• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

CFR - Code of Federal Regulations Title 21

  • Print
  • Share
  • E-mail
-
New Search
Help | More About 21CFR
[Code of Federal Regulations]
[Title 21, Volume 7]
[Revised as of April 1, 2013]
[CITE: 21CFR610]





TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER F--BIOLOGICS
 
PART 610GENERAL BIOLOGICAL PRODUCTS STANDARDS
 

Subpart A--Release Requirements

Sec. 610.1 Tests prior to release required for each lot.

No lot of any licensed product shall be released by the manufacturer prior to the completion of tests for conformity with standards applicable to such product. Each applicable test shall be made on each lot after completion of all processes of manufacture which may affect compliance with the standard to which the test applies. The results of all tests performed shall be considered in determining whether or not the test results meet the test objective, except that a test result may be disregarded when it is established that the test is invalid due to causes unrelated to the product.

Sec. 610.2 Requests for samples and protocols; official release.

(a)Licensed biological products regulated by CBER . Samples of any lot of any licensed product together with the protocols showing results of applicable tests, may at any time be required to be sent to the Director, Center for Biologics Evaluation and Research (see mailing addresses in 600.2 of this chapter). Upon notification by the Director, Center for Biologics Evaluation and Research, a manufacturer shall not distribute a lot of a product until the lot is released by the Director, Center for Biologics Evaluation and Research:Provided, That the Director, Center for Biologics Evaluation and Research, shall not issue such notification except when deemed necessary for the safety, purity, or potency of the product.

(b)Licensed biological products regulated by CDER . Samples of any lot of any licensed product together with the protocols showing results of applicable tests, may at any time be required to be sent to the Director, Center for Drug Evaluation and Research (see mailing addresses in 600.2) for official release. Upon notification by the Director, Center for Drug Evaluation and Research, a manufacturer shall not distribute a lot of a biological product until the lot is released by the Director, Center for Drug Evaluation and Research:Provided , That the Director, Center for Drug Evaluation and Research shall not issue such notification except when deemed necessary for the safety, purity, or potency of the product.

[40 FR 31313, July 25, 1975, as amended by 49 FR 23834, June 8, 1984; 50 FR 10941, Mar. 19, 1985; 55 FR 11013 and 11014, Mar. 26, 1990; 67 FR 9587, Mar. 4, 2002; 70 FR 14984, Mar. 24, 2005]

Subpart B--General Provisions

Sec. 610.9 Equivalent methods and processes.

Modification of any particular test method or manufacturing process or the conditions under which it is conducted as required in this part or in the additional standards for specific biological products in parts 620 through 680 of this chapter shall be permitted only under the following conditions:

(a) The applicant presents evidence, in the form of a license application, or a supplement to the application submitted in accordance with 601.12(b) or (c), demonstrating that the modification will provide assurances of the safety, purity, potency, and effectiveness of the biological product equal to or greater than the assurances provided by the method or process specified in the general standards or additional standards for the biological product; and

(b) Approval of the modification is received in writing from the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research.

[62 FR 39903, July 24, 1997, as amended at 70 FR 14984, Mar. 24, 2005]

Sec. 610.10 Potency.

Tests for potency shall consist of either in vitro or in vivo tests, or both, which have been specifically designed for each product so as to indicate its potency in a manner adequate to satisfy the interpretation of potency given by the definition in 600.3(s) of this chapter.

Sec. 610.11 General safety.

A general safety test for the detection of extraneous toxic contaminants shall be performed on biological products intended for administration to humans. The general safety test is required in addition to other specific tests prescribed in the additional standards for individual products in this subchapter, except that, the test need not be performed on those products listed in paragraph (g) of this section. The general safety test shall be performed as specified in this section, unless: Modification is prescribed in the additional standards for specific products, or variation is approved as a supplement to the product license under 610.9.

(a)Product to be tested. The general safety test shall be conducted upon a representative sample of the product in the final container from every final filling of each lot of the product. If any product is processed further after filling, such as by freeze-drying, sterilization, or heat treatment, the test shall be conducted upon a sample from each filling of each drying chamber run, sterilization chamber, or heat treatment bath.

(b)Test animals. Only overtly healthy guinea pigs weighing less than 400 grams each and mice weighing less than 22 grams each shall be used. The animals shall not have been used previously for any test purpose.

(c)Procedure. The duration of the general safety test shall be 7 days for both species, except that a longer period may be established for specific products in accordance with 610.9. Once the manufacturer has established a specific duration of the test period for a specific product, it cannot be varied subsequently, except, in accordance with 610.9. Each test animal shall be weighed and the individual weights recorded immediately prior to injection and on the last day of the test. Each animal shall be observed every working day. Any animal response including any which is not specific for or expected from the product and which may indicate a difference in its quality shall be recorded on the day such response is observed. The test product shall be administered as follows:

(1)Liquid product or freeze-dried product which has been reconstituted as directed on the label. Inject intraperitoneally 0.5 milliliter of the liquid product or the reconstituted product into each of at least two mice, and 5.0 milliliters of the liquid product or the reconstituted product into each of at least two guinea pigs.

(2)Freeze-dried product for which the volume of reconstitution is not indicated on the label . The route of administration, test dose, and diluent shall be as approved in accordance with 610.9. Administer the test product as approved on at least two mice and at least two guinea pigs.

(3)Nonliquid products other than freeze-dried product . The route of administration, test dose, and diluent shall be as in accordance with 610.9. Dissolve or grind and suspend the product in the approved diluent. Administer the test product as approved on at least two mice and at least two guinea pigs.

(d)Test requirements. A safety test is satisfactory if all animals meet all of the following requirements:

(1) They survive the test period.

(2) They do not exhibit any response which is not specific for or expected from the product and which may indicate a difference in its quality.

(3) They weigh no less at the end of the test period than at the time of injection.

(e)Repeat tests --(1)First repeat test. If a filling fails to meet the requirements of paragraph (d) of this section in the initial test, a repeat test may be conducted on the species which failed the initial test, as prescribed in paragraph (c) of this section. The filling is satisfactory only if each retest animal meets the requirements prescribed in paragraph (d) of this section.

(2)Second repeat test. If a filling fails to meet the requirements of the first repeat test, a second repeat test may be conducted on the species which failed the test:Provided, That 50 percent of the total number of animals in that species has survived the initial and first repeat tests. The second repeat test shall be conducted as prescribed in paragraph (c) of this section, except that the number of animals shall be twice that used in the first repeat test. The filling is satisfactory only if each second repeat test animal meets the requirements prescribed in paragraph (d) of this section.

(f) [Reserved]

(g)Exceptions --(1) The test prescribed in this section need not be performed for Whole Blood, Red Blood Cells, Cryoprecipitated AHF, Platelets, Plasma, or Cellular Therapy Products.

(2) For products other than those identified in paragraph (g)(1) of this section, a manufacturer may request from the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in 600.2 of this chapter), an exemption from the general safety test. The manufacturer must submit information as part of a biologics license application submission or supplement to an approved biologics license application establishing that because of the mode of administration, the method of preparation, or the special nature of the product a test of general safety is unnecessary to assure the safety, purity, and potency of the product or cannot be performed. The request must include alternate procedures, if any, to be performed. The Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research, upon finding that the manufacturer's request justifies an exemption, may exempt the product from the general safety test subject to any condition necessary to assure the safety, purity, and potency of the product.

[41 FR 10891, Mar. 15, 1976, as amended at 49 FR 15187, Apr. 18, 1984; 49 FR 23834, June 8, 1984; 50 FR 4133, Jan. 29, 1985; 51 FR 15607, Apr. 25, 1986; 55 FR 11013, Mar. 26, 1990; 59 FR 49351, Sept. 28, 1994; 63 FR 19403, Apr. 20, 1998; 63 FR 41718, Aug. 5, 1998; 68 FR 10160, Mar. 4, 2003; 70 FR 14984, Mar. 24, 2005]

Sec. 610.11a Inactivated influenza vaccine, general safety test.

For inactivated influenza vaccine, the general safety test shall be conducted in the manner indicated in 610.11 of this chapter except that, with reference to guinea pigs, the test shall be satisfied if the product provides satisfactory results using either the subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea pig. The requirements for general safety for inactivated influenza vaccine shall not be considered to be satisfied unless each lot of influenza vaccine is assayed for endotoxin in comparison to a reference preparation provided by the Food and Drug Administration, and such lot is found to contain no more endotoxin than the reference preparation.

[39 FR 40016, Nov. 13, 1974]

Sec. 610.12 Sterility.

(a)The test. Except as provided in paragraph (h) of this section, manufacturers of biological products must perform sterility testing of each lot of each biological product's final container material or other material, as appropriate and as approved in the biologics license application or supplement for that product.

(b)Test requirements. (1) The sterility test must be appropriate to the material being tested such that the material does not interfere with or otherwise hinder the test.

(2) The sterility test must be validated to demonstrate that the test is capable of reliably and consistently detecting the presence of viable contaminating microorganisms.

(3) The sterility test and test components must be verified to demonstrate that the test method can consistently detect the presence of viable contaminating microorganisms.

(c)Written procedures. Manufacturers must establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the following:

(1) The sterility test method to be used;

(i) If culture-based test methods are used, include, at a minimum:

(A) Composition of the culture media;

(B) Growth-promotion test requirements; and

(C) Incubation conditions (time and temperature).

(ii) If non-culture-based test methods are used, include, at a minimum:

(A) Composition of test components;

(B) Test parameters, including acceptance criteria; and

(C) Controls used to verify the method's ability to detect the presence of viable contaminating microorganisms.

(2) The method of sampling, including the number, volume, and size of articles to be tested;

(3) Written specifications for the acceptance or rejection of each lot; and

(4) A statement of any other function critical to the particular sterility test method to ensure consistent and accurate results.

(d)The sample. The sample must be appropriate to the material being tested, considering, at a minimum:

(1) The size and volume of the final product lot;

(2) The duration of manufacturing of the drug product;

(3) The final container configuration and size;

(4) The quantity or concentration of inhibitors, neutralizers, and preservatives, if present, in the tested material;

(5) For a culture-based test method, the volume of test material that results in a dilution of the product that is not bacteriostatic or fungistatic; and

(6) For a non-culture-based test method, the volume of test material that results in a dilution of the product that does not inhibit or otherwise hinder the detection of viable contaminating microorganisms.

(e)Verification. (1) For culture-based test methods, studies must be conducted to demonstrate that the performance of the test organisms and culture media are suitable to consistently detect the presence of viable contaminating microorganisms, including tests for each lot of culture media to verify its growth-promoting properties over the shelf-life of the media.

(2) For non-culture-based test methods, within the test itself, appropriate controls must be used to demonstrate the ability of the test method to continue to consistently detect the presence of viable contaminating microorganisms.

(f)Repeat test procedures. --(1) If the initial test indicates the presence of microorganisms, the product does not comply with the sterility test requirements unless a thorough investigation by the quality control unit can ascribe definitively the microbial presence to a laboratory error or faulty materials used in conducting the sterility testing.

(2) If the investigation described in paragraph (f)(1) of this section finds that the initial test indicated the presence of microorganisms due to laboratory error or the use of faulty materials, a sterility test may be repeated one time. If no evidence of microorganisms is found in the repeat test, the product examined complies with the sterility test requirements. If evidence of microorganisms is found in the repeat test, the product examined does not comply with the sterility test requirements.

(3) If a repeat test is conducted, the same test method must be used for both the initial and repeat tests, and the repeat test must be conducted with comparable product that is reflective of the initial sample in terms of sample location and the stage in the manufacturing process from which it was obtained.

(g)Records. The records related to the test requirements of this section must be prepared and maintained as required by 211.167 and 211.194 of this chapter.

(h)Exceptions. Sterility testing must be performed on final container material or other appropriate material as defined in the approved biologics license application or supplement and as described in this section, except as follows:

(1) This section does not require sterility testing for Whole Blood, Cryoprecipitated Antihemophilic Factor, Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood Cells, Anti-Human Globulin, and Blood Grouping Reagents.

(2) A manufacturer is not required to comply with the sterility test requirements if the Director of the Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research, as appropriate, determines that data submitted in the biologics license application or supplement adequately establish that the route of administration, the method of preparation, or any other aspect of the product precludes or does not necessitate a sterility test to assure the safety, purity, and potency of the product.

[77 FR 26174, May 3, 2012]

Sec. 610.13 Purity.

Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application. In addition, products shall be tested as provided in paragraphs (a) and (b) of this section.

(a)(1)Test for residual moisture. Each lot of dried product shall be tested for residual moisture and shall meet and not exceed established limits as specified by an approved method on file in the biologics license application. The test for residual moisture may be exempted by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research, when deemed not necessary for the continued safety, purity, and potency of the product.

(2)Records. Appropriate records for residual moisture under paragraph (a)(1) of this section shall be prepared and maintained as required by the applicable provisions of 211.188 and 211.194 of this chapter.

(b)Test for pyrogenic substances. Each lot of final containers of any product intended for use by injection shall be tested for pyrogenic substances by intravenous injection into rabbits as provided in paragraphs (b) (1) and (2) of this section:Provided, That notwithstanding any other provision of Subchapter F of this chapter, the test for pyrogenic substances is not required for the following products: Products containing formed blood elements; Cryoprecipitate; Plasma; Source Plasma; Normal Horse Serum; bacterial, viral, and rickettsial vaccines and antigens; toxoids; toxins; allergenic extracts; venoms; diagnostic substances and trivalent organic arsenicals.

(1)Test dose. The test dose for each rabbit shall be at least 3 milliliters per kilogram of body weight of the rabbit and also shall be at least equivalent proportionately, on a body weight basis, to the maximum single human dose recommended, but need not exceed 10 milliliters per kilogram of body weight of the rabbit, except that: (i) Regardless of the human dose recommended, the test dose per kilogram of body weight of each rabbit shall be at least 1 milliliter for immune globulins derived from human blood; (ii) for Streptokinase, the test dose shall be at least equivalent proportionately, on a body weight basis, to the maximum single human dose recommended.

(2)Test procedure, results, and interpretation; standards to be met. The test for pyrogenic substances shall be performed according to the requirements specified in United States Pharmacopeia XX.

(3)Retest. If the lot fails to meet the test requirements prescribed in paragraph (b)(2) of this section, the test may be repeated once using five other rabbits. The temperature rises recorded for all eight rabbits used in testing shall be included in determining whether the requirements are met. The lot meets the requirements for absence of pyrogens if not more than three of the eight rabbits show individual rises in temperature of 0.6 deg. C or more, and if the sum of the eight individual maximum temperature rises does not exceed 3.7 deg. C.

[38 FR 32056, Nov. 20, 1973, as amended at 40 FR 29710, July 15, 1975; 41 FR 10429, Mar. 11, 1976; 41 FR 41424, Sept. 22, 1976; 44 FR 40289, July 10, 1979; 46 FR 62845, Dec. 29, 1981; 49 FR 15187, Apr. 18, 1984; 50 FR 4134, Jan. 29, 1985; 55 FR 28381, July 11, 1990; 64 FR 56453, Oct. 20, 1999; 67 FR 9587, Mar. 4, 2002; 70 FR 14985, Mar. 24, 2005]

Sec. 610.14 Identity.

The contents of a final container of each filling of each lot shall be tested for identity after all labeling operations shall have been completed. The identity test shall be specific for each product in a manner that will adequately identify it as the product designated on final container and package labels and circulars, and distinguish it from any other product being processed in the same laboratory. Identity may be established either through the physical or chemical characteristics of the product, inspection by macroscopic or microscopic methods, specific cultural tests, or in vitro or in vivo immunological tests.

Sec. 610.15 Constituent materials.

(a)Ingredients, preservatives, diluents, adjuvants. All ingredients used in a licensed product, and any diluent provided as an aid in the administration of the product, shall meet generally accepted standards of purity and quality. Any preservative used shall be sufficiently nontoxic so that the amount present in the recommended dose of the product will not be toxic to the recipient, and in the combination used it shall not denature the specific substances in the product to result in a decrease below the minimum acceptable potency within the dating period when stored at the recommended temperature. Products in multiple-dose containers shall contain a preservative, except that a preservative need not be added to Yellow Fever Vaccine; Poliovirus Vaccine Live Oral; viral vaccines labeled for use with the jet injector; dried vaccines when the accompanying diluent contains a preservative; or to an Allergenic Product in 50 percent or more volume in volume (v/v) glycerin. An adjuvant shall not be introduced into a product unless there is satisfactory evidence that it does not affect adversely the safety or potency of the product. The amount of aluminum in the recommended individual dose of a biological product shall not exceed:

(1) 0.85 milligrams if determined by assay;

(2) 1.14 milligrams if determined by calculation on the basis of the amount of aluminum compound added; or

(3) 1.25 milligrams determined by assay provided that data demonstrating that the amount of aluminum used is safe and necessary to produce the intended effect are submitted to and approved by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in 600.2 of this chapter).

(b)Extraneous protein; cell culture produced vaccines. Extraneous protein known to be capable of producing allergenic effects in human subjects shall not be added to a final virus medium of cell culture produced vaccines intended for injection. If serum is used at any stage, its calculated concentration in the final medium shall not exceed 1:1,000,000.

(c)Antibiotics. A minimum concentration of antibiotics, other than penicillin, may be added to the production substrate of viral vaccines.

(d) The Director of the Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research may approve an exception or alternative to any requirement in this section. Requests for such exceptions or alternatives must be in writing.

[38 FR 32056, Nov. 20, 1973, as amended at 46 FR 51903, Oct. 23, 1981; 48 FR 13025, Mar. 29, 1983; 48 FR 37023, Aug. 16, 1983; 49 FR 23834, June 8, 1984; 50 FR 4134, Jan. 29, 1985; 51 FR 15607, Apr. 25, 1986; 55 FR 11013, Mar. 26, 1990; 70 FR 14985, Mar. 24, 2005; 76 FR 20518, Apr. 13, 2011]

Sec. 610.16 Total solids in serums.

Except as otherwise provided by regulation, no liquid serum or antitoxin shall contain more than 20 percent total solids.

Sec. 610.17 Permissible combinations.

Licensed products may not be combined with other licensed products either therapeutic, prophylactic or diagnostic, except as a license is obtained for the combined product. Licensed products may not be combined with nonlicensable therapeutic, prophylactic, or diagnostic substances except as a license is obtained for such combination.

Sec. 610.18 Cultures.

(a)Storage and maintenance. Cultures used in the manufacture of products shall be stored in a secure and orderly manner, at a temperature and by a method that will retain the initial characteristics of the organisms and insure freedom from contamination and deterioration.

(b)Identity and verification. Each culture shall be clearly identified as to source strain. A complete identification of the strain shall be made for each new stock culture preparation. Primary and subsequent seed lots shall be identified by lot number and date of preparation. Periodic tests shall be performed as often as necessary to verify the integrity of the strain characteristics and freedom from extraneous organisms. Results of all periodic tests for verification of cultures and determination of freedom from extraneous organisms shall be recorded and retained.

(c)Cell lines used for manufacturing biological products --(1)General requirements. Cell lines used for manufacturing biological products shall be:

(i) Identified by history;

(ii) Described with respect to cytogenetic characteristics and tumorigenicity;

(iii) Characterized with respect to in vitro growth characteristics and life potential; and

(iv) Tested for the presence of detectable microbial agents.

(2)Tests. Tests that are necessary to assure the safety, purity, and potency of a product may be required by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research.

(3)Applicability. This paragraph applies to diploid and nondiploid cell lines. Primary cell cultures that are not subcultivated and primary cell cultures that are subsequently subcultivated for only a very limited number of population doublings are not subject to the provisions of this paragraph (c).

(d)Records. The records appropriate for cultures under this section shall be prepared and maintained as required by the applicable provisions of 211.188 and 211.194 of this chapter.

[38 FR 32056, Nov. 20, 1973, as amended at 51 FR 44453, Dec. 10, 1986; 55 FR 11013, Mar. 26, 1990; 67 FR 9587, Mar. 4, 2002; 70 FR 14985, Mar. 24, 2005]

Subpart C--Standard Preparations and Limits of Potency

Sec. 610.20 Standard preparations.

Standard preparations made available by the Center for Biologics Evaluation and Research shall be applied in testing, as follows:

(a)Potency standards. Potency standards shall be applied in testing for potency all forms of the following:

Antibodies

Botulism Antitoxin, Type A.

Botulism Antitoxin, Type B.

Botulism Antitoxin, Type E.

Diphtheria Antitoxin.

Histolyticus Antitoxin.

Oedematiens Antitoxin.

Perfringens Antitoxin.

Antipertussis Serum.

Antirabies Serum.

Sordellii Antitoxin.

Staphylococcus Antitoxin.

Tetanus Antitoxin.

Vibrion Septique Antitoxin.

Antigens

Cholera Vaccine, Inaba serotype.

Cholera Vaccine, Ogawa serotype.

Diphtheria Toxin for Schick Test.

Pertussis Vaccine.

Tuberculin, Old.

Tuberculin, Purified Protein Derivative.

Typhoid Vaccine.

Blood Derivative

Thrombin.

(b)Opacity standard. The U.S. Opacity Standard shall be applied in estimating the bacterial concentration of all bacterial vaccines. The assigned value of the standard when observed visually is 10 units. The assigned value of the standard when observed with a photometer is (1) 10 units when the wavelength of the filter is 530 millimicrons, (2) 10.6 units when the wavelength of the filter is 650 millimicrons, and (3) 9 units when the wavelength of the filter is 420 millimicrons.

[38 FR 32056, Nov. 20, 1973, as amended at 41 FR 10429, Mar. 11, 1976; 41 FR 18295, May 3, 1976; 49 FR 23834, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

Sec. 610.21 Limits of potency.

The potency of the following products shall be not less than that set forth below and products dispensed in the dried state shall represent liquid products having the stated limitations.

Antibodies

Diphtheria Antitoxin, 500 units per milliliter.

Tetanus Antitoxin, 400 units per milliliter.

Tetanus Immune Globulin (Human), 250 units of tetanus antitoxin per container.

Antigens

Cholera Vaccine, 8 units each of Inaba and Ogawa serotype antigens per milliliter.

Pertussis Vaccine, 12 units per total human immunizing dose.

Typhoid Vaccine, 8 units per milliliter.

[41 FR 10429, Mar. 11, 1976, as amended at 41 FR 18295, May 3, 1976; 70 FR 75028, Dec. 19, 2005]

Subpart D--Mycoplasma

Sec. 610.30 Test forMycoplasma.

Except as provided otherwise in this subchapter, prior to clarification or filtration in the case of live virus vaccines produced from in vitro living cell cultures, and prior to inactivation in the case of inactivated virus vaccines produced from such living cell cultures, each virus harvest pool and control fluid pool shall be tested for the presence ofMycoplasma, as follows:

Samples of the virus for this test shall be stored either (1) between 2 and 8 deg. C for no longer than 24 hours, or (2) at -20 deg. C or lower if stored for longer than 24 hours. The test shall be performed on samples of the viral harvest pool and on control fluid pool obtained at the time of viral harvest, as follows: No less than 2.0 ml. of each sample shall be inoculated in evenly distributed amounts over the surface of no less than 10 plates of at least two agar media. No less than 1.0 ml. of sample shall be inoculated into each of four tubes containing 10 ml. of a semisolid broth medium. The media shall be such as have been shown to be capable of detecting knownMycoplasma and each test shall include control cultures of at least two known strains ofMycoplasma, one of which must beM. pneumoniae. One half of the plates and two tubes of broth shall be incubated aerobically at 36 deg. C +/-1 deg. C and the remaining plates and tubes shall be incubated anaerobically at 36 deg. C +/-1 deg. C in an environment of 5-10 percent CO2in N2. Aerobic incubation shall be for a period of no less than 14 days and the broth in the two tubes shall be tested after 3 days and 14 days, at which times 0.5 ml. of broth from each of the two tubes shall be combined and subinoculated on to no less than 4 additional plates and incubated aerobically. Anaerobic incubation shall be for no less than 14 days and the broth in the two tubes shall be tested after 3 days and 14 days, at which times 0.5 ml. of broth from each of the two tubes shall be combined and subinoculated onto no less than four additional plates and incubated anaerobically. All inoculated plates shall be incubated for no less than 14 days, at which time observation for growth ofMycoplasma shall be made at a magnification of no less than 300*. If the Dienes Methylene Blue-Azure dye or an equivalent staining procedure is used, no less than a one square cm. plug of the agar shall be excised from the inoculated area and examined for the presence ofMycoplasma. The presence of theMycoplasma shall be determined by comparison of the growth obtained from the test samples with that of the control cultures, with respect to typical colonial and microscopic morphology. The virus pool is satisfactory for vaccine manufacture if none of the tests on the samples show evidence of the presence ofMycoplasma.

[38 FR 32056, Nov. 20, 1973, as amended at 63 FR 16685, Apr. 6, 1998]

Subpart E--Testing Requirements for Communicable Disease Agents

Sec. 610.40 Test requirements.

(a)Human blood and blood components. Except as specified in paragraphs (c) and (d) of this section, you, an establishment that collects blood or blood components, must test each donation of human blood or blood component intended for use in preparing a product, including donations intended as a component of, or used to prepare, a medical device, for evidence of infection due to the following communicable disease agents:

(1) Human immunodeficiency virus, type 1;

(2) Human immunodeficiency virus, type 2;

(3) Hepatitis B virus;

(4) Hepatitis C virus;

(5) Human T-lymphotropic virus, type I; and

(6) Human T-lymphotropic virus, type II.

(b)Testing using one or more approved screening tests. To test for evidence of infection due to communicable disease agents designated in paragraph (a) of this section, you must use screening tests that the Food and Drug Administration (FDA) has approved for such use, in accordance with the manufacturer's instructions. You must perform one or more such tests as necessary to reduce adequately and appropriately the risk of transmission of communicable disease.

(c)Exceptions to testing for allogeneic transfusion or further manufacturing use --(1)Dedicated donations. (i) You must test donations of human blood and blood components from a donor whose donations are dedicated to and used solely by a single identified recipient under paragraphs (a), (b), and (e) of this section; except that, if the donor makes multiple donations for a single identified recipient, you may perform such testing only on the first donation in each 30-day period. If an untested dedicated donation is made available for any use other than transfusion to the single, identified recipient, then this exemption from the testing required under this section no longer applies.

(ii) Each donation must be labeled as required under 606.121 of this chapter and with a label entitled "INTENDED RECIPIENT INFORMATION LABEL" containing the name and identifying information of the recipient. Each donation must also have the following label, as appropriate:

Donor Testing StatusLabel
Tests negativeLabel as required under 606.121
Tested negative within the last 30 days"DONOR TESTED WITHIN THE LAST 30 DAYS"

(2)Source Plasma. You are not required to test donations of Source Plasma for evidence of infection due to the communicable disease agents listed in paragraphs (a)(5) and (a)(6) of this section.

(3)Medical device. (i) You are not required to test donations of human blood or blood components intended solely as a component of, or used to prepare, a medical device for evidence of infection due to the communicable disease agents listed in paragraphs (a)(5) and (a)(6) of this section unless the final device contains viable leukocytes.

(ii) Donations of human blood and blood components intended solely as a component of, or used to prepare, a medical device must be labeled "Caution: For Further Manufacturing Use as a Component of, or to Prepare, a Medical Device."

(4)Samples. You are not required to test samples of blood, blood components, plasma, or sera if used or distributed for clinical laboratory testing or research purposes and not intended for administration to humans or in the manufacture of a product.

(d)Autologous donations. You, an establishment that collects human blood or blood components from autologous donors, or you, an establishment that is a consignee of a collecting establishment, are not required to test donations of human blood or blood components from autologous donors for evidence of infection due to communicable disease agents listed in paragraph (a) of this section or by a serological test for syphilis under paragraph (i) of this section, except:

(1) If you allow any autologous donation to be used for allogeneic transfusion, you must assure that all autologous donations are tested under this section.

(2) If you ship autologous donations to another establishment that allows autologous donations to be used for allogeneic transfusion, you must assure that all autologous donations shipped to that establishment are tested under this section.

(3) If you ship autologous donations to another establishment that does not allow autologous donations to be used for allogeneic transfusion, you must assure that, at a minimum, the first donation in each 30-day period is tested under this section.

(4) Each autologous donation must be labeled as required under 606.121 of this chapter and with the following label, as appropriate:

Donor Testing StatusLabel
Untested"DONOR UNTESTED"
Tests negativeLabel as required under 606.121
Reactive on current collection/reactive in the last 30 days"BIOHAZARD" legend in 610.40(h)(2)(ii)(B)
Tested negative within the last 30 days"DONOR TESTED WITHIN THE LAST 30 DAYS"

(e)Further testing. You must further test each donation, including autologous donations, found to be reactive by a screening test performed under paragraphs (a) and (b) of this section, whenever a supplemental (additional, more specific) test has been approved for such use by FDA, except:

(1) For autologous donations, you must further test under this paragraph, at a minimum, the first reactive donation in each 30-day period; or

(2) If you have a record for that donor of a positive result on a supplemental (additional, more specific) test approved for such use by FDA, you do not have to further test an autologous donation.

(f)Testing responsibility. Required testing under this section, must be performed by a laboratory registered in accordance with part 607 of this chapter and either certified to perform such testing on human specimens under the Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) under 42 CFR part 493 or has met equivalent requirements as determined by the Health Care Financing Administration in accordance with those provisions.

(g)Release or shipment prior to testing. Human blood or blood components that are required to be tested for evidence of infection due to communicable disease agents designated in paragraphs (a) and (i) of this section may be released or shipped prior to completion of testing in the following circumstances provided that you label the blood or blood components under 606.121(h) of this chapter, you complete the tests for evidence of infection due to communicable disease agents as soon as possible after release or shipment, and that you provide the results promptly to the consignee:

(1) Only in appropriately documented medical emergency situations; or

(2) For further manufacturing use as approved in writing by FDA.

(h)Restrictions on shipment or use --(1)Reactive screening test. You must not ship or use human blood or blood components that have a reactive screening test for evidence of infection due to a communicable disease agent(s) designated in paragraphs (a) and (i) of this section or that are collected from a donor with a previous record of a reactive screening test for evidence of infection due to a communicable disease agent(s) designated in paragraphs (a) and (i) of this section, except as provided in paragraphs (h)(2)(i) through (h)(2)(vii) of this section.

(2)Exceptions. (i) You may ship or use blood or blood components intended for autologous use, including reactive donations, as described in paragraph (d) of this section.

(ii) You must not ship or use human blood or blood components that have a reactive screening test for evidence of infection due to a communicable disease agent(s) designated in paragraph (a) of this section or that are collected from a donor deferred under 610.41(a) unless you meet the following conditions:

(A) Except for autologous donations, you must obtain from FDA written approval for the shipment or use;

(B) You must appropriately label such blood or blood components as required under 606.121 of this chapter, and with the "BIOHAZARD" legend;

(C) Except for autologous donations, you must label such human blood and blood components as reactive for the appropriate screening test for evidence of infection due to the identified communicable disease agent(s);

(D) If the blood or blood components are intended for further manufacturing use into injectable products, you must include a statement on the container label indicating the exempted use specifically approved by FDA.

(E) Each blood or blood component with a reactive screening test and intended solely as a component of, or used to prepare a medical device, must be labeled with the following label, as appropriate:

Type of Medical DeviceLabel
A medical device other than an in vitro diagnostic reagent"Caution: For Further Manufacturing Use as a Component of a Medical Device For Which There Are No Alternative Sources"
An in vitro diagnostic reagent"Caution: For Further Manufacturing Into In Vitro Diagnostic Reagents For Which There Are No Alternative Sources"

(iii) The restrictions on shipment or use do not apply to samples of blood, blood components, plasma, or sera if used or distributed for clinical laboratory testing or research purposes, and not intended for administration in humans or in the manufacture of a product.

(iv) You may use human blood or blood components from a donor with a previous record of a reactive screening test(s) for evidence of infection due to a communicable disease agent(s) designated in paragraph (a) of this section, if:

(A) At the time of donation, the donor is shown or was previously shown to be suitable by a requalification method or process found acceptable for such purposes by FDA under 610.41(b); and

(B) tests performed under paragraphs (a) and (b) of this section are nonreactive.

(v) Anti-HBc reactive donations, otherwise nonreactive when tested as required under this section, may be used for further manufacturing into plasma derivatives without prior FDA approval or a "BIOHAZARD" legend as required under paragraphs (h)(2)(ii)(A) and (h)(2)(ii)(B) of this section.

(vi) You may use human blood or blood components, excluding Source Plasma, that test reactive by a screening test for syphilis as required under paragraph (i) of this section if, consistent with 640.5 of this chapter, the donation is further tested by an adequate and appropriate test which demonstrates that the reactive screening test is a biological false positive. You must label the blood or blood components with both test results.

(vii) You may use Source Plasma from a donor who tests reactive by a screening test for syphilis as required under 610.40(i) of this chapter, if the donor meets the requirements of 640.65(b)(2) of this chapter.

(i)Syphilis testing. In addition to the testing otherwise required under this section, you must test by a serological test for syphilis under 640.5(a), 640.14, 640.23(a), 640.33(a), 640.53(a), and 640.65(b)(1) and (b)(2) of this chapter.

[66 FR 31162, June 11, 2001, as amended at 77 FR 18, Jan. 3, 2012]

Sec. 610.41 Donor deferral.

(a) You, an establishment that collects human blood or blood components, must defer donors testing reactive by a screening test for evidence of infection due to a communicable disease agent(s) listed in 610.40(a) or reactive for a serological test for syphilis under 610.40(i), from future donations of human blood and blood components, except:

(1) You are not required to defer a donor who tests reactive for anti-HBc or anti-HTLV, types I or II, on only one occasion. When a supplemental (additional, more specific) test for anti-HBc or anti-HTLV, types I and II, has been approved for use under 610.40(e) by FDA, such a donor must be deferred;

(2) A deferred donor who tests reactive for evidence of infection due to a communicable disease agent(s) listed in 610.40(a) may serve as a donor for blood or blood components shipped or used under 610.40(h)(2)(ii);

(3) A deferred donor who showed evidence of infection due to hepatitis B surface antigen (HBsAg) when previously tested under 610.40(a), (b), and (e) subsequently may donate Source Plasma for use in the preparation of Hepatitis B Immune Globulin (Human) provided the current donation tests nonreactive for HBsAg and the donor is otherwise determined to be suitable;

(4) A deferred donor, who otherwise is determined to be suitable for donation and tests reactive for anti-HBc or for evidence of infection due to HTLV, types I and II, may serve as a donor of Source Plasma;

(5) A deferred donor who tests reactive for a communicable disease agent(s) described under 610.40(a) or reactive with a serological test for syphilis under 610.40(i), may serve as an autologous donor under 610.40(d).

(b) A deferred donor subsequently may be found to be suitable as a donor of blood or blood components by a requalification method or process found acceptable for such purposes by FDA. Such a donor is considered no longer deferred.

(c) You must comply with the requirements under 610.46 and 610.47 when a donor tests reactive by a screening test for HIV or HCV required under 610.40(a) and (b), or when you are aware of other reliable test results or information indicating evidence of HIV or HCV infection.

[66 FR 31164, June 11, 2001, as amended at 72 FR 48798, Aug. 24, 2007]

Sec. 610.42 Restrictions on use for further manufacture of medical devices.

(a) In addition to labeling requirements in subchapter H of this chapter, when a medical device contains human blood or a blood component as a component of the final device, and the human blood or blood component was found to be reactive by a screening test performed under 610.40(a) and (b) or reactive for syphilis under 610.40(i), then you must include in the device labeling a statement of warning indicating that the product was manufactured from a donation found to be reactive by a screening test for evidence of infection due to the identified communicable disease agent(s).

(b) FDA may approve an exception or alternative to the statement of warning required in paragraph (a) of this section based on evidence that the reactivity of the human blood or blood component in the medical device presents no significant health risk through use of the medical device.

[66 FR 31164, June 11, 2001]

Sec. 610.44 Use of reference panels by manufacturers of test kits.

(a) When available and appropriate to verify acceptable sensitivity and specificity, you, a manufacturer of test kits, must use a reference panel you obtain from FDA or from an FDA designated source to test lots of the following products. You must test each lot of the following products, unless FDA informs you that less frequent testing is appropriate, based on your consistent prior production of products of acceptable sensitivity and specificity:

(1) A test kit approved for use in testing donations of human blood and blood components for evidence of infection due to communicable disease agents listed in 610.40(a); and

(2) Human immunodeficiency virus (HIV) test kit approved for use in the diagnosis, prognosis, or monitoring of this communicable disease agent.

(b) You must not distribute a lot that is found to be not acceptable for sensitivity and specificity under 610.44(a). FDA may approve an exception or alternative to this requirement. Applicants must submit such requests in writing. However, in limited circumstances, such requests may be made orally and permission may be given orally by FDA. Oral requests and approvals must be promptly followed by written requests and written approvals.

[66 FR 31164, June 11, 2001]

Sec. 610.46 Human immunodeficiency virus (HIV) "lookback" requirements.

(a) If you are an establishment that collects Whole Blood or blood components, including Source Plasma and Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions:

(1) Within 3 calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection when tested under 610.40(a) and (b) or when you are made aware of other reliable test results or information indicating evidence of HIV infection, you must review all records required under 606.160(d) of this chapter, to identify blood and blood components previously donated by such a donor. For those identified blood and blood components collected:

(i) Twelve months and less before the donor's most recent nonreactive screening tests, or

(ii) Twelve months and less before the donor's reactive direct viral detection test, e.g., nucleic acid test or HIV p24 antigen test, and nonreactive antibody screening test, whichever is the lesser period, you must:

(A) Quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section if intended for use in another person or for further manufacture into injectable products, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures; and

(B) Notify consignees to quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section if intended for use in another person or for further manufacture into injectable products, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures;

(2) You must perform a supplemental (additional, more specific) test for HIV as required under 610.40(e) of this chapter on the reactive donation.

(3) You must notify consignees of the supplemental (additional, more specific) test results for HIV, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an investigational new drug application (IND) or investigational device exemption (IDE), is exempted for such use by FDA, within 45 calendar days after the donor tests reactive for evidence of HIV infection under 610.40(a) and (b) of this chapter. Notification of consignees must include the test results for blood and blood components identified under paragraph (a)(1) of this section that were previously collected from donors who later test reactive for evidence of HIV infection.

(4) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components, consistent with the results of the supplemental (additional, more specific) test performed under paragraph (a)(2) of this section or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, exempted for such use by FDA.

(b) If you are a consignee of Whole Blood or blood components, including Source Plasma and Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions:

(1) You must quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures, when notified by the collecting establishment.

(2) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components consistent with the results of the supplemental (additional, more specific) test performed under paragraph (a)(2) of this section, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, is exempted for such use by FDA.

(3) When the supplemental (additional, more specific) test for HIV is positive or when the screening test is reactive and there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE is exempted for such use by FDA, you must notify transfusion recipients of previous collections of blood and blood components at increased risk of transmitting HIV infection, or the recipient's physician of record, of the need for recipient HIV testing and counseling. You must notify the recipient's physician of record or a legal representative or relative if the recipient is a minor, deceased, adjudged incompetent by a State court, or, if the recipient is competent but State law permits a legal representative or relative to receive information on behalf of the recipient. You must make reasonable attempts to perform the notification within 12 weeks after receiving the supplemental (additional, more specific) test results for evidence of HIV infection from the collecting establishment, or after receiving the donor's reactive screening test result for HIV if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE is exempted for such use by FDA.

(c) Actions under this section do not constitute a recall as defined in 7.3 of this chapter.

[72 FR 48799, Aug. 24, 2007]

Sec. 610.47 Hepatitis C virus (HCV) "lookback" requirements.

(a) If you are an establishment that collects Whole Blood or blood components, including Source Plasma and Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions:

(1) Within 3 calendar days after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under 610.40(a) and (b) of this chapter or when you are made aware of other reliable test results or information indicating evidence of HCV infection, you must review all records required under 606.160(d) of this chapter, to identify blood and blood components previously donated by such a donor. For those identified blood and blood components collected:

(i) Twelve months and less before the donor's most recent nonreactive screening tests, or

(ii) Twelve months and less before the donor's reactive direct viral detection test, e.g., nucleic acid test and nonreactive antibody screening test, whichever is the lesser period, you must:

(A) Quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section if intended for use in another person or for further manufacture into injectable products, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures; and

(B) Notify consignees to quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section if intended for use in another person or for further manufacture into injectable products, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures;

(2) You must perform a supplemental (additional, more specific) test for HCV as required under 610.40(e) on the reactive donation.

(3) You must notify consignees of the supplemental (additional, more specific) test results for HCV, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an investigational new drug application (IND) or investigational device exemption (IDE), is exempted for such use by FDA, within 45 calendar days after the donor tests reactive for evidence of HCV infection under 610.40(a) and (b). Notification of consignees must include the test results for blood and blood components identified under paragraph (a)(1) of this section that were previously collected from donors who later test reactive for evidence of HCV infection.

(4) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components consistent with the results of the supplemental (additional, more specific) test performed under paragraph (a)(2) of this section, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, exempted for such use by FDA.

(b) If you are a consignee of Whole Blood or blood components, including Source Plasma or Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions:

(1) You must quarantine all previously collected in-date blood and blood components identified under paragraph (a)(1) of this section, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures, when notified by the collecting establishment.

(2) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components, consistent with the results of the supplemental (additional, more specific) test performed under paragraph (a)(2) of this section, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, is exempted for such use by FDA.

(3) When the supplemental (additional, more specific) test for HCV is positive or when the screening test is reactive and there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, is exempted for such use by FDA, you must notify transfusion recipients of previous collections of blood and blood components at increased risk of transmitting HCV infection, or the recipient's physician of record, of the need for recipient HCV testing and counseling. You must notify the recipient's physician of record or a legal representative or relative if the recipient is a minor, adjudged incompetent by a State court, or if the recipient is competent but State law permits a legal representative or relative to receive information on behalf of the recipient. You must make reasonable attempts to perform the notification within 12 weeks after receiving the supplemental (additional, more specific) test results for evidence of HCV infection from the collecting establishment, or after receiving the donor's reactive screening test result for HCV if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, is exempted for such use by FDA.

(c) Actions under this section do not constitute a recall as defined in 7.3 of this chapter.

[72 FR 48799, Aug. 24, 2007]

Sec. 610.48 Hepatitis C virus (HCV) "lookback" requirements based on review of historical testing records.

(a) Establishments that collect Whole Blood or blood components, including Source Plasma and Source Leukocytes, must complete the following actions by February 19, 2009.

(b) If you are an establishment that collects Whole Blood or blood components, including Source Plasma and Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions:

(1) You must:

(i) Review all records of donor testing for hepatitis C virus (HCV) performed before February 20, 2008. The review must include records dating back indefinitely for computerized electronic records, and to January 1, 1988, for all other records. Record review, quarantine, testing, notification, and disposition performed before February 20, 2008 that otherwise satisfy the requirements under 610.47, are exempt from this section.

(ii) Identify donors who tested reactive for evidence of HCV infection. Donors who tested reactive by a screening test and negative by an appropriate supplemental (additional, more specific) test under 610.40(e) for evidence of HCV infection on the same donation are not subject to further action.

(iii) Identify the blood and blood components previously collected from such donors:

(A) Twelve months and less before the donor's most recent nonreactive screening tests, or

(B) Twelve months and less before the donor's reactive direct viral detection test, e.g., nucleic acid test and nonreactive antibody screening test, whichever is the lesser period.

(2) If you did not perform a supplemental (additional, more specific) test at the time of the reactive donation, you may perform a supplemental test or a licensed screening test with known greater sensitivity than the test of record using either a frozen sample from the same reactive donation or a fresh sample from the same donor, if obtainable. If neither is available, proceed with paragraphs (b)(3), (b)(4), and (b)(5) of this section.

(3) You must, within 3 calendar days after identifying the blood and blood components previously collected from donors who tested reactive for evidence of HCV infection:

(i) Quarantine all previously collected in-date blood and blood components identified under paragraph (b)(1)(iii) of this section if intended for use in another person or for further manufacture into injectable products, except pooled components solely intended for further manufacturing into products that are manufactured using validated viral clearance procedures.

(ii) Notify consignees to quarantine all previously collected in-date blood and blood components identified under paragraph (b)(1)(iii) of this section if intended for use in another person or for further manufacture into injectable products, except pooled blood components intended solely for further manufacturing into products that are manufactured using validated viral clearance procedures; and

(iii) Notify consignees of the donor's test results, including the results of a supplemental (additional, more specific) test or a licensed screening test with known greater sensitivity than the test of record, if available at that time.

(4) You must notify consignees of the results of the supplemental (additional, more specific) test or the licensed screening test with known greater sensitivity than the test of record for HCV, if performed, within 45 calendar days of completing the further testing. Notification of consignees must include the test results for blood and blood components identified under paragraph (b)(1)(iii) of this section that were previously collected from a donor who later tests reactive for evidence of HCV infection.

(5) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components consistent with the results of the further testing performed under paragraph (b)(2) of this section or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an investigational new drug application (IND) or investigational device exemption (IDE), is exempted for such use by FDA.

(c) If you are a consignee of Whole Blood or blood components, including Source Plasma and Source Leukocytes, you must establish, maintain, and follow an appropriate system for the following actions, which you must complete within 1 year of the date of notification by the collecting establishment:

(1) You must quarantine all previously collected in-date blood and blood components identified under paragraph (b)(1)(iii) of this section, except pooled blood components solely intended for further manufacturing into products that are manufactured using validated viral clearance procedures, when notified by the collecting establishment.

(2) You must release from quarantine, destroy, or relabel quarantined in-date blood and blood components, consistent with the results of the further testing performed under paragraph (b)(2) of this section, or the results of the reactive screening test if there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE is exempted for such use by FDA.

(3) When the supplemental (additional, more specific) test for HCV is positive; or the supplemental test is indeterminate, but the supplemental test is known to be less sensitive than the screening test; or the screening test is reactive and there is no available supplemental test that is approved for such use by FDA, or if under an IND or IDE, is exempted for such use by FDA; or if supplemental testing is not performed, you must make reasonable attempts to notify transfusion recipients of previous collections of blood and blood components at increased risk of transmitting HCV infection, or the recipient's physician of record, of the need for recipient HCV testing and counseling. You must notify the recipient's physician of record or a legal representative or relative if the recipient is a minor, adjudged incompetent by a State court, or if the recipient is competent but State law permits a legal representative or relative to receive information on behalf of the recipient.

(d) Actions under this section do not constitute a recall as defined in 7.3 of this chapter.

(e) This section will expire on August 24, 2015.

[72 FR 48800, Aug. 24, 2007]

Subpart F--Dating Period Limitations

Sec. 610.50 Date of manufacture.

The date of manufacture shall be determined as follows:

(a) For products for which an official standard of potency is prescribed in either 610.20 or 610.21, or which are subject to official potency tests, the date of initiation by the manufacturer of the last valid potency test.

(b) For products that are not subject to official potency tests, (1) the date of removal from animals, (2) the date of extraction, (3) the date of solution, (4) the date of cessation of growth, or (5) the date of final sterile filtration of a bulk solution, whichever is applicable.

[38 FR 32056, Nov. 20, 1973, as amended at 42 FR 27582, May 31, 1977]

Sec. 610.53 Dating periods for licensed biological products.

(a)General. The minimum dating periods in paragraph (c) of this section are based on data relating to usage, clinical experience, or laboratory tests that establish the reasonable period beyond which the product cannot be expected to yield its specific results and retain its safety, purity, and potency, provided the product is maintained at the recommended temperatures. The standards prescribed by the regulations in this subchapter are designed to ensure the continued safety, purity, and potency of the products and are based on the dating periods set forth in paragraph (c) of this section. Package labels for each product shall recommend storage at the stated temperatures.

(b)When the dating period begins. The dating period for a product shall begin on the date of manufacture, as prescribed in 610.50. The dating period for a combination of two or more products shall be no longer than the dating period of the component with the shortest dating period.

(c)Table of dating periods. In using the table in this paragraph, a product in column A may be stored by the manufacturer at the prescribed temperature and length of time in either column B or C, plus the length of time in column D. The dating period in column D shall be applied from the day the product leaves the manufacturer's storage, provided the product has not exceeded its maximum storage period, as prescribed in column B or C. If a product is held in the manufacturer's storage beyond the period prescribed, the dating period for the product being distributed shall be reduced by a corresponding period.

ABCD
ProductManufacturer's storage period 1 to 5 deg. C (unless otherwise stated)Manufacturer's storage period 0 deg. C or colder (unless otherwise stated)Dating period after leaving manufacturer's storage when stored at 2 to 8 deg. C (unless otherwise stated)
Adenovirus Vaccine Live Oral6 monthsNot applicable6 months.
Albumin (Human)3 years......do(a) 5 years.
......do......do(b) 3 years, provided labeling recommends storage at room temperature, no warmer than 37 deg. C.
Not applicable......do(c) 10 years, if in a hermetically sealed metal container and provided labeling recommends storage between 2 and 8 deg. C.
Allergenic Extracts labeled "No U.S. Standard of Potency":
1. With 50 percent or more glycerin3 years......do3 years.
2. With less than 50 percent glycerin18 months......do18 months.
3. Products for which cold storage conditions are inappropriateNot applicable......do18 months (from date of manufacture), provided labeling recommends storage at 30 deg. C or colder.
4. Powders and tablets......do......do5 years (from date of manufacture), provided labeling recommends storage at 30 deg. C or colder.
5. Freeze-dried products:
a. Unreconstituted......do......do4 years (from date of manufacture).
b. Reconstituted......do......do18 months (cannot exceed 4-year unreconstituted dating period plus an additional 12 months).
Allergenic Extracts, Alum Precipitated labeled "No U.S. Standard of Potency"18 months......do18 months.
Anthrax Vaccine Adsorbed2 years......do1 year.
Antibody to Hepatitis B Surface Antigen:
1. Antibody to Hepatitis B Surface Antigen6 months......do6 months.
2. Lyophilized coated red blood cells......do......do Do.
3. Enzyme conjugated products......do......do Do.
Iodinated (125l) productsNot applicable......do45 days (from date of manufacture).
Antihemophilic Factor (Human)......do......do1 year (from date of manufacture).
Anti-Human Globulin Liquid......do......do2 years.
Anti-Inhibitor Coagulant Complex......do......do Do.
Antirabies Serum1 year......do Do.
Antivenin (Crotalidae) Polyvalent......do......do5 years with an initial 10 percent excess of potency, provided labeling recommends storage at 37 deg. C or colder.
Antivenin (Latrodectus Mactans)......do......do5 years with an initial 10 percent excess of potency.
Antivenin (Micurus fulvius)......do......do Do.
AsparaginaseNot applicable......do18 months from the date of the last valid potency test.
BCG Vaccine1 yearNot applicable6 months.
Blood Grouping Reagents
1. LiquidNot applicableNot applicable2 years.
2. Dried1 year2 years5 years.
Blood Group Substance AB......do......do2 years.
Blood Group Substance A......do......do Do.
Blood Group Substance B......do......do Do.
Botulism Antitoxin......doNot applicable5 years with an initial 20 percent excess of potency.
Cholera Vaccine......do......do18 months.
Coccidioidin......do......do3 years.
CollagenaseNot applicable......do4 years (from date of manufacture), provided labeling recommends storage at 37 deg. C or colder.
Cryoprecipitated AHF......do......do12 months from the date of collection of source blood, provided labeling recommends storage at -18 deg. C or colder.
Diphtheria Antitoxin:
1. Liquid1 year......do5 years with an initial 20 percent excess of potency.
2. Dried......do2 years5 years with an initial 10 percent excess of potency.
Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed......doNot applicable18 months.
Diphtheria and Tetanus Toxoids, Adsorbed......do......do2 years.
Diphtheria Toxin for Schick Test......do......do1 year.
Diphtheria Toxoid......do......do2 years.
Diphtheria Toxoid Adsorbed......do2 years Do.
Diphtheria Toxoid-Schick Test ControlNot applicableNot applicable1 year.
Factor IX Complex......do......do1 year (from date of manufacture).
Fibrinolysin (Human)1 year2 years2 years.
Fibrinolysin and Desoxyribonuclease Combined (Bovine)......do......do3 years, provided labeling recommends storage at 30 deg. C or colder.
Fibrinolysin and Desoxyribonuclease Combined (Bovine) with Chloramphenicol......do......do Do.
Hepatitis B Surface Antigen:
1. Unlyophilized coated red blood cellsNot applicable......do14 days (from date of manufacture).
2. Iodinated (125l) product......do......do45 days (from date of manufacture).
3. Enzyme conjugated product6 months......do6 months.
Histoplasmin1 yearNot applicable2 years.
Immunoglobulins:
1. Hepatitis B Immune Globulin (Human)Not applicable......do1 year.
2. Immune Globulin (Human)3 years......do3 years.
3. Immune Globulin Intravenous (Human)Not applicable......do1 year.
4. Lymphocyte Immune Globulin, Anti-Thymocyte Globulin (Equine)......doNot applicable2 years.
5. Pertussis Immune Globulin (Human)3 years......do3 years from date the dried or frozen bulk product is placed in final solution.
6. Rabies Immune Globulin (Human)1 year......do1 year.
7. Rho(D) Immune Globulin (Human)6 months......do6 months.
8. Tetanus Immune Globulin (Human)1 year......do3 years with an initial 10 percent excess of potency.
9. Vaccinia Immune Globulin (Human)3 years......do3 years.
10. Varicella-Zoster Immune Globulin (Human)Not applicable......do1 year.
Hepatitis B Vaccine2 years at 2 to 8 deg. CNot applicable3 years.
Influenza Virus Vaccine1 year......do18 months.
Limulus Amebocyte LysateNot applicableNot applicable18 months (from date of manufacture).
Measles, Mumps, and Rubella Virus Vaccine Live......do1 year (-20 deg. C or colder)1 year.
Measles and Mumps Virus Vaccine Live......do......do1 year.
Measles and Rubella Virus Vaccine Live......do......do Do.
Measles Live and Smallpox VaccineNot applicable......do1 year (from date of manufacture).
Measles Virus Vaccine Live......do......do1 year.
Meningococcal Polysaccharide Vaccine Group A:
1. Final bulk powder......do2 years (-20 deg. C or colder)Not applicable.
2. Final containerNot applicable3 years (-20 deg. C or colder)2 years.
Meningococcal Polysaccharide Vaccine Group C:
1. Final bulk powder......do2 years (-20 deg. C or colder)Not applicable.
2. Final container......do3 years (-20 deg. C or colder)2 years.
Meningococcal Polysaccharide Vaccine Groups A and C combined:
1. Final bulk powder......do2 years (-20 deg. C or colder)Not applicable.
2. Final container......do3 years (-20 deg. C or colder)2 years.
Meningococcal Polysaccharide Vaccine Groups A, C, Y, and W135 combined:
1. Final bulk power......do2 years (-20 deg. C or colder)Not applicable.
2. Final container......do3 years (-20 deg. C or colder)2 years.
Mumps Skin Test Antigen6 monthsNot applicable18 months.
Mumps Virus Vaccine LiveNot applicable1 year (-20 deg. C or colder)1 year.
Normal Horse Serum1 year2 years5 years.
Pertussis Vaccine......doNot applicable18 months.
Pertussis Vaccine Adsorbed......do......do Do.
Plague Vaccine......do......do Do.
Plasma products:
1. Fresh Frozen PlasmaNot applicable......do1 year from date of collection of source blood (-18 deg. C or colder).
2. Liquid Plasma......do......do(a) 26 days from date of collection of source blood (between 1 and 6 deg. C).
(b) 40 days from date of collection of source blood only when CPDA-1 solution is used as the anticoagulant (between 1 and 6 deg. C).
3. Plasma......do......do5 years from date of collection of source blood (-18 deg. C or colder).
4. Platelet Rich Plasma......do......do72 hours from time of collection of source blood, provided labeling recommends storage (20 to 24 deg. C or between 1 and 6 deg. C). 5 days if certain approved containers are used (20 to 24 deg. C).
5. Source Leukocytes......do......doIn lieu of expiration date, the collection date shall appear on the label.
6. Source Plasma......do......do10 years (at the recommended storage temperature stated on the label).
7. Therapeutic Exchange Plasma......do......do10 years.
Plasma Protein Fraction (Human)1 year......do(a) 5 years.(b) 3 years provided labeling recommends storage at room temperature, no warmer than 30 deg. C).
PlateletsNot applicable......do72 hours from time of collection of source blood, provided labeling recommends storage at 20 to 24 deg. C or between 1 and 6 deg. C, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, Center for Biologics Evaluation and Research (CBER).
Pneumococcal Vaccine Polyvalent:
1. Final bulk powder......do24 months after potency assay (-20 deg. C or colder)Not applicable.
2. Final container......doNot applicable2 years (from date of manufacture).
Poliovirus Vaccine Inactivated1 year......do1 year.
Poliovirus Vaccine Live Oral Trivalent:
1. FrozenNot applicable1 year (-10 deg. C or colder)1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state.
2. Liquid......doNot applicable30 days, provided labeling recommends storage between 2 and 8 deg. C and container has been unopened.
Poliovirus Vaccine Live Oral Type I:
1. Frozen......do1 year (-10 deg. C or colder)1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state.
2. Liquid......doNot applicable30 days, provided labeling recommends storage between 2 and 8 deg. C and container has been unopened.
Poliovirus Vaccine Live Oral Type II:
1. Frozen......do1 year (-10 deg. C or colder)1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state.
2. Liquid......doNot applicable30 days, provided labeling recommends storage between 2 and 8 deg. C and container has been unopened.
Poliovirus Vaccine Live Oral Type III:
1. Frozen......do1 year (-10 deg. C or colder)1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state.
2. Liquid......doNot applicable30 days, provided labeling recommends storage between 2 and 8 deg. C and container has been unopened.
Polyvalent bacterial antigens with "No U.S. Standard of Potency" liquid1 year......do18 months.
Polyvalent bacterial vaccines with "No U.S. Standard of Potency" liquid......do......do Do.
Rabies Vaccine:
1. Dried......do2 years Do.
2. Liquid3 monthsNot applicable6 months.
Reagent red blood cellsNot applicableNot applicableThirty-five days from earliest date of collection if kept in liquid form (indefinite storage of reagent red blood cell source material at -65 deg. C or colder).
ACD Red Blood Cells......do......do(a) 21 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is broken during processing.
CPD Red Blood Cells......do......do(a) 21 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is broken during processing.
CPDA-1 Red Blood Cells......do......do(a) 35 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 deg. C and the hermetic seal is broken during processing.
Red Blood Cells Deglycerolized......do......do24 hours after removal from storage at -65 deg. C or colder, provided labeling recommends storage between 1 and 6 deg. C, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, CBER.
Red Blood Cells Frozen......do......do10 years from date of collection of source blood, provided labeling recommends storage at -65 deg. C or colder, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, CBER.
Rubella and Mumps Virus Vaccine Live......do1 year (-20 deg. C or colder)1 year.
Rubella Virus Vaccine Live......do......do Do.
Skin Test Antigens for Cellular Hypersensitivity6 monthsNot applicable Do.
Smallpox Vaccine:
1. LiquidNot applicable9 months (-10 deg. C or colder, if product is maintained as glycerinated or equivalent vaccine in bulk or final containers)3 months, provided labeling recommends storage at 0 deg. C or colder.
2. Dried6 monthsNot applicable18 months.
StreptokinaseNot applicable......do Do.
Tetanus and Diphtheria Toxoids Adsorbed for Adult Use1 year......do2 years.
Tetanus Antitoxin:
1. Liquid......do......do5 years with an initial 20 percent excess or potency.
2. Dried......do2 years5 years with an initial 10 percent excess or potency.
Tetanus Toxoid......doNot applicable2 years.
Tetanus Toxoid Adsorbed......do......do Do.
Thrombin......do2 year3 years.
Thrombin Impregnated PadNot applicableNot applicable1 year, or 6 months at 20 to 24 deg. C.
Tuberculin:
1. Purified Protein Derivative, diluted6 months......do1 year.
2. Old or Purified Protein Derivative dried on multiple puncture device1 year (not to exceed 30 deg. C; do not refrigerate)......do2 years, provided labeling recommends storage at a temperature not to exceed 30 deg. C. Do not refrigerate.
3. Old on multiple puncture device......do......do Do.
Typhoid Vaccine1 year......do18 months.
ACD Whole BloodNot applicable......do21 days from date of collection, provided labeling recommends storage between 1 and 6 deg. C.
CPD Whole Blood......do......do Do.
CPDA-1 Whole Blood......do......do35 days from date of collection, provided labeling recommends storage between 1 and 6 deg. C.
Heparin Whole Blood......do......do48 hours from date of collection, provided labeling recommends storage between 1 and 6 deg. C.
Yellow Fever Vaccine......do1 year (-20 deg. C or colder)1 year, provided labeling recommends storage at 5 deg. C or colder.

(d)Exemptions. Exemptions or modifications shall be made only upon written approval, in the form of a supplement to the biologics license application, issued by the Director, Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research.

[50 FR 4134, Jan. 29, 1985, as amended at 51 FR 15607, Apr. 25, 1986; 51 FR 19750, June 2, 1986; 52 FR 37450, Oct. 7, 1987; 53 FR 12764, Apr. 19, 1988; 62 FR 15110, Mar. 31, 1997; 64 FR 56453, Oct. 20, 1999; 70 FR 14985, Mar. 24, 2005; 72 FR 45887, Aug. 16, 2007; 72 FR 54208, Sept. 24, 2007; 73 FR 49942, Aug. 25, 2008]

Subpart G--Labeling Standards

Sec. 610.60 Container label.

(a)Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a full label:

(1) The proper name of the product;

(2) The name, address, and license number of manufacturer;

(3) The lot number or other lot identification;

(4) The expiration date;

(5) The recommended individual dose, for multiple dose containers.

(6) The statement: "`Rx only'" for prescription biologicals.

(7) If a Medication Guide is required under part 208 of this chapter, the statement required under 208.24(d) of this chapter instructing the authorized dispenser to provide a Medication Guide to each patient to whom the drug is dispensed and stating how the Medication Guide is provided, except where the container label is too small, the required statement may be placed on the package label.

(b)Package label information. If the container is not enclosed in a package, all the items required for a package label shall appear on the container label.

(c)Partial label. If the container is capable of bearing only a partial label, the container shall show as a minimum the name (expressed either as the proper or common name), the lot number or other lot identification and the name of the manufacturer; in addition, for multiple dose containers, the recommended individual dose. Containers bearing partial labels shall be placed in a package which bears all the items required for a package label.

(d)No container label. If the container is incapable of bearing any label, the items required for a container label may be omitted, provided the container is placed in a package which bears all the items required for a package label.

(e)Visual inspection. When the label has been affixed to the container a sufficient area of the container shall remain uncovered for its full length or circumference to permit inspection of the contents.

[38 FR 32056, Nov. 20, 1973, as amended at 47 FR 22518, May 25, 1982; 63 FR 66400, Dec. 1, 1998; 67 FR 4907, Feb. 1, 2002]

Sec. 610.61 Package label.

The following items shall appear on the label affixed to each package containing a product:

(a) The proper name of the product;

(b) The name, address, and license number of manufacturer;

(c) The lot number or other lot identification;

(d) The expiration date;

(e) The preservative used and its concentration, or if no preservative is used and the absence of a preservative is a safety factor, the words "no preservative";

(f) The number of containers, if more than one;

(g) The amount of product in the container expressed as (1) the number of doses, (2) volume, (3) units of potency, (4) weight, (5) equivalent volume (for dried product to be reconstituted), or (6) such combination of the foregoing as needed for an accurate description of the contents, whichever is applicable;

(h) The recommended storage temperature;

(i) The words "Shake Well", "Do not Freeze" or the equivalent, as well as other instructions, when indicated by the character of the product;

(j) The recommended individual dose if the enclosed container(s) is a multiple-dose container;

(k) The route of administration recommended, or reference to such directions in an enclosed circular;

(l) Known sensitizing substances, or reference to an enclosed circular containing appropriate information;

(m) The type and calculated amount of antibiotics added during manufacture;

(n) The inactive ingredients when a safety factor, or reference to an enclosed circular containing appropriate information;

(o) The adjuvant, if present;

(p) The source of the product when a factor in safe administration;

(q) The identity of each microorganism used in manufacture, and, where applicable, the production medium and the method of inactivation, or reference to an enclosed circular containing appropriate information;

(r) Minimum potency of product expressed in terms of official standard of potency or, if potency is a factor and no U.S. standard of potency has been prescribed, the words "No U.S. standard of potency."

(s) The statement: "`Rx only'" for prescription biologicals.

[38 FR 32056, Nov. 20, 1973, as amended at 47 FR 22518, May 25, 1982; 55 FR 10423, Mar. 21, 1990; 67 FR 4907, Feb. 1, 2002]

Sec. 610.62 Proper name; package label; legible type.

(a)Position. The proper name of the product on the package label shall be placed above any trademark or trade name identifying the product and symmetrically arranged with respect to other printing on the label.

(b)Prominence. The point size and typeface of the proper name shall be at least as prominent as the point size and typeface used in designating the trademark and trade name. The contrast in color value between the proper name and the background shall be at least as great as the color value between the trademark and trade name and the background. Typography, layout, contrast, and other printing features shall not be used in a manner that will affect adversely the prominence of the proper name.

(c)Legible type. All items required to be on the container label and package label shall be in legible type. "Legible type" is type of a size and character which can be read with ease when held in a good light and with normal vision.

Sec. 610.63 Divided manufacturing responsibility to be shown.

If two or more licensed manufacturers participate in the manufacture of a biological product, the name, address, and license number of each must appear on the package label, and on the label of the container if capable of bearing a full label.

[64 FR 56453, Oct. 20, 1999]

Sec. 610.64 Name and address of distributor.

The name and address of the distributor of a product may appear on the label provided that the name, address, and license number of the manufacturer also appears on the label and the name of the distributor is qualified by one of the following phrases: "Manufactured for _____", "Distributed by ______", "Manufactured by _____ for _____", "Manufactured for _____ by ____", "Distributor: _____", or "Marketed by _____". The qualifying phrases may be abbreviated.

[61 FR 57330, Nov. 6, 1996]

Sec. 610.65 Products for export.

Labels on packages or containers of products for export may be adapted to meet specific requirements of the regulations of the country to which the product is to be exported provided that in all such cases the minimum label requirements prescribed in 610.60 are observed.

Sec. 610.67 Bar code label requirements.

Biological products must comply with the bar code requirements at 201.25 of this chapter. However, the bar code requirements do not apply to devices regulated by the Center for Biologics Evaluation and Research or to blood and blood components intended for transfusion. For blood and blood components intended for transfusion, the requirements at 606.121(c)(13) of this chapter apply instead.

[69 FR 9171, Feb. 26, 2004]

Sec. 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile.

(a) The appropriate FDA Center Director may grant an exception or alternative to any provision listed in paragraph (f) of this section and not explicitly required by statute, for specified lots, batches, or other units of a biological product, if the Center Director determines that compliance with such labeling requirement could adversely affect the safety, effectiveness, or availability of such product that is or will be included in the Strategic National Stockpile.

(b)(1)(i) A Strategic National Stockpile official or any entity that manufactures (including labeling, packing, relabeling, or repackaging), distributes, or stores a biological product that is or will be included in the Strategic National Stockpile may submit, with written concurrence from a Strategic National Stockpile official, a written request for an exception or alternative described in paragraph (a) of this section to the Center Director.

(ii) The Center Director may grant an exception or alternative described in paragraph (a) of this section on his or her own initiative.

(2) A written request for an exception or alternative described in paragraph (a) of this section must:

(i) Identify the specified lots, batches, or other units of the biological product that would be subject to the exception or alternative;

(ii) Identify the labeling provision(s) listed in paragraph (f) of this section that are the subject of the exception or alternative request;

(iii) Explain why compliance with such labeling provision(s) could adversely affect the safety, effectiveness, or availability of the specified lots, batches, or other units of the biological product that are or will be included in the Strategic National Stockpile;

(iv) Describe any proposed safeguards or conditions that will be implemented so that the labeling of the product includes appropriate information necessary for the safe and effective use of the product, given the anticipated circumstances of use of the product;

(v) Provide a draft of the proposed labeling of the specified lots, batches, or other units of the biological product subject to the exception or alternative; and

(vi) Provide any other information requested by the Center Director in support of the request.

(c) The Center Director must respond in writing to all requests under this section.

(d) A grant of an exception or alternative under this section will include any safeguards or conditions deemed appropriate by the Center Director so that the labeling of product subject to the exception or alternative includes the information necessary for the safe and effective use of the product, given the anticipated circumstances of use.

(e) If you are a sponsor receiving a grant of a request for an exception or alternative to the labeling requirements under this section:

(1) You need not submit a supplement under 601.12(f)(1) through (f)(2) of this chapter; however,

(2) You must report any grant of a request for an exception or alternative under this section as part of your annual report under 601.12(f)(3) of this chapter.

(f) The Center Director may grant an exception or alternative under this section to the following provisions of this chapter, to the extent that the requirements in these provisions are not explicitly required by statute:

(1) 610.60;

(2) 610.61(c) and (e) through (r);

(3) 610.62;

(4) 610.63;

(5) 610.64;

(6) 610.65; and

(7) 312.6.

[72 FR 73600, Dec. 28, 2007]

Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 264.
Source: 38 FR 32056, Nov. 20, 1973, unless otherwise noted.

-
-