (i) A warning statement that explains: The device is for use by laboratory professionals in a clinical laboratory setting; (ii) A warning statement that explains: The test is not a standalone test but an adjunct to other clinical information. A diagnosis of pMGN or secondary MGN should not be made based on a single test result. The clinical symptoms, results on physical examination, and laboratory tests ( e.g., (iii) A warning statement that explains: Absence of circulating PLA2R autoantibody does not rule out a diagnosis of pMGN; and (iv) A warning statement that explains: The assay has not been demonstrated to be effective for monitoring the stage of disease or its response to treatment. (3) The labeling required under § 809.10(b) of this chapter must include a description of the protocol and performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results. [90 FR 40725, Aug. 21, 2025] § 866.5785 Anti- Saccharomyces cerevisiae S. cerevisiae (a) Identification. Saccharomyces cerevisiae S. cerevisiae S. cerevisiae S. cerevisiae (b) Classification. Saccharomyces cerevisiae S. cerevisiae [65 FR 70307, Nov. 22, 2000] § 866.5800 Seminal fluid (sperm) immunological test system. (a) Identification. (b) Classification. [54 FR 25047, June 12, 1989, as amended at 66 FR 38793, July 25, 2001] § 866.5820 Systemic lupus erythematosus immunological test system. (a) Identification. (b) Classification. § 866.5830 Brain trauma assessment test. (a) Identification. (b) Classification. (1) The 21 CFR 809.10(b) compliant labeling must include detailed descriptions of and results from performance testing conducted to evaluate precision, accuracy, linearity, analytical sensitivity, interference, and cross-reactivity. This information must include the following: (i) Performance testing of device precision must, at minimum, use one unmodified clinical specimen from the intended use population with concentration of the brain injury biomarker(s) near the medical decision point. Contrived specimens that have been generated from pooling of multiple samples or spiking of purified analyte to cover the measuring range may be used, but the contrived samples must be prepared to mimic clinical specimens as closely as possible. This testing must evaluate repeatability and reproducibility using a protocol from an FDA-recognized standard. (ii) Device performance data must be demonstrated through a clinical study and must include the following: (A) Data demonstrating clinical validity including the clinical sensitivity and specificity, and positive and negative predictive value of the test in the intended use population of patients with suspected mild traumatic brain injury ( i.e., (B) Study must be performed using the operators and in settings that are representative of the types of operators and settings for which the device is intended to be used. (C) All eligible subjects must meet the well-defined study inclusion and exclusion criteria that define the intended use population. The prevalence of diseased or injured subjects in the study population must reflect the prevalence of the device's intended use population, or alternatively, statistical measures must be used to account for any bias due to enrichment of subpopulations of the intended use population. (D) All eligible subjects must have undergone a head computerized tomography (CT) scan or other appropriate clinical diagnostic standard used to determine the presence of an intracranial lesion as part of standard of care and must also be evaluated by the subject device. All clinical diagnostic standards used in the clinical study must follow standard clinical practice in the United States. (E) Relevant demographic variables and baseline characteristics including medical history and neurological history. In addition, head injury characteristics, neurological assessments, and physical evidence of trauma must be provided for each subject. This information includes but is not limited to the following: Time since head injury, time from head injury to CT scan, time from head injury to blood draw, GCS score or equivalent, experience of loss of consciousness, presence of confusion, episodes of vomiting, post-traumatic amnesia characteristics, presence of post-traumatic seizures, drug or alcohol intoxication, mechanism of injury, acute intracranial lesion type, neurosurgical lesion, and cranial fracture. (F) Each CT scan or other imaging result must be independently evaluated in a blinded manner by at least two board-certified radiologists to determine whether it is positive or negative as defined by the presence or absence of acute intracranial lesions. This independent review must be conducted without access to test results of the device. Prior to conducting the review, the criteria and procedures to be followed for scoring the images must be established, including the mechanism for determining consensus. (G) All the clinical samples must be tested with the subject device blinded to the TBI status and the neurological-lesion-status of the subject. (H) Details on how missing values in data are handled must be provided. (I) For banked clinical samples, details on storage conditions and storage period must be provided. In addition, a specimen stability study must be conducted for the duration of storage to demonstrate integrity of archived clinical samples. The samples evaluated in the assay test development must not be used to establish the clinical validity of the assays. (iii) Performance testing of device analytical specificity must include the most commonly reported concomitant medications present in specimens from the intended use population. Additionally, potential cross-reacting endogenous analytes must be evaluated at the highest concentration reported in specimens from the intended use population. (iv) Expected/reference values generated by testing a statistically appropriate number of samples from apparently healthy normal individuals. (2) The 21 CFR 809.10(a) and (b) compliant labeling must include the following limitations: (i) A limiting statement that this device is not intended to be used a stand-alone device but as an adjunct to other clinical information to aid in the evaluation of patients who are being considered for standard of care neuroimaging. (ii) A limiting statement that reads “A negative result is generally associated with the absence of acute intracranial lesions. An appropriate neuroimaging method is required for diagnosis of acute intracranial lesions.” (iii) As applicable, a limiting statement that reads “This device is for use by laboratory professionals in a clinical laboratory setting.” [83 FR 27701, June 14, 2018] § 866.5840 Alzheimer's disease pathology assessment test. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) Detailed documentation of studies demonstrating analytical performance, including precision, linearity, assay interference, cross-reactivity, detection capability, specimen and reagent stability, and hook effect, as applicable. For devices measuring multiple analytes, the detailed documentation must include studies demonstrating the analytical performance of the device in regard to each individual analyte, including precision, linearity, assay interference, cross-reactivity, detection capability, specimen and reagent stability, and hook effect, as applicable. (ii) Detailed documentation of studies demonstrating clinical performance in the intended use patient population. All eligible subjects must meet the appropriate study inclusion and exclusion criteria that define the intended use population. Relevant demographic and patient characteristics must be documented, including the time from specimen collection for testing with the subject device to PET imaging acquisition; patient cognitive, neurological, and psychiatric assessments; Apolipoprotein E (APOE) carrier status; and patient education level. All specimens must be tested with the users of the subject device blinded to the disease status and PET scan results of the subject from whom the specimen was obtained. Each PET scan must use an FDA-approved PET tracer and must be independently evaluated in a blinded manner and interpreted according to the FDA-required labeling for the PET tracer. For banked specimens, details on storage conditions and storage period must be documented. In addition, documentation must include evidence to support the stability of the archived specimens for the duration of storage. (iii) Detailed documentation of studies, which are performed using specimens from persons established to be cognitively normal, that establish the upper and lower limits of reference intervals for the output provided by the device. For banked specimens, the detailed documentation must include details on storage conditions and storage period. In addition, the detailed documentation must include evidence to support the stability of the archived specimens for the duration of storage. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use that provides a description of the measurand(s) ( i.e., (ii) Limiting statements indicating that: (A) This device is not intended to be used as a stand-alone test and the test results must be interpreted in conjunction with other diagnostic tools and clinical information. (B) The safety and effectiveness of the device have not been established for predicting development of dementia or other neurologic conditions or for monitoring the effect of any therapeutic product. (C) A positive result is associated with the presence of amyloid plaques or neurofibrillary tangles in the brain but does not establish a diagnosis of AD as would be established by neuropathological examination. (iii) A detailed summary of the performance testing, including results, required under paragraph (b)(1) of this section. [91 FR 21381, Apr. 22, 2026] § 866.5860 Total spinal fluid immunological test system. (a) Identification. (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 61 FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, 2001] § 866.5870 Thyroid autoantibody immunological test system. (a) Identification. (b) Classification. § 866.5880 Transferrin immunological test system. (a) Identification. (b) Classification. § 866.5890 Inter- alpha (a) Identification. alpha alpha alpha (b) Classification. [47 FR 50823, Nov. 9, 1982, as amended at 53 FR 11253, Apr. 6, 1988; 65 FR 2313, Jan. 14, 2000] § 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system. (a) Identification. (b) Classification. [70 FR 61738, Oct. 26, 2005] § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. (b) Classification. [72 FR 1176, Jan. 10, 2007, as amended at 84 FR 71811, Dec. 30, 2019] § 866.5920 Postnatal chromosomal copy number variation detection system. (a) Identification. (b) Classification. (1) Design verification and validation must include the following information: (i) A detailed description of all components in the test system that includes: (A) A description of the assay components, array composition and layout, all required reagents, instrumentation, and equipment, including illustrations or photographs of non-standard equipment or methods; (B) A description of the design of the array in terms of chromosomal coverage and probe density for different regions; (C) An identification of the number of probes and size of the CNVs reported at the lower range of the assay; (D) Detailed documentation of the device software, including standalone software applications and hardware-based devices that incorporate software; (E) Methodology and protocols for detecting copy number and visualizing results; (F) A description of the result outputs along with sample reports, and a description of any links to external databases provided by the device to the user or accessed by the device; (G) Specifications for the methods to be used in specimen collection, extraction (including DNA criteria for DNA quality and quantity to perform the assay), and storage; and (H) A description of appropriate internal and external controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. (ii) Information that demonstrates the performance characteristics of the system, including: (A) Device reproducibility data generated, at a minimum, using three sites, with two operators at each site, for three non-consecutive days using at least three instruments. A well-characterized panel of samples that provide a wide range of CNVs ( i.e., (B) Device accuracy data using cell lines and clinical samples representing a variety of CNVs and syndromes. In this analytical study, accuracy must be determined for every CNV detected in a particular sample. The accuracy data provided must include the copy number state determination and endpoint accuracy. The accuracy samples must cover different genomic variations across the genome ( i.e., (C) Assay performance data for CNVs reported at the lower range of the assay for both gains and losses; (D) Device analytical sensitivity data, including DNA input and limit of detection for mosaicism, if applicable; (E) Device analytical specificity data, including interference, carryover, and cross-contamination data; (F) Device stability data, including real-time stability under various storage times, temperatures, and freeze-thaw conditions; (G) Specimen matrix comparison data if more than one specimen type or anticoagulant can be tested with the device; (H) Data that demonstrates the clinical validity, including diagnostic yield, of the device using a minimum of 800 retrospective clinical samples that were collected prospectively and obtained from three or more clinical laboratories, with results interpretation equally divided between two or more qualified healthcare professionals ( e.g., (I) Data that demonstrates device results when a minimum of 100 apparently healthy, phenotypically normal individuals are tested and interpreted by one or more cytogeneticists blinded to the patient status. (iii) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) The labeling required under § 809.10 of this chapter must include: (i) A warning statement that the device is not intended to be used for standalone diagnostic purposes, pre-implantation or prenatal testing or screening, population screening, or for the detection of, or screening for, acquired or somatic genetic aberrations; (ii) Limitations regarding the assay's performance with respect to validated CNVs reported at the lower range of the assay, stratified by size range and range of probe numbers for gains and losses separately; and limitations regarding problematic (hypervariable) regions, loss of heterozygosity, mosaicism, and inability to detect balanced translocations, as appropriate; (iii) A warning statement that interpretation of assay results is intended to be performed by qualified healthcare professionals such as clinical cytogeneticists or molecular geneticists; and, (iv) A description of the performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results. [90 FR 40715, Aug. 21, 2025] § 866.5930 Newborn screening test for severe combined immunodeficiency disorder (SCID). (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) The intended use must indicate: (A) The test is not intended for diagnostic use, or for screening of SCID-like syndromes, such as DiGeorge syndrome or Omenn syndrome; and (B) The test is not intended to screen for less acute SCID syndromes, such as leaky SCID or variant SCID. (ii) A detailed description of all components in the test that includes: (A) A detailed description of the test components, all required reagents, instrumentation and equipment, including illustrations or photographs of nonstandard equipment or methods; (B) Detailed documentation of the device software including, but not limited to, standalone software applications and hardware-based devices that incorporate software; (C) Specifications for the filter paper, which must be appropriately labeled for in vitro diagnostic use, to be used in specimen collection and how it will be used in specimen collection validation. These specifications must include: descriptive characteristics of the filter paper, instructions on how a lab should choose the appropriate filter paper, chemical properties of the filter paper, interference concerns associated with the chemicals in the filter paper, absorption properties of the filter paper, punch size, absorption capacity, testing for homogeneity of punches, diameter of the circle for the dried blood spot aliquot, absorption time, physical composition, and number and size of punches to be tested; (D) Methodology and protocols for detection of T-cell receptor excision circles and methods for determination of results. The cutoff must be selected before conducting clinical and analytical studies; (E) A description of the result outputs along with sample reports. Sample reports must include the scale used in reporting of results ( e.g., (F) A description of appropriate internal and external controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. (iii) Information that demonstrates the performance characteristics of the test, including: (A) Data that demonstrates the clinical validity of the device, using well characterized prospectively or retrospectively obtained clinical specimens representative of the intended use population. A minimum of 10 to 15 confirmed positive specimens must be obtained from more than 1 site, including relevant annotation, and, at 1 year or beyond, a SCID diagnosis by flow cytometry or clinically meaningful information regarding the status of the subject must be obtained. Additional specimens should have been obtained that are characterized by other disorders that can be found by screening specimens that have low or absent TREC ( e.g., i.e., (B) Device reproducibility data generated, using a minimum of three sites of which at least two must be external sites, with two operators at each site. Each site must conduct a minimum of five runs per operator over five nonconsecutive days evaluating a minimum of six different relevant TREC concentrations that span and are well distributed over the measuring range and include the clinical cutoff. Specimens must include cord blood and cord blood diluted with ABO matched adult blood specimens. Identical specimens from the same sample panel must be tested at each site. Each specimen must be run in triplicate and include controls run in triplicate. Results must be reported as the standard deviation and percentage coefficient of variation for each level tested. Results must also be displayed as a dichotomous variable around the cutoff. Total variation must be partitioned into the sum of within-lab and between-lab variations with pre-specified acceptance criteria and 95 percent confidence intervals for all data. Pre-specified acceptance criteria must be provided and followed; (C) Device precision data using clinical samples to evaluate the within-lot, between-lot, within-run, between run, and total variation. A range of TREC levels of the specimen must include samples within the measuring range, samples above and below the measuring range, as well as with samples very near above and below the cutoff value. At least three replicates of each specimen must be tested with controls and calibrator(s) according to the device instructions for use. The precision study must use well characterized samples using different lots, instruments, and operators. Results must be summarized in tabular format. Pre-specified acceptance criteria must be provided and followed; (D) Linearity of the test must be demonstrated using a dilution panel from clinical samples. The range of dilution samples must include samples within the measuring range, samples above and below the measuring range, as well as with samples very near above and below the cutoff value. Results of the regression analysis must be summarized in tabular format and fitted into a linear regression model with the individual measurement results against the dilution factors. Pre-specified acceptance criteria must be provided and followed; (E) Device analytic sensitivity data, including limit of blank, limit of detection, and limit of quantification; (F) Device specificity data, including interference, carryover, cross-contamination, and in silico analysis of potential off-target genomic sequences; (G) Device stability data, including real-time stability of samples under various storage times, temperatures, and freeze-thaw conditions. A separate shipping stability study must be performed; (H) Lot-to-lot reproducibility study of each filter paper that will be validated with the test. The lot-to-lot study must include a minimum of three lots of each blood spot card that will be validated with the test and be conducted over five nonconsecutive days. The sample panel must consist of specimens with a range of TREC levels and include samples within the measuring range, samples above and below the measuring range, and samples very near above and below the cutoff value. Multiple punches must be obtained from each card for demonstration of homogeneity of the analyte across the dried blood spot. Comparability of the test performance for each filter paper must be demonstrated. Stability and storage of TREC DNA on each blood spot card must be demonstrated. Results of the lot-to-lot study must be summarized providing the mean, standard deviation, and percentage coefficient of variation in a tabular format. Data must be calculated for within-run, between-run, within-lot, and between-lot. Data demonstrating the concordance between results across different filter papers must be provided. Study acceptance criteria must be provided and followed; and (I) If applicable, a thermocycler reproducibility study must be performed using thermocyclers from three independent thermocyler manufacturers. The sample panel must consist of specimens with a range of TREC levels and must include samples within the measuring range, samples above and below the measuring range, and samples very near above and below the cutoff value. The study must be done using three filter paper lots and conducted over five nonconsecutive days. Results of the thermocycler reproducibility study must be summarized providing the mean, standard deviation, and percentage coefficient of variance in a tabular format. Data must be calculated for the within-run, between-run, within-lot, between-lot, and between thermocycler manufacturer study results. Study acceptance criteria must be provided and followed. (iv) Identification of risk mitigation elements used by your device, including a description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) Your § 809.10 compliant labeling must include: (i) A warning statement that reads “This test is not intended for diagnostic use, preimplantation or prenatal testing, or for screening of SCID-like syndromes, such as DiGeorge syndrome or Omenn syndrome. It is also not intended to screen for less acute SCID syndromes, such as leaky SCID or variant SCID.”; (ii) A warning statement that reads “Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods and clinical evaluation, as appropriate.”; (iii) A description of the performance studies listed in paragraph (b)(1)(iii) and a summary of the results; and (iv) A description of the filter paper specifications required for the test. [82 FR 50079, Oct. 30, 2017] § 866.5940 Autosomal recessive carrier screening gene mutation detection system. (a) Identification. (b) Classification. (1) If the device is offered over-the-counter, the device manufacturer must provide information to a potential purchaser or actual test report recipient about how to obtain access to a board-certified clinical molecular geneticist or equivalent to assist in pre- and post-test counseling. (2) The device must use a collection device that is FDA cleared, approved, or classified as 510(k) exempt, with an indication for in vitro diagnostic use in DNA testing. (3) The device's labeling must include a prominent hyperlink to the manufacturer's public Web site where the manufacturer shall make the information identified in this section publicly available. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access. If the device can be purchased from the Web site or testing using the device can be ordered from the Web site, the same information must be found on the Web page for ordering the device or provided in a prominently placed and publicly accessible hyperlink on the Web page for ordering the device. Any changes to the device that could significantly affect safety or effectiveness would require new data or information in support of such changes, which would also have to be posted on the manufacturer's Web site. The information must include: (i) A detailed device description including: (A) Gene (or list of the genes if more than one) and variants the test detects (using standardized nomenclature, Human Genome Organization (HUGO) nomenclature, and coordinates). (B) Scientifically established clinical validity of each variant detected and reported by the test, which must be well-established in peer-reviewed journal articles, authoritative summaries of the literature such as Genetics Home Reference ( http://ghr.nlm.nih.gov/ http://www.ncbi.nlm.nih.gov/books/NBK1116/ ( 1 ( 2 ( 3 (C) The specimen type ( e.g., (D) Assay steps and technology used. (E) Specification of required ancillary reagents, instrumentation, and equipment. (F) Specification of the specimen collection, processing, storage, and preparation methods. (G) Specification of risk mitigation elements and description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (H) Information pertaining to the probability of test failure ( e.g., i.e., (I) Specification of the criteria for test result interpretation and reporting. (ii) Information that demonstrates the performance characteristics of the device, including: (A) Accuracy (method comparison) of study results for each claimed specimen type. ( 1 ( 2 ( 3 i.e., e.g., ( 4 4 i 4 ii ( i ( ii (B) Precision (reproducibility): Precision data must be generated using multiple instruments and multiple operators, on multiple non-consecutive days, and using multiple reagent lots. The sample panel must include specimens with claimed sample type ( e.g. i.e., i.e., (C) Analytical specificity data: Data must be generated evaluating the effect on test performance of potential endogenous and exogenous interfering substances relevant to the specimen type, evaluation of cross-reactivity of known cross-reactive alleles and pseudogenes, and assessment of cross-contamination. (D) Analytical sensitivity data: Data must be generated demonstrating the minimum amount of DNA that will enable the test to perform accurately in 95 percent of runs. (E) Device stability data: The manufacturer must establish upper and lower limits of input nucleic acid and sample stability that will achieve the claimed accuracy and reproducibility. Data supporting such claims must be described. (F) Specimen type and matrix comparison data: Specimen type and matrix comparison data must be generated if more than one specimen type or anticoagulant can be tested with the device, including failure rates for the different specimen types. (iii) If the device is offered over-the-counter, including cases in which the test results are provided direct-to-consumer, the manufacturer must conduct a study that assesses user comprehension of the device's labeling and test process and provide a concise summary of the results of the study. The following items must be included in the user study: (A) The test manufacturer must perform pre- and post-test user comprehension studies to assess user ability to understand the possible results of a carrier test and their clinical meaning. The comprehension test questions must directly evaluate the material being presented to the user in the test reports. (B) The test manufacturer must provide a carrier testing education module to potential and actual test report recipients. The module must define terms that are used in the test reports and explain the significance of carrier status. (C) The user study must meet the following criteria: ( 1 ( 2 e.g., ( 3 ( 4 ( 5 ( 6 i.e. (D) A summary of the user comprehension study must be provided and include the following: ( 1 ( 2 ( 3 (4) Your 21 CFR 809.10 compliant labeling and any test report generated must include the following warning and limitation statements, as applicable: (i) A warning that reads “The test is intended only for autosomal recessive carrier screening in adults of reproductive age.” (ii) A statement accurately disclosing the genetic coverage of the test in lay terms, including, as applicable, information on variants not queried by the test, and the proportion of incident disease that is not related to the gene(s) tested. For example, where applicable, the statement would have to include a warning that the test does not or may not detect all genetic variants related to the genetic disease, and that the absence of a variant tested does not rule out the presence of other genetic variants that may be disease-related. Or, where applicable, the statement would have to include a warning that the basis for the disease for which the genetic carrier status is being tested is unknown or believed to be non-heritable in a substantial number of people who have the disease, and that a negative test result cannot rule out the possibility that any offspring may be affected with the disease. The statement would have to include any other warnings needed to accurately convey to consumers the degree to which the test is informative for carrier status. (iii) For prescription use tests, the following warnings that read: (A) “The results of this test are intended to be interpreted by a board-certified clinical molecular geneticist or equivalent and should be used in conjunction with other available laboratory and clinical information.” (B) “This device is not intended for disease diagnosis, prenatal testing of fetuses, risk assessment, prognosis or pre-symptomatic testing, susceptibility testing, or newborn screening.” (iv) For over-the-counter tests, a statement that reads “This test is not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On its own, this test is also not intended to tell you anything about the health of your fetus, or your newborn child's risk of developing a particular disease later on in life.” (v) For over-the-counter tests, the following warnings that read: (A) “This test is not a substitute for visits to a healthcare provider. It is recommended that you consult with a healthcare provider if you have any questions or concerns about your results.” (B) “The test does not diagnose any health conditions. Results should be used along with other clinical information for any medical purposes.” (C) “The laboratory may not be able to process your sample. The probability that the laboratory cannot process your saliva sample can be up to [actual probability percentage].” (D) “Your ethnicity may affect how your genetic health results are interpreted.” (vi) For a positive result in an over-the-counter test when the positive predictive value for a specific population is less than 50 percent and more than 5 percent, a warning that reads “The positive result you obtained may falsely identify you as a carrier. Consider genetic counseling and followup testing.” (vii) For a positive result in an over-the-counter test when the positive predictive value for a specific population is less than 5 percent, a warning that reads “The positive result you obtained is very likely to be incorrect due to the rarity of this variant. Consider genetic counseling and followup testing.” (5) The testing done to comply with paragraph (b)(3) of this section must show the device meets or exceeds each of the following performance specifications: (i) The accuracy must be shown to be equal to or greater than 99 percent for both PPA and NPA. Variants that have a point estimate for PPA or NPA of less than 99 percent (incorrect test results as compared to bidirectional sequencing or other methods identified as appropriate by FDA) must not be incorporated into test claims and reports. (ii) Precision (reproducibility) performance must meet or exceed 99 percent for both positive and negative results. (iii) The user comprehension study must obtain values of 90 percent or greater user comprehension for each comprehension concept. (6) The distribution of this device, excluding the collection device described in paragraph (b)(2) of this section, shall be limited to the manufacturer, the manufacturer's subsidiaries, and laboratories regulated under the Clinical Laboratory Improvement Amendments. [80 FR 65630, Oct. 27, 2015, as amended at 82 FR 51570, Nov. 7, 2017] § 866.5950 Genetic health risk assessment system. (a) Identification. (b) Classification. e.g., (1) The 21 CFR 809.10 compliant labeling and any prepurchase page and test report generated, unless otherwise specified, must include: (i) A section addressed to users with the following information: (A) The limiting statement explaining that this test provides genetic risk information based on assessment of specific genetic variants but does not report on a user's entire genetic profile. This test [does not/may not, as appropriate] detect all genetic variants related to a given disease, and the absence of a variant tested does not rule out the presence of other genetic variants that may be related to the disease. (B) The limiting statement explaining that other companies offering a genetic risk test may be detecting different genetic variants for the same disease, so the user may get different results using a test from a different company. (C) The limiting statement explaining that other factors such as environmental and lifestyle risk factors may affect the risk of developing a given disease. (D) The limiting statement explaining that some people may feel anxious about getting genetic test health results. This is normal. If the potential user feels very anxious, such user should speak to his or her doctor or other health care professional prior to collection of a sample for testing. This test is not a substitute for visits to a doctor or other health care professional. Users should consult with their doctor or other health care professional if they have any questions or concerns about the results of their test or their current state of health. (E) Information about how to obtain access to a genetic counselor, board-certified clinical molecular geneticist, or equivalent health care professional about the results of a user's test. (F) The limiting statement explaining that this test is not intended to diagnose a disease, tell you anything about your current state of health, or be used to make medical decisions, including whether or not you should take a medication or how much of a medication you should take. (G) A limiting statement explaining that the laboratory may not be able to process a sample, and a description of the next steps to be taken by the manufacturer and/or the customer, as applicable. (ii) A section in your 21 CFR 809.10 labeling and any test report generated that is for health care professionals who may receive the test results from their patients with the following information: (A) The limiting statement explaining that this test is not intended to diagnose a disease, determine medical treatment, or tell the user anything about their current state of health. (B) The limiting statement explaining that this test is intended to provide users with their genetic information to inform lifestyle decisions and conversations with their doctor or other health care professional. (C) The limiting statement explaining that any diagnostic or treatment decisions should be based on testing and/or other information that you determine to be appropriate for your patient. (2) The genetic test must use a sample collection device that is FDA-cleared, -approved, or -classified as 510(k) exempt, with an indication for in vitro diagnostic use in over-the-counter DNA testing. (3) The device's labeling must include a hyperlink to the manufacturer's public Web site where the manufacturer shall make the information identified in paragraph (b)(3) of this section publicly available. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a hyperlink to the Web page containing this information and must allow unrestricted viewing access. If the device can be purchased from the Web site or testing using the device can be ordered from the Web site, the same information must be found on the Web page for ordering the device or provided in a publicly accessible hyperlink on the Web page for ordering the device. Any changes to the device that could significantly affect safety or effectiveness would require new data or information in support of such changes, which would also have to be posted on the manufacturer's Web site. The information must include: (i) An index of the material being provided to meet the requirements in paragraph (b)(3) of this section and its location. (ii) A section that highlights summary information that allows the user to understand how the test works and how to interpret the results of the test. This section must, at a minimum, be written in plain language understandable to a lay user and include: (A) Consistent explanations of the risk of disease associated with all variants included in the test. If there are different categories of risk, the manufacturer must provide literature references that support the different risk categories. If there will be multiple test reports and multiple variants, the risk categories must be defined similarly among them. For example, “increased risk” must be defined similarly between different test reports and different variant combinations. (B) Clear context for the user to understand the context in which the cited clinical performance data support the risk reported. This includes, but is not limited to, any risks that are influenced by ethnicity, age, gender, environment, and lifestyle choices. (C) Materials that explain the main concepts and terminology used in the test that include: ( 1 Definitions: ( 2 Prepurchase page: e.g., ( i ( ii ( iii ( iv ( 3 Frequently asked questions (FAQ) page: (iii) A technical information section containing the following information: (A) Gene(s) and variant(s) the test detects using standardized nomenclature, Human Genome Organization nomenclature and coordinates as well as Single Nucleotide Polymorphism Database (dbSNP) reference SNP numbers (rs#). (B) Scientifically established disease-risk association of each variant detected and reported by the test. This risk association information must include: ( 1 ( 2 ( 3 ( i ( ii (C) The specimen type ( e.g., (D) Assay steps and technology used. (E) Specification of required ancillary reagents, instrumentation, and equipment. (F) Specification of the specimen collection, processing, storage, and preparation methods. (G) Specification of risk mitigation elements and description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (H) Information pertaining to the probability of test failure ( i.e., i.e., (I) Specification of the criteria for test result interpretation and reporting. (J) Information that demonstrates the performance characteristics of the test, including: ( 1 ( i ( ii ( iii ( iv ( v 4 DD, 4 Dd 4 dd i.e., 4 4 4 DD Dd dd ( vi ( vii 1 vi 1 iv ( viii e.g., 1 ix xi ( ix ( x 1 vi ( xi ( 2 e.g., e.g., i.e., i.e., e.g., ( 3 Analytical specificity data: ( 4 Interfering variant data: ( 5 Analytical sensitivity data: ( 6 Reagent stability: ( 7 Specimen type and matrix comparison data: (K) Clinical performance summary. ( 1 ( 2 e.g., e.g., e.g., ( i ( ii (L) Materials that explain the main concepts and terminology used in the test that includes, but is not limited to: ( 1 Definitions: ( 2 Prepurchase page: e.g., ( i ( ii ( iii ( iv ( 3 (M) User comprehension study: Information on a study that assesses comprehension of the test process and results by potential users of the test must be provided. ( 1 ( 2 ( 3 ( 4 ( i ( ii ( iii ( iv ( v ( vi i.e., ( vii e.g., (4) The intended use of the device must not include the following indications for use: (i) Prenatal testing; (ii) Determining predisposition for cancer where the result of the test may lead to prophylactic screening, confirmatory procedures, or treatments that may incur morbidity or mortality to the patient; (iii) Assessing the presence of genetic variants that impact the metabolism, exposure, response, risk of adverse events, dosing, or mechanisms of prescription or over-the-counter medications; or (iv) Assessing the presence of deterministic autosomal dominant variants. [82 FR 51561, Nov. 7, 2017, as amended at 83 FR 25914, June 5, 2018] § 866.5960 Human leukocyte antigen typing companion diagnostic test. (a) Identification. (b) Classification. (1) The intended use of the device must specify the target HLA allele(s) or antigen(s), the patient population(s), and the corresponding therapeutic product(s). (2) Design verification and validation must include: (i) Detailed documentation of an analytical accuracy study that uses well-characterized samples including clinical samples from intended use population(s) focusing on the target allele(s) needed for patient selection; (ii) Detailed documentation of precision studies (repeatability, reproducibility) that evaluate possible sources of variation that may affect test results; (iii) Detailed documentation of a study determining range of input sample concentrations that meet performance specifications; (iv) Detailed description of the ambiguity resolution method, if applicable; (v) For a sequencing-based assay, documentation of coverage and predefined coverage threshold of target genomic regions, pertinent variant types, and sequence contexts; (vi) For multiplex assays, documentation of a risk assessment and design specifications that are in place to prevent incorrect reactivity assignment; (vii) Description of a plan on how to ensure the performance of the device does not change when new HLA alleles are identified, and/or when reactivity assignments are changed; and (viii) Detailed description of device software including standalone software, or software and bioinformatics analysis pipeline, if applicable, incorporated in the instruments, and documentation of software including the level of concern and associated risks, software requirement specifications, software design specifications ( e.g., (3) Clinical validity data (which may include summary reports from clinical trials, comparison studies using clinical samples, or through an alternative approach determined to be appropriate by FDA), demonstrating the following, as applicable: (i) Which patients identified by the HLA CDx test are most likely to benefit from the corresponding therapeutic product; and (ii) Which patients identified by the HLA CDx test are likely to be at increased risk for serious adverse reactions as a result of treatment with the corresponding therapeutic product. (4) If the HLA test used in the clinical trials is different from the HLA CDx test in the premarket notification submission, the submission must include results of a bridging study, or an alternative approach determined to be appropriate by FDA. [87 FR 79252, Dec. 27, 2022] § 866.5970 Inherited nucleotide repeat disorder DNA test. (a) Identification. (b) Classification. (1) The intended use on the device's label required under § 809.10(a)(2) of this chapter and device's labeling required under § 809.10(b)(2) of this chapter must include a statement that assay results are solely intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, and that reflex testing, clinical genetic evaluation, and genetic counseling should be offered as appropriate. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A warning that mosaicism detected in one tissue may not reflect mosaicism in other tissues and that the significance of mosaicism should be interpreted with caution in conjunction with other laboratory and clinical information ( e.g., (ii) A prominent statement that this test is not indicated for use for fetal diagnostic testing, newborn screening or for stand-alone diagnostic purposes. (iii) Information that addresses how to interpret different result outputs specific to the technology, such as (peaks) in the electropherograms. (3) Design verification and validation must include the following: (i) Appropriate design features and control elements incorporated into the testing procedure that mitigate the risk of incorrect clinical results. These include controls as determined acceptable by FDA that: (A) Enable the user to determine when the amplification may yield incorrect results, (B) Enable the user to determine when cross contamination may have occurred; (C) Software risk control measures that address device system hazards; (D) Provide software traceability that ensures all hazards are adequately controlled and that all controls have been validated in the final device design; and (E) Ensure the instructions for use and test reports appropriately inform the user about the limitations of the assay. (ii) Validated and acceptable, as determined by FDA, criteria for test result interpretation and reporting, including result outputs. (iii) Acceptable, as determined by FDA, evidence demonstrating the clinical validity of the device which supports each indicated diagnostic use, including for each genotype and associated phenotype used in providing a clinical determination for the target population. (iv) Evidence demonstrating acceptable, as determined by FDA, analytical device performance. Patient specimens must represent the full spectrum of expected clinical results and be obtained through unbiased collection. Specimens must be representative of all categories of results and across the range of repeat sizes ( e.g., (A) Agreement with a comparator method(s) determined to be acceptable by FDA. This evidence must demonstrate the accuracy for detecting the size of the nucleotide repeats and the diagnostic categorical calls in DNA in the indicated specimen type(s) from patients that are representative of the intended use population. Accuracy must be assessed for both diagnostic and carrier subsets independently. (B) Device precision including repeatability and reproducibility, using clinical samples. The study must evaluate all possible sources of variability including, as appropriate, between-site and between operator at a minimum of three sites of which two must be external with a minimum of two operators per site, between-day on a minimum of 3 non-consecutive days, between-run, within-run, between-lot in a minimum of three lots, and between instrument on a minimum of three instruments. Precision must be demonstrated per specimen and determine for both categorical call and by the size of the repeat ( i.e., (C) Device performance at the limit of detection of each allele across the range of sizes and as a function of the indicated DNA input for the assay. (D) Specificity of the reagents for their targets, absence of cross-reactivity, evaluation of sources of interference relevant to the specimen type, and a demonstration of the absence of cross contamination. (E) Performance of the pre-analytical methods, including DNA extraction methods. (F) Performance of the device across the range of indicated DNA input concentrations for the assay. (G) Specimen stability throughout indicated specimen storage ranges, including under expected storage and transport conditions. (v) Robust evidence demonstrating that the number and frequency of incorrect results due to mosaicism are clinically acceptable, as determined by FDA. (vi) An appropriate traceability plan to minimize the risk of incorrect results over time, including a description of the molecular size standards and other reagents that may be required for result interpretation, as applicable, that demonstrate the reliable interpretation of the size of the fragments. (vii) Acceptable, as determined by FDA, device stability protocols and acceptance criteria, that are sufficient to ensure indicated analytical and clinical performance throughout the indicated device stability period. The protocols and acceptance criteria must be adequate to demonstrate that there is no degradation in signal intensity of full mutations when testing a specimen at the latest indicated time point within the indicated device stability that is comprised of the lowest indicated DNA input that can be used. [90 FR 22631, May 29, 2025] § 866.5980 Spinal Muscular Atrophy newborn screening test system. (a) Identification. (b) Classification. (1) Design verification and validation must include the following: (i) A detailed device description, including all device parts ( e.g., (ii) A detailed explanation of the technology, method(s) of data processing from signal acquisition to result assignment, and pre-specified cut-offs used to interpret the data and generate results and sample reports. (iii) A description of appropriate internal and external controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. (iv) Detailed specifications for the filter paper to be used as part of the device, which must be appropriately labeled for in vitro diagnostic use. Specifications must include punch size and address any properties of the filter paper that may interfere with obtaining test results. (v) Detailed documentation of the following analytical and clinical studies, including the study protocols containing descriptions of the test methods, prescribed methods of data analysis and acceptance criteria, final study reports, and data line listings: (A) A study demonstrating the clinical performance of the device using well characterized prospectively or retrospectively obtained clinical specimens from the intended use population and include homozygous and heterozygous specimens of sufficient number to be determined to be acceptable to FDA. Confirmed positive specimens must have a diagnosis based on confirmatory diagnostic methods. The confirmed positives must include samples from SMA types 1-4. Additionally, samples with SMN2 (Survival Motor Neuron 2) copy number ranging to 4 must be evaluated to determine the risk of false negative (unaffected) results due to assay cross reactivity with the SMN2 gene. A description of the sample collection strategy and accountability must be included. Specimens used in the study must be from patients other than those used to design the test, and validation testing must be based on a pre-specified clinical decision point ( i.e., (B) A study demonstrating device accuracy in comparison to the results obtained by a reference or comparator method determined to be acceptable by FDA. (C) A study demonstrating device reproducibility generated using a minimum of three sites, of which at least two must be external sites, with at least two operators at each site using the specified extraction method(s) and protocol. The evaluation must include multiple runs, days, different instruments, and different reagent lots. The study must include heterozygous deleted, homozygous deleted, and unaffected specimens. Identical specimens from the same sample panel must be tested at each site. Results must be summarized in a tabular format and reported as standard deviation and 95 percent confidence intervals for the quantitative result and agreement for qualitative results for between-site, between-operator, between-day/run, and within-run (repeatability) for each specimen. (D) A lot-to-lot reproducibility study of each filter paper intended to be used with the test. The lot-to-lot study must include a minimum of three lots of each blood spot card that will be validated with the test and be conducted over five nonconsecutive days. The sample panel must consist of at least one positive and one negative specimen. Multiple punches must be obtained from each card for demonstration of homogeneity of the analyte across the dried blood spot. Comparability of the test performance for each filter paper must be demonstrated. Stability and storage of SMN1 DNA on each blood spot card must be demonstrated. Results of the lot-to-lot study must be summarized by providing the agreement within replicates on the assay final result for positive and negative specimens with pre-specified acceptance criteria and 95 percent confidence intervals for all data. Data must be calculated for within-lot and between-lot reproducibility. Data demonstrating the concordance between results across different filter papers must be provided. Study acceptance criteria must be provided and followed. (E) A study demonstrating device specificity, including interference, carryover/cross-contamination, and analysis of potential off-target genomic sequences, including evaluation of SMN2 amplification, to evaluate the risk of clinically false negative or false positive results. (F) Studies performed to support the stability of samples using the indicated specimen collection method(s) under various storage times, temperatures, and freeze-thaw conditions, as applicable. (G) Studies performed to demonstrate on-board and in-use reagent stability, including the test method(s), data analysis plans, acceptance criteria, final study reports, and data line listings. Such documentation must include studies to demonstrate reagent shelf-life for the assay kit, including study protocols containing descriptions of the test method(s), data analysis plans, and acceptance criteria. (H) Studies performed to evaluate the risk of false positive and false negative results ( e.g., (I) A shipping stability study, separate from the study described in paragraph (b)(1)(v)(G) of this section, must be performed that demonstrates acceptable stability of the parts that comprise the kit. (vi) A detailed description of the impacts of any software, including software applications and hardware-based devices that incorporate software, on the device's functions. (vii) Identification of all risk mitigation elements used by the device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with using the device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use statement that includes: (A) A detailed description of the target(s) the device detects; and (B) The clinical indications appropriate for test use. (ii) Prominent and conspicuous limiting statements clearly explaining: (A) This test is not intended to screen for SMA subtypes other than those specifically stated in the intended use, nor is it intended for carrier screening, as a stand-alone diagnostic test, or for determining eligibility for therapeutic products. (B) Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation of presumptive positive results by diagnostic confirmatory testing and clinical evaluation, as appropriate. (iii) Description of the device information required under paragraphs (b)(1)(i) through (iv) of this section. (iv) A summary of the results of the studies required under paragraphs (b)(1)(v)(A) through (G) of this section. [91 FR 35386, June 11, 2026] Subpart G—Tumor Associated Antigen immunological Test Systems § 866.6000 Whole exome sequencing constituent device. (a) Identification. (b) Classification. (1) The intended use on the device's label and labeling required under § 809.10 of this chapter must include: (i) The indicated variant types for which acceptable, as determined by FDA, validation data has been provided. Distinct variant types are considered as single nucleotide variant, insertion, deletion, tandem repeats, copy number variants, or gene rearrangements, and validated for specific sizes and lengths, as applicable. (ii) The indicated specimen type(s) for which acceptable, as determined by FDA, validation data has been provided. (2) The labeling required under § 809.10(b) of this chapter must include: (i) The identification of, or the specifications for, the collection device or devices to be used for sample collection, as applicable. (ii) A description of the reportable range, which is the region of the genome for which the assay is intended to provide results, as well as a description of the targeted regions of the genome that have enhanced coverage. This must include a description of any genomic regions that are excluded from the reportable region due to unacceptable risk of erroneous results, or for other reasons. A description of the clinically relevant genes excluded from the reportable range must also be included, if applicable. (iii) A description of the design features and control elements, including the quality metrics and thresholds which are used for reporting the analytical range (the genomic DNA in the reportable range that passed the quality metrics in the run required for reporting to the user) that are incorporated into the testing procedure, that mitigate the risk of incorrect clinical results. The following metrics are considered applicable in the generation of high confidence data and the established thresholds for these metrics for reporting must be described and be determined to be acceptable by FDA: cluster density and percent of cluster pass quality filter, percent of bases meeting the minimum base quality score, average coverage of reads, percent of reads mapped on target, percent of reportable region with coverage meeting the minimum requirement, percent of unassigned read indices, percent of reads for non-human DNA, allele fraction, and strand bias. Any alternate metrics used must be described and an acceptable, as determined by FDA, rationale for applicability must be provided. (iv) A representative sample of the device output report(s) provided to users, which must include any relevant limitations of the device, as determined applicable by FDA. (3) Design verification and validation must include: (i) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's function. (ii) Acceptable data, as determined by FDA, demonstrating how the key quality metrics and quality metric thresholds in the list in paragraph (b)(2)(iii) of this section for reporting were established and optimized for accuracy using appropriate DNA standards with established reference genomic sequence. Data must include, as applicable, base quality score, allele fraction for heterozygosity and coverage, and other applicable metrics. (iii) Data demonstrating acceptable, as determined by FDA, analytical device performance using patient specimens representing the full spectrum of expected variant types reported across the genome and in genomic regions that are difficult to sequence. The number of specimens tested must be sufficient to obtain estimates of device performance that are representative of the device performance that can be expected for the reportable region and clinically relevant subsets of the reportable region, as applicable. For each study, data must include a summary of the key quality metric data; the number and percentage of true positives (TP), false positives (FP), and false negatives (FN); number and percentage of no-calls; positive percent agreement (PPA); negative percent agreement (NPA); positive predictive value (PPV); technical positive percent value (TPPV); and non-reference concordance (NRC). These data must be provided per sample and stratified by variant type. The variant data must also be further stratified by size and zygosity (homozygous common allele, heterozygous, homozygous rare allele). Data demonstrating the accuracy assay based on guanine and cytosine (GC) content, pseudogenes, and proximity to short tandem repeats must also be presented. The data must be presented for the entire exome and also for clinically relevant subsets of the reportable region. For each study, the number of run failures and repeat/requeued specimens must be summarized. (iv) Documentation of acceptance criteria that are applied to analytical and clinical validation studies, which must be justified based on the estimated risk of erroneous results on clinically significant genes and variants and must be clinically acceptable, as determined by FDA. The acceptance criteria must be pre-specified prior to clinical and analytical validation studies, and all validation testing results must be documented with respect to those acceptance criteria. (v) Analytical validation must be demonstrated by conducting studies that provide: (A) Data demonstrating acceptable, as determined by FDA, accuracy based on agreement with an acceptable, as determined by FDA, comparator method(s) that has been validated to have high accuracy and reproducibility. Accuracy of the test shall be evaluated with reference standards and clinical specimens for each indicated specimen type of a number determined acceptable by FDA, collected and processed in a manner consistent with the test's instructions for use. (B) Data demonstrating acceptable, as determined by FDA, precision from a precision study using clinical samples to adequately evaluate intra-run, inter-run, and total variability across operator, instrument, lot, day, and site, as applicable. The samples must include the indicated range of DNA input. Precision, including repeatability and reproducibility, must be assessed by agreement between replicates, and also supported by sequencing quality metrics for targeted regions across the panel. Precision must be demonstrated per specimen and in aggregate. Precision data must be calculated and presented with and without no calls/invalid results. (C) Data demonstrating acceptable, as determined by FDA, accuracy in the presence of clinically relevant levels of potential interfering substances that are present in the specimen type and intended use population, including, for example, endogenous substances, exogenous substances, and microbes, as applicable. (D) Data demonstrating the absence of sample cross contamination due to index swapping (misassignment). (E) Data demonstrating that the pre-analytical steps such as DNA extraction are robust such that sources of variability in these steps and procedures do not diminish the accuracy and precision of the device. (F) Data demonstrating that acceptable, as determined by FDA, device performance is maintained across the range of claimed DNA input concentrations for the assay. (vi) Design verification and validation for software within the whole exome sequencing constituent device must include the following: (A) Detailed description of the software, including specifications and requirements for the format of data input and output, such that users can determine if the device conforms to user needs and intended uses. (B) Device design must include a detailed strategy to ensure cybersecurity risks that could lead to loss of genetic data security, are adequately addressed and mitigated (including device interface specifications and how safe reporting of the genetic test is maintained when software is updated). Verification and validation must include security testing to demonstrate effectiveness of the associated controls. (C) Device design must ensure that a record of critical events, including a record of all genetic test orders using the whole exome sequencing constituent device, device malfunctions, and associated acknowledgments, is stored and accessible for an adequate period to allow for auditing of communications between the whole exome sequencing constituent device and downstream clinical genetic tests, and to facilitate the sharing of pertinent information with the responsible parties for those devices. (vii) A protocol reviewed and determined acceptable by FDA, that specifies the verification and validation activities that will be performed for anticipated bioinformatic software modifications to reevaluate performance claims or performance specifications. This protocol must include a process for assessing whether a modification to the bioinformatics software could significantly affect the safety or effectiveness of the device. The protocol must include assessment metrics, acceptance criteria, and analytical methods for the performance testing of changes, as applicable. The protocol must also include the process for communicating to developers of downstream clinical genetic tests the impact of the bioinformatics software change on the whole exome sequencing constituent system genetic data output so they may implement appropriate corresponding actions. [89 FR 73566, Sept. 11, 2024] § 866.6010 Tumor-associated antigen immunological test system. (a) Identification. (b) Classification. [62 FR 66005, Dec. 17, 1997] § 866.6020 Immunomagnetic circulating cancer cell selection and enumeration system. (a) Identification. (b) Classification. [69 FR 26038, May 11, 2004] § 866.6030 AFP-L3% immunological test system. (a) Identification. (b) Classification. [70 FR 57749, Oct. 4, 2005] § 866.6040 Gene expression profiling test system for breast cancer prognosis. (a) Identification. (b) Classification. [72 FR 26291, May 9, 2007] § 866.6050 Ovarian adnexal mass assessment score test system. (a) Identification. (b) Classification. see (c) Black box warning. [76 FR 16294, Mar. 23, 2011, as amended at 76 FR 82131, Dec. 30, 2011] § 866.6060 BCR-ABL quantitation test. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) The indication for use must indicate the variant(s) for which the assay was designed and validated, for example BCR-ABL e13a2 and/or e14a2. (ii) A detailed description of all components in the test, including the following: (A) A detailed description of the test components, all required reagents, instrumentation and equipment, including illustrations or photographs of non-standard equipment or methods; (B) Detailed documentation of the device software including, but not limited to, standalone software applications and hardware-based devices that incorporate software; (C) Methodology and protocols for control procedures for the assay to allow reporting on the International Scale; (D) A description of the result outputs, analytical sensitivity of the assay, and the range of values that will be reported; and (E) A description of appropriate internal and external controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. (iii) Information that demonstrates the performance characteristics of the test, including: (A) For indications for use based on a threshold established in a predicate device of this generic type, device performance data from either a method comparison study to the predicate device or through a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population; (B) For indications for use based on a threshold not established in a predicate device of this generic type, device performance data from a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population; (C) Device reproducibility data generated, using a minimum of three sites, of which at least two sites must be external sites, with two operators at each site. Each site must conduct a minimum of three runs per operator over non-consecutive days evaluating a minimum of five different BCR-ABL concentrations that span and are well distributed over the measuring range and include MR3 (0.1 percent IS). Results shall be reported as the standard deviation and percentage coefficient of variation for each level tested. Prespecified acceptance criteria must be provided and followed; (D) Device precision data using clinical samples to evaluate the within-lot, between-lot, within-run, between run, and total variation; (E) Device linearity data using a dilution panel created from clinical samples; (F) Device analytic sensitivity data, including limit of blank, limit of detection, and limit of quantification; (G) Device specificity data, including interference and cross-contamination; and (H) Device stability data, including real-time stability of samples under various storage times, temperatures, and freeze-thaw conditions. (iv) Identification of risk mitigation elements used by your device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing using your device. (2) Your 21 CFR 809.10 compliant labeling must include the following: (i) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) complaint labeling must include an indication for use statement that reads “This test is not intended for the diagnosis of CML”; and (ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(iii) of this section and a summary of the results. (3) Your device output must include results on the International Scale (IS) and your assay must include multipoint calibration controls traceable to a relevant international reference panel ( e.g., [82 FR 50532, Nov. 1, 2017] § 866.6070 Mutation detection test for myeloproliferative neoplasms. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) A detailed description of all components in the test, including the following: (A) A detailed description, including illustrations or photographs of non-standard equipment or methods, of the test components, including all required reagents, instrumentation, and equipment. (B) Detailed documentation of the device software, including standalone software applications and hardware-based devices that incorporate software. (C) A detailed description of methodology and assay procedures including appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. (D) A detailed specification for sample collection, processing, and storage. (E) A description of the criteria for test result interpretation and reporting including result outputs, analytical sensitivity of the assay, and the values that will be reported. (ii) Information that demonstrates the performance characteristics of the test, including: (A) For indications for use based on a threshold established in a predicate device of this generic type, device performance data from either a method comparison study to the predicate device or through a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population. (B) For indications for use based on a threshold not established in a predicate device of this generic type, device performance data from a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population. (C) Device reproducibility data generated, using a minimum of three sites, of which at least two sites must be external sites, with two operators at each site. Each site must conduct a study that includes at least two operators per site, two runs per operator per day over a minimum of three non-consecutive days evaluating a sample panel that contains allelic frequencies that span the claimed measuring range, and include the clinical threshold allelic frequency. Pre-specified acceptance criteria must be provided and followed. (D) Information on device traceability and a description of the value assignment process for calibrators and controls. (E) Device precision data using clinical samples and controls to evaluate the within-lot, between-lot, within-run, between-run, and total variation. (F) Device linearity data generated from samples covering the device measuring range and for any standards used in the quantitation of allelic frequencies. (G) Device analytic sensitivity data, including limit of blank and limit of detection. (H) Device specificity data, including interference and cross-contamination. (I) Device and clinical specimen stability data, including real-time stability (long-term storage and in-use stability) and stability evaluating various storage times, temperatures, and freeze-thaw conditions, as appropriate. (iii) Identification of risk mitigation elements used by the device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing using the device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) An intended use statement, including an indication for use that includes the variant(s) for which the assay was designed and validated, for example, JAK2 G1849T. (ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(ii) of this section and a summary of the results. [90 FR 40723, Aug. 21, 2025] § 866.6080 Next generation sequencing based tumor profiling test. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) A detailed description of all somatic mutations that are intended to be detected by the test and that are adequately supported in accordance with paragraph (b)(1)(v) of this section and reported in the test results in accordance with paragraph (b)(2)(iv) of this section, including: (A) A listing of mutations that are cancer mutations with evidence of clinical significance. (B) As appropriate, a listing of mutations that are cancer mutations with potential clinical significance. (ii) The indications for use must specify the following: (A) The test is indicated for previously diagnosed cancer patients. (B) The intended specimen type(s) and matrix ( e.g., (C) The mutation types ( e.g., (D) The name of the testing facility or facilities, as applicable. (iii) A detailed device description including the following: (A) A description of the test in terms of genomic coverage, as follows: ( 1 ( 2 (B) Specifications for specimen requirements including any specimen collection devices and preservatives, specimen volume, minimum tumor content, specimen handling, DNA extraction, and criteria for DNA quality and quantity metrics that are prerequisite to performing the assay. (C) A detailed description of all test components, reagents, instrumentation, and software required. Detailed documentation of the device software including but not limited to, software applications and hardware-based devices that incorporate software. (D) A detailed description of the methodology and protocols for each step of the test, including description of the quality metrics, thresholds, and filters at each step of the test that are implemented for final result reporting and a description of the metrics for run-failures, specimen-failures, invalids, as applicable. (E) A list of links provided by the device to the user or accessed by the device for internal or external information ( e.g., (F) A description of internal and external controls that are recommended or provided and control procedures. The description must identify those control elements that are incorporated into the testing procedure. (iv) Information demonstrating analytical validity of the device according to analytical performance characteristics, evaluated either specifically for each gene/mutation or, when clinically and practically justified, using a representative approach based on other mutations of the same type, including: (A) Data that adequately supports the intended specimen type ( e.g., (B) A summary of the empirical evidence obtained to demonstrate how the analytical quality metrics and thresholds were optimized. (C) Device precision data using clinical samples to adequately evaluate intra-run, inter-run, and total variability. The samples must cover all mutation types tested (both positive and negative samples) and include samples near the limit of detection of the device. Precision must be assessed by agreement within replicates on the assay final result for each representative mutation, as applicable, and also supported by sequencing quality metrics for targeted regions across the panel. (D) Description of the protocols and/or data adequately demonstrating the interchangeability of reagent lots and multiplexing barcodes. (E) A description of the nucleic acid assay input concentration range and the evidence to adequately support the range. (F) A description of the data adequately supporting the limit of detection of the device. (G) A description of the data to adequately support device accuracy using clinical specimens representing the intended specimen type and range of tumor types, as applicable. ( 1 ( 2 e.g., e.g., e.g., e.g., e.g., ( 3 2 (H) Adequate device stability information. (v) Information that adequately supports the clinical significance of the panel must include: (A) Criteria established on what types and levels of evidence will clinically validate a mutation as a cancer mutation with evidence of clinical significance versus a cancer mutation with potential clinical significance. (B) For representative mutations of those designated as cancer mutations with evidence of clinical significance, a description of the clinical evidence associated with such mutations, such as clinical evidence presented in professional guidelines, as appropriate, with method comparison performance data as described in paragraph (b)(1)(iv)(G) of this section. (C) For all other mutations designated as cancer mutations with potential clinical significance, a description of the rationale for reporting. (2) The 21 CFR 809.10 compliant labeling and any product information and test report generated, must include the following, as applicable: (i) The intended use statement must specify the following: (A) The test is indicated for previously diagnosed cancer patients. (B) The intended specimen type(s) and matrix ( e.g., (C) The mutation types ( e.g., (D) The name of the testing facility or facilities, as applicable. (ii) A description of the device and summary of the results of the performance studies performed in accordance with paragraphs (b)(1)(iii), (b)(1)(iv), and (b)(1)(v) of this section. (iii) A description of applicable test limitations, including, for device specific mutations validated with method comparison data to a medically established test in the same intended specimen type, appropriate description of the level of evidence and/or the differences between next generation sequencing results and results from the medically established test ( e.g., (iv) A listing of all somatic mutations that are intended to be detected by the device and that are reported in the test results under the following two categories or equivalent designations, as appropriate: “cancer mutations panel with evidence of clinical significance” or “cancer mutations panel with potential clinical significance.” (v) For mutations reported under the category of “cancer mutations panel with potential clinical significance,” a limiting statement that states “For the mutations listed in [cancer mutations panel with potential clinical significance or equivalent designation], the clinical significance has not been demonstrated [with adequate clinical evidence ( e.g., (vi) For mutations under the category of “cancer mutations panel with evidence of clinical significance,” or equivalent designation, link(s) for physicians to access internal or external information concerning decision rules or conclusions about the level of evidence for clinical significance that is associated with the marker in accordance with paragraph (b)(1)(v) of this section. [83 FR 28995, June 22, 2018] § 866.6090 Cancer predisposition risk assessment system. (a) Identification. (b) Classification. (1) The labeling required under § 809.10 of this chapter and any pre-purchase page and test report generated, unless otherwise specified, must include: (i) An intended use that specifies in the indications for use the genetic variants detected by the test. The specific variants must be appropriately validated as described in paragraphs (b)(4)(xii) and (b)(4)(xiii) of this section. (ii) A section addressed to users with the following information: (A) A warning statement accurately disclosing the genetic coverage of the test in lay terms, including information on variants not queried by the test, and the proportion of pathogenic variants in the genes that the assay detects in a specific population as identified in paragraph (b)(1)(i) of this section. The warning statement must indicate that the test [does not/may not, as appropriate] detect all genetic variants related to the genetic disease, and that the absence of a variant tested does not rule out the presence of other genetic variants that may impact cancer risk. The warning statement must also include the relevant population for which the variants reported by the test are most relevant. (B) A limiting statement explaining that some people may feel anxious about getting genetic test health results. This is normal. If the potential user feels very anxious, such user should speak to his or her doctor or other healthcare professional prior to collection of a sample for testing. This test is not a substitute for visits to a doctor or other healthcare professional. Users should consult with their doctor or other healthcare professional if they have any questions or concerns about the results of their test or their current state of health. (C) A limiting statement that a user's ethnicity may affect whether the test is relevant for them and may also affect how their genetic health results are interpreted. (D) A warning statement that the test is not a substitute for visits to a healthcare professional for recommended screenings, and should not be used to determine any treatments or medical interventions. (E) A warning statement that the test does not diagnose cancer or any other health conditions and should not be used to make medical decisions. The warning statement must indicate that the results should be confirmed in a clinical setting before taking any medical action. (F) A limiting statement explaining that other companies offering a genetic risk test may be detecting different genetic variants for the same disease, so the user may get different results using a test from a different company. (G) If applicable, a limiting statement that states the test does not test for variants in other genes linked to hereditary cancer. (H) A limiting statement explaining that this test does not account for non-genetic factors and that other factors such as environmental and lifestyle risk factors may affect the risk of developing a given disease. (I) Information to a potential purchaser or actual test report recipient about how to obtain access to a board-certified clinical molecular geneticist or equivalent to assist in pre- and post-test counseling. (J) A limiting statement explaining that this test is not intended to tell you anything about your current state of health, or be used to make medical decisions, including whether or not you should take a medication or how much of a medication you should take. (K) A limiting statement explaining that the laboratory may not be able to process a sample, and a description of the next steps to be taken by the manufacturer and/or the customer, as applicable. (iii) A section in the labeling required under § 809.10 of this chapter and any test report generated that is for healthcare professionals who may receive the test results from their patients with the following information: (A) A limiting statement explaining that this test is not intended to diagnose a disease, determine medical treatment or other medical intervention, or tell the user anything about their current state of health. (B) A limiting statement explaining that this test is intended to provide users with their genetic information to inform health-related lifestyle decisions and conversations with their doctor or other healthcare professional. (C) A limiting statement explaining that any diagnostic or treatment decisions should be based on confirmatory prescription testing and/or other information that is determined to be appropriate for the patient ( e.g., (2) The genetic test must use a sample collection device that is FDA-cleared, -approved, or -classified as 510(k) exempt, with an indication for in vitro diagnostic use in over-the-counter DNA testing. (3) The device's labeling must include a hyperlink to the manufacturer's public website where the manufacturer must make the information identified in paragraph (b)(3) of this section publicly available. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a hyperlink to the web page containing this information and must allow unrestricted viewing access. If the device can be purchased from the website or testing using the device can be ordered from the website, the same information must be found on the web page for ordering the device or provided in a publicly accessible hyperlink on the web page for ordering the device. Any changes to the device that could significantly affect safety or effectiveness would require new data or information in support of such changes, which must also be posted on the manufacturer's website. The information must include: (i) An index of the material being provided to meet the requirements in paragraph (b)(3) of this section and its location. (ii) Technical information about the device, as specified in paragraph (b)(4) of this section. (iii) A section that highlights summary information that allows the user to understand how the test works and how to interpret the results of the test. This section must, at a minimum, be written in plain language understandable to a lay user and include: (A) Consistent explanations of the risk of disease associated with all variants included in the test, variants not included in the test, and specific considerations by ethnicity. If there are different categories of risk, the manufacturer must provide literature references and/or data that support the different risk categories. If there will be multiple test reports and multiple variants, the risk categories must be defined similarly among them. For example, “increased risk” must be defined similarly between different test reports and different variant combinations. (B) Clear context for the user to understand the context in which the cited clinical performance data support the risk reported. This includes any risks that are influenced by ethnicity, age, gender, environment, and lifestyle choices. (C) Materials that explain the main concepts and terminology used in the test that include: ( 1 ( 2 e.g., ( i ( ii ( iii ( iv ( v ( vi ( 3 (4) The device labeling must include a technical information section containing the following information: (i) Gene(s) and variant(s) the test detects using standardized nomenclature, Human Genome Organization (HUGO) nomenclature and coordinates, as well as Single Nucleotide Polymorphism Database (dbSNP) reference SNP numbers (rs#). (ii) A statement indicating that more than 1,000 variants in the BRCA1 and BRCA2 genes are known to increase cancer risk, as applicable. (iii) Scientifically established disease-risk association of each variant detected and reported by the test. This risk association information must include: (A) Genotype-phenotype information for the reported variants. (B) When available, a table of expected frequency in the general population and different ethnicities, and risks of developing the disease in relevant ethnic populations and the general population. (C) Information such as peer-reviewed published literature and/or professional guidelines used to determine what types and levels of evidence will distinguish whether the selected variants are reported as “are associated with increased risk” versus “may be associated with increased risk” of developing other cancers. All selected variants must be appropriately validated as required under paragraph (b)(1)(i) of this section. For selected variants reported as “are associated with increased risk,” the clinical evidence must be demonstrated with sufficient information ( e.g., (D) A statement about the current professional guidelines for testing these specific gene(s) and variant(s) for the specified disease(s). ( 1 ( 2 (iv) The specimen type ( e.g., (v) Assay steps and technology used. (vi) Specification of required ancillary reagents, instrumentation, and equipment. (vii) Specification of the specimen collection, processing, storage, and preparation methods. (viii) Specification of risk mitigation elements and description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (ix) Information pertaining to the probability of test failure ( e.g., e.g., (x) When available, information specifying the probability of a false negative and false positive analytical result and any additional considerations by ethnicity. (xi) Specification of the criteria for test result interpretation and reporting, including any distinctions between risk categories ( i.e., (xii) Information that demonstrates the performance characteristics of the test including: (A) Accuracy of study results for each claimed specimen type. ( 1 ( 2 ( 3 ( 4 ( 5 i.e., e.g., ( 6 (B) Precision and reproducibility data must be provided using multiple instruments and multiple operators, on multiple non-consecutive days, and using multiple reagent lots. The sample panel must include specimens from the claimed sample type ( e.g., e.g., i.e., e.g., (C) Analytical specificity data: data must be provided evaluating the test performance ( e.g., (D) Analytical sensitivity data: data must be provided demonstrating the minimum amount of DNA that will enable the test to perform correctly in 95 percent of runs. (E) Device stability data: the manufacturer must establish upper and lower limits of input nucleic acid, sample, and reagent stability that will achieve the test's claimed accuracy and reproducibility. The manufacturer must evaluate stability using wild-type, heterozygous, and homozygous samples. Data supporting such claims must be provided. (F) Specimen type and matrix comparison data: specimen type and matrix comparison data must be generated if more than one specimen type can be tested with this device, including failure rates for the different specimens. (xiii) Clinical Performance Summary. (A) Information to support the clinical performance of each variant in the specific condition which is labeled as “are associated with increased risk” and reported by the test must be provided, as identified in paragraph (b)(4)(iii)(C) of this section. (B) Manufacturers must organize information by the specific variant combination as appropriate ( e.g., e.g., e.g., (xiv) User comprehension study: information on a study that assesses comprehension of the test process and results by potential users of the test must be provided, including the following, as appropriate: (A) The test manufacturer must provide a genetic health risk education module to naïve user comprehension study participants prior to their participation in the user comprehension study. The module must define terms that are used in the test reports and explain the significance of genetic risk reports. (B) The test manufacturer must perform pre- and post-test user comprehension studies. The comprehension test questions must directly evaluate the material being presented to the user as described in paragraph (b)(3)(ii) of this section. (C) The manufacturer must provide a justification from a physician and/or genetic counselor that identifies the appropriate general and variant-specific concepts contained within the material being tested in the user comprehension study to ensure that all relevant concepts are incorporated in the study. (D) The user comprehension study must meet the following criteria: ( 1 ( 2 e.g., ( 3 ( 4 ( 5 ( 6 i.e., ( 7 ( i ( ii ( iii e.g., [90 FR 40718, Aug. 21, 2025] § 866.6100 DNA-based test to measure minimal residual disease in hematological malignancies. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) A detailed description of the device, including: (A) A detailed description of all test components, reagents, instrumentation, and software, including software applications and any hardware-based devices that incorporate software. (B) A detailed description of all genomic regions that are detected and quantified by the assay. (C) A detailed description of the methodology and protocols for each step of the test, including description of the quality metrics, thresholds, and filters at each step of the test that are implemented for final result reporting and a description of the metrics for run-failures, specimen-failures, and invalids, as appropriate. (D) Detailed specifications and procedures for sample collection, processing, and storage. (E) A description of the internal and external controls that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure. If appropriate, this description must include a description of the controls and control procedures used during the sequencing and data analysis. (ii) Identification of risk mitigation elements used by the device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with use of the device. (iii) As part of the risk management activities, an appropriate end user device training program must be offered as an effort to mitigate the risk of failure from user error, as appropriate. (iv) Description of analytical and clinical studies, including: (A) Device performance data that demonstrates the ability to measure minimal residual disease in the claimed specimen type(s) from patients that are representative of the intended use population. Data can be obtained via: ( 1 ( 2 (B) Device precision (repeatability and reproducibility) data using clinical samples covering the range of minimal residual disease frequencies reported by the test and covering the stated range of DNA inputs that are indicated as allowable for use with the test. Results shall be reported as the standard deviation and/or percentage coefficient of variation with the 95 percent confidence interval for each level tested. The study must evaluate all sources of variability, including, as appropriate, between-site and between operator (minimum of three sites of which two must be external with a minimum of two operators per site), between-day (minimum of 3 days), between-run, within-run, between-lot (minimum of three lots), between instrument (minimum of three instruments), and total variation. (C) Device linearity data generated from samples covering the device measuring range using a dilution panel created from clinical samples. (D) Device accuracy by comparison to flow cytometry across the measuring interval or to the predicate method across the measuring interval. (E) Device analytic sensitivity data, including limit of blank, limit of detection, and limit of quantitation, using a dilution panel created from clinical samples. (F) Analytical specificity data, including interference and cross-contamination, and index cross-contamination, as appropriate. (G) Validation of pre-analytical methods, including DNA extraction methods and cell enrichment methods, as appropriate. (H) Device stability data, including real-time stability of reagents under various storage times and temperatures. (I) Specimen and prepared sample stability data established for each specimen matrix in the anticoagulant combinations and storage/use conditions that will be indicated, including specimen transport, as appropriate. (2) The intended use for the labeling required under § 809.10(a)(4) of this chapter and for the labeling required under § 809.10(b)(5)(ii) of this chapter, as applicable, must include: (i) The clinical hematopoietic malignancy for which the assay was designed and validated ( e.g., (ii) Specimen type ( e.g., (iii) The specific DNA regions that are being identified and quantified ( e.g., (iv) A statement that the results are indicated to be interpreted by qualified healthcare professionals in accordance with professional guidelines for clinical decision-making in conjunction with other clinicopathological features. (3) The labeling required under § 809.10(b) of this chapter must include information that demonstrates the performance characteristics of the test, including a detailed summary of the performance studies conducted and their results, as described in paragraphs (b)(1)(iv)(A) through (I) of this section. (4) The device output, including any test report, must include the estimated minimal residual disease (MRD) frequency and an appropriate range of the uncertainty of that frequency based on the amount of DNA that was evaluated by the test and the number of specific nucleic acid sequences that were detected ( e.g., −5 −6 −5 [90 FR 19640, May 9, 2025] § 866.6110 Circulating tumor cell enrichment device. (a) Identification. (b) Classification. (1) Any device used for specimen collection and transport must be FDA-cleared, -approved, or -classified as 510(k) exempt for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device. (2) The labeling required under § 809.10(b) of this chapter must include: (i) Detailed specifications and procedures for sample collection, processing, and storage. (ii) An intended use statement that includes: (A) The intended specimen type(s) for which acceptable, as determined by FDA, validation data has been provided ( e.g., (B) The identification of, or the specifications for, the collection device or devices to be used for sample collection. (C) Information on the device output(s) ( e.g., (D) The specific tumor type(s) for which the device is intended to be used. (E) A statement for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices. (F) A statement that the standalone device is not intended for diagnostic, prognostic, or monitoring use with CTCs, including as an aid in any disease management and/or treatment decisions. (iii) Prominent and conspicuous limiting statements clearly explaining: (A) The use of the device is intended for the collection of CTCs from previously diagnosed cancer patients. (B) The standalone device is not intended for cell enumeration. (C) The users for whom the device is intended, including any training specifications. (D) The performance characteristics of this device have not been established for general downstream diagnostic assays and that end users need to validate use with any subsequent tests and collection devices. (E) An insufficient number of CTCs or even no circulating tumor cells may be collected. (F) Results from the standalone device do not provide information to the patient regarding their current state of health. (G) The standalone device does not diagnose any health conditions and is not a substitute for visits to a doctor or other healthcare professional. (H) The device is intended only for enriching CTC content in specimens so that the enriched specimens can then be used in further processing/analysis using additional independent methods. (I) The variability of the number of CTCs and other cells harvested by the device may impact the success of any subsequent analysis. (iv) A troubleshooting section that includes clear instructions for resolving any common device-related issues. (v) A description of the device mechanism of action to enrich CTCs. (vi) A detailed summary of the analytical and clinical performance studies required under paragraph (b)(3) of this section. (3) Design verification and validation must include the following: (i) Documentation of studies that provide: (A) Data demonstrating acceptable, as determined by FDA, analytical device performance using samples representative of the range of those with which the device is intended for use. The number of specimens tested must be sufficient to obtain estimates of device performance that is representative of the device performance within the full spectrum of the device's intended use. (B) Data demonstrating acceptable precision, as determined by FDA, to adequately evaluate intra-run, inter-run, and total variability across operator, instrument, lot, day, and site, as applicable. (C) Data demonstrating the detection limit of the device. (D) Recovery study data demonstrating the range of the device. (E) Data demonstrating appropriate validation of device design features and specifications such that the device reproducibly and reliably collects and isolates CTCs. At a minimum, the data must include: ( 1 ( 2 ( 3 ( 4 e.g., (ii) Documentation of clinical studies using the device on intended use clinical specimens that demonstrate the device can enrich or capture an appropriate number of CTCs, as determined by FDA, to support the intended use of the device. [91 FR 24345, May 6, 2026]

Related documents

• 50 CFR Part 600 — Magnuson-Stevens Act Provisions#512148
• 50 CFR Part 622 — Fisheries of the Caribbean, Gulf of America, and South Atlantic#512149
• 50 CFR Part 635 — Atlantic Highly Migratory Species#512150
• 50 CFR Part 648 — Fisheries of the Northeastern United States#512151
• 50 CFR Part 660 — Fisheries off West Coast States#512152