21 C.F.R. PART 680—ADDITIONAL STANDARDS FOR MISCELLANEOUS PRODUCTS
Title 21 - Food and Drugs
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42 U.S.C. 216, 262, 263, 263a, 264.
Source: 38 FR 32100, Nov. 20, 1973, unless otherwise noted. 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. (a) Definition. Allergenic Products are products that are administered to man for the diagnosis, prevention or treatment of allergies. (b) Source materials—(1) Criteria for source material. Only specifically identified allergenic source materials that contain no more than a total of 1.0 percent of detectable foreign materials shall be used in the manufacture of Allergenic Products, except that this requirement shall not apply to molds and animals described under paragraphs (b) (2) and (3) of this section, respectively. Source materials such as pelts, feathers, hairs, and danders shall be collected in a manner that will minimize contamination of the source material. (2) Molds. (i) Molds (excluding rusts and smuts) used as source material in the manufacture of Allergenic Products shall meet the requirements of §610.18 of this chapter and §680.2 (a) and (b). (ii) Mold cultures shall be free of contaminating materials (including microorganisms) prior to harvest, and care shall be taken to minimize contamination during harvest and subsequent processing. (iii) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified individual, that will ensure the identity of the seed culture, prescribe adequate processing of the mold, and specify the acceptable limits and kinds of contamination. These limits shall be based on results of appropriate tests performed by the manufacturer on at least three consecutive lots of a mold that is a representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the standard operating procedures and test data from the three representative lots described above shall be submitted to and approved by the Director, Center for Biologics Evaluation and Research (see mailing addresses in §600.2). (3) Mammals and birds—(i) Care of animals. Animals intended as a source material for Allergenic Products shall be maintained by competent personnel in facilities or designated areas that will ensure adequate care. Competent veterinary care shall be provided as needed. (ii) Health of animals. Only animals in good health and free from detectable skin diseases shall be used as a source material for Allergenic Products. The determination of good health prior to collection of the source material shall be made by a licensed veterinarian or a competent individual under the supervision and instruction of a licensed veterinarian provided that the licensed veterinarian certifies in writing that the individual is capable of determining the good health of the animals. (iii) Immunization against tetanus. Animals of the equine genus intended as a source material for Allergenic Products shall be treated to maintain immunity to tetanus. (iv) Reporting of certain diseases. In cases of actual or suspected infection with foot and mouth disease, glanders, tetanus, anthrax, gas gangrene, equine infectious anemia, equine encephalomyelitis, or any of the pock diseases among animals intended for use or used as source material in the manufacture of allergenic Products, the manufacturer shall immediately notify the Director, Center for Biologics Evaluation and Research (see mailing addresses in §600.2). (v) Dead animals. Dead animals may be used as source material in the manufacture of Allergenic Products: Provided, That (a) the carcasses shall be frozen or kept cold until the allergen can be collected, or shall be stored under other acceptable conditions so that the postmortal decomposition processes do not adversely affect the allergen, and (b) when alive, the animal met the applicable requirements prescribed in paragraphs (b)(3) (i), (ii), and (iii) of this section. (vi) Mammals and birds inspected by the U.S. Department of Agriculture. Mammals and birds, subject to inspection by the U.S. Department of Agriculture at the time of slaughter and found suitable as food, may be used as a source material, and the requirements of paragraph (b)(3) (i) through (iv) of this section do not apply in such a case. Notwithstanding U.S. Department of Agriculture inspection, the carcasses of such inspected animals shall be frozen or kept cold until the allergen is collected, or shall be stored under other acceptable conditions so that the postmortal decomposition processes do not adversely affect the allergen. (c) Listing of source materials and suppliers. Each licensed manufacturer shall initially list with the Director, Center for Biologics Evaluation and Research (see mailing addresses in §600.2), the name and address of each of the manufacturer's source material suppliers. The listing shall identify each source material obtained from each source material supplier. The licensed manufacturers shall update the listing annually to include new source material suppliers or to delete those no longer supplying source materials. (d) Exemptions. (1) Exemptions or modifications from the requirements under paragraph (b) of this section shall be made only upon written approval by the Director, Center for Biologics Evaluation and Research. (2) Nonlicensed source material suppliers are exempt from drug registration. [38 FR 32100, Nov. 20, 1973, as amended at 49 FR 25432, June 21, 1984; 49 FR 31395, Aug. 7, 1984; 55 FR 11014, Mar. 26, 1990; 67 FR 9587, Mar. 4, 2002; 70 FR 14986, Mar. 24, 2005] (a) Extraneous allergenic substances. All manufacturing steps shall be performed so as to insure that the product will contain only the allergenic and other substances intended to be included in the final product. (b) Cultures derived from microorganisms. Culture media into which organisms are inoculated for the manufacture of Allergenic Products shall contain no allergenic substances other than those necessary as a growth requirement. Neither horse protein nor any allergenic derivative of horse protein shall be used in culture media. (c) Liquid products for oral administration. Liquid products intended for oral administration that are filled in multiple dose final containers shall contain a preservative in a concentration adequate to inhibit microbial growth. (d) Residual pyridine. Products for which pyridine is used in manufacturing shall have no more residual pyridine in the final product than 25 micrograms per milliliter. (e) [Reserved] (f) Records. A record of the history of the manufacture or propagation of each lot of source material intended for manufacture of final Allergenic Products shall be available at the establishment of the manufacturer of the source material, as required by §211.188 of this chapter. A summary of the history of the manufacture or propagation of the source material shall be available at the establishment of the manufacturer of the final product. [38 FR 32100, Nov. 20, 1973, as amended at 49 FR 25433, June 21, 1984; 67 FR 9587, Mar. 4, 2002] (a) Identity. When a specific identity test meeting the provisions of §610.14 of this chapter cannot be performed, the manufacture of each lot shall be separated from the manufacture of other products in a manner that will preclude adulteration, and records made in the course of manufacture shall be in sufficient detail to verify the identity of the product. (b) Safety. A safety test shall be performed on the contents of a final container of each lot of each product as prescribed in §610.11 of this chapter, except for the following: (1) For lots consisting of no more than 20 final containers or 20 sets of individual dilutions, or where the final container contains no more than one intended human dose, the safety test need not be performed on the contents of a final container provided the safety test is performed on each lot of stock concentrate and on each lot of diluent contained in the final product. Only stock concentrates and diluents which have passed the general safety test shall be kept in the work areas used for the manufacture of Allergenic Products. A stock concentrate is an extract derived from a single allergenic source and used in the manufacture of more than one lot of product, and from which final dilutions or mixtures, are prepared directly. (2) For powders for scratch tests, a sample shall be suspended in a suitable diluent and injected into each animal, and the sample size shall be the single human dose recommended. (c) Sterility. A sterility test shall be performed on each lot of each Allergenic Product as prescribed in §610.12 of this chapter, with the following exceptions: (1) When bulk material is not prepared, the sterility test prescribed for bulk material shall be performed on each container of each stock concentrate at the time a stock concentrate is prepared, and the test sample shall be no less than 1 ml. from each stock concentrate container. (2) For lots consisting of no more than 5 final containers, the final container test shall be performed in accordance with §610.12(g)(6) of this chapter using the sample therein prescribed or using a sample of no less than 0.25 ml. of product from each final container, divided in approximately equal proportions for testing in Fluid Thioglycollate and Soybean-Casein Digest Media. The test sample in the later alternative method may be an overfill in the final container. (3) For products prepared in sets of individual dilution series, a test sample of 0.25 ml. shall be taken from a final container of each dilution, which samples may be pooled and one half of the pooled material used for the test with Fluid Thioglycollate Medium and one half used for the test with Soybean-Casein Digest Medium. (4) Tablets and capsules need not be tested for sterility provided aseptic techniques are employed in their manufacture. (d) [Reserved] (e) Potency. The potency of each lot of each Allergenic Product shall be determined as prescribed in §610.10 of this chapter. Except as provided in this section, the potency test methods shall measure the allergenic activity of the product. Until manufacturers are notified by the Director, Center for Biologics Evaluation and Research, of the existence of a potency test that measures the allergenic activity of an allergenic product, manufacturers may continue to use unstandardized potency designations. (f) Records. The records related to the testing requirements of this section shall be prepared and maintained as required by §§211.165, 211.167, 211.188, and 211.194 of this chapter. [38 FR 32100, Nov. 20, 1973, as amended at 39 FR 19777, June 6, 1974; 41 FR 4015, Jan. 28, 1976; 52 FR 37607, Oct. 8, 1987; 55 FR 11013, Mar. 26, 1990; 67 FR 9587, Mar. 4, 2002]
Title 21: Food and Drugs
PART 680—ADDITIONAL STANDARDS FOR MISCELLANEOUS PRODUCTS
Section Contents
§ 680.1 Allergenic Products.
§ 680.2 Manufacture of Allergenic Products.
§ 680.3 Tests.
§ 680.1 Allergenic Products.
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§ 680.2 Manufacture of Allergenic Products.
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§ 680.3 Tests.
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