PART 864—HEMATOLOGY AND PATHOLOGY DEVICES Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360 l, Editorial Note: Nomenclature changes to part 864 appear at 73 FR 35341, June 23, 2008. Subpart A—General Provisions § 864.1 Scope. (a) This part sets forth the classification of hematology and pathology devices intended for human use that are in commercial distribution. (b) The identification 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) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted. (d) Guidance documents referenced in this part are available on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. [52 FR 17732, May 11, 1987, as amended at 69 FR 12273, Mar. 16, 2004; 78 FR 18233, Mar. 26, 2013; 79 FR 50552, Aug. 25, 2014] § 864.3 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 paragraph (b) 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. [52 FR 17732, May 11, 1987] § 864.9 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 2310, Jan. 14, 2000] Subpart B—Biological Stains § 864.1850 Dye and chemical solution stains. (a) Identification. (b) Classification. [45 FR 60583, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 864.1860 Immunohistochemistry reagents and kits. (a) Identification. (b) Classification of immunohistochemistry devices. (2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer. (3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section. (c) Date of PMA or notice of completion of a PDP is required. [63 FR 30142, June 3, 1998] § 864.1865 Cervical intraepithelial neoplasia (CIN) test system. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) The indications for use must specify the biomarker that is intended to be identified and its adjunct use ( e.g., (ii) Summary of professional society recommendations, as applicable. (iii) A detailed device description including: (A) A detailed description of all test components, including all provided reagents and required, but not provided, ancillary reagents. (B) 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, stand-alone software applications and hardware-based devices that incorporate software. (D) A detailed description of appropriate positive and negative controls that are recommended or provided. (E) Detailed specifications for sample collection, processing, and storage. (F) A detailed description of methodology and assay procedure. (G) A description of the assay cutoff (the medical decision point between positive and negative) or other relevant criteria that distinguishes positive and negative results, including the rationale for the chosen cutoff or other relevant criteria and results supporting validation of the cutoff. (H) Detailed specification of the criteria for test results interpretation and reporting. (iv) Detailed information demonstrating the performance characteristics of the device, including: (A) Analytical specificity studies such as, but not limited to, antibody characterization ( e.g., (B) Device analytical sensitivity data generated by testing an adequate number of samples from individuals with the target condition including limit of blank, limit of detection, and limit of quantification, as applicable. (C) Device precision/reproducibility data to evaluate within-run, between-run, between-day, between-lot, between-site, between-reader, within-reader and total precision, as applicable, using a panel of samples covering the device measuring range and/or the relevant disease categories ( e.g. (D) Device robustness/guardbanding studies to assess the tolerance ranges for various critical test and specimen parameters. (E) Device stability data, including real-time stability and shipping stability under various storage times, temperatures, and freeze-thaw conditions. (F) 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. The study must evaluate the consistency of the diagnosis of CIN, for example, by comparing the levels of agreements of diagnoses rendered by community pathologists to those rendered by a panel of expert pathologists. Agreement for each CIN diagnostic category ( e.g., e.g., i.e., i.e., i.e., i.e., (G) The staining performance of the device as determined by the community pathologists during review of the study slides must be evaluated. The staining performance criteria assessed must include overall staining acceptability, background staining acceptability, and morphology acceptability, as applicable. (H) Appropriate training requirements for users, including interpretation manual, as applicable. (I) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing. (2) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol, including the information described in paragraph (b)(1)(ii) of this section, as applicable, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ii) of this section, as applicable. [83 FR 234, Jan. 3, 2018] § 864.1866 Lynch syndrome test systems. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information, as appropriate: (i) A detailed description of all test components, including all provided reagents, and required but not provided, ancillary reagents. (ii) A detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals. (iii) Detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (iv) A detailed description of quality controls including appropriate positive and negative controls that are recommended or provided. (v) Detailed specifications for sample collection, processing, and storage. (vi) A detailed description of methodology and assay procedure. (vii) A description of the assay cut-off ( i.e., (viii) Detailed specification of the criteria for test result interpretation and reporting. (ix) Detailed information demonstrating the performance characteristics of the device, including: (A) Data from an appropriate study demonstrating clinical accuracy using well-characterized clinical specimens representative of the intended use population ( i.e., (B) Appropriate device reproducibility data investigating all sources of variance ( e.g., (C) Data demonstrating reader reproducibility, both within-reader and between-reader, assessed by three readers over 3 nonconsecutive days at each site, including a 2 week washout period between reads, as appropriate. (D) Device precision data using clinical samples spanning the measuring range and controls to evaluate the within-lot, between-lot, within-run, between run, and total variation. (E) Analytical specificity studies including as appropriate, western blots, peptide inhibition, testing in normal tissues and neoplastic tissues, interference by endogenous and exogenous substances, and cross-reactivity and cross contamination testing. (F) Device analytical sensitivity data generated by testing an adequate number of samples from individuals with the target condition such that prevalence of the biomarker in the target population is established. (G) Device stability data, including real-time stability and in-use stability, and stability evaluating various storage times, temperatures, and freeze-thaw conditions, as appropriate. (H) The staining performance criteria assessed must include overall staining acceptability, background staining acceptability, and morphology acceptability, as appropriate. (I) Appropriate training requirements for users, including interpretation manual, as applicable. (J) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing. (2) The device's § 809.10(b) of this chapter compliant labeling must include a detailed description of the protocol, including the information described in paragraphs (b)(1)(i) through (viii) of this section, as appropriate, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ix) of this section, as appropriate. [83 FR 8357, Feb. 27, 2018] § 864.1870 Early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization. (a) Identification. (b) Classification. (1) Premarket notification submissions must also include the following information: (i) A detailed description of all probes included in the kit; (ii) Purpose of each probe; (iii) Probe molecular specificity; (iv) Probe specificity; (v) Probe limits; (vi) Probe sensitivity; (vii) Specification of required ancillary reagents, instrumentation, and equipment; (viii) Specification of the specimen collection, processing, storage and slide preparation methods; (ix) Specification of the assay procedure; (x) Specification of control elements that are incorporated into the recommended testing procedures; (xi) Specification of risk mitigation elements: Description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing; (xii) Specification of the criteria for test result interpretation and reporting; (xiii) Device analytical sensitivity data; (xiv) Device analytical specificity data; (xv) Device reference limit data; (xvi) Device precision/reproducibility data; (xvii) Device stability data to include: (A) Real-time stability, (B) Freeze-thaw stability, (C) Transport and temperature stability, (D) Post-hybridization signal stability, (E) Photostability of probe, and (xviii) Documentation that demonstrates the clinical validity of the device. The documentation must include data from clinical studies, a minimum of two peer-reviewed published literature references using the specific device seeking marketing clearance, or both. Documentation for the clinical studies and peer-reviewed published literature references cited must include the following elements: (A) Documentation that the sponsor's probe was used in the literature reference, (B) Number and type of specimens, (C) Target population studied, (D) Upper reference limit, and (E) Range of positive probe results. (2) Your § 809.10(b)(12) of this chapter compliant labeling must include a statement summarizing the data identified in paragraphs (b)(1)(xiii) through (xviii) of this section and a description of the studies supporting the information, including the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met. (3) Your § 809.10 of this chapter compliant labeling must include: (i) A warning that reads “The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist.” (ii) A warning that reads “This device is not for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening.” (iii) A warning that reads “The use of this device for diagnosis, monitoring or risk assessment has not been established.” [79 FR 52196, Sept. 3, 2014] § 864.1880 Fluorescence in situ hybridization (FISH)-based detection of chromosomal abnormalities from patients with hematologic malignancies. (a) Identification. e.g., (b) Classification. (1) Design verification and validation must include: (i) A detailed description of all probes included in the kit; (ii) Purpose of each probe; (iii) Probe molecular specificity; (iv) Probe specificity; (v) Probe limits; (vi) Probe sensitivity; (vii) Specification of required ancillary reagents, instrumentation, and equipment; (viii) Specification of the specimen collection, processing, storage and slide preparation methods; (ix) Specification of the assay procedure; (x) Specification of control elements that are incorporated into the recommended testing procedures; (xi) Specification of the criteria for test result interpretation and reporting; (xii) Documentation demonstrating analytical validation that includes: (A) Device analytical sensitivity data with a minimum of 25 specimens from karyotypically normal males. (B) Device analytical specificity data with a minimum of five specimens from karyotypically normal males. (C) Description of how the clinical threshold was assigned and verification of the assigned clinical threshold. (D) Device precision/reproducibility data with a minimum of six clinical specimens including two negative specimens, two positive specimens near the clinical decision threshold (cut-off) and two positive specimens. The data must include results obtained from three sites (as applicable), with two operators at each site, with the assay run for a minimum of 3-5 non-consecutive days and each specimen run in duplicate for a minimum of 30 replicates. (E) Between-reagent lot reproducibility using three reagent lots and three clinical specimens representing negative, near cut-off/low positive, and positive. (F) Device stability data to include: ( 1 ( 2 ( 3 ( 4 ( 5 (xiii) Documentation demonstrating the clinical validity of the device that includes: (A) A summary of the prevalence and clinical thresholds reported in three peer-reviewed published literature references for the intended use population of the device and device performance data demonstrating conformance with the published prevalence as reported in peer-reviewed published literature references based on testing clinical specimens, selected without bias ( e.g., e.g., (B) Documentation for peer-reviewed published literature references must include the following elements: ( 1 ( 2 ( 3 ( 4 ( 5 (C) In the absence of clinical data obtained from paragraphs (b)(1)(xiii)(A) and (B) of this section, clinical data obtained from a method comparison to the predicate with positives and negative clinical specimens. (2) The intended use required on the label under § 809.10(a)(4) of this chapter and on the labeling required under § 809.10(b)(5)(ii) of this chapter must include a statement that “The test is not intended for use as a stand-alone diagnostic, disease screening, or as a companion diagnostic.” (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) through (xiii) of this section. The labeling required under § 809.10(b) of this chapter must include the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met. (4) The labeling required under § 809.10(b) of this chapter must include the following limiting statements: (i) “Reporting and interpretation of FISH results should be consistent with professional standards of practice and should take into consideration other clinical and diagnostic information. This kit is intended as an adjunct to other diagnostic laboratory tests and therapeutic action should not be initiated on the basis of the FISH result alone. Failure to adhere to the protocol may affect the performance and lead to false results.” (ii) “Each lab is responsible for establishing their own cut-off values. Each laboratory should test sufficiently large number of samples to establish normal population distribution of the signal levels and to assign a cut-off value. The product is for professional use only and is intended to be interpreted by a qualified pathologist or cytogeneticist.” [90 FR 27233, June 26, 2025] § 864.1890 xxx Link to an amendment published at 91 FR 53190, Aug. 17, 2026. Subpart C—Cell And Tissue Culture Products § 864.2220 Synthetic cell and tissue culture media and components. (a) Identification. (b) Classification. [45 FR 60583, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 27024, May 16, 2001; 66 FR 38789, July 25, 2001] § 864.2240 Cell and tissue culture supplies and equipment. (a) Identification. (b) Classification. [45 FR 60584, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 864.2260 Chromosome culture kit. (a) Identification. (b) Classification. [45 FR 60585, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.2280 Cultured animal and human cells. (a) Identification. (b) Classification. [45 FR 60585, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.2360 Mycoplasma detection media and components. (a) Identification. (b) Classification. [45 FR 60586, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.2800 Animal and human sera. (a) Identification. (b) Classification. [45 FR 60586, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.2875 Balanced salt solutions or formulations. (a) Identification. (b) Classification. [45 FR 60586, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] Subpart D—Pathology Instrumentation and Accessories § 864.3010 Tissue processing equipment. (a) Identification. (b) Classification. [45 FR 60587, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 864.3250 Specimen transport and storage container. (a) Identification. (b) Classification. [54 FR 47206, Nov. 13, 1989, as amended at 65 FR 2310, Jan. 14, 2000; 65 FR 18234, Apr. 7, 2000; 90 FR 55981, Dec. 4, 2025] § 864.3260 OTC test sample collection systems for drugs of abuse testing. (a) Identification. (b) Classification. [65 FR 18234, Apr. 7, 2000, as amended at 90 FR 55981, Dec. 4, 2025] § 864.3300 Cytocentrifuge. (a) Identification. (b) Classification. [45 FR 60588, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.3400 Device for sealing microsections. (a) Identification. (b) Classification. [45 FR 60589, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.3600 Microscopes and accessories. (a) Identification. (1) Phase contrast microscopes, which permit visualization of unstained preparations by altering the phase relationship of light that passes around the object and through the object. (2) Fluorescense microscopes, which permit examination of specimens stained with fluorochromes that fluoresce under ultraviolet light. (3) Inverted stage microscopes, which permit examination of tissue cultures or other biological specimens contained in bottles or tubes with the light source mounted above the specimen. (b) Classification. [45 FR 60590, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001;90 FR 55981, Dec. 4, 2025 ] § 864.3700 Whole slide imaging system. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) The indications for use must specify the tissue specimen that is intended to be used with the whole slide imaging system and the components of the system. (ii) A detailed description of the device and bench testing results at the component level, including for the following, as appropriate: (A) Slide feeder; (B) Light source; (C) Imaging optics; (D) Mechanical scanner movement; (E) Digital imaging sensor; (F) Image processing software; (G) Image composition techniques; (H) Image file formats; (I) Image review manipulation software; (J) Computer environment; and (K) Display system. (iii) Detailed bench testing and results at the system level, including for the following, as appropriate: (A) Color reproducibility; (B) Spatial resolution; (C) Focusing test; (D) Whole slide tissue coverage; (E) Stitching error; and (F) Turnaround time. (iv) Detailed information demonstrating the performance characteristics of the device, including, as appropriate: (A) Precision to evaluate intra-system and inter-system precision using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included. (B) Reproducibility data to evaluate inter-site variability using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included. (C) Data from a clinical study to demonstrate that viewing, reviewing, and diagnosing digital images of surgical pathology slides prepared from tissue slides using the whole slide imaging system is non-inferior to using an optical microscope. The study should evaluate the difference in major discordance rates between manual digital (MD) and manual optical (MO) modalities when compared to the reference ( e.g., (D) A detailed human factor engineering process must be used to evaluate the whole slide imaging system user interface(s). (2) Labeling compliant with 21 CFR 809.10(b) must include the following: (i) The intended use statement must include the information described in paragraph (b)(1)(i) of this section, as applicable, and a statement that reads, “It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using this device.” (ii) A description of the technical studies and the summary of results, including those that relate to paragraphs (b)(1)(ii) and (iii) of this section, as appropriate. (iii) A description of the performance studies and the summary of results, including those that relate to paragraph (b)(1)(iv) of this section, as appropriate. (iv) A limiting statement that specifies that pathologists should exercise professional judgment in each clinical situation and examine the glass slides by conventional microscopy if there is doubt about the ability to accurately render an interpretation using this device alone. [83 FR 22, Jan. 2, 2018] § 864.3750 Software algorithm device to assist users in digital pathology. (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) Specimen type; (ii) Information on the device input(s) ( e.g., (iii) Information on the device output(s) ( e.g., (iv) Intended users; (v) Necessary input/output devices ( e.g., (vi) A limiting statement that addresses use of the device as an adjunct; and (vii) A limiting statement that users should use the device in conjunction with complete standard of care evaluation of the WSI. (2) The labeling required under § 809.10(b) of this chapter must include: (i) A detailed description of the device, including the following: (A) Detailed descriptions of the software device, including the detection/analysis algorithm, software design architecture, interaction with input/output devices, and necessary third-party software; (B) Detailed descriptions of the intended user(s) and recommended training for safe use of the device; and (C) Clear instructions about how to resolve device-related issues ( e.g., (ii) A detailed summary of the performance testing, including test methods, dataset characteristics, results, and a summary of sub-analyses on case distributions stratified by relevant confounders, such as anatomical characteristics, patient demographics, medical history, user experience, and scanning equipment, as applicable. (iii) Limiting statements that indicate: (A) A description of situations in which the device may fail or may not operate at its expected performance level ( e.g., (B) The data acquired using the device should only be interpreted by the types of users indicated in the intended use statement; and (C) Qualified users should employ appropriate procedures and safeguards (e.g., quality control measures, etc.) to assure the validity of the interpretation of images obtained using this device. (3) Design verification and validation must include: (i) A detailed description of the device software, including its algorithm and its development, that includes a description of any datasets used to train, tune, or test the software algorithm. This detailed description of the device software must include: (A) A detailed description of the technical performance assessment study protocols (e.g., regions of interest (ROI) localization study) and results used to assess the device output(s) (e.g., image overlays, image heatmaps, etc.); (B) The training dataset must include cases representing different pre-analytical variables representative of the conditions likely to be encountered when used as intended (e.g., fixation type and time, histology slide processing techniques, challenging diagnostic cases, multiple sites, patient demographics, etc.); (C) The number of WSI in an independent validation dataset must be appropriate to demonstrate device accuracy in detecting and localizing ROIs on scanned WSI, and must include subsets clinically relevant to the intended use of the device; (D) Emergency recovery/backup functions, which must be included in the device design; (E) System level architecture diagram with a matrix to depict the communication endpoints, communication protocols, and security protections for the device and its supportive systems, including any products or services that are included in the communication pathway; and (F) A risk management plan, including a justification of how the cybersecurity vulnerabilities of third-party software and services are reduced by the device's risk management mitigations in order to address cybersecurity risks associated with key device functionality (such as loss of image, altered metadata, corrupted image data, degraded image quality, etc.). The risk management plan must also include how the device will be maintained on its intended platform ( e.g. (ii) Data demonstrating acceptable, as determined by FDA, analytical device performance, by conducting analytical studies. For each analytical study, relevant details must be documented (e.g., the origin of the study slides and images, reader/annotator qualifications, method of annotation, location of the study site(s), challenging diagnoses, etc.). The analytical studies must include: (A) Bench testing or technical testing to assess device output, such as localization of ROIs within a pre-specified threshold. Samples must be representative of the entire spectrum of challenging cases likely to be encountered when the device is used as intended; and (B) Data from a precision study that demonstrates device performance when used with multiple input devices (e.g., WSI scanners) to assess total variability across operators, within-scanner, between-scanner and between-site, using clinical specimens with defined, clinically relevant, and challenging characteristics likely to be encountered when the device is used as intended. Samples must be representative of the entire spectrum of challenging cases likely to be encountered when the device is used as intended. Precision, including performance of the device and reproducibility, must be assessed by agreement between replicates. (iii) Data demonstrating acceptable, as determined by FDA, clinical validation must be demonstrated by conducting studies with clinical specimens. For each clinical study, relevant details must be documented (e.g., the origin of the study slides and images, reader/annotator qualifications, method of annotation, location of the study site(s) (on-site/remote), challenging diagnoses, etc.). The studies must include: (A) A study demonstrating the performance by the intended users with and without the software device (e.g., unassisted and device-assisted reading of scanned WSI of pathology slides). The study dataset must contain sufficient numbers of cases from relevant cohorts that are representative of the scope of patients likely to be encountered given the intended use of the device (e.g., subsets defined by clinically relevant confounders, challenging diagnoses, subsets with potential biopsy appearance modifiers, concomitant diseases, and subsets defined by image scanning characteristics, etc.) such that the performance estimates and confidence intervals for these individual subsets can be characterized. The performance assessment must be based on appropriate diagnostic accuracy measures (e.g., sensitivity, specificity, predictive value, diagnostic likelihood ratio, etc.). (B) [Reserved] [88 FR 7009, Feb. 2, 2023] § 864.3800 Automated slide stainer. (a) Identification. (b) Classification. [45 FR 60591, Sept. 12, 1980, as amended at 54 FR 25044, June 12, 1989; 66 FR 38789, July 25, 2001] § 864.3875 Automated tissue processor. (a) Identification. (b) Classification. [45 FR 60591, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38789, July 25, 2001] Subpart E—Specimen Preparation Reagents § 864.4010 General purpose reagent. (a) A general purpose reagent is a chemical reagent that has general laboratory application, that is used to collect, prepare, and examine specimens from the human body for diagnostic purposes, and that is not labeled or otherwise intended for a specific diagnostic application. It may be either an individual substance, or multiple substances reformulated, which, when combined with or used in conjunction with an appropriate analyte specific reagent (ASR) and other general purpose reagents, is part of a diagnostic test procedure or system constituting a finished in vitro diagnostic (IVD) test. General purpose reagents are appropriate for combining with one or more than one ASR in producing such systems and include labware or disposable constituents of tests; but they do not include laboratory machinery, automated or powered systems. General purpose reagents include cytological preservatives, decalcifying reagents, fixative and adhesives, tissue processing reagents, isotonic solutions and pH buffers. Reagents used in tests for more than one individual chemical substance or ligand are general purpose reagents (e.g., Thermus aquaticus (b) Classification. [45 FR 60592, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 62 FR 62260, Nov. 21, 1997; 66 FR 38789, July 25, 2001; 90 FR 55981, Dec. 4, 2025] § 864.4020 Analyte specific reagents. (a) Identification. (1) In vitro diagnostic manufacturers; or (2) Organizations that use the reagents to make tests for purposes other than providing diagnostic information to patients and practitioners, e.g., forensic, academic, research, and other nonclinical laboratories. (b) Classification. (2) Class II (special controls/guidance documents), when the analyte is used in blood banking tests that have been classified as class II devices (e.g., certain cytomegalovirus serological and treponema pallidum nontreponemal test reagents). Guidance Documents: 1. “Specifications for Immunological Testing for Infectious Disease; Approved Guideline,” NCCLS Document I/LA18-A, December 1994. 2. “Assessment of the Clinical Accuracy of Laboratory Tests Using Receiver Operating Characteristic (ROC) Plots; Tentative Guideline,” NCCLS Document KGP10-T, December 1993. 3. “Review Criteria for Assessment of In Vitro Diagnostic Devices for Direct Detection of Mycobacterium spp,” FDA, July 6, 1993, and its “Attachment 1,” February 28, 1994. 4. “Draft Review Criteria for Nucleic Acid Amplification-Based In Vitro Diagnostic Devices for Direct Detection of Infectious Microorganisms,” FDA, July 6, 1993. 5. The Center for Biologics Evaluation and Research, FDA, “Points to Consider in the Manufacture and Clinical Evaluation of In Vitro Tests to Detect Antibodies to the Human Immunodeficiency Virus, Type I” (54 FR 48943, November 28, 1989). (3) Class III (premarket approval), when: (i) The analyte is intended as a component in a test intended for use in the diagnosis of a contagious condition that is highly likely to result in a fatal outcome and prompt, accurate diagnosis offers the opportunity to mitigate the public health impact of the condition (e.g., human immunodeficiency virus (HIV/AIDS)or tuberculosis (TB)); or (ii) The analyte is intended as a component in a test intended for use in donor screening for conditions for which FDA has recommended or required testing in order to safeguard the blood supply or establish the safe use of blood and blood products (e.g., tests for hepatitis or tests for identifying blood groups). (c) Date of 510(k), or date of PMA or notice of completion of a product development protocol is required. (2) For postamendments ASR's; November 23, 1998. (d) Restrictions. [62 FR 62260, Nov. 21, 1997] § 864.4400 Enzyme preparations. (a) Identification. (1) To disaggregate tissues and cells already in established cultures for preparation into subsequent cultures (e.g., trypsin); (2) To disaggregate fluid specimens for cytological examination (e.g., papain for gastric lavage or trypsin for sputum liquefaction); (3) To aid in the selective staining of tissue specimens (e.g., diastase for glycogen determination). (b) Classification. [45 FR 60592, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38789, July 25, 2001] Subpart F—Automated and Semi-Automated Hematology Devices § 864.5200 Automated cell counter. (a) Identification. (b) Classification. [45 FR 60593, Sept. 12, 1980] § 864.5220 Automated differential cell counter. (a) Identification. (b) Classification. [67 FR 1607, Jan. 14, 2002] § 864.5240 Automated blood cell diluting apparatus. (a) Identification. (b) Classification. [45 FR 60596, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.5260 Automated cell-locating device. (a) Identification. (b) Classification. [45 FR 60597, Sept. 12, 1980] § 864.5300 Red cell indices device. (a) Identification. (b) Classification. [45 FR 60597, Sept. 12, 1980] § 864.5350 Microsedimentation centrifuge. (a) Identification. (b) Classification. [45 FR 60598, Sept. 12, 1980, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38789, July 25, 2001] § 864.5400 Coagulation instrument. (a) Identification. (b) Classification. [45 FR 60598, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.5425 Multipurpose system for in vitro coagulation studies. (a) Identification. (b) Classification. [45 FR 60599, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.5430 Coagulation system for the measurement of whole blood viscoelastic properties in perioperative patients. (a) Identification. (b) Classification. (1) Design verification and validation must include detailed documentation of, and results from, the following: (i) A study assessing precision using protocols determined to be acceptable by FDA, to cover the measurement range for each reported parameter (test output). Testing must include native specimens with coagulation profiles representative of the intended use population. In order to cover the measuring range, testing may include a limited number of contrived specimens, not to exceed 10 to 20 percent, or as otherwise deemed appropriate by FDA. The contrived specimens must be prepared to resemble clinical specimens. This testing must evaluate repeatability and reproducibility and provide assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system; (ii) Studies that demonstrate the performance of each parameter (test output) throughout the claimed measurement range, to include linearity studies or dose-response studies, as applicable to the parameter (test output); (iii) Potential interferent study that includes evaluation of hemolyzed and lipemic samples as potential interferents; exogenous and endogenous interferents associated with each patient population intended for use with the device, and which might be expected to affect assay performance, must be evaluated; and potential interferents that are specific for, or related to, the technology or methodology of the device. Evaluation of all potential interferents must be performed using a protocol determined to be acceptable to the FDA ( e.g., (iv) A study that evaluates specimen stability under the intended conditions for specimen collection, handling, and storage, using samples that cover the coagulation profiles representative of the intended use population, and using protocols determined to be acceptable by FDA; (v) A multisite clinical study, determined to be acceptable by FDA, demonstrating performance, relative to clinically relevant and clinically validated laboratory test(s) for each parameter (test output). Further, the study must meet all of the following criteria: (A) The study must be performed in the intended use population and include representation from all patient populations for whom the device is intended to be used. Potential endogenous and exogenous interferents for each target patient population must be evaluated or known prior to the study; (B) The study must be conducted at a minimum of three external sites representative of the intended use setting by the intended operators; (C) Test samples must be collected at time intervals relevant to the device's use in the intended use population; (D) Clinical specimens, which cover coagulation profiles representative of the intended use population, must be evaluated at each of the three clinical sites in the study; (E) Analysis of the concordance of clinical interpretation of patient coagulation status made from individual test parameter (test output) results as compared to clinical interpretation of coagulation status from a clinically relevant laboratory test or tests ( e.g., (F) Expected (reference) values for each parameter (test output) must be demonstrated by testing a statistically appropriate number of samples from apparently healthy normal individuals; (vi) For a device with a user interface that has information that needs to be interpreted by the user in correctly using the device to achieve the intended test results or a device that does not provide a final output that is a comprehensive interpretation of all parameter (test output) results, a study evaluating the ability of device users to correctly interpret results; (vii) For any device indicated to guide blood product use, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding blood product use; and (viii) For any device indicated to guide use of medication, a clinical outcome study determined to be acceptable by FDA that specifically validates the device's indicated use in guiding use of medication. (2) The labeling required under § 809.10(b) of this chapter must include the following: (i) A summary of results from the study required by paragraph (b)(1)(i) of this section, including repeatability, reproducibility, and assessments of within-run, within-day, between-run, between-day, between-reagent lot, between-instrument, between-site, and between-operator precision, as applicable to the system. (ii) The claimed measurement range of each parameter (test output), as supported by demonstrated performance of the parameter (test output) throughout the claimed measurement range, including studies required by paragraphs (b)(1)(i) through (iii) and (v) of this section, and, if applicable, paragraphs (b)(1)(vii) and (viii) of this section. (iii) Identification of known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to each parameter (test output). The information must include the concentration(s) or level(s) at which interference was found to occur and the concentration range or levels at which interference was not found to occur. (iv) Information regarding the multisite clinical study required by paragraph (b)(1)(v) of this section, including: (A) Each patient population evaluated; (B) Each intended use setting and the operators; (C) A summary of the results, including the concordance analysis to clinically relevant laboratory test(s); and (D) Demonstrated expected (reference) values for each parameter (test output). (3) The labeling required under § 809.10 of this chapter must include the following: (i) A limiting statement that the result(s) from the device is(are) not intended to be used as the sole basis for a patient diagnosis. (ii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(vii) of this section that specifically validate an indication for the device's use in guiding blood product use, a limiting statement that the device has not been evaluated to guide blood product use. (iii) Unless appropriate clinical outcome studies are done in accordance with paragraph (b)(1)(viii) of this section that specifically validate an indication for the device's use in guiding use of medication, a limiting statement that the device has not been evaluated to guide use of medication. [90 FR 19630, May 9, 2025] § 864.5600 Automated hematocrit instrument. (a) Identification. (b) Classification. [45 FR 60600, Sept. 12, 1980] § 864.5620 Automated hemoglobin system. (a) Identification. (b) Classification. [45 FR 60601, Sept. 12, 1980] § 864.5680 Automated heparin analyzer. (a) Identification. (b) Classification. [45 FR 60601, Sept. 12, 1980, as amended at 52 FR 17733, May 11, 1987; 58 FR 51571, Oct. 4, 1993] § 864.5700 Automated platelet aggregation system. (a) Identification. (b) Classification. [45 FR 60602, Sept. 12, 1980] § 864.5800 Automated sedimentation rate device. (a) Identification. (b) Classification. [45 FR 60602, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.5850 Automated slide spinner. (a) Identification. (b) Classification. [45 FR 60603, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.5950 Blood volume measuring device. (a) Identification. (b) Classification. [45 FR 60603, Sept. 12, 1980] Subpart G—Manual Hematology Devices § 864.6100 Bleeding time device. (a) Identification. (b) Classification. [45 FR 60604, Sept. 12, 1980, as amended at 63 FR 59225, Nov. 3, 1998] § 864.6150 Capillary blood collection tube. (a) Identification. (b) Classification. [45 FR 60604, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 65 FR 2310, Jan. 14, 2000] § 864.6160 Manual blood cell counting device. (a) Identification. (b) Classification. [45 FR 60605, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.6400 Hematocrit measuring device. (a) Identification. (b) Classification. [45 FR 60606, Sept. 12, 1980, as amended at 63 FR 59225, Nov. 3, 1998] § 864.6550 Occult blood test. (a) Identification. (b) Classification. [45 FR 60606, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.6600 Osmotic fragility test. (a) Identification. (b) Classification. [45 FR 60607, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.6650 Platelet adhesion test. (a) Identification. (b) Classification. [45 FR 60608, Sept. 12, 1980] § 864.6675 Platelet aggregometer. (a) Identification. (b) Classification. [45 FR 60608, Sept. 12, 1980] § 864.6700 Erythrocyte sedimentation rate test. (a) Identification. (b) Classification. [45 FR 60608, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] Subpart H—Hematology Kits and Packages § 864.7010 Flow cytometric test system for hematopoietic neoplasms. (a) Identification. (b) Classification. (1) Premarket notification submissions must include the following information: (i) The indications for use must indicate the clinical hematopoietic neoplasms for which the assay was designed and validated, for example, chronic leukemia or lymphoma. (ii) A detailed device description including the following: (A) A detailed description of all test components, all required reagents, and all 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) A detailed description of methodology and assay procedure. (D) A description of appropriate internal and external quality control materials that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure, if applicable. (E) Detailed specifications for sample collection, processing, and storage. (F) Detailed specification of the criteria for test results interpretation and reporting including pre-established templates. (G) If applicable, based on the output of the results, a description of the specific number of events to collect, result outputs, and analytical sensitivity of the assay that will be reported. (iii) Information that demonstrates the performance characteristics of the test, including: (A) Device performance data from either a method comparison study comparing the specific lymphocyte cell markers to a predicate device or data collected through a clinical study demonstrating clinical validity using well-characterized clinical specimens. Samples must be representative of the intended use population of the device including hematologic neoplasms and the specific sample types for which the test is indicated for use. (B) If applicable, device performance data from a clinical study demonstrating clinical validity for parameters not established in a predicate device of this generic type using well-characterized prospectively obtained clinical specimens including all hematologic neoplasms and the specific sample types for which the device is indicated for use. (C) Device precision data using clinical samples to evaluate the within-lot, between-lot, within-run, between run, site-to-site and total variation using a minimum of three sites, of which at least two sites must be external sites. Results shall be reported as the standard deviation and percentage coefficient of variation for each level tested. (D) Reproducibility data generated using a minimum of three lots of reagents to evaluate mean fluorescence intensity and variability of the recovery of the different markers and/or cell populations. (E) Data from specimen and reagent carryover testing performed using well-established methods ( e.g., (F) Specimen and prepared sample stability data established for each specimen matrix in the anticoagulant combinations and storage/use conditions that will be indicated. (G) A study testing anticoagulant equivalency in all claimed specimen type/anticoagulant combinations using clinical specimens that are representative of the intended use population of the device. (H) Analytic sensitivity data using a dilution panel created from clinical samples. (I) Analytical specificity data, including interference and cross-contamination. (J) Device stability data, including real-time stability of reagents under various storage times and temperatures. (K) For devices that include polyclonal antibodies, Fluorescence Minus One (FMO) studies to evaluate non-specific binding for all polyclonal antibodies. Each FMO tube is compared to reagent reference to demonstrate that no additional population appears when one marker is absent. Pre-specified acceptance criteria must be provided and followed. (L) For devices indicated for use as a semi-quantitative test, linearity data using a dilution panel created from clinical samples. (M) For devices indicated for use as a semi-quantitative test, clinically relevant analytical sensitivity data, including limit of blank, limit of detection, and limit of quantification. (iv) 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 the device. (2) The 21 CFR 809.10 compliant labeling must include the following: (i) The intended use statement in the 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include a statement that the results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. The intended use statement must also include information on what the device detects and measures, whether the device is qualitative, semi-quantitative, and/or quantitative, the clinical indications for which the device is to be used, and the specific population(s) for which the device is intended. (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) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, product labeling and instruction manuals must include clear examples of all expected phenotypic patterns and gating strategies using well-defined clinical samples representative of both abnormal and normal cellular populations. These samples must be selected based upon the indications described in paragraph (b)(1)(i) of this section. [82 FR 61165, Dec. 27, 2017, as amended at 90 FR 55981, Dec. 4, 2025] § 864.7040 Adenosine triphosphate release assay. (a) Identification. (b) Classification. [45 FR 60609, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7060 Antithrombin III assay. (a) Identification. (b) Classification. [45 FR 60609, Sept. 12, 1980] § 864.7100 Red blood cell enzyme assay. (a) Identification. (b) Classification. [45 FR 60610, Sept. 12, 1980] § 864.7140 Activated whole blood clotting time tests. (a) Identification. (b) Classification. [45 FR 60611, Sept. 12, 1980] § 864.7250 Erythropoietin assay. (a) Identification. (b) Classification. [45 FR 60612, Sept. 12, 1980, as amended at 52 FR 17733, May 11, 1987; 65 FR 17144, Mar. 31, 2000] § 864.7275 Euglobulin lysis time tests. (a) Identification. (b) Classification. [45 FR 60612, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7280 Factor V Leiden DNA mutation detection systems. (a) Identification. (b) Classification. [69 FR 12273, Mar. 16, 2004] § 864.7290 Factor deficiency test. (a) Identification. (b) Classification. [45 FR 60613, Sept. 12, 1980] § 864.7293 Von Willebrand factor assay. (a) Identification. (b) Classification. (1) Design verification and validation must include: (i) Detailed documentation of studies demonstrating acceptable, as determined by FDA, analytical performance, including, as applicable, precision, linearity, assay interference, detection capability, specimen and reagent stability, and hook effect, with a sufficient number of specimens tested in order to obtain unbiased estimates of analytical performance. 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 a comparison study of clinical samples demonstrating performance relative to clinically relevant and appropriate, as determined by FDA, clinically validated laboratory tests. Further, the studies must meet all of the following criteria: (A) All eligible subjects must meet appropriate study inclusion and exclusion criteria that define the intended use population. Specimens must be representative of the intended use population(s) and must representatively cover the full range of the device output and any clinically relevant decision points, as appropriate; (B) The study must be conducted at a minimum of three external sites representative of the intended use setting by operators representative of the intended user population; (C) For all intended pediatric patient populations, clinical outcome validation studies must study those populations in accordance with paragraphs (b)(1)(ii)(A) and (B) of this section; and (D) Expected (reference) values for test output must be demonstrated by testing a statistically appropriate number of samples from apparently healthy normal individuals in all relevant subpopulations ( i.e., (2) The labeling required under § 809.10(b) of this chapter must include: (i) Limiting statements indicating, as applicable: (A) This device should always be used in conjunction with the patient's medical history, clinical presentation, and other laboratory findings. (B) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur. (ii) A detailed summary of the performance testing results of analytical and clinical performance testing, including results of concordance evaluation (overall agreement, positive percentage agreement and negative percentage agreement) as required under paragraph (b)(1) of this section. [91 FR 32338, June 1, 2026] § 864.7295 Heparin and direct oral factor Xa inhibitor drug test system. (a) Identification. (b) Classification. (1) Design verification and validation must include the following: (i) Detailed documentation of analytical device performance studies and results demonstrating acceptable analytical performance with a sufficient number of specimens tested in order to obtain unbiased estimates of analytical performance. This documentation shall include the following as appropriate to the technology, specimen types tested, and intended use of the device: (A) Studies and results for that demonstrate device precision including repeatability and reproducibility, using quality controls and clinical samples, when appropriate. Precision studies must assess specimens for each indicated drug at concentrations throughout the measuring range of the device including near clinically relevant levels, as appropriate. The study must evaluate different sources of variability including, as appropriate, between-run, between-operator, between-lot, between-instrument, between-day, and between-site; (B) Studies and results that demonstrate that the device is free from clinically significant interference, from endogenous and exogenous interferents associated with the target population(s), and interferents that are specific for, or related to, the technology or methodology of the device; (C) Data to demonstrate appropriate specimen stability for the intended sample matrices under the intended conditions for specimen collection, handling, and storage described in the device labeling; (D) Studies and results that demonstrate the linear range, limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ), as applicable to the technology of the device; and (E) For any devices intended for use for near patient testing, studies and results that demonstrate the robustness of the device in the hands of the intended user, including the entire testing procedure, pre-analytical specimen processing steps, and results interpretation. (ii) Detailed documentation of clinical performance testing in which the performance is analyzed relative to a comparator that FDA has determined is appropriate. Specimens must be representative of the intended use population(s) and must cover the full range of the device output and any clinically relevant decision points as appropriate. (2) The labeling required under § 809.10(b) of this chapter must include: (i) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur; (ii) A prominent statement that the device is not intended for use in monitoring patients taking heparin or direct oral factor Xa inhibitors; and (iii) Limiting statements indicating, as applicable: (A) That the device should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures; and (B) That the device is not specific to the direct oral factor Xa inhibitor that has been evaluated and may detect the presence of other direct factor Xa inhibitors that have not been evaluated. [89 FR 72317, Sept. 5, 2024] § 864.7300 Fibrin monomer paracoagulation test. (a) Identification. (b) Classification. [45 FR 60614, Sept. 12, 1980, as amended at 52 FR 17733, May 11, 1987; 65 FR 17144, Mar. 31, 2000, 84 FR 71799, Dec. 30, 2019] § 864.7320 Fibrinogen/fibrin degradation products assay. (a) Identification. (b) Classification. [45 FR 60615, Sept. 12, 1980] § 864.7340 Fibrinogen determination system. (a) Identification. (b) Classification. [45 FR 60615, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7360 Erythrocytic glucose-6-phosphate dehydrogenase assay. (a) Identification. (b) Classification. [45 FR 60616, Sept. 12, 1980] § 864.7375 Glutathione reductase assay. (a) Identification. (b) Classification. [45 FR 60616, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7400 Hemoglobin A 2 (a) Identification. 2 2 2 (b) Classification. [45 FR 60617, Sept. 12, 1980] § 864.7415 Abnormal hemoglobin assay. (a) Identification. (b) Classification. [45 FR 60618, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7425 Carboxyhemoglobin assay. (a) Identification. (b) Classification. [45 FR 60619, Sept. 12, 1980] § 864.7440 Electrophoretic hemoglobin analysis system. (a) Identification. (b) Classification. [45 FR 60620, Sept. 12, 1980] § 864.7455 Fetal hemoglobin assay. (a) Identification. (b) Classification. [45 FR 60620, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7470 Glycosylated hemoglobin assay. (a) Identification. 1a 1b 1c (b) Classification. [45 FR 60621, Sept. 12, 1980] § 864.7490 Sulfhemoglobin assay. (a) Identification. (b) Classification. [45 FR 60621, Sept. 12, 1980] § 864.7500 Whole blood hemoglobin assays. (a) Identification. (b) Classification. [45 FR 60622, Sept. 12, 1980, as amended at 84 FR 71799, Dec. 30, 2019] § 864.7525 Heparin assay. (a) Identification. (b) Classification. [45 FR 60623, Sept. 12, 1980] § 864.7660 Leukocyte alkaline phosphatase test. (a) Identification. (b) Classification. [45 FR 60623, Sept. 12, 1980, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38790, July 25, 2001] § 864.7675 Leukocyte peroxidase test. (a) Identification. (b) Classification. [45 FR 60624, Sept. 12, 1980, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38790, July 25, 2001] § 864.7695 Platelet factor 4 radioimmunoassay. (a) Identification. (b) Classification. [45 FR 60625, Sept. 12, 1980; 46 FR 14890, Mar. 3, 1981] § 864.7720 Prothrombin consumption test. (a) Identification. (b) Classification. [45 FR 60625, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.7735 Prothrombin-proconvertin test and thrombotest. (a) Identification. (b) Classification. [45 FR 60626, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.7750 Prothrombin time test. (a) Identification. (b) Classification. [45 FR 60626, Sept. 12, 1980] § 864.7825 Sickle cell test. (a) Identification. (b) Classification. [45 FR 60627, Sept. 12, 1980] § 864.7875 Thrombin time test. (a) Identification. (b) Classification. [45 FR 60628, Sept. 12, 1980] § 864.7900 Thromboplastin generation test. (a) Identification. (b) Classification. [45 FR 60628, Sept. 12, 1980, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38790, July 25, 2001] § 864.7925 Partial thromboplastin time tests. (a) Identification. (b) Classification. [45 FR 60629, Sept. 12, 1980] Subpart I—Hematology Reagents § 864.8100 Bothrops atrox reagent. (a) Identification. (b) Classification. [45 FR 60629, Sept. 12, 1980] § 864.8150 Calibrator for cell indices. (a) Identification. (b) Classification. [45 FR 60631, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.8165 Calibrator for hemoglobin or hematocrit measurement. (a) Identification. (b) Classification. [45 FR 60632, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.8175 Calibrator for platelet counting. (a) Identification. (b) Classification. [45 FR 60633, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.8185 Calibrator for red cell and white cell counting. (a) Identification. (b) Classification. [45 FR 60634, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.8200 Blood cell diluent. (a) Identification. (b) Classification. [45 FR 60635, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.8500 Lymphocyte separation medium. (a) Identification. (b) Classification. [45 FR 60636, Sept. 12, 1980, as amended at 59 FR 63007, Dec. 7, 1994; 66 FR 38790, July 25, 2001] § 864.8540 Red cell lysing reagent. (a) Identification. (b) Classification. [45 FR 60636, Sept. 12, 1980, as amended at 54 FR 25045, June 12, 1989; 66 FR 38790, July 25, 2001] § 864.8625 Hematology quality control mixture. (a) Identification. (b) Classification. [45 FR 60637, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.8950 Russell viper venom reagent. (a) Identification. (b) Classification. [45 FR 60637, Sept. 12, 1980] Subpart J—Products Used In Establishments That Manufacture Blood and Blood Products § 864.9050 Blood bank supplies. (a) Identification. (b) Classification. [45 FR 60638, Sept. 12, 1980, as amended at 53 FR 11253, Apr. 6, 1988] § 864.9100 Empty container for the collection and processing of blood and blood components. (a) Identification. (b) Classification. [45 FR 60638, Sept. 12, 1980] § 864.9115 Container system for the processing and storage of Red Blood Cell components under reduced oxygen conditions. (a) Identification. (b) Classification. (1) The intended use of the device must specify: (i) The Red Blood Cell components that can be processed and stored including acceptable anticoagulants and additive solutions; (ii) The hold time after Red Blood Cell component collection; (iii) The processing capacity (volume) of the device; and (iv) The storage temperature and dating period of processed Red Blood Cell components. (2) Studies must demonstrate that the device is biocompatible and include detailed documentation of the biocompatibility evaluation. (3) Performance testing and nonclinical studies must include a detailed study of leached materials extracted under conditions similar to clinical usage of the device, and a toxicologic risk assessment of those extracted or leached materials. (4) Performance testing must support sterility of the device and include sterilization validation, endotoxin testing, and container closure integrity evaluation. (5) Nonclinical and clinical studies must include evaluation of red blood cell quality throughout the duration of storage based on in vitro and in vivo studies, including hemolysis and red blood cell survival and recovery. (6) Performance studies must include: (i) Detailed documentation of functional and mechanical testing, including evaluation of oxygen and, if applicable, carbon dioxide levels during Red Blood Cell components storage; and (ii) Detailed documentation of device shelf-life testing demonstrating continued sterility, package integrity, and functionality over the identified shelf life. (7) The labeling must include a contraindication against processing Red Blood Cell components collected from donors with hemoglobin S. [88 FR 77199, Nov. 9, 2023] § 864.9125 Vacuum-assisted blood collection system. (a) Identification. (b) Classification. [45 FR 60639, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9145 Processing system for frozen blood. (a) Identification. (b) Classification. [45 FR 60639, Sept. 12, 1980] § 864.9160 Blood group substances of nonhuman origin for in vitro diagnostic use. (a) Identification. (b) Classification. [45 FR 60640, Sept. 12, 1980, as amended at 53 FR 11253, Apr. 6, 1988; 63 FR 59225, Nov. 3, 1998] § 864.9165 Blood establishment computer software and accessories. (a) Identification. (b) Classification. (1) Software performance and functional requirements including detailed design specifications ( e.g., (2) Verification and validation testing and hazard analysis must be performed. (3) Labeling must include: (i) Software limitations; (ii) Unresolved anomalies, annotated with an explanation of the impact on safety or effectiveness; (iii) Revision history; and (iv) Hardware and peripheral specifications. (4) Traceability matrix must be performed. (5) Performance testing to ensure the safety and effectiveness of the system must be performed, including when adding new functional requirements ( e.g., [83 FR 23217, June 18, 2018] § 864.9175 Automated blood grouping and antibody test system. (a) Identification. (b) Classification. [45 FR 60641, Sept. 12, 1980] § 864.9185 Blood grouping view box. (a) Identification. (b) Classification. [45 FR 60641, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. (b) Classification. [45 FR 60642, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9205 Blood and plasma warming device. (a) Nonelectromagnetic blood or plasma warming device Identification. (2) Classification. (b) Electromagnetic blood and plasma warming device Identification. (2) Classfication. (c) Date PMA or notice of completion of a PDP is required. [45 FR 60642, Sept. 12, 1980, as amended at 52 FR 17733, May 11, 1987] § 864.9225 Cell-freezing apparatus and reagents for in vitro diagnostic use. (a) Identification. (b) Classification. [45 FR 60643, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9245 Automated blood cell separator. (a) Identification. (b) Classification. [72 FR 67644, Nov. 30, 2007] § 864.9275 Blood bank centrifuge for in vitro diagnostic use. (a) Identification. (b) Classification. [45 FR 60645, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. (b) Classification. [45 FR 60646, Sept. 12, 1980] § 864.9300 Automated Coombs test systems. (a) Identification. (b) Classification. [45 FR 60646, Sept. 12, 1980] § 864.9320 Copper sulfate solution for specific gravity determinations. (a) Identification. (b) Classification. [45 FR 60647, Sept. 12, 1980, as amended at 65 FR 2310, Jan. 14, 2000] § 864.9400 Stabilized enzyme solution. (a) Identification. (b) Classification. [45 FR 60647, Sept. 12, 1980, as amended at 84 FR 71800, Dec. 30, 2019] § 864.9550 Lectins and protectins. (a) Identification. (b) Classification. [45 FR 60648, Sept. 12, 1980, as amended at 63 FR 59226, Nov. 3, 1998] § 864.9575 Environmental chamber for storage of platelet concentrate. (a) Identification. (b) Classification. [45 FR 60648, Sept. 12, 1980, as amended at 63 FR 59226, Nov. 3, 1998] § 864.9600 Potentiating media for in vitro diagnostic use. (a) Identification. (b) Classification. [45 FR 60649, Sept. 12, 1980, as amended at 63 FR 59226, Nov. 3, 1998] § 864.9650 Quality control kit for blood banking reagents. (a) Identification. (b) Classification. [45 FR 60649, Sept. 12, 1980] § 864.9700 Blood storage refrigerator and blood storage freezer. (a) Identification. (b) Classification. [45 FR 60650, Sept. 12, 1980, as amended at 63 FR 59226, Nov. 3, 1998] § 864.9750 Heat-sealing device. (a) Identification. (b) Classification. [45 FR 60650, Sept. 12, 1980, as amended at 65 FR 2311, Jan. 14, 2000] § 864.9875 Transfer set. (a) Identification. (b) Classification. [45 FR 60651, Sept. 12, 1980] Subpart K—Products Used In Establishments That Manufacture Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) § 864.9900 Cord blood processing system and storage container. (a) Identification. (b) Classification. [72 FR 4638, Feb. 1, 2007]