PART 600—BIOLOGICAL PRODUCTS: GENERAL Authority: 21 U.S.C. 321, 351, 352, 353, 355, 356c, 356e, 360, 360i, 371, 374, 379k-l; 42 U.S.C. 216, 262, 263, 263a, 264. Cross References: For U.S. Customs Service regulations relating to viruses, serums, and toxins, see 19 CFR 12.21-12.23. For U.S. Postal Service regulations relating to the admissibility to the United States mails see parts 124 and 125 of the Domestic Mail Manual, that is incorporated by reference in 39 CFR part 111. Subpart A—General Provisions § 600.2 Mailing addresses. (a) Licensed biological products regulated by the Center for Biologics Evaluation and Research (CBER). (b) Licensed biological products regulated by the Center for Drug Evaluation and Research (CDER). (1) Biological Product Deviation Reporting (CDER). (2) Advertising and Promotional Labeling (CDER). (c) Samples and Protocols for licensed biological products regulated by CBER or CDER. (2) Radioactive biological products required under § 610.2 of this chapter must be sent by courier service to: Food and Drug Administration, Center for Biologics Evaluation and Research, ATTN: Sample Custodian, c/o White Oak Radiation Safety Program, 10903 New Hampshire Ave., Bldg. 52-72, Rm. G406A, Silver Spring, MD 20993-0002. (d) Address information for submissions to CBER and CDER other than those listed in parts 600 through 680 of this chapter are included directly in the applicable regulations. (e) Obtain updated mailing address information for biological products regulated by CBER at http://www.fda.gov/BiologicsBloodVaccines/default.htm http://www.fda.gov/Drugs/default.htm. [70 FR 14981, Mar. 24, 2005, as amended at 74 FR 13114, Mar. 26, 2009; 78 FR 19585, Apr. 2, 2013; 80 FR 18091, Apr. 3, 2015; 79 FR 33090, June 10, 2014] § 600.3 Definitions. As used in this subchapter: (a) Act (b) Secretary (c) Commissioner of Food and Drugs (d) Center for Biologics Evaluation and Research (e) State (f) Possession (g) Products (h) Biological product (1) A virus is interpreted to be a product containing the minute living cause of an infectious disease and includes but is not limited to filterable viruses, bacteria, rickettsia, fungi, and protozoa. (2) A therapeutic serum is a product obtained from blood by removing the clot or clot components and the blood cells. (3) A toxin is a product containing a soluble substance poisonous to laboratory animals or to man in doses of 1 milliliter or less (or equivalent in weight) of the product, and having the property, following the injection of non-fatal doses into an animal, of causing to be produced therein another soluble substance which specifically neutralizes the poisonous substance and which is demonstrable in the serum of the animal thus immunized. (4) An antitoxin is a product containing the soluble substance in serum or other body fluid of an immunized animal which specifically neutralizes the toxin against which the animal is immune. (5) A product is analogous: (i) To a virus if prepared from or with a virus or agent actually or potentially infectious, without regard to the degree of virulence or toxicogenicity of the specific strain used. (ii) To a therapeutic serum, if composed of whole blood or plasma or containing some organic constituent or product other than a hormone or an amino acid, derived from whole blood, plasma, or serum. (iii) To a toxin or antitoxin, if intended, irrespective of its source of origin, to be applicable to the prevention, treatment, or cure of disease or injuries of man through a specific immune process. (6) A protein is any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. When two or more amino acid chains in an amino acid polymer are associated with each other in a manner that occurs in nature, the size of the amino acid polymer for purposes of this paragraph (h)(6) will be based on the total number of amino acids in those chains, and will not be limited to the number of amino acids in a contiguous sequence. (i) Trivalent organic arsenicals (j) A product is deemed applicable to the prevention, treatment, or cure of diseases or injuries of man (k) Proper name, (l) Dating period (m) Expiration date (n) The word standards (o) The word continued (p) The word safety (q) The word sterility (r) Purity Purity (s) The word potency (t) Manufacturer (u) Manufacture (v) Location (w) Establishment (x) Lot (y) A filling (z) Process (aa) Selling agent distributor (bb) Container (cc) Package (dd) Label (ee) Radioactive biological product (ff) Amendment (gg) Supplement (hh) Distributed (ii) Control (jj) Assess the effects of the change (kk) Specification acceptance criteria (ll) Complete response letter (mm) Resubmission [38 FR 32048, Nov. 20, 1973, as amended at 40 FR 31313, July 25, 1975; 55 FR 11014, Mar. 26, 1990; 61 FR 24232, May 14, 1996; 62 FR 39901, July 24, 1997; 64 FR 56449, Oct. 20, 1999; 65 FR 66634, Nov. 7, 2000; 69 FR 18766, Apr. 8, 2004; 70 FR 14982, Mar. 24, 2005; 73 FR 39610, July 10, 2008; 77 FR 26174, May 3, 2012; 85 FR 10063, Feb. 21, 2020] Subpart B—Establishment Standards § 600.10 Personnel. (a) [Reserved] (b) Personnel. (c) Restrictions on personnel Specific duties. (2) Sterile operations. (3) Pathogenic viruses and spore-forming organisms. (4) Live vaccine work areas. [38 FR 32048, Nov. 20, 1973, as amended at 49 FR 23833, June 8, 1984; 55 FR 11014, Mar. 26, 1990; 62 FR 53538, Oct. 15, 1997; 68 FR 75119, Dec. 30, 2003] § 600.11 Physical establishment, equipment, animals, and care. (a) Work areas. (b) Equipment. (c) Laboratory and bleeding rooms. (d) Animal quarters and stables. (e) Restrictions on building and equipment use Work of a diagnostic nature. (2) Spore-forming organisms for supplemental sterilization procedure control test. Provided, (3) Work with spore-forming microorganisms. (ii) If process containment is employed in a multiproduct manufacturing area, procedures must be in place to demonstrate adequate removal of the spore-forming microorganism(s) from the manufacturing area for subsequent manufacture of other products. These procedures must provide for adequate removal or decontamination of the spore-forming microorganisms on and within manufacturing equipment, facilities, and ancillary room items as well as the removal of disposable or product dedicated items from the manufacturing area. Environmental monitoring specific for the spore-forming microorganism(s) must be conducted in adjacent areas during manufacturing operations and in the manufacturing area after completion of cleaning and decontamination. (4) Live vaccine processing. (i)(A) Using a dedicated manufacturing area that is either in a separate building, in a separate wing of a building, or in quarters at the blind end of a corridor and includes adequate space and equipment for all processing steps up to, but not including, filling into final containers; and (B) Not conducting test procedures that potentially involve the presence of microorganisms other than the vaccine strains or the use of tissue culture cell lines other than primary cultures in space used for processing live vaccine; or (ii) If manufacturing is conducted in a multiproduct manufacturing building or area, using procedural controls, and where necessary, process containment. Process containment is deemed to be necessary unless procedural controls are sufficient to prevent cross contamination of other products and other manufacturing areas within the building. Process containment is a system designed to mechanically isolate equipment or an area that involves manufacturing using live vaccine organisms. All product, equipment, and personnel movement between distinct live vaccine processing areas and between live vaccine processing areas and other manufacturing areas, up to, but not including, filling in final containers, must be conducted under conditions that will prevent cross contamination of other products and manufacturing areas within the building, including the introduction of live vaccine organisms into other areas. In addition, written procedures and effective processes must be in place to adequately remove or decontaminate live vaccine organisms from the manufacturing area and equipment for subsequent manufacture of other products. Written procedures must be in place for verification that processes to remove or decontaminate live vaccine organisms have been followed. (5) Equipment and supplies—contamination. (f) Animals used in manufacture Care of animals used in manufacturing. (2) Quarantine of animals General. (ii) Quarantine of monkeys. (3) Immunization against tetanus. (4) Immunization and bleeding of animals used as a source of products. (5) [Reserved] (6) Reporting of certain diseases. (7) Monkeys used previously for experimental or test purposes. (8) Necropsy examination of monkeys. (g) Filling procedures. (h) Containers and closures. et seq. [38 FR 32048, Nov. 20, 1973, as amended at 41 FR 10428, Mar. 11, 1976; 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990; 68 FR 75119, Dec. 30, 2003; 70 FR 14982, Mar. 24, 2005; 72 FR 59003, Oct. 18, 2007; 80 FR 18092, Apr. 3, 2015] § 600.12 Records. (a) Maintenance of records. (b) Records retention General. (2) Records of recall. (3) Suspension of requirement for retention. Provided, (c) Records of sterilization of equipment and supplies. (d) Animal necropsy records. (e) Records in case of divided manufacturing responsibility. [38 FR 32048, Nov. 20, 1973, as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990; 70 FR 14982, Mar. 24, 2005] § 600.13 Retention samples. Manufacturers shall retain for a period of at least 6 months after the expiration date, unless a different time period is specified in additional standards, a quantity of representative material of each lot of each product, sufficient for examination and testing for safety and potency, except Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, and Source Plasma and Allergenic Products prepared to a physician's prescription. Samples so retained shall be selected at random from either final container material, or from bulk and final containers, provided they include at least one final container as a final package, or package-equivalent of such filling of each lot of the product as intended for distribution. Such sample material shall be stored at temperatures and under conditions which will maintain the identity and integrity of the product. Samples retained as required in this section shall be in addition to samples of specific products required to be submitted to the Center for Biologics Evaluation and Research or the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Exceptions may be authorized by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research, when the lot yields relatively few final containers and when such lots are prepared by the same method in large number and in close succession. [41 FR 10428, Mar. 11, 1976, as amended at 49 FR 23833, June 8, 1984; 50 FR 4133, Jan. 29, 1985; 55 FR 11013, Mar. 26, 1990; 70 FR 14982, Mar. 24, 2005] § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report under this section? (2) Exceptions: (i) Persons who manufacture only in vitro diagnostic products that are not subject to licensing under section 351 of the Public Health Service Act do not report biological product deviations for those products under this section but must report in accordance with part 803 of this chapter; (ii) Persons who manufacture blood and blood components, including licensed manufacturers, unlicensed registered blood establishments, and transfusion services, do not report biological product deviations for those products under this section but must report under § 606.171 of this chapter; (iii) Persons who manufacture Source Plasma or any other blood component and use that Source Plasma or any other blood component in the further manufacture of another licensed biological product must report: (A) Under § 606.171 of this chapter, if a biological product deviation occurs during the manufacture of that Source Plasma or any other blood component; or (B) Under this section, if a biological product deviation occurs after the manufacture of that Source Plasma or any other blood component, and during manufacture of the licensed biological product. (b) What do I report under this section? (1) Either: (i) Represents a deviation from current good manufacturing practice, applicable regulations, applicable standards, or established specifications that may affect the safety, purity, or potency of that product; or (ii) Represents an unexpected or unforeseeable event that may affect the safety, purity, or potency of that product; and (2) Occurs in your facility or another facility under contract with you; and (3) Involves a distributed biological product. (c) When do I report under this section? (d) How do I report under this section (e) Where do I report under this section? (2) For biological products regulated by the Center for Drug Evaluation and Research (CDER), send the completed Form FDA-3486 to the Division of Compliance Risk Management and Surveillance (HFD-330) (see mailing addresses in § 600.2). CDER does not currently accept electronic filings. (3) If you make a paper filing, you should identify on the envelope that a biological product deviation report (BPDR) is enclosed. (f) How does this regulation affect other FDA regulations? [65 FR 66634, Nov. 7, 2000, as amended at 70 FR 14982, Mar. 24, 2005; 80 FR 18092, Apr. 3, 2015] § 600.15 Temperatures during shipment. The following products shall be maintained during shipment at the specified temperatures: (a) Products. Product Temperature Cryoprecipitated AHF −18 °C or colder. Measles and Rubella Virus Vaccine Live 10 °C or colder. Measles Live and Smallpox Vaccine Do. Measles, Mumps, and Rubella Virus Vaccine Live Do. Measles and Mumps Virus Vaccine Live Do. Measles Virus Vaccine Live Do. Mumps Virus Vaccine Live Do. Fresh Frozen Plasma −18 °C or colder. Liquid Plasma 1 to 10 °C. Plasma −18 °C or colder. Platelet Rich Plasma Between 1 and 10 °C if the label indicates storage between 1 and 6 °C, or all reasonable methods to maintain the temperature as close as possible to a range between 20 and 24 °C, if the label indicates storage between 20 and 24 °C. Platelets Between 1 and 10 °C if the label indicates storage between 1 and 6 °C, or all reasonable methods to maintain the temperature as close as possible to a range between 20 to 24 °C, if the label indicates storage between 20 and 24 °C. Poliovirus Vaccine Live Oral Trivalent 0 °C or colder. Poliovirus Vaccine Live Oral Type I Do. Poliovirus Vaccine Live Oral Type II Do. Poliovirus Vaccine Live Oral Type III Do. Red Blood Cells (liquid product) Between 1 and 10 °C. Red Blood Cells Frozen −65 °C or colder. Rubella and Mumps Virus Vaccine Live 10 °C or colder. Rubella Virus Vaccine Live Do. Smallpox Vaccine (Liquid Product) 0 °C or colder. Source Plasma −5 °C or colder. Source Plasma Liquid 10 °C or colder. Whole Blood Blood that is transported from the collecting facility to the processing facility shall be transported in an environment capable of continuously cooling the blood toward a temperature range of 1 to 10 °C, or at a temperature as close as possible to 20 to 24 °C for a period not to exceed 6 hours. Blood transported from the storage facility shall be placed in an appropriate environment to maintain a temperature range between 1 to 10 °C during shipment. Yellow Fever Vaccine 0 °C or colder. (b) Exemptions. [39 FR 39872, Nov. 12, 1974, as amended at 49 FR 23833, June 8, 1984; 50 FR 4133, Jan. 29, 1985; 50 FR 9000, Mar. 6, 1985; 55 FR 11013, Mar. 26, 1990; 59 FR 49351, Sept. 28, 1994; 64 FR 56449, Oct. 20, 1999] Subpart C—Establishment Inspection § 600.20 Inspectors. Inspections shall be made by an officer of the Food and Drug Administration having special knowledge of the methods used in the manufacture and control of products and designated for such purposes by the Commissioner of Food and Drugs, or by any officer, agent, or employee of the Department of Health and Human Services specifically designated for such purpose by the Secretary. [38 FR 32048, Nov. 20, 1973] § 600.21 Time of inspection. The inspection of an establishment for which a biologics license application is pending need not be made until the establishment is in operation and is manufacturing the complete product for which a biologics license is desired. [38 FR 32048, Nov. 20, 1973, as amended at 48 FR 26314, June 7, 1983; 64 FR 56449, Oct. 20, 1999; 84 FR 12508, Apr. 2, 2019] § 600.22 [Reserved] Subpart D—Reporting of Adverse Experiences Source: 59 FR 54042, Oct. 27, 1994, unless otherwise noted. § 600.80 Postmarketing reporting of adverse experiences. (a) Definitions. Adverse experience. Blood Component. Disability. Individual case safety report (ICSR). ICSR attachments. Life-threatening adverse experience. Serious adverse experience. Unexpected adverse experience (b) Review of adverse experiences. (c) Reporting requirements. (1)(i) Postmarketing 15-day “Alert reports”. (ii) Postmarketing 15-day “Alert reports”—followup. (iii) Submission of reports. (A) A copy of all adverse biological product experience reports submitted to the applicant of the final product; (B) The date the report was received by the person; (C) The date the report was submitted to the applicant of the final product; and— (D) The name and address of the applicant of the final product. (2) Periodic adverse experience reports. (ii) Each periodic report is required to contain: (A) Descriptive information. 1 ( 2 ( 3 ( 4 (B) ICSRs for serious, expected and, nonserious adverse experiences. (iii) Periodic reporting, except for information regarding 15-day Alert reports, does not apply to adverse experience information obtained from postmarketing studies (whether or not conducted under an investigational new drug application), from reports in the scientific literature, and from foreign marketing experience. (d) Scientific literature. (e) Postmarketing studies. (f) Information reported on ICSRs for nonvaccine biological products. (1) Patient information. (i) Patient identification code; (ii) Patient age at the time of adverse experience, or date of birth; (iii) Patient gender; and (iv) Patient weight. (2) Adverse experience. (i) Outcome attributed to adverse experience; (ii) Date of adverse experience; (iii) Date of report; (iv) Description of adverse experience (including a concise medical narrative); (v) Adverse experience term(s); (vi) Description of relevant tests, including dates and laboratory data; and (vii) Other relevant patient history, including preexisting medical conditions. (3) Suspect medical product(s). (i) Name; (ii) Dose, frequency, and route of administration used; (iii) Therapy dates; (iv) Diagnosis for use (indication); (v) Whether the product is a combination product as defined in § 3.2(e) of this chapter; (vi) Whether the product is a prescription or nonprescription product; (vii) Whether adverse experience abated after product use stopped or dose reduced; (viii) Whether adverse experience reappeared after reintroduction of the product; (ix) Lot number; (x) Expiration date; (xi) National Drug Code (NDC) number, or other unique identifier; and (xii) Concomitant medical products and therapy dates. (4) Initial reporter information. (i) Name, address, and telephone number; (ii) Whether the initial reporter is a health care professional; and (iii) Occupation, if a health care professional. (5) Applicant information. (i) Applicant name and contact office address; (ii) Telephone number; (iii) Report source, such as spontaneous, literature, or study; (iv) Date the report was received by applicant; (v) Application number and type; (vi) Whether the ICSR is a 15-day “Alert report”; (vii) Whether the ICSR is an initial report or followup report; and (viii) Unique case identification number, which must be the same in the initial report and any subsequent followup report(s). (g) Information reported on ICSRs for vaccine products. (1) Patient information. (i) Patient name, address, telephone number; (ii) Patient age at the time of vaccination, or date of birth; (iii) Patient gender; and (iv) Patient birth weight for children under age 5. (2) Adverse experience. (i) Outcome attributed to adverse experience; (ii) Date and time of adverse experience; (iii) Date of report; (iv) Description of adverse experience (including a concise medical narrative); (v) Adverse experience term(s); (vi) Illness at the time of vaccination; (vii) Description of relevant tests, including dates and laboratory data; and (viii) Other relevant patient history, including preexisting medical conditions. (3) Suspect medical product(s), including vaccines administered on the same date. (i) Name; (ii) Dose, frequency, and route or site of administration used; (iii) Number of previous vaccine doses; (iv) Vaccination date(s) and time(s); (v) Diagnosis for use (indication); (vi) Whether the product is a combination product (as defined in § 3.2(e) of this chapter); (vii) Whether the adverse experience abated after product use stopped or dose reduced; (viii) Whether the adverse experience reappeared after reintroduction of the product; (ix) Lot number; (x) Expiration date; (xi) National Drug Code (NDC) number, or other unique identifier; and (xii) Concomitant medical products and therapy dates. (4) Vaccine(s) administered in the 4 weeks prior to the vaccination date. (i) Name of vaccine; (ii) Manufacturer; (iii) Lot number; (iv) Route or site of administration; (v) Date given; and (vi) Number of previous doses. (5) Initial reporter information. (i) Name, address, and telephone number; (ii) Whether the initial reporter is a health care professional; and (iii) Occupation, if a health care professional. (6) Facility and personnel where vaccine was administered. (i) Name of person who administered vaccine; (ii) Name of responsible physician at facility where vaccine was administered; and (iii) Name, address (including city, county, and state), and telephone number of facility where vaccine was administered. (7) Applicant information. (i) Applicant name and contact office address; (ii) Telephone number; (iii) Report source, such as spontaneous, literature, or study; (iv) Date received by applicant; (v) Application number and type; (vi) Whether the ICSR is a 15-day “Alert report”; (vii) Whether the ICSR is an initial report or followup report; and (viii) Unique case identification number, which must be the same in the initial report and any subsequent followup report(s). (h) Electronic format for submissions. (2) Persons subject to the requirements of paragraph (c) of this section may request, in writing, a temporary waiver of the requirements in paragraph (h)(1) of this section. These waivers will be granted on a limited basis for good cause shown. FDA will issue guidance on requesting a waiver of the requirements in paragraph (h)(1) of this section. Requests for waivers must be submitted in accordance with § 600.90. (i) Multiple reports. (j) Patient privacy. (k) Recordkeeping. (l) Revocation of biologics license. (m) Exemptions. (1) Whole blood or components of whole blood. (2) In vitro diagnostic products, including assay systems for the detection of antibodies or antigens to retroviruses. These products are subject to the reporting requirements for devices. (n) Disclaimer. [59 FR 54042, Oct. 27, 1994, as amended at 62 FR 34168, June 25, 1997; 62 FR 52252, Oct. 7, 1997; 63 FR 14612, Mar. 26, 1998; 64 FR 56449, Oct. 20, 1999; 70 FR 14982, Mar. 24, 2005; 79 FR 33090, June 10, 2014] § 600.81 Distribution reports. (a) Reporting requirements. (b)(1) Electronic format. (2) Waivers. [59 FR 54042, Oct. 27, 1994, as amended at 64 FR 56449, Oct. 20, 1999; 70 FR 14983, Mar. 24, 2005; 79 FR 33091, June 10, 2014] § 600.82 Notification of a permanent discontinuance or an interruption in manufacturing. (a) Notification of a permanent discontinuance or an interruption in manufacturing. (i) The biological product is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such biological product used in emergency medical care or during surgery; and (ii) The biological product is not a radiopharmaceutical biological product. (2) An applicant of blood or blood components for transfusion, which is licensed under section 351 of the Public Health Service Act, and which may be dispensed only under prescription under section 503(b) of the Federal Food, Drug, and Cosmetic Act, must notify FDA in writing of a permanent discontinuance of manufacture of any product listed in its license or an interruption in manufacturing of any such product that is likely to lead to a significant disruption in supply of that product in the United States if: (i) The product is life supporting, life sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition, including any such product used in emergency medical care or during surgery; and (ii) The applicant is a manufacturer of a significant percentage of the U.S. blood supply. (b) Submission and timing of notification. (1) At least 6 months prior to the date of the permanent discontinuance or interruption in manufacturing; or (2) If 6 months' advance notice is not possible because the permanent discontinuance or interruption in manufacturing was not reasonably anticipated 6 months in advance, as soon as practicable thereafter, but in no case later than 5 business days after such a permanent discontinuance or interruption in manufacturing occurs. (c) Information included in notification. (1) The name of the biological product subject to the notification, including the National Drug Code for such biological product, or an alternative standard for identification and labeling that has been recognized as acceptable by the Center Director; (2) The name of the applicant of the biological product; (3) Whether the notification relates to a permanent discontinuance of the biological product or an interruption in manufacturing of the biological product; (4) A description of the reason for the permanent discontinuance or interruption in manufacturing; and (5) The estimated duration of the interruption in manufacturing. (d)(1) Public list of biological product shortages. (i) The names and National Drug Codes for such biological products, or the alternative standards for identification and labeling that have been recognized as acceptable by the Center Director; (ii) The name of each applicant for such biological products; (iii) The reason for the shortage, as determined by FDA, selecting from the following categories: Requirements related to complying with good manufacturing practices; regulatory delay; shortage of an active ingredient; shortage of an inactive ingredient component; discontinuation of the manufacture of the biological product; delay in shipping of the biological product; demand increase for the biological product; or other reason; and (iv) The estimated duration of the shortage. (2) Confidentiality. (e) Noncompliance letters. (1) Not later than 30 calendar days after the issuance of such a letter, the applicant must submit to FDA a written response setting forth the basis for noncompliance and providing the required notification under paragraph (a) of this section and including the information required under paragraph (c) of this section; and (2) Not later than 45 calendar days after the issuance of a letter under this paragraph, FDA will make the letter and the applicant's response to the letter public, unless, after review of the applicant's response, FDA determines that the applicant had a reasonable basis for not notifying FDA as required under paragraph (a) of this section. (f) Definitions. Biological product shortage shortage Intended for use in the prevention or treatment of a debilitating disease or condition Life supporting or life sustaining Meaningful disruption Significant disruption [80 FR 38939, July 8, 2015] § 600.90 Waivers. (a) An applicant may ask the Food and Drug Administration to waive under this section any requirement that applies to the applicant under §§ 600.80 and 600.81. A waiver request under this section is required to be submitted with supporting documentation. The waiver request is required to contain one of the following: (1) An explanation why the applicant's compliance with the requirement is unnecessary or cannot be achieved, (2) A description of an alternative submission that satisfies the purpose of the requirement, or (3) Other information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The applicant's compliance with the requirement is unnecessary or cannot be achieved, (2) The applicant's alternative submission satisfies the requirement, or (3) The applicant's submission otherwise justifies a waiver. [59 FR 54042, Oct. 27, 1994, as amended at 79 FR 33092, June 10, 2014]