cfr_sections
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125 rows where part_number = 113 and title_number = 9 sorted by section_id
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| section_id ▼ | title_number | title_name | chapter | subchapter | part_number | part_name | subpart | subpart_name | section_number | section_heading | agency | authority | source_citation | amendment_citations | full_text |
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| 9:9:1.0.1.5.51.0.74.1 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.1 Compliance. | APHIS | The regulations in this part apply to each serial or subserial of a licensed biological product manufactured in a licensed establishment and to each serial or subserial of a biological product in each shipment imported for distribution and sale. | ||||||
| 9:9:1.0.1.5.51.0.74.10 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.10 Testing of bulk material for export or for further manufacture. | APHIS | [49 FR 45846, Nov. 21, 1984] | When a product is prepared in a licensed establishment for export in large multiple-dose containers as provided in § 112.8(d) or (e) of this subchapter or for further manufacturing purposes as provided in § 114.3(d) of this subchapter, samples of the bulk material shall be subjected to all required tests prescribed in the filed Outline of Production or Standard Requirements for the product. Samples of concentrated liquid product shall be diluted to a volume equal to the contents of the sample times the concentration factor prior to initiating potency tests. | |||||
| 9:9:1.0.1.5.51.0.74.2 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.2 Testing aids. | APHIS | [39 FR 21041, June 18, 1974, as amended at 40 FR 758, Jan. 3, 1975; 50 FR 21799, May 29, 1985; 56 FR 66784, Dec. 26, 1991] | To better ensure consistent and reproducible test results when Standard Requirement tests prescribed in the regulations are conducted, National Veterinary Services Laboratories, U.S. Department of Agriculture, may provide testing aids, when available, to licensees, permittees, and applicants for licenses and permits. Such aids shall be as follows: (a) Supplemental Assay Method (SAM) is a technical bulletin containing detailed instructions for conducting a test. Such instructions shall be in accordance with the procedures currently being followed at National Veterinary Services Laboratories and as improved, proven procedures are developed, shall be revised and reissued prior to application. (b) Standard Reference Preparation is a serum, virus, bacterial culture, or antigen to be used in test systems for direct comparison with serials of biological products under test. (c) Standard Test Reagent is a serum, antitoxin, fluorescent antibody conjugate, toxin, virus, bacterial cultural, or antigen to be used in test systems but not for direct comparison with serials of biological products under test. (d) Seed cultures are small quantities of standard organisms to be propagated by the recipient to establish a supply for use. (e) Test Code Number is a number assigned by Animal and Plant Health Inspection Service to each test procedure specified in the Standard Requirements and in each filed Outline of Production where such test is conducted to support a request for release of a serial or subserial. | |||||
| 9:9:1.0.1.5.51.0.74.3 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.3 Sampling of biological products. | APHIS | [38 FR 29886, Oct. 30, 1973, as amended at 40 FR 758, Jan. 3, 1975; 40 FR 49768, Oct. 24, 1975; 41 FR 56627, Dec. 29, 1976; 48 FR 9506, Mar. 7, 1983; 48 FR 57473, Dec. 30, 1983; 50 FR 21799, May 29, 1985; 56 FR 66784, Dec. 26, 1991; 60 FR 14356, Mar. 17, 1995; 67 FR 15713, Apr. 3, 2002] | Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or imported into the United States as prescribed in this section. Additional samples may be purchased in the open market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the Department of Agriculture, of the licensee, or of the permittee, as designated by the Administrator shall select prerelease samples of biological product in the number prescribed in paragraph (b) of this section. Each sample shall be marked for identification by the person making the selection after which they shall be packaged by the licensee or permittee, as the case may be, and forwarded to National Veterinary Services Laboratories; except that an employee of the Department may forward or deliver the samples to National Veterinary Services Laboratories if such action deemed advisable by the Administrator. (1) Selection shall be made as follows: (i) Nonviable liquid biological products—either bulk or final container samples of completed product shall be selected for purity, safety, or potency tests. Biological product in final container shall be selected to test for viable bacteria and fungi. (ii) Viable liquid biological products; samples shall be in final containers and shall be randomly selected at the end of the filling operation. Bulk containers of completed product may be sampled when authorized by the Administrator. (iii) Desiccated biological products; samples shall be in final containers and shall be randomly selected if desiccated in the final container. Biological products desiccated in bulk shall be sampled at the end of the filling operation. (iv) Representative samples of each serial or subserial in each shipment of imported biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant Health Inspection Service, the licensee, and the permittee for similar tests. (3) When bulk samples of completed … | |||||
| 9:9:1.0.1.5.51.0.74.4 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.4 Exemptions to tests. | APHIS | [38 FR 29887, Oct. 30, 1973, as amended at 56 FR 66784, Dec. 26, 1991] | (a) The test methods and procedures contained in all applicable Standard Requirements shall be complied with unless otherwise exempted by the Administrator and provided that such exemption is noted in the filed Outline of Production for the product. (b) Test methods and procedures by which the biological products shall be evaluated shall be designated in the Outline of Production for such products. | |||||
| 9:9:1.0.1.5.51.0.74.5 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.5 General testing. | APHIS | [34 FR 18004, Nov. 4, 1969, as amended at 39 FR 25463, July 11, 1974; 40 FR 45420, Oct. 2, 1975; 40 FR 46093, Oct. 6, 1975; 41 FR 6751, Feb. 13, 1976; 48 FR 57473, Dec. 30, 1983; 56 FR 66784, Dec. 26, 1991; 79 FR 55969, Sept. 18, 2014] | (a) No biological product shall be released prior to the completion of tests prescribed in a filed Outline of Production or Standard Requirements for the product to establish the product to be pure, safe, potent, and efficacious. (b) Tests of biological products shall be observed by a competent employee of the manufacturer during all critical periods. A critical period shall be the time when certain specified reactions must occur in required tests to properly evaluate the results. (c) Records of all tests shall be kept in accordance with part 116 of this chapter. Results of all required tests prescribed in the filed Outline of Production or the Standard Requirements for the product shall be submitted to Animal and Plant Health Inspection Service. Blank forms shall be furnished upon request to Animal and Plant Health Inspection Service. (d) When the initial or any subsequent test is declared a No Test, the reasons shall be reported in the test records, the results shall not be considered as final, and the test may be repeated. When a test is declared satisfactory, the test designation is considered to be a final conclusion. When a test is declared unsatisfactory, the test designation is considered to be a final conclusion. When the initial or any subsequent test is declared inconclusive, the reasons shall be reported in the test records, the result shall not be considered as final, and the test may be repeated as established in the filed Outline of Production or Standard Requirement. If a test is designated inconclusive or No Test and the biological product is not further tested, the test designation of unsatisfactory is the final conclusion. (e) When new test methods are developed and approved by Animal and Plant Health Inspection Service, biological products tested thereafter shall be evaluated by such methods, and if not found to be satisfactory when so tested shall not be released. | |||||
| 9:9:1.0.1.5.51.0.74.6 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.6 Animal and Plant Health Inspection Service testing. | APHIS | [34 FR 18004, Nov. 7, 1969, as amended at 40 FR 45420, Oct. 2, 1975; 40 FR 53378, Nov. 18, 1975; 41 FR 6751, Feb. 13, 1976; 56 FR 66784, Dec. 26, 1991] | A biological product shall with reasonable certainty yield the results intended when used as recommended or suggested in its labeling or proposed labeling prior to the expiration date. (a) The Administrator is authorized to cause a biological product, manufactured in the United States or imported into the United States, to be examined and tested for purity, safety, potency, or efficacy; in which case, the licensee or permittee shall withhold such product from the market until a determination has been made. (b) The final results of each test conducted by the licensee and Animal and Plant Health Inspection Service shall be considered in evaluating a biological product. A serial or subserial which has been found unsatisfactory by a required test prescribed in a filed Outline of Production or Standard Requirement is not in compliance with the regulations and shall not be released for market. | |||||
| 9:9:1.0.1.5.51.0.74.7 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.7 Multiple fractions. | APHIS | [34 FR 18004, Nov. 7, 1969, as amended at 40 FR 46093, Oct. 6, 1975; 56 FR 66785, Dec. 26, 1991] | (a) When a biological product contains more than one immunogenic fraction, the completed product shall be evaluated by tests applicable to each fraction. (b) When similar potency tests are required for more than one fraction of a combination biological product, different animals must be used to evaluate each fraction except when written Standard Requirements or outlines of production make provisions and set forth conditions for use of the same animals for testing different fractions. (c) When the same safety test is required for more than one fraction, requirements are fulfilled by satisfactory results from one test of the completed product. (d) When an inactivated fraction(s) is used as a diluent for a live virus fraction(s), the inactivated fraction(s) may be tested separately and the live virus fraction(s) may be tested separately: Provided, That, the viricidal test requirements prescribed in § 113.100 are complied with. (e) Virus titrations for a multivirus product shall be conducted by methods which will quantitate each virus. | |||||
| 9:9:1.0.1.5.51.0.74.8 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.8 In vitro tests for serial release. | APHIS | [49 FR 22625, May 31, 1984, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 62 FR 19038, Apr. 18, 1997; 72 FR 72564, Dec. 21, 2007; 79 FR 31021, May 30, 2014] | (a) Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seed for production as specified in the Standard Requirements or in the filed Outline of Production. The Administrator may exempt a product from a required animal potency test for release when an evaluation can, with reasonable certainty, be made by: (1) Subjecting the master seed to the applicable requirements prescribed in §§ 113.64, 113.100, 113.200, and 113.300; (2) Testing the Master Seed for immunogenicity in a manner acceptable to the Animal and Plant Health Inspection Service (APHIS); (3) Establishing satisfactory potency for the product in accordance with the following provisions: (i) Potency for live products may be determined by log 10 virus titer or determining the live bacterial count based on the protective dose used in the Master Seed immunogenicity test plus an adequate overage for adverse conditions and test error; and (ii) Potency for inactivated products may be determined using tests for relative antigen content by comparing the antigen content of the test serial to a reference preparation using a parallel line immunoassay or equivalent method which measures linearity, specificity, and reproducibility in a manner acceptable to APHIS. (b) In the case of live products, each serial and subserial of desiccated product derived from an approved Master Seed and bulk or final container samples of each serial of completed liquid product derived from an approved Master Seed shall be evaluated by a test procedure acceptable to APHIS. On the basis of the results of the test, as compared with the required minimum potency, each serial and subserial shall either be released to the firm for marketing or withheld from the market. The evaluation of such products shall be made in accordance with the following criteria: (1) If the initial test shows the count or titer to equal or exceed the required minimum, the serial or subserial is satisfactory without additional testing. (2) If the initial test shows … | |||||
| 9:9:1.0.1.5.51.0.74.9 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.9 New potency test. | APHIS | [40 FR 14084, Mar. 28, 1975, as amended at 56 FR 66784, Dec. 26, 1991] | A potency test written into the filed Outline of Production for a product shall be considered confidential information by Animal and Plant Health Inspection Service until at least two additional product licenses are issued for the product or unless use of the test is authorized by the licensee, in which case, such potency test may be published as part of the Standard Requirement for the product. (a) Until a potency test is published as part of the Standard Requirement for the product, reference to such a test shall be made in the filed Outline of Production and the test shall be conducted. (b) When a potency test has been published as part of the Standard Requirement, such test shall be conducted unless the product is specifically exempted as provided in § 113.4. | |||||
| 9:9:1.0.1.5.51.0.75.11 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.25 Culture media for detection of bacteria and fungi. | APHIS | [35 FR 16039, Oct. 13, 1970, as amended at 37 FR 2430, Feb. 1, 1972; 41 FR 27715, July 6, 1976; 56 FR 66784, Dec. 26, 1991] | (a) Ingredients for which standards are prescribed in the United States Pharmacopeia, or elsewhere in this part, shall conform to such standards. In lieu of preparing the media from the individual ingredients, they may be made from dehydrated mixtures which, when rehydrated with purified water, have the same or equivalent composition as such media and have growth-promoting buffering, and oxygen tension-controlling properties equal to or better than such media. The formulas for the composition of the culture media prescribed in §§ 113.26 and 113.27 are set forth in the United States Pharmacopeia, 19th Edition. (b) The licensee shall test each quantity of medium prepared at one time from individual ingredients and the first quantity prepared from each lot of commercial dehydrated medium for growth-promoting qualities. If any portion of a lot of commercial dehydrated medium is held for 90 days or longer after being so tested, it shall be retested before use. Two or more strains of micro-organisms that are exacting in their nutritive requirements shall be used. More than one dilution shall be used to demonstrate the adequacy of the medium to support the growth of a minimum number of micro-organisms. (c) The sterility of the medium shall be confirmed by incubating an adequate number of test vessels and examining each for growth. Additional control may be used by incubation of representative uninoculated test vessels for the required incubation period during each test. (d) A determination shall be made by the licensee for each biological product of the ratio of inoculum to medium which shall result in sufficient dilution of such product to prevent bacteriostatic and fungistatic activity. The determination may be made by tests on a representative biological product for each group of comparable products containing identical preservatives at equal or lower concentrations. Inhibitors or neutralizers of preservatives, approved by the Administrator, may be considered in determining the proper ratio. | |||||
| 9:9:1.0.1.5.51.0.75.12 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.26 Detection of viable bacteria and fungi except in live vaccine. | APHIS | [35 FR 16039, Oct. 13, 1970, as amended at 37 FR 2430, Feb. 1, 1972; 39 FR 21042, June 18, 1974; 40 FR 758, Jan. 3, 1975; 40 FR 14084, Mar. 28, 1975; 56 FR 66784, Dec. 26, 1991] | Each serial and subserial of biological product except live vaccines shall be tested as prescribed in this section unless otherwise specified by the Administrator. When cell lines, primary cells, or ingredients of animal origin used in the preparation of a biological product are required to be free of viable bacteria and fungi, they shall also be tested as prescribed in this section. (a) The media to be used shall be as follows: (1) Fluid Thioglycollate Medium with 0.5 percent beef extract shall be used to test for bacteria in biological products containing clostridial toxoids, bacterins, and bacterin-toxoids. (2) Fluid Thioglycollate Medium with or without 0.5 percent beef extract shall be used to test for bacteria in biological products other than clostridial toxoids, bacterins, and bacterin-toxoids. (3) Soybean-Casein Digest Medium shall be used to test biological products for fungi; provided, that Fluid Thioglycollate Medium without beef extract shall be substituted when testing biological products containing mercurial preservatives. (b) Test procedure: (1) Ten test vessels shall be used for each of two media selected in accordance with paragraph (a)(1), (a)(2), or (a)(3) of this section. Each test vessel shall contain sufficient medium to negate the bacteriostatic or fungistatic activity in the inoculum as determined in § 113.25(d). (2) Inoculum: (i) When completed product is tested, 10 final container samples from each serial and each subserial shall be tested. One ml from each sample shall be inoculated into a corresponding individual test vessel of culture medium: Provided, That, if each final container sample contains less than 2 ml, one-half of the contents shall be used as inoculum for each test vessel. (ii) When cell lines, primary cells, or ingredients of animal origin are tested, at least a 20 ml test sample from each lot shall be tested. One ml shall be inoculated into each test vessel of medium. (3) Incubation shall be for an observation period of 14 days at 30 °to 35 °C. to test for b… | |||||
| 9:9:1.0.1.5.51.0.75.13 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.27 Detection of extraneous viable bacteria and fungi in live vaccines. | APHIS | [48 FR 28430, June 22, 1983, as amended at 56 FR 66784, Dec. 26, 1991] | Unless otherwise specified by the Administrator or elsewhere exempted in this part, each serial and subserial of live vaccine and each lot of Master Seed Virus and Master Seed Bacteria shall be tested for extraneous viable bacteria and fungi as prescribed in this section. A Master Seed found unsatisfactory shall not be used in vaccine production and a serial found unsatisfactory shall not be released. (a) Live viral vaccines. Each serial and subserial of live viral vaccine shall be tested for purity as prescribed in this paragraph. However, products of chicken embryo origin recommended for administration other than by parenteral injection may be tested as provided in paragraph (e) of this section. (1) Soybean Casein Digest Medium shall be used. (2) Ten final container samples from each serial and subserial shall be tested. (3) Immediately prior to starting the test, frozen liquid vaccine shall be thawed, and desiccated vaccine shall be rehydrated as recommended on the label with accompanying diluent or with sterile purified water. (4) To test for bacteria, place 0.2 ml of vaccine from each final container into a corresponding individual vessel containing at least 120 ml of Soybean Casein Digest Medium. Additional medium shall be used if the determination required in § 113.25(d) indicates the need for a greater dilution of the product. Incubation shall be at 30 °to 35 °C for 14 days. (5) To test for fungi, place 0.2 ml of vaccine from each final container sample into a corresponding individual vessel containing at least 40 ml of Soybean Casein Digest Medium. Additional medium shall be used if the determination required in § 113.25(d) indicates the need for a greater dilution of the product. Incubation shall be at 20 °to 25 °C for 14 days. (6) Examine the contents of all test vessels macroscopically for microbial growth at the end of the incubation period. If growth in a vessel cannot be reliably determined by visual examination, judgment shall be confirmed by subcultures, microscopic examination, or both.… | |||||
| 9:9:1.0.1.5.51.0.75.14 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.28 Detection of mycoplasma contamination. | APHIS | [38 FR 29887, Oct. 30, 1973, as amended at 41 FR 6752, Feb. 13, 1976; 41 FR 32882, Aug. 6, 1976] | The heart infusion test, using heart infusion broth and heart infusion agar, provided in this section shall be conducted when a test for mycoplasma contamination is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. (a) Media additives provided in this paragraph shall be prepared as follows: (1) DPN-Cysteine Solution: (i) Use Nicotinamide adenine dinucleotide (oxidized) and L-Cysteine hydrochloride. (ii) Prepare 1 gram/100 milliliters (ml) purified water (1 percent solution) of each. Mix the solutions together; the cysteine reduces the DPN. Filter sterilize, dispense in appropriate amounts and store frozen at −20 degrees centigrade. (2) Inactivated horse serum—horse serum which has been inactivated at 56 °C for 30 minutes. (b) Heart infusion broth shall be prepared as provided in this paragraph. (1) Dissolve in 970 ml of purified water, 25 grams of heart infusion broth, 10 grams of proteose peptone No. 3, and either 5 grams of yeast autolysate or 5 ml of fresh yeast extract. (2) Add the following: (3) Adjust pH to 7.9 with NaOH, filter sterilize, and dispense 100 ml aliquots into 125 ml flasks and store until needed. (4) Add 2 ml of DPN-Cysteine solution to each 100 ml of broth on day of use. (c) Heart Infusion Agar shall be prepared as provided in this paragraph. (1) Dissolve in 900 ml of purified water by boiling the following: (2) Cool the medium and adjust pH to 7.9 with NaOH. (3) Autoclave the medium. (4) Cool the medium 30 minutes in a 56 °C waterbath. (5) Dissolve 5 grams of yeast autolysate in 100 ml of distilled water, filter sterilize, and add to the medium. (6) Add to the medium: 126 ml of inactivated horse serum 21 ml of DPN-Cysteine solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60 × 15 mm disposable culture dishes or petri dishes. 126 ml of inactivated horse serum 21 ml of DPN-Cysteine solution 525,000 units of Penicillin. Dispense 10 ml aliquots into 60 × 15 mm disposable culture dishes or pet… | |||||
| 9:9:1.0.1.5.51.0.75.15 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.29 Determination of moisture content in desiccated biological products. | APHIS | [68 FR 57608, Oct. 6, 2003] | Methods provided in this section must be used when a determination of moisture content in desiccated biological products is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. Firms currently using methods other than those provided in this section for determining the moisture content in desiccated biological products have until November 5, 2004 to update their Outlines of Production to be in compliance with this requirement. (a) Final container samples of completed product shall be tested. The weight loss of the sample due to drying in a vacuum oven shall be determined. All procedures should be performed in an environment with a relative humidity less than 45 percent. The equipment necessary to perform the test is as follows: (1) Cylindrical weighing bottles with airtight glass stoppers. (2) Vacuum oven equipped with validated thermometer and thermostat. A suitable air-drying device should be attached to the inlet valve. (3) Balance, accurate to 0.1 mg (rated precision ±0.01mg). (4) Desiccator jar equipped with phosphorous pentoxide, silica gel, or equivalent. (5) Desiccated vaccine in original sealed vial. Sample and control should be kept at room temperature in their original airtight containers until use. (b) Test procedure: (1) Thoroughly cleaned and labeled sample-weighing bottles with stoppers should be allowed to dry at 60 ±3 °C under vacuum at less than 2.5 kPa. (i) Transfer hot bottles and stoppers into the desiccator and allow to cool to room temperature. (ii) After bottles have cooled, insert stoppers and weigh and record the weights of the bottles as “A.” (iii) Return weighing bottles to the desiccator. (2) Remove the sample container seal. (i) Using a spatula, break up the sample plug and transfer the required amount of sample to the previously tared weighing bottle. (ii) Insert the stopper and weigh and record the weights of the weighing bottles as “B.” (3) Place the weighing bottle with the stopper at an angle in the vacuum oven. Se… | |||||
| 9:9:1.0.1.5.51.0.75.16 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.30 Detection of Salmonella contamination. | APHIS | [38 FR 29888, Oct. 30, 1973] | The test for detection of Salmonella contamination provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. (a) Samples shall be collected from the bulk suspension before bacteriostatic or bactericidal agents have been added. When tissue culture products are to be tested, 1 ml of tissue extract used as the source of cells or 1 ml of the minced tissue per se shall be tested. (b) Five ml of the liquid vaccine suspension shall be used to inoculate each 100 ml of liquid broth medium (tryptose and either selenite F or tetrathionate). The inoculated media shall be incubated 18-24 hours at 35-37 °C. (c) Transfers shall be made to either MacConkey agar or Salmonella-Shigella agar, incubated for 18-24 hours and examined. (d) If no growth typical of Salmonella is noted, the plates shall be incubated an additional 18-24 hours and again examined. (e) If suspicious colonies are observed, further subculture on suitable media shall be made for positive identification. If Salmonella is found, the bulk suspension is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.17 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.31 Detection of avian lymphoid leukosis. | APHIS | [38 FR 29888, Oct. 30, 1973, as amended at 38 FR 32917, Nov. 29, 1973; 39 FR 21042, June 18, 1974; 56 FR 66784, Dec. 26, 1991] | The complement-fixation test for detection of avian lymphoid leukosis provided in this section shall be conducted on all biological products containing virus which has been propagated in substrates of chicken origin: Provided, An inactivated viral product shall be exempt from this requirement if the licensee can demonstrate to Animal and Plant Health Inspection Service that the agent used to inactivate the vaccine virus would also inactivate lymphoid leukosis virus. (a) Propagation of contaminating lymphoid leukosis viruses, if present, shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo fibroblast cells, shall be effectively neutralized, inactivated, or separated so that minimal amounts of lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine virus cannot be effectively neutralized, inactivated, or separated, a sample of another vaccine prepared the same week from material harvested from each source flock (or other sampling procedure acceptable to Animal and Plant Health Inspection Service) used for the preparation of the questionable vaccine virus that cannot be neutralized, inactivated, or separated shall be tested each week during the preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell suspension as prepared for seeding of production cell cultures shall be used as inoculum. When vaccines are tested, the equivalent of 200 doses of Newcastle disease vaccine or 500 doses of other vaccines for use in poultry, or one dose of vaccine for use in other animals shall be used as inoculum. Control cultures shall be prepared from the same cell suspension as the cultures for testing the vaccine. (3) Uninoculated chick embryo fibroblast cell cultures shall act as negative controls. One set of chick fibroblast cultures inoculated with subgroup A virus and another set inoculated with subgroup B virus shall act as positive controls, A and B respectively. (4) The cell cultures sha… | |||||
| 9:9:1.0.1.5.51.0.75.18 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.32 Detection of Brucella contamination. | APHIS | [38 FR 29888, Oct. 30, 1973] | The test for detection of Brucella contamination provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in a filed Outline of Production for the product. (a) One ml of the minced tissue used as the source of cells or 1 ml of the extract of the tissue prior to the addition of antibiotics, diluent and stabilizer, shall be inoculated onto each of three tryptose agar plates and incubated in a 10 percent CO 2 atmosphere at a temperature of 35-37 °C for at least 7 days. (b) If colonies are identified as Brucella, the biological product is unsatisfactory. (c) If colonies suspicious of Brucella are observed but cannot be identified as a Brucella species, either (1) The biological product shall be regarded as unsatisfactory and destroyed; or (2) Further subculture or other procedures shall be carried out until a positive identification can be made. | |||||
| 9:9:1.0.1.5.51.0.75.19 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.33 Mouse safety tests. | APHIS | [38 FR 34727, Dec. 18, 1973, as amended at 39 FR 16857, May 10, 1974; 72 FR 72564, Dec. 21, 2007] | One of the mouse safety tests provided in this section shall be conducted when such test is prescribed in a Standard Requirement or in the filed Outline of Production for a biological product recommended for animals other than poultry: Provided, That if the inherent nature of one or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for the animals for which it is recommended, the licensee shall demonstrate the safety of such product by an acceptable test written into such Outline of Production. (a) Final container samples of completed product from live virus vaccines shall be tested for safety using young adult mice in accordance with the test provided in this paragraph. (1) Vaccine prepared for use as recommended on the label shall be tested by inoculating eight mice intraperitoneally or subcutaneously with 0.5 mL (the inoculation volume may be divided among more than one injection site), and the animals observed for 7 days. (2) If unfavorable reactions attributable to the product occur in any of the mice during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial or subserial shall be declared unsatisfactory. (b) Bulk or final container samples of completed product from liquid products, such as but not limited to antiserums and bacterins, shall be tested for safety in accordance with the test provided in this paragraph. (1) Unless otherwise prescribed in the Standard Requirement or approved in a filed Outline of Production for the product, a 0.5 ml dose shall be injected intraperitoneally or subcutaneously into eight mice and the animals observed for 7 days. (2) If unfavorable reactions attributable to the product occur in any of the mice during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributa… | |||||
| 9:9:1.0.1.5.51.0.75.20 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.34 Detection of hemagglutinating viruses. | APHIS | [38 FR 29889, Oct. 30, 1973] | The test for detection of hemagglutinating viruses provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. (a) Final container samples of completed product rehydrated as recommended on the label shall be used as inoculum: Provided, That poultry vaccines distributed without diluent shall be rehydrated with 30 ml of sterile distilled water per 1,000 doses and used as inoculum. When one or more fractions are to be used in combination with Newcastle Disease Vaccine, test samples shall be collected from bulk suspensions of each prior to mixing with the Newcastle Disease Vaccine. (b) Each of ten 9- to 10-day-old embryonating eggs from Newcastle disease susceptible flocks shall be inoculated into the allantoic cavity with 0.2 ml of the undiluted inoculum. (1) Test five uninoculated embryos of the same age and from the same flock as those used for the test as negative controls. (2) Test an allantoic fluid sample of Newcastle disease virus as a positive control. (c) Three to five days post-inoculation, a sample of allantoic fluid from each egg shall be tested separately by a rapid plate test for hemagglutinating activity using a 0.5 percent suspension of fresh chicken red blood cells. (d) If the results are inconclusive, one or two blind passages shall be made using fluids from each of the original test eggs. Fluids from dead and live embryos may be pooled separately for inoculum in these passages. (e) If hemagglutinating activity attributable to the product is observed, the serial is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.21 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.35 Detection of viricidal activity. | APHIS | [44 FR 25412, May 1, 1979, as amended at 56 FR 66784, Dec. 26, 1991; 64 FR 43044, Aug. 9, 1999] | The test for detection of viricidal activity provided in this section shall be conducted when such a test is prescribed in an applicable standard requirement or in the filed Outline of Production for each inactivated liquid biological product used as diluent for a desiccated live virus vaccine in a combination package. (a) Bulk or final container samples of completed product from each serial shall be tested. (b) The product shall be tested with each virus fraction for which it is to be used as a diluent. If the vaccine to be rehydrated contains more than one virus fraction, the test shall be conducted with each fraction after neutralization of the other fraction(s), and/or dilution of the vaccine beyond the titer range of the other fraction(s), or the test shall be conducted using representative single-fraction desiccated vaccines which are prepared by the licensee and which are licensed. Provided, That the Administrator may authorize licensees to prepare and use unlicensed single-fraction vaccines for this purpose. (c) Test procedure: (1) Rehydrate at least two vials of the vaccine with the liquid product under test according to label recommendations and pool the contents. (2) Rehydrate at least two vials of the vaccine with the same volume of sterile purified water and pool the contents. (3) Neutralize to remove other fractions, if necessary. (4) Hold the two pools of vaccine at room temperature (20 °to 25 °C) for 2 hours. The holding period shall begin when rehydration is completed. (5) Titrate the virus(es) in each pool of vaccine as provided in the filed Outline of Production or an applicable standard requirement. (6) Compare respective titers. (d) If the titer of the vaccine virus(es) rehydrated with the product under test is more than 0.7 log 10 below the titer of the vaccine virus(es) rehydrated with sterile purified water, the product is unsatisfactory for use as diluent. (e) If the product is unsatisfactory in the first test, one retest to rule out faulty techniques may be conducted using f… | |||||
| 9:9:1.0.1.5.51.0.75.22 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.36 Detection of pathogens by the chicken inoculation test. | APHIS | [38 FR 29889, Oct. 30, 1973, as amended at 39 FR 21042, June 18, 1974; 43 FR 7610, Feb. 24, 1978] | The test for detection of extraneous pathogens provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. (a) The biological product to be tested shall be prepared for use as recommended on the label, or in the case of desiccated vaccine to be used in poultry, rehydrated with sterile distilled water at the rate of 30 ml per 1,000 doses. (b) At least 25 healthy susceptible young chickens, properly identified and obtained from the same source and hatch, shall be immunized at least 14 days prior to being put on test. The immunizing agent shall be the same as the product to be tested but from a serial previously tested and found satisfactory. (c) At least 20 of the previously immunized birds shall be inoculated with 10 label doses of the vaccine being tested by each of the following routes: Subcutaneous, intratracheal, eye-drop, and comb scarification (1 cm 2 ). Twenty birds may be used for each route or combination of routes. (d) At least five birds shall be isolated as control birds. (e) All birds shall be observed for 21 days for signs of septicemic diseases, respiratory diseases, or other pathologic conditions. (f) If the controls remain healthy and unfavorable reactions attributable to the product occur in the vaccinates, the serial or subserial tested is unsatisfactory. If the controls do not remain healthy or if unfavorable reactions not attributable to the product occur in the vaccinates, or both, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial of subserial tested shall be considered unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.23 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.37 Detection of pathogens by the chicken embryo inoculation test. | APHIS | [38 FR 29889, Oct. 30, 1973, as amended at 39 FR 21042, June 18, 1974] | The test for detection of extraneous pathogens provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in the filed Outline of Production for the product. (a) The biological product to be tested shall be prepared for use as recommended on the label, or in the case of desiccated vaccine to be used in poultry, rehydrated with sterile distilled water at the rate of 30 ml per 1,000 doses. (b) One volume of the prepared vaccine shall be mixed with up to nine volumes of sterile heat-inactivated specific antiserum to neutralize the vaccine virus in the product. Each lot of antiserum shall be demonstrated by virus neutralization tests not to inhibit other viruses known to be possible contaminants. (c) After neutralization, 0.2 ml of the vaccine-serum mixture shall be inoculated into each of at least 20 fully susceptible chicken embryos. (1) Twenty embryos, 9 to 11 days old, shall be inoculated on the chorio-allantoic membrane (CAM) with 0.1 ml, and in the allantoic sac with 0.1 ml. (2) Eggs shall be candled daily for 7 days. Deaths occurring during the first 24 hours shall be disregarded but at least 18 viable embryos shall survive 24 hours post-inoculation for a valid test. Examine all embryos and CAM's from embryos which die after the first day. When necessary, embryo subcultures shall be made to determine the cause of a death. The test shall be concluded on the seventh day post-inoculation and the surviving embryos (including CAM's) examined. (d) If death and/or abnormality attributable to the inoculum occur, the serial is unsatisfactory: Provided, That, if there is a vaccine virus override, the test may be repeated, using a higher titered antiserum. | |||||
| 9:9:1.0.1.5.51.0.75.24 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.38 Guinea pig safety test. | APHIS | [39 FR 16857, May 10, 1974; 39 FR 20368, June 10, 1974] | The guinea pig safety test provided in this section shall be conducted when prescribed in a Standard Requirement or approved Outline of Production for a biological product. When desiccated products are tested, final container samples of completed product prepared for administration in the manner recommended on the label shall be used. When liquid products are tested, either bulk or final container samples of completed product shall be used. (a) Unless otherwise specified in the Standard Requirement or approved Outline of Production for the product, a 2 ml dose shall be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals observed for 7 days. (b) If unfavorable reactions attributable to the product occur in either of the guinea pigs during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial or subserial shall be declared unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.25 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.39 Cat safety tests. | APHIS | [44 FR 58898, Oct. 12, 1979, as amended at 56 FR 66784, Dec. 26, 1991] | The safety tests provided in this section shall be conducted when prescribed in a standard requirement or in the filed Outline of Production for a biological product recommended for use in cats. (a) The cat safety test provided in this paragraph shall be used when the Master Seed Virus is tested for safety. (1) The test animals shall be determined to be susceptible to the virus under test as follows: (i) Throat swabs shall be collected from each cat and individually tested on susceptible cell cultures for the presence of the virus. Blood samples shall also be drawn and individual serum samples tested for antibody to the virus. (ii) The cats shall be considered susceptible if swabs are negative for virus isolation and the serums are free of virus antibody at the 1:2 final dilution in a 50 percent plaque reduction test or other serum-neutralization test of equal sensitivity. (iii) When determining susceptibility to a virus which does not lend itself to the methods in paragraphs (a)(1)(i) and (ii) of this section, a method acceptable to Animal and Plant Health Inspection Service shall be used. (2) Each of at least 10 susceptible cats shall be administered a sample of the Master Seed Virus equivalent to the amount of virus to be used in one cat dose of the vaccine, by the method to be recommended on the label, and the cats observed each day for 14 days. (3) If unfavorable reactions attributable to the virus occur in any of the cats during the observation period, the Master Seed Virus is unsatisfactory. If unfavorable reactions occur which are not attributable to the Master Seed Virus, the test shall be declared a No Test and repeated: Provided, That, if not repeated, the Master Seed Virus shall be unsatisfactory. (b) The cat safety test provided in this paragraph shall be used when a serial of vaccine is tested for safety before release. (1) Each of two healthy cats shall be administered 10 cat doses by the method recommended on the label and the cats observed each day for 14 days. (2) If unfavorable reac… | |||||
| 9:9:1.0.1.5.51.0.75.26 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.40 Dog safety tests. | APHIS | [60 FR 14358, Mar. 17, 1995] | The safety tests provided in this section shall be conducted when prescribed in a Standard Requirement or in the filed Outline of Production for a biological product recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the procedures in this section may not be released for shipment. (a) The dog safety test provided in this paragraph shall be used when the Master Seed Virus is tested for safety. (1) The test animals shall be determined to be susceptible to the virus under test by a method acceptable to the Animal and Plant Health Inspection Service. (2) Each of at least 10 susceptible dogs shall be administered a sample of the Master Seed Virus equivalent to the amount of virus to be used in one dog dose of the vaccine, by the method recommended on the label, and the dog shall be observed each day for 14 days. (3) If unfavorable reactions attributable to the virus occur in any of the dogs during the observation period, the Master Seed Virus is unsatisfactory. If unfavorable reactions occur which are not attributable to the Master Seed Virus, the test shall be declared a No Test and may be repeated: Provided: That, if the test is not repeated, the Master Seed Virus shall be considered unsatisfactory. (b) The dog safety test provided in this paragraph shall be used when a serial of vaccine is tested for safety before release. (1) Each of two healthy dogs shall be administered 10 dog doses by the method recommended on the label and the dogs shall be observed each day for 14 days. (2) If unfavorable reactions attributable to the biological product occur during the observation period, the serial is unsatisfactory. If unfavorable reactions occur which are not attributable to the biological product, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial shall be considered unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.27 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.41 Calf safety test. | APHIS | [39 FR 27428, July 29, 1974] | The calf safety test provided in this section shall be conducted when prescribed in a Standard Requirement or in the filed Outline of Production for a product. (a) Test procedure. Each of two calves shall be injected with the equivalent of 10 doses of vaccine administered in the manner recommended on the label and observed each day for 21 days. (b) Interpretation. If unfavorable reactions attributable to the product occur in either of the calves during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial or subserial shall be declared unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.28 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.42 Detection of lymphocytic choriomeningitis contamination. | APHIS | [42 FR 6794, Feb. 4, 1977] | The test for detection of lymphocytic choriomeningitis (LCM) virus provided in this section shall be conducted when such a test is prescribed in an applicable Standard Requirement or in a filed Outline of Production. Vaccine virus may be neutralized with specific antiserum when necessary. (a) Each of at least 10 mice obtained from a source free of LCM shall be injected in the footpad of a hindfoot with 0.02 ml of the material being tested and observed each day for 21 days. (b) If any of the mice show swelling in the injected footpad or if more than one becomes systemically abnormal, the material being tested is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.29 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.43 Detection of chlamydial agents. | APHIS | [44 FR 58899, Oct. 12, 1979] | The test for chlamydial agents provided in this section shall be conducted when such a test is prescribed in an applicable standard requirement or in a filed Outline of Production. (a) The yolk sac of 6-day-old chicken embryos shall be injected. Three groups of 10 embryos shall be used sequentially. (1) The inoculum for each embryo in the first group shall consist of 0.5 ml of a mixture of equal parts of the seed virus with phosphate buffered saline that may contain Streptomycin, Vancomycin, Kanamycin, or a combination thereof. Not more than 2 mg/ml of each antibiotic shall be used. (2) On the 10th day postinoculation, the yolk sac of viable embryos shall be harvested, pooled, homogenized as a 20 percent suspension in phosphate buffered saline antibiotic diluent, and 0.5 ml of the mixture injected into the second group of chicken embryos. This process shall be repeated for the injection of the third group of embryos using the yolk sacs of viable embryos from the second group. (3) For each of the three passages, embryo deaths occurring within 48 hours of injection shall be disregarded, except that if more than three such deaths occur at any passage, that passage shall be repeated. (b) If one or more embryo deaths occur at any passage after 48 hours postinjection, the yolk sacs from each of the dead embryos shall be subcultured into 10 additional embryos. If one or more embryo deaths again occur due to chlamydial agents, the Master Seed Virus is unsatisfactory for use to produce vaccine. | |||||
| 9:9:1.0.1.5.51.0.75.30 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.44 Swine safety test. | APHIS | [48 FR 33476, July 22, 1983] | The swine safety test provided in this section shall be conducted when prescribed in a Standard Requirement or in the filed Outline of Production for a product. (a) Test procedure. (1) Inject each of two swine of the minimum age for which the product is recommended with the equivalent of two doses of bacterial vaccine or 10 doses of viral vaccine. (2) Administer vaccine in the manner recommended on the label. (3) Observe swine each day for 21 days. (b) Interpretation. If unfavorable reactions attributable to the product occur in either of the swine during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated; Provided, That, if the test is not repeated, the serial or subserial shall be declared unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.31 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.45 Sheep safety test. | APHIS | [48 FR 33476, July 22, 1983] | The sheep safety test provided in this section shall be conducted when prescribed in a Standard Requirement or in the filed Outline of Production for a product. (a) Test procedure. (1) Inject each of two sheep of the minimum age for which the product is recommended with the equivalent of two doses of bacterial vaccine or 10 doses of viral vaccine. (2) Administer vaccine in the manner recommended on the label. (3) Observe sheep each day for 21 days. (b) Interpretation. If unfavorable reactions attributable to the product occur in either of the sheep during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated; Provided, That, if the test is not repeated, the serial or subserial shall be declared unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.32 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.46 Detection of cytopathogenic and/or hemadsorbing agents. | APHIS | [50 FR 441, Jan. 4, 1985, as amended at 58 FR 50252, Sept. 27, 1993] | The tests for detection of cytopathogenic and/or hemadsorbing agents provided in this section shall be conducted when prescribed in an applicable Standard Requirement or in the filed Outline of Production for a product. (a) Test for cytopathogenic agents. One or more monolayers that are at least 6 cm 2 and at least 7 days from the last subculture shall be tested as provided in this paragraph. (1) Stain each monolayer with a suitable cytological stain. (2) Examine the entire area of each stained monolayer for evidence of inclusion bodies, abnormal number of giant cells, or other cytopathology indicative of cell abnormalities attributable to an extraneous agent. (b) Test for hemadsorbing agents. One or more monolayers that are at least 6 cm 2 and at least 7 days from the last subculture shall be tested as provided in this paragraph. (1) Wash the monolayer with several changes of phosphate buffered saline. (2) Add an appropriate volume of a 0.2 percent red blood cell suspension to uniformly cover the surface of the monolayer of cultured cells. Suspensions of washed guinea pig and chicken red blood cells shall be used. These suspensions may be mixed before addition to the monolayer or they may be added separately to individual monolayers. (3) Incubate the monolayer at 4 °C for 30 minutes, wash with phosphate buffered saline, and examine for hemadsorption. (4) If no hemadsorption is apparent, repeat step (b)(2) of this section and incubate the monolayers at 20-25 °C for 30 minutes, wash with phosphate buffered saline, and examine again for hemadsorption. If desired, separate monolayers may be used for each incubation temperature. (c) If specific cytopathology or hemadsorption attributable to an extraneous agent is found, the material under test is unsatisfactory and shall not be used to prepare biological products. If an extraneous agent is suspected because of cytopathology or hemadsorption and cannot be eliminated as a possibility by additional testing, the material under test is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.75.33 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.47 Detection of extraneous viruses by the fluorescent antibody technique. | APHIS | [60 FR 24548, May 9, 1995] | The test for detection of extraneous viruses by the fluorescent antibody technique provided in this section shall be conducted when prescribed in an applicable Standard Requirement or in a filed Outline of Production for a product. (a) Monolayer cultures of cells (monolayers), at least 7 days after the last subculturing, shall be processed and stained with the appropriate antiviral fluorochrome-conjugated antibody as specified in paragraph (b) of this section. (1) Three groups of one or more monolayers shall be required for each specific virus prescribed in paragraph (b) of this section. (i) At the time of the last subculturing, one group of test monolayers shall be inoculated with approximately 100-300 FAID 50 of the specific virus being tested for as positive controls. (ii) One group of monolayers shall be the “material under test.” (iii) One group of monolayers, that are of the same type of cells as the test monolayers and that have been tested as prescribed in §§ 113.51 or 113.52 (whichever is applicable), shall be prepared as negative controls. (2) Each group of monolayers shall have a total area of at least 6 cm 2 . (3) Positive control monolayers may be fixed (processed so as to arrest growth and assure attachment of the monolayer to the surface of the vessel in which they are grown) before 7 days after subculturing if fluorescence is enhanced by doing so, Provided, That a monolayer of the material under test is also fixed at the same time as the positive control and a monolayer of the material under test is also fixed at least seven days after subculturing. Monolayers that are fixed before 7 days after subculturing shall be stained at the same time as the test monolayers and negative controls fixed at least 7 days after subculturing. (b) The antiviral fluorochrome-conjugated antibodies to be used shall depend on the type of cells required to be tested for extraneous viruses as specified in an applicable Standard Requirement or in a filed Outline of Production. Antiviral fluorochrome-conjugate… | |||||
| 9:9:1.0.1.5.51.0.76.34 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.50 Ingredients of biological products. | APHIS | [38 FR 29889, Oct. 30, 1973] | All ingredients used in a licensed biological product shall meet accepted standards of purity and quality; shall be sufficiently nontoxic so that the amount present in the recommended dose of the product shall not be toxic to the recipient; and in the combinations used shall not denature the specific substances in the product below the minimum acceptable potency within the dating period when stored at the recommended temperature. | |||||
| 9:9:1.0.1.5.51.0.76.35 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.51 Requirements for primary cells used for production of biologics. | APHIS | [50 FR 442, Jan. 4, 1985, as amended at 60 FR 24549, May 9, 1995] | Primary cells used to prepare biological products shall be derived from normal tissue of healthy animals. When prescribed in an applicable Standard Requirement or in the filed Outline of Production, each batch of primary cells used to prepare a biological product shall be tested as prescribed in this section. A batch of primary cells found unsatisfactory by any prescribed test shall not be used. A serial of biological product shall not be released if produced from primary cells that are found unsatisfactory by any prescribed test. (a) Final container samples of completed product or samples of the final pool of harvested material or samples of each subculture of cells used to prepare the biological product shall be shown free of mycoplasma as prescribed in § 113.28. The sample for testing shall consist of at least 75 cm 2 of actively growing cells or the equivalent in harvest fluids; Provided, That all sources of cells in the batch of primary cells are represented. (b) Final container samples of completed product or samples of the final pool of harvested material or samples of each subculture of cells used to prepare the biological product shall be shown free of bacteria and fungi as prescribed in § 113.26 or § 113.27 (whichever is applicable). (c) A monolayer at least 75 cm 2 from each batch of primary cells or each subculture of primary cells used to prepare a biological product shall be shown free of extraneous agents as prescribed in this paragraph. (1) The test monolayer shall be maintained using the medium (with additives) and under conditions similar to those used to prepare biological products. (i) Monolayers of avian origin shall be maintained for at least 14 days and shall be subcultured at least once during the maintenance period. All but the last subculture shall result in a new monolayer of at least 75 cm 2 . The last subculture shall meet the minimum area requirement specified in §§ 113.46 and 113.47. (ii) Monolayers not of avian origin shall be maintained for at least 28 days and sha… | |||||
| 9:9:1.0.1.5.51.0.76.36 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.52 Requirements for cell lines used for production of biologics. | APHIS | [50 FR 442, Jan. 4, 1985; 50 FR 3316, Jan. 24, 1985, as amended at 56 FR 66784, Dec. 26, 1991; 60 FR 24549, May 9, 1995] | When prescribed in an applicable Standard Requirement or in a filed Outline of Production each cell line used to prepare a biological product shall be tested as prescribed in this section. A cell line found unsatisfactory by any prescribed test shall not be used. A serial of biological product shall not be released if produced from a cell line that is found unsatisfactory by any prescribed test. (a) General requirements. (1) A complete record of the cell line shall be kept, such as, but not limited to, the source, passage history, and medium used for propagation. (2) A Master Cell Stock (MCS) shall be established at a specified passage level for each cell line. The passage level and identity of the MCS and the highest passage level (MCS + n) intended for use in the preparation of a biological product shall be specified in the Outline of Production for the product. (3) Sufficient 1.0 ml or larger aliquots of MCS and MCS + n shall be prepared, kept in a frozen state, and made available to Animal and Plant Health Inspection Service (APHIS) upon request for performing the tests prescribed in this section. (4) Each lot of cells shall be monitored for the characteristics determined to be normal for the cell line, such as, but not limited to, microscopic appearance, growth rate, acid production, or other observable features. (b) The MCS shall be shown to be of the same species of origin as that reported in paragraph (a)(1) of this section by the following method: (1) At least four monolayers with a total area of at least 6 cm 2 shall be grown to at least 80 percent confluency. (2) The monolayers shall be removed from their media, processed, stained, and examined. (i) At least two monolayers shall be stained with an antispecies fluorchrome-conjugated antibody unrelated to the species of origin of the MCS. (ii) At least two monolayers shall be stained with an antispecies fluorochrome-conjugated antibody specific to the species of origin of the MCS. (iii) All monolayers shall be examined for evidence of spec… | |||||
| 9:9:1.0.1.5.51.0.76.37 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.53 Requirements for ingredients of animal origin used for production of biologics. | APHIS | [50 FR 442, Jan. 4, 1985; 50 FR 3316, Jan. 24, 1985, as amended at 56 FR 66784, Dec. 26, 1991; 60 FR 24549, May 9, 1995] | Each lot of ingredient of animal origin which is not subjected to heat sterilization or other sterilization methods acceptable to Animal and Plant Health Inspection Service (APHIS), such as, but not limited to serum and albumin, used to prepare a biological product shall be tested as prescribed in this section by the licensee or a laboratory acceptable to VS. Results of all tests shall be recorded by the testing laboratory and made a part of the licensee's records. A lot of ingredient found unsatisfactory by any prescribed test shall not be used to prepare a biological product. A serial of biological product shall not be released if produced using an ingredient that is found unsatisfactory by any prescribed test. (a) Samples of each lot of ingredient of animal origin which is not subjected to heat sterilization, used to prepare a biological product shall be shown free of mycoplasma by the method prescribed in § 113.28. (b) Samples of each lot of ingredient or animal origin which is not subjected to heat sterilization of other sterilization methods acceptable to APHIS used to prepare a biological product shall be shown free of bacteria and fungi as prescribed in § 113.26. (c) Samples of each lot of ingredient of animal origin, except porcine trypsin, which is not subjected to heat sterilization or other viricidal procedure acceptable to APHIS used in the preparation of biological products shall be tested as prescribed in this paragraph; (1) Monolayers at least 75 cm 2 of Vero (African green monkey kidney) cell line and of primary cells or a cell line of the same species of origin as the ingredient shall be used in the test. Cell lines used shall have been found satisfactory when tested as prescribed in § 113.52 and primary cells used shall have been found satisfactory when tested as prescribed in § 113.51. (2) At least 3.75 ml or 15 percent of the ingredient shall be used in the growth medium for the preparation of at least 75 cm 2 test monolayers. The ingredient shall also be used in the growth medium … | |||||
| 9:9:1.0.1.5.51.0.76.38 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.54 Sterile diluent. | APHIS | [39 FR 27428, July 29, 1974, as amended at 56 FR 66784, Dec. 26, 1991] | Sterile Diluent shall be supplied in a final container by the licensee when such diluent is required for rehydration or dilution of the vaccine. (a) Sterile Diluent may be distilled or deionized water or it may be a special liquid solution formulated in accordance with an acceptable outline on file with Animal and Plant Health Inspection Service. (b) Each quantity prepared at one time in a single container and bottled into final containers shall be designated as a serial. Each serial shall be given a number which shall be used in records, test reports, and on the final container label. (c) Final container samples from each serial shall be tested for bacteria and fungi in accordance with the test provided in § 113.26. Any serial found to be unsatisfactory shall not be released. | |||||
| 9:9:1.0.1.5.51.0.76.39 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.55 Detection of extraneous agents in Master Seed Virus. | APHIS | [50 FR 444, Jan. 4, 1985, as amended at 56 FR 66784, Dec. 26, 1991] | Unless otherwise prescribed in a Standard Requirement or in a filed Outline of Production, each Master Seed Virus (MSV) shall be tested as prescribed in this section. A MSV found unsatisfactory by any prescribed test shall not be used. A serial of biological product shall not be released if produced from a MSV that is found unsatisfactory by any prescribed test. (a) At least a 1.0 ml aliquot per cell culture of MSV shall be dispensed onto monolayers (at least 75 cm 2 in area) of: (1) Vero (African green monkey kidney) cell line; (2) Embryonic cells, neonatal cells, or a cell line of the species for which the vaccine is recommended; and (3) Embryonic cells, neonatal cells, or a cell line of the species of cells in which the MSV is presently being propagated if different than prescribed in paragraphs (a)(1) and (a)(2) of this section. Cell lines used shall have been found satisfactory when tested as prescribed in § 113.52 and primary cells used shall have been found satisfactory when tested as prescribed in § 113.51. If the MSV is cytopathic for or causes hemadsorption in the cells in which it is to be tested, the MSV shall be neutralized with monospecific antiserum supplied or approved by Animal and Plant Health Inspection Service (APHIS) or counteracted by a method approved by APHIS. (b) At least one monolayer of each cell type used in the test shall be maintained as an uninoculated control. (c) Each monolayer shall be maintained at least 14 days. (d) Cells shall be subcultured at least once during the maintenance period. All but the last subculture shall result in at least one new monolayer at least 75 cm 2 . The last subculture shall meet the minimum area requirement specified in §§ 113.46 and 113.47. (e) Monolayers shall be examined regularly throughout the 14-day maintenance period for evidence of cytopathogenic agents. If evidence of a cytopathogenic agent is found, the MSV is unsatisfactory. (f) At the conclusion of the 14-day maintenance period, monolayers shall be tested for: (1) Cytopathog… | |||||
| 9:9:1.0.1.5.51.0.77.40 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.64 General requirements for live bacterial vaccines. | APHIS | [48 FR 33476, July 22, 1983, as amended at 54 FR 19352, May 5, 1989; 56 FR 66784, Dec. 26, 1991; 68 FR 57608, Oct. 6, 2003] | When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a live bacterial vaccine shall meet the requirements in this section. (a) Purity test. Final container samples of completed product from each serial and subserial, and samples of each lot of Master Seed Bacteria shall be tested for the presence of extraneous viable bacteria and fungi in accordance with the test provided in § 113.27(b). (b) Safety tests. (1) Samples of completed product from each serial or first subserial and samples of each lot of Master Seed Bacteria shall be tested for safety in young adult mice in accordance with the test provided in § 113.33(b) unless: (i) The bacteria or agents in the vaccine are inherently lethal for mice. (ii) The vaccine is recommended for poultry. (2) Samples of completed product from each serial or first subserial of live bacterial vaccine shall be tested for safety in one of the species for which the product is recommended as follows: (i) Live bacterial vaccine recommended for use in dogs shall be tested as provided in § 113.40, except that dogs shall be injected with the equivalent of two doses of vaccine administered as recommended on the label. (ii) Live bacterial vaccine recommended for use in cattle shall be tested as provided in § 113.41, except that calves shall be injected with the equivalent of two doses of vaccine administered as recommended on the label. (iii) Live bacterial vaccine recommended for use in sheep shall be tested as provided in § 113.45. (iv) Live bacterial vaccine recommended for use in swine shall be tested as provided in § 113.44. (c) Identity test. At least one of the identity tests provided in this paragraph shall be conducted for the Master Seed Bacteria and final container samples from each serial or first subserial of completed biological product. A known positive control (reference) provided or approved by Animal and Plant Health Inspection Service shall be included in such tests. (1) Fluorescent antibody test. The direct flu… | |||||
| 9:9:1.0.1.5.51.0.77.41 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.65 Brucella Abortus Vaccine. | APHIS | [39 FR 16857, May 10, 1974. Redesignated at 39 FR 25463, July 11, 1974, and amended at 40 FR 758, Jan. 3, 1975; 50 FR 23794, Jan. 6, 1985] | Brucella Abortus Vaccine shall be prepared as a desiccated live culture bacterial vaccine from smooth colonial forms of the Brucella abortus organism, identified as Strain 19. Each serial and subserial shall be tested for purity, potency, and moisture content. A serial or subserial found unsatisfactory by a prescribed test shall not be released. (a) Purity tests. Each serial and subserial shall be tested for purity as provided in this paragraph. (1) Macroscopic and microscopic examination shall be made on bulk samples from production containers. If organisms not typical of Brucella abortus organisms are evident, the serial or subserial is unsatisfactory. (2) Two final container vials of completed product shall be tested by inoculating one tube of Dextrose Andrades broth with gas tube and one tube of thioglycollate broth from each vial. The inoculated media shall be incubated at 35 to 37 °C for 96 hours. If growth not typical of Brucella abortus organisms is evident, the serial or subserial is unsatisfactory. (3) Bacterial dissociation test. Final container samples of completed product from each serial and subserial shall be tested for bacterial dissociation. Smooth colonies are the desired form. Rough colonies are undesirable terminal dissociation forms. Intermediate and intermediate-to-rough are also undesirable. (i) The sample container shall be rehydrated and streaked on one potato agar plate in such a manner as to produce confluent colonies. Artificial reflected light shall be used so that the rays pass through the plate at a 45 °angle. (ii) If the vaccine contains more than 5 percent rough colonies or more than 15 percent total undesirable colonies, the serial or subserial is unsatisfactory. If organisms or growth not characteristic of Brucella abortus are found, the serial or subserial is unsatisfactory. The test may be repeated one time using double the number of samples: Provided, That, if the test is not repeated, the serial or subserial is unsatisfactory. (b) Bacterial count requirem… | |||||
| 9:9:1.0.1.5.51.0.77.42 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.66 Anthrax Spore Vaccine—Nonencapsulated. | APHIS | [50 FR 23794, June 6, 1985, as amended at 56 FR 66784, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Anthrax Spore Vaccine—Nonencapsulated shall be a live spore suspension prepared from nonencapsulated variants of Bacillus anthracis. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.64 and the requirements in this section. (b) Each lot of Master Seed shall be tested for immunogenicity as follows: (1) Forty-two susceptible guinea pigs from the same source each weighing 400 to 500 grams, shall be used as test animals (30 vaccinates and 12 controls). (2) An arithmetic mean spore count of vaccine produced from the highest passage of the Master Seed shall be established before the immunogenicity test is conducted. The guinea pigs used as vaccinates shall be injected as recommended on the label with a predetermined number of vaccine spores. To confirm the dosage, five replicate spore counts shall be conducted on a sample of the vaccine dilution used. (3) Fourteen to fifteen days postvaccination the vaccinates and controls shall each be challenged with not less than 4,500 guinea pig LD 50 of a virulent suspension of Bacillus anthracis furnished or approved by Animal and Plant Health Inspection Service and observed for 10 days. (4) If at least 10 of the 12 controls do not die from Bacillus anthracis within the 10-day postchallenge observation period the test is invalid and may be repeated. (5) If at least 27 of 30 of the vaccinates do not survive the 10-day postchallenge observation period, the Master Seed is unsatisfactory. (6) An Outline of Production change shall be made before authority for use of a new lot of Master Seed shall be granted by Animal and Plant Health Inspection Service. (c) Test Requirements for Release. Each serial and subserial shall meet the applicable general requirements prescribed in 9 CFR 113.64 and the requirements in this paragraph. … | |||||
| 9:9:1.0.1.5.51.0.77.43 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.67 Erysipelothrix Rhusiopathiae Vaccine. | APHIS | [50 FR 23795, June 6, 1985, as amended at 56 FR 66784, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Erysipelothrix Rhusiopathiae Vaccine shall be prepared as a desiccated live culture of an avirulent or modified strain of Erysipelothrix rhusiopathiae. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for vaccine production. (a) The Master Seed shall meet the applicable requirements prescribed in § 113.64 and the requirements in this section. (b) Each lot of Master Seed used for vaccine production shall be tested for immunogenicity. The selected bacterial count from the lot of Master Seed shall be established as follows: (1) Thirty Erysipelothrix rhusiopathiae susceptible swine shall be used as test animals (20 vaccinates and 10 controls) for each route of administration recommended on the label. (2) An arithmetic mean count of the colony forming units from vaccine produced from the highest passage of the Master Seed shall be established before the immunogenicity test is conducted. The 20 swine to be used as vaccinates shall be injected as recommended on the label with a predetermined quantity of vaccine bacteria. The 10 control swine shall be held separately from the vaccinates. To confirm the dosage calculation, an arithmetic mean count shall be established by conducting five replicate titrations on a sample of the bacterial vaccine dilution used. Only plates containing between 30 and 300 colonies shall be considered in a valid test. (3) The vaccinates and controls shall be examined and their average body temperature determined prior to challenge. Fourteen to twenty-one days postvaccination, the vaccinates and controls shall be challenged with a virulent Erysipelothrix rhusiopathiae culture and observed for 7 days. The challenge culture and instructions for preparation and use shall be obtained from Animal and Plant Health Inspection Service. (4) A satisfactory challenge shall be evidenced in the controls by a high body temperature or clinical signs including, but not limited to acute illness with hyperemia of the abdomen and ears, possibly terminating in sudd… | |||||
| 9:9:1.0.1.5.51.0.77.44 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.68 Pasteurella Haemolytica Vaccine, Bovine. | APHIS | [55 FR 35559, Aug. 31, 1990, as amended at 72 FR 72564, Dec. 21, 2007] | Pasteurella Haemolytica Vaccine, Bovine, shall be prepared as a desiccated live culture bacterial vaccine of an avirulent or modified strain of Pasteurella haemolytica, identified as serotype 1. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.64 and the requirements in this section. (b) Each lot of Master Seed used for vaccine production shall be tested for immunogenicity. The immunogenicity of a selected bacterial count from the lot of Master Seed shall be established as follows: (1) Fifteen Pasteurella haemolytica susceptible calves shall be used as test animals (10 vaccinates and 5 controls) for each route of administration recommended on the label. (2) An arithmetic mean count of the colony forming units from vaccine produced from the highest passage of the Master Seed shall be established before the immunogenicity test is conducted. The 10 calves to be used as vaccinates shall be injected as recommended on the label with a predetermined quantity of vaccine bacteria. The five control calves shall be held separately from the vaccinates. To confirm the dosage calculation, five replicate titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies shall be considered a valid test. (3) The vaccinates and controls shall be examined and their average body temperature determined prior to challenge. Fourteen to twenty-one days post vaccination, the vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia producing Pasteurella haemolytica culture and observed for 4 to 7 days. The challenge culture and instructions for preparation for use shall be furnished or approved by the Animal and Plant Health Inspection Service. (4) A satisfactory challenge shall be evidenced in… | |||||
| 9:9:1.0.1.5.51.0.77.45 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.69 Pasteurella Multocida Vaccine, Bovine. | APHIS | [55 FR 35560, Aug. 31, 1990, as amended at 72 FR 72564, Dec. 21, 2007] | Pasteurella Multocida Vaccine, Bovine, shall be prepared as a desiccated live culture bacterial vaccine of an avirulent or modified strain of Pasteurella multocida, of bovine origin. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.64 and the requirements in this section. (b) Each lot of Master Seed used for vaccine production shall be tested for immunogenicity. The immunogenicity of a selected bacterial count from the lot of Master Seed shall be established as follows: (1) Fifteen Pasteurella multocida susceptible calves shall be used as test animals (10 vaccinates and 5 controls) for each route of administration recommended on the label. (2) An arithmetic mean count of the colony forming units from vaccine produced from the highest passage of the Master Seed shall be established before the immunogenicity test is conducted. The 10 calves to be used as vaccinates shall be injected as recommended on the label with a predetermined quantity of vaccine bacteria. The five control calves shall be held separately from the vaccinates. To confirm the dosage calculation, arithmetic mean count shall be established by conducting five replicate titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies shall be considered a valid test. (3) The vaccinates and controls shall be examined and their average body temperature determined prior to challenge. Fourteen to twenty-one days post vaccination, the vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia producing Pasteurella multocida culture and observed for 4 to 10 days. The challenge culture and instructions for preparation for use shall be furnished or approved by the Animal and Plant Health Inspection Service. (4) A sa… | |||||
| 9:9:1.0.1.5.51.0.77.46 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.70 Pasteurella Multocida Vaccine, Avian Isolate. | APHIS | [55 FR 35560, Aug. 31, 1990, as amended at 59 FR 19633, Apr. 25, 1994; 64 FR 43044, Aug. 9, 1999; 72 FR 72564, Dec. 21, 2007] | Pasteurella Multocida Vaccine, Avian Isolate, shall be prepared as a desiccated live culture of an avirulent or modified strain of Pasteurella multocida. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for vaccine production. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.64 and the requirements in this section. (b) Each lot of Master Seed used for vaccine production shall be tested for immunogenicity in each species and for each serotype for which the Master Seed is claimed to give protection. (1) Thirty Pasteurella multocida susceptible birds shall be used as test animals (20 vaccinates and 10 controls) for each bird species, route of administration, and serotype for which protection is claimed on the label. (2) An arithmetic mean count of colony forming units from vaccine produced from the highest passage of Master Seed shall be established before the immunogenicity test is conducted. The 20 birds to be used as vaccinates shall be inoculated, as recommended on the label with a predetermined quantity of vaccine bacteria. The 10 control birds shall be held separately from the vaccinates. To confirm the dosage calculation, an arithmetic mean count shall be established by conducting five replicate titrations on a sample of the bacterial vaccine used. Only plates containing between 30 and 300 colonies shall be considered in a valid test. (3) Not less than 14 days after vaccination, each of 20 vaccinates and each of 10 unvaccinated controls shall be challenged intramuscularly or by other methods acceptable to the Animal and Plant Health Inspection Service with a virulent Pasteurella multocida strain, for which protection is claimed, and observed daily for a 14 day post-challenge period. (4) Eight or more of the unvaccinated controls must die for the test to be valid. If at least 16 of 20 of the vaccinates do not survive the 14-day postchallenge period, the Master Seed is unsatisfactory at the selected bacterial count. (c) … | |||||
| 9:9:1.0.1.5.51.0.77.47 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. | APHIS | [55 FR 35561, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be prepared from chlamydia-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable requirements prescribed in § 113.300 and the requirements in this section. Master Seed propagated in chicken embryos shall be tested for pathogens by the chicken embryo test prescribed in § 113.37. If found unsatisfactory by any prescribed test, the Master Seed shall not be used. (b) Each lot of Master Seed used for vaccine production shall be tested for immunogenicity. The immunogenicity of a selected dose from the lot of Master Seed shall be established as follows: (1) Thirty feline pneumonitis susceptible cats shall be used as test animals (20 vaccinates and 10 controls). Blood samples shall be drawn and individual serum samples tested. The cats shall be considered suitable for use if all serums are negative for pneumonitis antibody in a complement fixation test or other test of equal sensitivity. (2) A geometric mean titer of the dried vaccine produced from the highest passage of the Master Seed shall be established before the immunogenicity test is conducted. The 20 cats used as vaccinates shall be administered a predetermined quantity of vaccine by the method to be recommended on the label and the remaining 10 cats shall be held as controls. To confirm the dosage calculations, five replicate titrations shall be conducted on a sample of the vaccine dilution used. If two doses are used, five replicate confirming titrations shall be conducted on each dose. (3) Fourteen or more days after the final dose of vaccine, the vaccinates and controls shall each be challenged intranasally with a minimum of 10,000 yolk sac LD50 of virulent feline pneumonitis furnished or approved by the Animal and Plant He… | |||||
| 9:9:1.0.1.5.51.0.78.48 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.100 General requirements for inactivated bacterial products. | APHIS | [39 FR 16862, May 10, 1974. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 60 FR 14355, Mar. 17, 1995; 68 FR 35283, June 13, 2003; 79 FR 31021, May 30, 2014] | Unless otherwise prescribed in an applicable Standard Requirement or in the filed Outline of Production, an inactivated bacterial product shall meet the applicable requirements in this section. (a) Purity tests. (1) Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (2) Each lot of Master Seed Bacteria shall be tested for the presence of extraneous viable bacteria and fungi in accordance with the test provided in § 113.27(d). (b) Safety tests. Bulk or final container samples of completed product from each serial shall be tested for safety in young adult mice in accordance with the test provided in § 113.33(b) unless: (1) The product contains material which is inherently lethal for mice. In such instances, the guinea pig safety test provided in § 113.38 shall be conducted in place of the mouse safety test. (2) The product is recommended for poultry. In such instances, the product shall be safety tested in poultry as defined in the specific Standard Requirement or Outline of Production for the product. (3) The product is recommended for fish, other aquatic species, or reptiles. In such instances, the product shall be safety tested in fish, other aquatic species, or reptiles as required by specific Standard Requirement or Outline of Production for the product. (c) Identity test. Methods of identification of Master Seed Bacteria to the genus and species level by laboratory tests shall be sufficient to distinguish the bacteria from other similar bacteria according to criteria described in the most recent edition of “Bergey's Manual of Systematic Bacteriology” or the American Society for Microbiology “Manual of Clinical Microbiology”. If Master Seed Bacteria are referred to by serotype, serovar, subtype, pilus type, strain or other taxonomic subdivision below the species level, adequate testing must be used to identify the bacteria to that level. Tests which may be used to identify Master Seed Bacteria incl… | |||||
| 9:9:1.0.1.5.51.0.78.49 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.101 Leptospira Pomona Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 20067, May 8, 1975; 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Leptospira Pomona Bacterin shall be produced from a culture of Leptospira pomona which has been inactivated and is nontoxic. Each serial of biological product containing Leptospira pomona fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product shall be diluted with physiological saline so that each 0.25 ml contains not more than 1/800th of the dose recommended on the label and shall be tested for potency, using the two-stage test provided in this paragraph. (1) Vaccinates. Inject each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either subcutaneously or intramuscularly, in accordance with the label recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3) Challenge. From 14 to 18 days postvaccination, challenge each of 10 vaccinates and each of 10 controls intraperitoneally with a suspension of virulent Leptospira pomona organisms, using a dose of 10-10,000 hamster LD 50 as determined by titration. (4) Post-challenge period. Observe the vaccinates and controls for 14 days post-challenge and record all deaths. If eight or more controls die of leptospirosis, the test is valid and the results shall be evaluated according to the following table: (5) If three or four vaccinates die in the first stage, the second stage shall be conducted in a manner identical to the first stage. (6) If the… | |||||
| 9:9:1.0.1.5.51.0.78.50 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.102 Leptospira Icterohaemorrhagiae Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Leptospira Icterohaemorrhagiae Bacterin shall be produced from a culture of Leptospira icterohaemorrhagiae which has been inactivated and is nontoxic. Each serial of biological product containing Leptospira icterohaemorrhagiae fraction shall meet the applicable requirements in § 113.100 and be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product shall be diluted with physiological saline so that each 0.25 ml contains not more than 1/80th of the dose recommended on the label and shall be tested for potency, using the two-stage test provided in this paragraph. (1) Vaccinates. Inject each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either subcutaneously or intramuscularly, in accordance with the label recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3) Challenge. From 14 to 18 days postvaccination, challenge each of 10 vaccinates and each of 10 controls intraperitoneally with a suspension of virulent Leptospira icterohaemorrhagiae organisms, using a dose of 10-10,000 hamster LD 50 as determined by titration. (4) Post-challenge period. Observe the vaccinates and controls for 14 days post-challenge and record all deaths. If eight or more controls die from leptospirosis, the test is valid and the results shall be evaluated according to the following table: (5) If three or four vaccinates die in the first stage, the second stage shall be used. The second… | |||||
| 9:9:1.0.1.5.51.0.78.51 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.103 Leptospira Canicola Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Leptospira Canicola Bacterin shall be produced from a culture of Leptospira canicola which has been inactivated and is nontoxic. Each serial of biological product containing Leptospira canicola fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. Serials found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product shall be diluted with physiological saline so that each 0.25 ml contains not more than 1/80th of the dose recommended on the label and shall be tested for potency, using the two-stage test provided in this paragraph. (1) Vaccinates. Inject each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either subcutaneously or intramuscularly, in accordance with the label recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3) Challenge. From 14 to 18 days postvaccination, challenge each of 10 vaccinates and each of 10 controls intraperitoneally with a suspension of virulent Leptospira canicola organisms, using a dose of 10-10,000 hamster LD 50 as determined by titration. (4) Post-challenge period. Observe the vaccinates and controls for 14 days post-challenge and record all deaths. If eight or more controls die from leptospirosis, test is valid and the results shall be evaluated according to the following table: (5) If three or four vaccinates die in the first stage, the second stage shall be used. The second stage shall be conducted in a manner ident… | |||||
| 9:9:1.0.1.5.51.0.78.52 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.104 Leptospira Grippotyphosa Bacterin. | APHIS | [40 FR 17003, Apr. 16, 1975, as amended at 40 FR 23989, June 4, 1975; 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Leptospira Grippotyphosa Bacterin shall be produced from a culture of Leptospira grippotyphosa which has been inactivated and is nontoxic. Each serial of biological product containing Leptospira grippotyphosa fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product shall be diluted with physiological saline so that each 0.25 ml contains not more than 1/800th of the dose recommended on the label and shall be tested for potency, using the two-stage test provided in this paragraph. (1) Vaccinates. Inject each of at least 10 but not more than 12 young adult hamsters, each weighing 50 to 90 grams, with 0.25 ml of the diluted bacterin either subcutaneously or intramuscularly, in accordance with the label recommendations for use. (2) Controls. Retain at least 10 but not more than 12 additional hamsters from the same group as unvaccinated controls. (3) Challenge. From 14 to 18 days postvaccination, challenge each of 10 vaccinates and each of 10 controls intraperitoneally with a suspension of virulent Leptospira grippotyphosa organisms, using a dose of 10-10,000 hamster LD 50 as determined by titration. (4) Post-challenge period. Observe the vaccinates and controls for 14 days post-challenge and record all deaths. If eight or more controls die of leptospirosis, the test is valid and the results shall be evaluated according to the following table: Cumulative Totals (5) If three or four vaccinates die in the first stage, the second stage shall be conducted in a m… | |||||
| 9:9:1.0.1.5.51.0.78.53 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.105 Leptospira Hardjo Bacterin. | APHIS | [40 FR 17003, Apr. 16, 1975, as amended at 40 FR 20067, May 8, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Leptospira Hardjo Bacterin shall be produced from a culture of Leptospira hardjo which has been inactivated and is nontoxic. Each serial of biological product containing Leptospira hardjo fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the test written into the filed Outline of Production. | |||||
| 9:9:1.0.1.5.51.0.78.54 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.106 Clostridium Chauvoei Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990 and amended at 56 FR 66784, 66785, Dec. 26, 1991] | Clostridium Chauvoei Bacterin shall be produced from a culture of Clostridium chauvoei which has been inactivated and is nontoxic. Each serial of biological product containing Clostridium chauvoei fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. Serials found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the two-stage test provided in this paragraph. (1) Each of at least 8 but not more than 10 guinea pigs, each weighing 300 to 500 grams, shall be injected subcutaneously with a guinea pig dose. A second guinea pig dose shall be injected 21 to 23 days after the first dose. Each guinea pig dose shall be one-fifth of the dose recommended on the label for a calf. (2) Clostridium chauvoei challenge material, available upon request from Animal and Plant Health Inspection Service, shall be used for challenge 14 to 15 days following the last injection of the product. Each of eight vaccinates and each of five additional nonvaccinated guinea pigs for controls shall be injected intramuscularly with approximately 100 LD 50 of challenge material. This dose shall be determined by statistical analysis of results of titrations of the challenge material. The vaccinates and controls shall be observed for 3 days postchallenge and all deaths recorded. (3) For a valid test, at least 80 percent of the controls shall die within the 3 day post-challenge observation period. If this requirement is met, the results of the potency test shall be evaluated according to the following table: The … | |||||
| 9:9:1.0.1.5.51.0.78.55 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.107 Clostridium Haemolyticum Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 20067, May 8, 1975; 45 FR 40100, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66785, Dec. 26, 1991] | Clostridium Haemolyticum Bacterin shall be produced from a culture of Clostridium haemolyticum which has been inactivated and is nontoxic. Each serial of biological product containing Clostridium haemolyticum fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the two-stage test provided in this paragraph. (1) Each of at least 8 but not more than 10 guinea pigs, each weighing 300 to 500 grams, shall be injected subcutaneously with a guinea pig dose. A second guinea pig dose shall be injected 21 to 23 days after the first dose. Each guinea pig dose shall be one-fifth of the dose recommended on the label for a calf. (2) Clostridium haemolyticum challenge material, available upon request from Animal and Plant Health Inspection Service, shall be used for challenge 14 to 15 days following the last injection of the product. Each of eight vaccinates and each of five additional nonvaccinated guinea pigs for controls shall be injected intramuscularly with approximately 100 LD 50 of challenge material. This dose shall be determined by statistical analysis of results of titrations of the challenge material. The vaccinates and controls shall be observed for 3 days postchallenge and all deaths recorded. (3) For a valid test, at least 80 percent of the controls shall die within the 3 day post-challenge observation period. If this requirement is met, the results of the potency test shall be evaluated according to the follo… | |||||
| 9:9:1.0.1.5.51.0.78.56 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.108 Clostridium Novyi Bacterin-Toxoid. | APHIS | [39 FR 16862, May 10, 1974, as amended at 45 FR 40101, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990; 56 FR 37825, Aug. 9, 1991, as amended at 56 FR 66784, 66785, Dec. 26, 1991] | Clostridium Novyi Bacterin-Toxoid shall be produced from a culture of Clostridium novyi which has been inactivated and is nontoxic. Each serial of biological product containing Clostridium novyi fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the Alpha toxin-neutralization test provided in this paragraph. (1) When used in this test, the following words and terms shall mean: (i) International antitoxin unit. (I.U.) That quantity of Alpha Antitoxin which reacts with Lo and L + doses of Standard Toxin according to their definitions. (ii) Lo dose. The largest quantity of toxin which can be mixed with one unit of Standard Antitoxin and not cause sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard antitoxin. The Alpha Antitoxin preparation which has been standardized as to antitoxin unitage on the basis of the International Clostridium novyi Alpha Antitoxin Standard and which is either supplied by or acceptable to the Animal and Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v) Standard toxin. The Alpha toxin preparation which is supplied by or is acceptable to the Animal and Plant Health Inspection Service. (vi) Diluent. The solution used to make proper dilutions prescribed in this test. Such soluti… | |||||
| 9:9:1.0.1.5.51.0.78.57 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.109 Clostridium Sordellii Bacterin-Toxoid. | APHIS | [39 FR 16862, May 10, 1974, as amended at 42 FR 61247, Dec. 2, 1977; 45 FR 40101, June 13, 1980. Redesignated at 55 FR 35562, Aug. 31, 1990; 56 FR 37826, Aug. 9, 1991; 56 FR 66784, 66785, Dec. 26, 1991; 79 FR 55969, Sept. 18, 2014] | Clostridium Sordellii Bacterin-Toxoid shall be produced from a culture of Clostridium sordellii which has been inactivated and is nontoxic. Each serial of biological product containing Clostridium sordellii fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the toxin-neutralization test provided in this paragraph. (1) When used in this test, the following words and terms shall mean: (i) International antitoxin unit. (I.U.) That quantity of antitoxin which reacts with Lo and L + doses of Standard Toxin according to their definitions. (ii) Lo dose. The largest quantity of toxin which can be mixed with one unit of Standard Antitoxin and not cause sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard antitoxin. The antitoxin preparation which has been standardized as to antitoxin unitage on the basis of the International Clostridium sordellii Antitoxin Standard and which is either supplied by or acceptable to the Animal and Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v) Standard toxin. The toxin preparation which is supplied by or is acceptable to the Animal and Plant Health Inspection Service. (vi) Diluent. The solution used to make proper dilutions prescribed in this test. Such solutions shall be m… | |||||
| 9:9:1.0.1.5.51.0.78.58 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.110 Clostridium Botulinum Type C Bacterin-Toxoid. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 759, Jan. 3, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Clostridium Botulinum Type C Bacterin-Toxoid shall be produced from a culture of Clostridium botulinum Type C which has been inactivated and is nontoxic. Each serial of biological product containing Clostridium botulinum Type C fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency, using susceptible mink as test animals. At least five vaccinates and three unvaccinated controls of the same source and approximately the same age shall be used. (1) Each of the vaccinates shall be injected subcutaneously with the dose recommended on the label for mink. Twenty-one to twenty-eight days post-injection, the vaccinates and the controls shall be challenged intraperitoneally with botulinum Type C toxin which has been titrated in mice to provide for a 10 4.0 mouse MLD dose. The titration technique shall include inoculation of the mice intraperitoneally. (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.78.59 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.111 Clostridium Perfringens Type C Toxoid and Bacterin-Toxoid. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 759, Jan. 3, 1975; 40 FR 41088, Sept. 5, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66785, Dec. 26, 1991; 62 FR 31330, June 9, 1997; 79 FR 55969, Sept. 18, 2014] | Clostridium Perfringens Type C Toxoid and Clostridium Perfringens Type C Bacterin-Toxoid shall be produced from a culture of Clostridium perfringens Type C which has been inactivated and is nontoxic. Each serial shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. Any serial found unsatisfactory by a prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the Beta toxin-neutralization test provided in this paragraph. (1) When used in this test, the following words and terms shall mean: (i) International antitoxin unit. (I.U.) That quantity of Beta Antitoxin which reacts with L 0 and L + doses of Standard Toxin according to their definitions. (ii) L 0 dose. The largest quantity of toxin which can be mixed with one unit of Standard Antitoxin and not cause sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard antitoxin. The Beta Antitoxin preparation which has been standardized as to antitoxin unitage on the basis of the International Clostridium perfringens Beta Antitoxin Standard and which is either supplied by or acceptable to Animal and Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v) Standard toxin. The Beta toxin preparation which is supplied by or is acceptable to Animal and Plant Health Inspection Service. (vi) Diluent. The solution used to make proper dilutions prescribed in this t… | |||||
| 9:9:1.0.1.5.51.0.78.60 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.112 Clostridium Perfringens Type D Toxoid and Bacterin-Toxoid. | APHIS | [39 FR 16865, May 10, 1974; 39 FR 20783, June 14, 1974. Redesignated at 39 FR 25463, July 11, 1974, and amended at 40 FR 759, Jan. 3, 1975; 40 FR 41088, Sept. 5, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66785, Dec. 26, 1991; 62 FR 31331, June 9, 1997; 79 FR 55969, Sept. 18, 2014] | Clostridium Perfringens Type D Toxoid and Clostridium Perfringens Type D Bacterin-Toxoid shall be produced from a culture of Clostridium perfringens Type D which has been inactivated and is nontoxic. Each serial shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. Any serial found unsatisfactory by a prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the Epsilon toxin-neutralization test provided in this paragraph. (1) When used in this test, the following words and terms shall mean: (i) International antitoxin unit. (I.U.) That quantity of Epsilon Antitoxin which reacts with L 0 and L + doses of Standard Toxin according to their definitions. (ii) L 0 dose. The largest quantity of toxin which can be mixed with one-tenth unit of Standard Antitoxin and not cause sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one-tenth unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard antitoxin. The Epsilon Antitoxin preparation which has been standardized as to antitoxin unitage on the basis of the International Clostridium perfringens Epsilon Antitoxin Standard and which is either supplied by or acceptable to Animal and Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v) Standard toxin. The Epsilon toxin preparation which is supplied by or is acceptable to Animal and Plant Health Inspection Service. (vi) Diluent. The solution used to make proper dilutions… | |||||
| 9:9:1.0.1.5.51.0.78.61 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.113 Autogenous biologics. | APHIS | [57 FR 38756, Aug. 27, 1992, as amended at 59 FR 67616, Dec. 30, 1994; 64 FR 43044, Aug. 9, 1999; 67 FR 15714, Apr. 3, 2002; 75 FR 20773, Apr. 21, 2010] | Autogenous biologics shall be prepared from cultures of microorganisms which have been inactivated and are nontoxic. Such products shall be prepared only for use by or under the direction of a veterinarian under a veterinarian-client-patient relationship, Provided, That, such products may be prepared for use under the direction of a person of appropriate expertise in specialized situations such as aquaculture, if approved by the Administrator. Each serial of an autogenous biologic shall meet the requirements in this section, and if found unsatisfactory by any prescribed test shall not be used. (a) Seed requirements. The microorganisms used as seed to prepare autogenous biologics shall be microorganisms which are isolated from sick or dead animals in the herd of origin and which there is reason to believe are the causative agent(s) of the current disease affecting such animals. (1) More than one microorganism isolated from the same herd may be used as seed. (2) Under normal circumstances, microorganisms from one herd must not be used to prepare an autogenous biologic for another herd. The Administrator, however, may authorize preparation of an autogenous biologic for use in herds adjacent to the herd of origin, when adjacent herds are considered to be at risk. To request authorization to prepare a product for use in herds adjacent to the herd of origin, the establishment seeking authorization must submit to the Administrator (in c/o the Director, Center for Veterinary Biologics, Inspection and Compliance, 1920 Dayton Avenue, P.O. Box 844, Ames, IA 50010) the following information. (If any of the data are unavailable, the applicant for authorization should indicate that such data are unavailable and why.) (i) Name, address, and phone number of the owner of the herd of origin. (ii) Attending veterinarian's name, address, and phone number. (iii) Animal species and number in herd of origin. (iv) Identification of microorganism(s), at least to genus. (v) Diagnosis or clinical signs of the disease observed.… | |||||
| 9:9:1.0.1.5.51.0.78.62 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.114 Tetanus Toxoid. | APHIS | [39 FR 16862, May 10, 1974, as amended at 46 FR 23224, Apr. 24, 1981; 50 FR 24905, June 14, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 37827, Aug. 9, 1991; 56 FR 66785, Dec. 26, 1991] | Tetanus Toxoid shall be produced from a culture of Clostridium tetani which has been inactivated and is nontoxic. The toxoid may be either absorbed, precipitated, or purified and concentrated. Each serial of biological product containing tetanus toxoid fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial or subserial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency. A group of 10 guinea pigs consisting of an equal number of males and females weighing 450 to 550 grams shall each be injected subcutaneously with 0.4 of the largest dose recommended on the product labels. (1) Six weeks after injection, all surviving guinea pigs shall be bled and equal portions of serum, but not less than 0.5 ml from each, shall be pooled. For a valid test, the pool shall contain the serum from at least eight animals. (2) The antitoxin titer of the pooled serum shall be determined in antitoxin units (A.U.) per ml using an enzyme-linked immunosorbent assay method acceptable to the Animal and Plant Health Inspection Service. (3) If the antitoxin titer of the serum pool is at least 2.0 A.U. per ml, the serial is satisfactory. If the antitoxin titer of the serum pool is less than 2.0 A.U. per ml, the serial may be retested by the following procedure: Provided, That, if the serial is not retested, it shall be declared unsatisfactory. (4) For serials in which the serum pool contains less than 2.0 A.U. per ml, the individual serum that constituted the pool may be tested by the enzyme-linked imm… | |||||
| 9:9:1.0.1.5.51.0.78.63 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.115 Staphylococcus Aureus Bacterin-Toxoid. | APHIS | [39 FR 16862, May 10, 1974. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Staphylococcus Aureus Bacterin-Toxoid shall be prepared from toxoided broth cultures of selected toxogenic strains of Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product containing Staphylococcus Aureus Bacterin-Toxoid shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product shall be tested for safety as provided in § 113.33(b). Also, the rabbits used in the potency test provided in paragraph (c) of this section shall constitute an additional safety test. If unfavorable reactions attributable to the product occur in any of the rabbits during the observation period, the serial is unsatisfactory. (c) Potency test. Rabbits, each weighing 2000-3000 grams, shall be used as test animals. Either a five rabbit individual serum test or an eight rabbit pooled serum test shall be conducted. At the start of the test, individual serums from the five rabbits or pooled serums from the eight rabbits shall contain less than 0.2 alpha antitoxin units per ml. (1) Each rabbit shall be given a series of not more than three intramuscular injections at 7 day intervals (1.0 ml, 2.0 ml, 3.0 ml) and observed from 7-14 days following the third injection. At the end of the observation period, a blood sample shall be taken from each rabbit. (2) The sample of serum from each rabbit, if the five rabbit individual test is conducted or a pooled sample of equal quantities of serum from the rabbits if the eight rabbit pooled serum test is conducted, shall be tested to determine the staphylococcus alpha antitoxin units per ml as provided in paragraphs (c)(3), (4), (5), (6), (7), and (8) of this section. (3) Inactivate ra… | |||||
| 9:9:1.0.1.5.51.0.78.64 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.116 Pasteurella Multocida Bacterin, Avian Isolate, Type 4. | APHIS | [47 FR 5795, Feb. 4, 1982; 47 FR 6817, Feb. 17, 1982, as amended at 52 FR 9117, Mar. 23, 1987. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Pasteurella Multocida Bacterin, Avian Isolate, Type 4 shall be prepared from cultures of Pasteurella multocida, avian isolate, Type 4 (Little and Lyons classification), which have been inactivated, and are nontoxic. Each serial of biological product containing Pasteurella Multocida Bacterin, Avian Isolate, Type 4, shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency, as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in 9 CFR 113.26. (b) Safety test. Observation of the vaccinated turkeys during the prechallenge period of the potency test provided in paragraph (c) of this section shall constitute the safety test. If unfavorable reactions that are attributable to the product occur, the serial is unsatisfactory. If unfavorable reactions that are not attributable to the product occur in one turkey, test results shall be determined by observing the remaining 20 turkeys. The test is a No Test and may be repeated if unfavorable reactions that are not attributable to the product occur in two or more turkeys, but the serial is unsatisfactory if the test is not repeated. (c) Potency test. Bulk or final container samples of completed product shall be tested for potency of the Type 4 strain, using the two-stage test provided in this paragraph. Turkeys at least 6 weeks old obtained from the same source and hatch shall be properly identified and used as provided in this paragraph. (1) Vaccinates. Each of not more than 21 turkeys shall be vaccinated with the dose and by the route recommended on the label. A second dose shall be given after 3 weeks and the turkeys observed for an additional 2-week prechallenge period. (2) Unvaccinated controls. Each of not more than 11 turkeys shall be held as controls. (3) Challenge. Not less than 14 days after the second dose, each of 20 vaccinates, a… | |||||
| 9:9:1.0.1.5.51.0.78.65 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.117 Pasteurella Multocida Bacterin, Avian Isolate, Type 1. | APHIS | [39 FR 16866, May 10, 1974; 39 FR 20368, June 10, 1974, as amended at 40 FR 759, Jan. 3, 1975; 40 FR 23989, June 4, 1975; 47 FR 5195, Feb. 4, 1982; 52 FR 9118, Mar. 23, 1987. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Pasteurella Multocida Bacterin, Avian Isolate, Type 1, shall be prepared from cultures of Pasteurella multocida, avian isolate, Type 1 (Little and Lyons classification), which have been inactivated and are nontoxic. Each serial of biological product containing Pasteurella Multocida Bacterin, Avian Isolate, Type 1, shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Observation of the vaccinated chickens during the prechallenged period of the potency test provided in paragraph (c) of this section shall constitute the safety test. If unfavorable reactions that are attributable to the product occur, the serial is unsatisfactory. If unfavorable reactions that are not attributable to the product occur in one chicken, test results shall be determined by observing the remaining 20 chickens. The test is a No Test and may be repeated if unfavorable reactions that are not attributable to the product occur in two or more chickens, but the serial is unsatisfactory if the test is not repeated. (c) Potency test. Bulk or final container samples of completed product shall be tested for potency of the Type 1 strain, using the two-stage test provided in this paragraph. Chickens, at least 12 weeks of age, obtained from the same source and hatch, shall be properly identified and used as provided in this paragraph. (1) Vaccinates. Each of not more than 21 chickens shall be injected with the dose and by the route recommended on the label. A second dose shall be injected after 3 weeks and the chickens observed for an additional 2 week prechallenge period. (2) Unvaccinated controls. Each of not more than 11 chickens shall be held as controls. (3) Challenge. Not less than 14 days after the second injection, each of… | |||||
| 9:9:1.0.1.5.51.0.78.66 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.118 Pasteurella Multocida Bacterin, Avian Isolate, Type 3. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 759, Jan. 3, 1975; 47 FR 5196, Feb. 4, 1982; 52 FR 9118, Mar. 23, 1987. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Pasteurella Multocida Bacterin, Avian Isolate, Type 3, shall be prepared from culture of Pasteurella multocida, avian isolate, Type 3 (Little and Lyons classification), which have been inactivated and are nontoxic. Each serial of biological product containing Pasteurella Multocida Bacterin, Avian Isolate, Type 3, shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency, as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Observation of the vaccinated turkeys during the prechallenge period of the potency test provided in paragraph (c) of this section shall constitute the safety test. If unfavorable reactions that are attributable to the product occur, the serial is unsatisfactory. If unfavorable reactions that are not attributable to the product occur in one turkey, test results shall be determined by observing the remaining 20 turkeys. The test is a No Test and may be repeated if unfavorable reactions that are not attributable to the product occur in two or more turkeys, but the serial is unsatisfactory if the test is not repeated. (c) Potency test. Bulk or final container samples of completed product shall be tested for potency of the Type 3 strain, using the two-stage test provided in this paragraph. Turkeys, at least 6 weeks of age, obtained from the same source and hatch, shall be properly identified and used as provided in this paragraph. (1) Vaccinates. Each of not more than 21 turkeys shall be injected with the dose and by the route recommended on the label. A second dose shall be injected after 3 weeks and the turkeys observed for an additional 2 week prechallenge period. (2) Unvaccinated controls. Each of not more than 11 turkeys shall be held as controls. (3) Challenge. Not less than 14 days after the second injection, each of 20 vaccin… | |||||
| 9:9:1.0.1.5.51.0.78.67 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.119 Erysipelothrix Rhusiopathiae Bacterin. | APHIS | [39 FR 16862, May 10, 1974, as amended at 40 FR 759, Jan. 3, 1975; 40 FR 20067, May 8, 1975; 40 FR 51414, Nov. 5, 1975; 44 FR 71408, Dec. 11, 1979; 50 FR 23795, June 6, 1985; 51 FR 23731, July 1, 1986. Redesignated at 55 FR 35562, Aug. 31, 1990; 56 FR 66558, Dec. 24, 1991; 56 FR 66784, 66785, Dec. 26, 1991] | Erysipelothrix Rhusiopathiae Bacterin shall be produced from a culture of Erysipelothrix rhusiopathiae which has been inactivated and is nontoxic. Each serial of biological product containing Erysipelothrix rhusiopathiae shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.38. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the mouse protection test provided in this paragraph. A mouse dose shall be 1/10 of the least dose recommended on the label for swine. Such swine dose shall not be less than 1 ml. (1) The ability of the bacterin being tested (Unknown) to protect mice shall be compared with a Standard Reference Bacterin (Standard) which is either supplied by or acceptable to Animal and Plant Health Inspection Service. (2) At least three threefold dilutions shall be made with the Standard and the same threefold dilutions shall be made for each Unknown. Dilutions shall be made with physiological saline solution. (3) For each dilution of the Standard and each dilution of an Unknown, a group of at least 20 mice, each weighing 16 to 22 grams, shall be used. Each mouse in each group shall be injected subcutaneously with one mouse dose of the appropriate dilution. (4) Each of 20 injected mice from each group shall be challenged subcutaneously 14 to 21 days after being injected. A dose containing at least 100 mouse LD 50 of a suitable culture of Erysipelothrix rhusiopathiae shall be used. All survivors in each group of mice shall be recorded 10 days postchallenge. (5) T… | |||||
| 9:9:1.0.1.5.51.0.78.68 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.120 Salmonella Typhimurium Bacterin. | APHIS | [40 FR 17003, Apr. 16, 1975, as amended at 42 FR 59487, Nov. 18, 1977; 48 FR 31008, July 6, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66785, Dec. 26, 1991] | Salmonella Typhimurium Bacterin shall be prepared from a culture of Salmonella typhimurium which has been inactivated and is nontoxic. Each serial of biological product containing Salmonella typhimurium fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the mouse test provided in this paragraph. A mouse dose shall be 1/20 of the least dose recommended on the label for other animals which shall not be less than 2 ml. (1) The ability of the bacterin being tested (Unknown) to protect mice shall be compared with a Standard Reference Bacterin (Standard) which is either supplied by or acceptable to Animal and Plant Health Inspection Service. (2) At least three tenfold dilutions shall be made with the Standard and the same tenfold dilutions shall be made for each Unknown. The dilutions shall be made in Phosphate Buffered Saline. (3) For each dilution of the Standard and each dilution of an Unknown, a group of at least 20 mice, each weighing 16-22 grams, shall be used. Each mouse in a group shall be injected intraperitoneally with one mouse dose of the appropriate dilution. Each mouse shall be revaccinated on day 14, using the same schedule. (4) Each of 20 vaccinated mice per group shall be challenged intraperitoneally 7-10 days after the second vaccination with a 0.25 ml dose containing 100-10,000 mouse LD 50 as determined by titration, of a suitable culture of Salmonella typhimurium. All survivors in each group of mice shall be recorded 14 d… | |||||
| 9:9:1.0.1.5.51.0.78.69 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.121 Pasteurella Multocida Bacterin. | APHIS | [40 FR 17004, Apr. 16, 1975, as amended at 42 FR 59487, Nov. 18, 1977; 48 FR 31008, July 6, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66785, Dec. 26, 1991] | Pasteurella Multocida Bacterin shall be prepared from a culture of Pasteurella multocida strains other than avian which have been inactivated and are nontoxic. Each serial of biological product containing Pasteurella multocida fraction shall meet the applicable requirements in § 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product from each serial and each subserial shall be tested for viable bacteria and fungi as provided in § 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in § 113.33(b). The subcutaneous route is to be used. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the mouse test provided in this paragraph. A mouse dose shall be 1/20 of the least dose recommended on the label for other animals which shall not be less than 2 ml. (1) The ability of the bacterin being tested (Unknown) to protect mice shall be compared with a Standard Reference Bacterin (Standard) which is either supplied by or acceptable to Animal and Plant Health Inspection Service. (2) At least three fivefold dilutions shall be made with the Standard and the same fivefold dilutions shall be made for each Unknown. The dilutions will be made in Phosphate Buffered Saline. (3) For each dilution of the Standard and each dilution of each Unknown, a group of at least 20 mice, each weighing 16-22 grams, shall be used. Each mouse in a group shall be injected intraperitoneally with one mouse dose of the appropriate dilution. Each mouse shall be revaccinated on day 14, using the same schedule. (4) Each of 20 injected mice per group shall be challenged intraperitoneally 10-12 days after the second vaccination with a 0.2 ml dose containing 100-10,000 mouse LD 50 , as determined by titration, of a suit… | |||||
| 9:9:1.0.1.5.51.0.78.70 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.122 Salmonella Choleraesuis Bacterin. | APHIS | [43 FR 25077, June 9, 1978, as amended at 48 FR 31008, July 6, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Salmonella Choleraesuis Bacterin shall be prepared from a culture of Salmonella choleraesuis which has been inactivated and is nontoxic. Each serial of biological product containing Salmonella choleraesuis fraction shall meet the applicable requirements in 9 CFR 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in 9 CFR 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in 9 CFR 113.33(b). The subcutaneous route shall be used when the product is in combination with Pasteurella Multocida Bacterin. (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the mouse test provided in this paragraph. A mouse dose shall be 1/20 of the least dose recommended on the label for other animals which shall not be less than 2 ml. (1) The ability of the bacterin being tested (Unknown) to protect mice shall be compared with a Standard Reference Bacterin (Standard) which is either supplied by or acceptable to Veterinary Services. (2) At least three fivefold dilutions shall be made with the Standard and the same fivefold dilution shall be made for each Unknown. The dilutions shall be made in Phosphate-Buffered Saline. (3) For each dilution of the Standard and each dilution of an Unknown, a group of at least 20 mice, each weighing 16 to 22 grams, shall be used. Each mouse in a group shall be injected intraperitoneally with one mouse dose of the appropriate dilution. Each mouse shall be revaccinated on day 14, using the same schedule. (4) Each of 20 vaccinated mice per group shall be challenged intraperitoneally 7 to 10 days after the second vaccination with a 0.25 ml dose containing 10-1,000 mouse LD 50 as determined by titration of … | |||||
| 9:9:1.0.1.5.51.0.78.71 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.123 Salmonella Dublin Bacterin. | APHIS | [43 FR 25077, June 9, 1978, as amended at 48 FR 31009, July 6, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66785, Dec. 26, 1991] | Salmonella Dublin Bacterin shall be prepared from a culture of Salmonella dublin which has been inactivated and is nontoxic. Each serial of biological product containing Salmonella dublin fraction shall meet the applicable requirements in 9 CFR 113.100 and shall be tested for purity, safety, and potency as prescribed in this section. A serial found unsatisfactory by any prescribed test shall not be released. (a) Purity test. Final container samples of completed product shall be tested for viable bacteria and fungi as provided in 9 CFR 113.26. (b) Safety test. Bulk or final container samples of completed product from each serial shall be tested for safety as provided in 9 CFR 113.33(b). (c) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency using the mouse test provided in this paragraph. A mouse dose shall be 1/20 of the least dose recommended on the label for other animals which shall not be less than 2 ml. (1) The ability of the bacterin being tested (Unknown) to protect mice shall be compared with a Standard Reference Bacterin (Standard) which is either supplied by or acceptable to Veterinary Services. (2) At least three tenfold dilutions shall be made with the Standard and the same tenfold dilutions shall be made for each Unknown. The dilutions shall be made in Phosphate-Buffered Saline. (3) For each dilution of the Standard and each dilution of an Unknown, a group of at least 20 mice, each weighing 16 to 22 grams, shall be used. Each mouse in a group shall be injected intraperitoneally with one mouse dose of the appropriate dilution. Each mouse shall be revaccinated on day 14, using the same schedule. (4) Each of 20 vaccinated mice per group shall be challenged intraperitoneally 7 to 10 days after the second vaccination with a 0.25 ml dose containing 1,000-100,000 mouse LD 50 as determined by titration of a suitable culture of Salmonella dublin. All survivors in each group of mice shall be recorded 14 days postchallenge. (5)… | |||||
| 9:9:1.0.1.5.51.0.79.72 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.200 General requirements for killed virus vaccines. | APHIS | [39 FR 27428, July 29, 1974, as amended at 40 FR 23989, June 4, 1975; 43 FR 49528, Oct. 24, 1978. Redesignated at 55 FR 35562, Aug. 31, 1990; 68 FR 35283, June 13, 2003; 79 FR 31021, May 30, 2014] | When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a killed virus vaccine shall meet the applicable requirements in this section. (a) Killing agent. The vaccine virus shall be killed (inactivated) by an appropriate agent. The procedure involved may be referred to as inactivation. Suitable tests to assure complete inactivation shall be written into the filed Outline of Production. (b) Cell culture requirements. If cell cultures are used in the preparation of the vaccine, primary cells shall meet the requirements in § 113.51 and cell lines shall meet the requirements in § 113.52. (c) Purity tests —(1) Bacteria and fungi. Final container samples of completed product from each serial shall be tested as prescribed in § 113.26. (2) Avian origin vaccine. Bulk pooled material or final container samples from each serial shall also be tested for: (i) Salmonella contamination as prescribed in § 113.30; and (ii) Lymphoid leukosis virus contamination as prescribed in § 113.31; and (iii) Hemagglutinating viruses as prescribed in § 113.34. (3) Mycoplasma. If the licensee cannot demonstrate that the agent used to kill the vaccine virus would also kill mycoplasma, each serial of the vaccine shall be tested for mycoplasma as prescribed in § 113.28, prior to adding the killing agent. Material found to contain mycoplasma is unsatisfactory for use. (4) Extraneous viruses. Each lot of Master Seed Virus used to prepare killed virus vaccine recommended for animals other than poultry shall meet the requirements for extraneous viruses as prescribed in § 113.55. (d) Safety tests. Final container samples of completed product from each serial shall be tested for safety in guinea pigs as prescribed in § 113.38 and for safety in mice as prescribed in § 113.33: Provided, That, vaccines recommended for use only in poultry are exempt from this requirement. (e) Viricidal activity test. Only serials tested for viricidal activity in accordance with the test provided in § 1… | |||||
| 9:9:1.0.1.5.51.0.79.73 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | §§ 113.201-113.203 [Reserved] | APHIS | |||||||
| 9:9:1.0.1.5.51.0.79.74 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.204 Mink Enteritis Vaccine, Killed Virus. | APHIS | [39 FR 27428, July 29, 1974. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991; 60 FR 14361, Mar. 17, 1995] | Mink Enteritis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that have developed mink enteritis following inoculation with virulent mink enteritis virus. Each serial shall meet the applicable requirements prescribed in § 113.200 and special requirements prescribed in this section. Any serial found unsatisfactory by a prescribed test shall not be released. (a) Safety test. Vaccinates used in the potency test in paragraph (b) of this section shall be observed each day prior to challenge. If unfavorable reactions attributable to the vaccine occur, the serial is unsatisfactory. If unfavorable reactions not attributable to the vaccine occur, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial is unsatisfactory. (b) Potency test. Bulk or final container samples of completed product shall be tested for potency using 10 mink enteritis susceptible mink (five vaccinates and five controls) as follows: (1) Vaccination. Each of the five vaccinates shall be injected with one dose of vaccine as recommended on the label and observed each day for 14 days. (2) Challenge. At least 2 weeks after the last inoculation, the five vaccinates and the five controls shall be challenged with virulent mink enteritis virus and observed each day for 12 days. Fecal material shall be collected on one day between days 4-8 (inclusive) postchallenge from each test animal that remains free of enteric signs and tested for the presence of mink enteritis virus by cell culture with fluorescent antibody examination. (3) Interpretation. A serial is satisfactory if at least 80 percent of the vaccinates remain free of enteric signs and do not shed virus in the feces, while at least 80 percent of the controls develop clinical signs of mink enteritis or shed virus in the feces. If at least 80 percent of the vaccinates remain free of enteric signs and do not shed virus in the feces, while less than 80 percent of the cont… | |||||
| 9:9:1.0.1.5.51.0.79.75 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.205 Newcastle Disease Vaccine, Killed Virus. | APHIS | [39 FR 27428, July 29, 1974. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991] | Newcastle Disease Vaccine (Killed Virus) shall be prepared from virus-bearing tissues or fluids obtained from embryonated chicken eggs or cell cultures. With the exception of § 113.200(c)(2)(iii), each serial shall meet the applicable general requirements prescribed in § 113.200 and special requirements prescribed in this section. A serial found unsatisfactory by a prescribed test shall not be released. (a) Safety test. The prechallenge part of the potency test in paragraph (b) of this section shall constitute a safety test. If unfavorable reactions attributable to the product occur in any of the vaccinates, the serial is unsatisfactory. If unfavorable reactions which are not attributable to the product occur, the test shall be declared a No Test and may be repeated: Provided, That, if the test is not repeated, the serial shall be declared unsatisfactory. (b) Potency test. A vaccination-challenge test shall be conducted using susceptible chickens 2 to 6 weeks of age at time of vaccination, properly identified and obtained from the same source and hatch. (1) Ten or more chickens shall be vaccinated as recommended on the label and kept isolated under observation for at least 14 days. (2) After at least 14 days post-vaccination, the vaccinates and at least 10 unvaccinated chickens that have been kept isolated as controls shall be challenged with a virulent strain of Newcastle disease virus supplied by or approved by Veterinary Services and the vaccinates observed each day for 14 days. (3) If at least 90 percent of the controls do not show typical signs of Newcastle disease or die, the test is a No Test and may be repeated. If at least 90 percent of the vaccinates do not remain normal, the serial is unsatisfactory. | |||||
| 9:9:1.0.1.5.51.0.79.76 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.206 Wart Vaccine, Killed Virus. | APHIS | [40 FR 14084, Mar. 28, 1975, as amended at 40 FR 23989, June 4, 1975; 40 FR 30803, July 23, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991; 81 FR 59436, Aug. 30, 2016] | Wart Vaccine, Killed Virus, shall be prepared from virus-bearing epidermal tumors (warts) obtained from a bovine. Each serial shall meet the requirements prescribed in this section and any serial found unsatisfactory by a prescribed test shall not be released. (a) Purity. Final container samples of completed product shall meet the requirements for purity as prescribed in § 113.200 (c)(1) and (3). (b) Safety. Bulk or final container samples of completed product shall meet the requirements for safety as prescribed in §§ 113.33(b) and 113.38. (c) Formaldehyde content. Bulk or final container samples of completed product shall meet the requirements for formaldehyde content as prescribed in § 113.200(f). (d) Potency and efficacy. The efficacy of wart vaccine has been demonstrated to the satisfaction of Veterinary Services as being a valuable biological product. The inherent nature of the product precludes the possible development of serial to serial potency tests and none is required: Provided, That, (1) The vaccine shall be a tissue extract representing at least 10 percent weight to volume suspension of wart tissue; and (2) The vaccine shall be limited to use in the prevention of warts in cattle. Labeling recommendations shall be in accordance with § 112.7(h). | |||||
| 9:9:1.0.1.5.51.0.79.77 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.207 Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. | APHIS | [39 FR 44714, Dec. 27, 1974, as amended at 40 FR 14084, Mar. 28, 1975; 42 FR 45284, Sept. 9, 1977. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991; 61 FR 67930, Dec. 26, 1996] | Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Each serial or subserial shall meet the requirements prescribed in this section and the general requirements prescribed in § 113.200, except those in § 113.200(d). Any serial or subserial found unsatisfactory by a prescribed test shall not be released. (a) Safety test. Bulk samples of completed product from each serial shall be tested for encephalomyelitis virus inactivation. (1) Each of at least ten 6 to 12 hour old chickens shall be injected subcutaneously with 0.5 ml of the product and the chickens observed each day for 10 days. (2) If unfavorable reactions attributable to the product occur in the chickens during the observation period, the serial is unsatisfactory. If unfavorable reactions not attributable to the product occur, the test is a No Test and may be repeated: Provided, That, if the test is not repeated, the serial is unsatisfactory. (b) Potency test. Bulk or final container samples of completed product from each serial shall be tested for potency in accordance with the two-stage test provided in this paragraph. For each fraction contained in the product—Eastern type, Western type, or Venezuelan type—the serological interpretations required in this test shall be made independently. A serial or subserial found unsatisfactory for any of the fractions shall not be released. (1) For this test, a guinea pig dose shall be one-half the amount recommended on the label for a horse and shall be administered as recommended for a horse. Each of 10 healthy guinea pigs (vaccinates) shall be injected with two guinea pig doses with an interval of 14 to 21 days between doses. Two additional guinea pigs from the same source shall be held as controls. (2) Fourteen to 21 days after the second injection, serum samples from each vaccinate and each control shall be tested by a plaque reduction, serum neutralization test using Vero 76 cells. (3) If the control serum samples show … | |||||
| 9:9:1.0.1.5.51.0.79.78 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. | APHIS | [39 FR 12958, Dec. 27, 1974, as amended at 40 FR 41088, Sept. 5, 1975. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991] | Avian Encephalomyelitis Vaccine (Killed Virus) shall be prepared from virus-bearing tissues or fluids obtained from embryonated chicken eggs. Each serial shall meet the general requirements prescribed in § 113.200 and the requirements prescribed in this section. Any serial found unsatisfactory by a prescribed test shall not be released. (a) Safety tests. (1) The prechallenge part of the potency test prescribed in paragraph (b) of this section shall constitute a safety test. If any of the vaccinates develop clinical signs of disease or die due to causes attributable to the product, the serial is unsatisfactory. (2) An inactivation test for viable avian encephalomyelitis (AE) virus shall be conducted on each serial. The test shall be conducted using susceptible chicken embryos: Provided, That, if a non-embryo adapted virus is used for vaccine production, the test shall be conducted in susceptible chickens. (i) Chicken Embryo Test. Each of 15 or more AE susceptible 5 or 6 day old embryos shall be injected in the yolk sac with 0.2 ml of the vaccine. For a valid test, at least 80 percent of the embryos shall survive for 48 hours post-inoculation (PI). Eleven to 13 days PI, all embryos surviving the 48 hour PI period shall be examined for gross lesions of AE; all these embryos shall be normal or the serial is unsatisfactory. Concurrently, five additional embryos from the same source shall be injected with live AE virus of the production strain to serve as positive controls. At least 4 of the 5 embryos shall show evidence of AE virus infection during the 11 to 13 day PI period or the test shall be considered a No Test and repeated: Provided, That, if the test is not repeated, the serial shall be declared unsatisfactory. (ii) Chicken test. Each of 10 or more AE susceptible 7 day old chickens shall be injected intracerebrally with 0.1 ml vaccine each. The chickens shall be observed each day for 28 days. If any chickens show clinical signs of AE, the serial is unsatisfactory. Concurrently, 5 additional chicke… | |||||
| 9:9:1.0.1.5.51.0.79.79 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.209 Rabies Vaccine, Killed Virus. | APHIS | [39 FR 44715, Dec. 27, 1974, as amended at 42 FR 6794, Feb. 4, 1977; 43 FR 49528, Oct. 24, 1978; 50 FR 20090, May 14, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990; 56 FR 66784, 66786, Dec. 26, 1991; 61 FR 31823, June 21, 1996; 64 FR 45420, Aug. 20, 1999; 69 FR 18803, Apr. 9, 2004; 75 FR 20773, Apr. 21, 2010] | Rabies Vaccine (Killed Virus) shall be prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies infection following injection with rabies virus. Only Master Seed Virus which has been established as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.200 and the requirements prescribed in this section. (1) Each lot of Master Seed Virus propagated in tissue or cells of avian origin shall also be tested for extraneous pathogens by procedures prescribed in § 113.37. (2) Each lot of Master Seed Virus propagated in primary cell cultures of mouse or hamster origin or brain tissues of mouse origin shall be tested for lymphocytic choriomeningitis (LCM) virus by the procedure prescribed in § 113.42. If LCM virus is detected, the Master Seed Virus is unsatisfactory. (b) The immunogenicity of vaccine prepared with virus at the highest passage from the Master Seed shall be established in each species for which the vaccine is recommended. Tests shall be conducted in accordance with a protocol filed with Animal and Plant Health Inspection Service before initiation of the tests. The vaccine shall be prepared using methods prescribed in the Outline of Production. If Rabies Vaccine is to be in combination with other fractions, the product to be tested shall include all fractions to be tested. (1) The preinactivation virus titer must be established as soon as possible after harvest by at least five separate virus titrations. A mean relative potency value of the vaccine to be used in the host animal potency test must be established by at least five replicate potency tests conducted in accordance with the standard NIH test for potency in chapter 37 of “Laboratory Techniques in Rabies,” Fourth Edition (1996), edited by F.X. Meslin, M.M… | |||||
| 9:9:1.0.1.5.51.0.79.80 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.210 Feline Calicivirus Vaccine, Killed Virus. | APHIS | [50 FR 433, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991] | Feline Calicivirus Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.200. (b) The Master Seed shall be tested for chlamydial agents as prescribed in § 113.43. (c) The immunogenicity of vaccine prepared from the Master Seed in accordance with the Outline of Production shall be established by a method acceptable to Animal and Plant Health Inspection Service. Vaccine used for this test shall be at the highest passage from the Master Seed and prepared at the minimum preinactivation titer specified in the Outline of Production. (d) Test requirements for release. Each serial and subserial shall meet the applicable general requirements prescribed in § 113.200 and the special requirements provided in this paragraph. Any serial or subserial found unsatisfactory by a prescribed test shall not be released. (1) Safety. Vaccinates used in the potency test in paragraph (d)(2) of this section shall be observed each day during the prechallenge period. If unfavorable reactions occur, including oral lesions, which are attributable to the vaccine, the serial is unsatisfactory. If unfavorable reactions occur which are not attributable to the vaccine, the test is inconclusive and may be repeated. If the test is not repeated, the serial is unsatisfactory. (2) Potency. Bulk or final container samples of completed product shall be treated for potency as follows: (i) Eight feline calicivirus susceptible cats (five vaccinates and three controls) shall be used as test animals. Throat and nasal swabs shall be collected from each cat and individually tested on susceptible cell cultures for the presence of feline calicivirus. Blood samples shall be drawn and individual serum sample… | |||||
| 9:9:1.0.1.5.51.0.79.81 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.211 [Reserved] | APHIS | |||||||
| 9:9:1.0.1.5.51.0.79.82 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.212 Bursal Disease Vaccine, Killed Virus. | APHIS | [50 FR 434, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 79 FR 55969, Sept. 18, 2014] | Bursal Disease Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable requirements prescribed in § 113.200. (b) Each lot of Master Seed shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. (c) The immunogenicity of vaccine prepared in accordance with the Outline of Production shall be established by a method acceptable to Animal and Plant Health Inspection Service. Vaccine used for this test shall be at the highest passage from the Master Seed and prepared at the minimum preinactivation titer specified in the Outline of Production. The test shall establish that the vaccine, when used as recommended on the label, is capable of inducing an immune response in dams of sufficient magnitude to provide significant protection to offspring. (d) Test requirements for release. Each serial and subserial shall meet the applicable general requirements prescribed in § 113.200 and the special requirements in this paragraph. Any serial or subserial found unsatisfactory by a prescribed test shall not be released. (1) Safety. Vaccinates used in the potency test in paragraph (d)(2) of this section shall be observed each day during the prechallenge period. If unfavorable reactions attributable to the vaccine occur, the serial is unsatisfactory. If unfavorable reactions which are not attributable to the vaccine occur, the test is a No Test and may be repeated. If the test is not repeated, the serial is unsatisfactory. (2) Potency. Bulk or final container samples of completed product from e… | |||||
| 9:9:1.0.1.5.51.0.79.83 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | §§ 113.213-113.214 [Reserved] | APHIS | |||||||
| 9:9:1.0.1.5.51.0.79.84 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. | APHIS | [55 FR 35562, Aug. 31, 1990] | Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus which has been established as pure, safe, and immunogenic shall be used for preparing seed cultures for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.200 and the requirements of this section. (b) The immunogenicity of vaccine prepared from the Master Seed in accordance with the Outline of Production shall be established by a method acceptable to the Animal and Plant Health Inspection Service. Vaccine used for this test shall be at the highest passage from the Master Seed and at the minimum preinactivation titer provided in the Outline of Production. (c) Test requirements for release. Each serial and subserial shall meet the applicable general requirements prescribed in § 113.200 and the special requirements provided in this paragraph. Any serial or subserial found unsatisfactory by a prescribed test shall not be released. (1) Safety. Vaccinates used in the potency test in paragraph (c)(2) of this section shall be observed each day during the prechallenge period. If unfavorable reactions occur, including respiratory signs, which are attributable to the vaccine, the serial is unsatisfactory. If unfavorable reactions occur which are not attributable to the vaccine, the test is a No Test and may be repeated one time. If results of the second test are not satisfactory, or if the test is not repeated, the serial is unsatisfactory. (2) Potency. Bulk or final container samples of completed product shall be tested for potency using the method described in this paragraph. (i) Eight bovine virus diarrhea susceptible calves (five vaccinates and three controls) shall be used as test animals. Individual serum samples shall be collected, inactivated, and individually tested for neutralizing antibody. (ii) A constant virus decreas… | |||||
| 9:9:1.0.1.5.51.0.79.85 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus. | APHIS | [55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991] | Infectious Bovine Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus which has been established as pure, safe, and immunogenic shall be used for preparing seed cultures for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.200 and the requirements of this section. (b) The immunogenicity of vaccine prepared in accordance with the Outline of Production shall be established by a method acceptable to the Animal and Plant Health Inspection Service. Vaccine used for this test shall be at the highest passage from the Master Seed and at the minimum preinactivation titer provided in the Outline of Production. (c) Test requirements for release. Each serial and subserial shall meet the requirements prescribed in § 113.200 and the special requirements provided in this paragraph. Any serial or subserial found unsatisfactory by a prescribed test shall not be released. (1) Safety. Vaccinates used in the potency test in paragraph (c)(2) of this section shall be observed each day during the prechallenge period. If unfavorable reactions occur, which are attributable to the vaccine, the serial is unsatisfactory. If unfavorable reactions occur which are not attributable to the vaccine, the test is a No Test and may be repeated one time. If the results of the second test are not satisfactory, or if the test is not repeated, the serial is unsatisfactory. (2) Potency. Bulk or final container samples of completed product shall be tested for potency using the method described in this paragraph. (i) Eight infectious bovine rhinotracheitis susceptible calves (five vaccinates, three controls) shall be used as test animals. Individual serum samples shall be collected, inactivated, and individually tested for neutralizing antibody. (ii) A constant virus decreasing serum neutralization test in cell cultur… | |||||
| 9:9:1.0.1.5.51.0.80.100 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.315 Feline Rhinotracheitis Vaccine. | APHIS | [44 FR 58899, Oct. 12, 1979, as amended at 48 FR 33472, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Feline Rhinotracheitis Vaccine shall be prepared from virus-bearing cell culture fluids. Only Master Seed Virus which has been established as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable general requirements prescribed in § 113.300. (b) The Master Seed Virus shall be tested for chlamydial agents as prescribed in § 113.43. (c) Each lot of Master Seed Virus used for vaccine production shall be tested for immunogenicity. The selected virus dose from the lot of Master Seed Virus shall be established as follows: (1) Thirty feline rhinotracheitis susceptible cats shall be used as test animals (20 vaccinates and 10 controls). Throat swabs shall be collected from each cat and individually tested on susceptible cell cultures for the presence of feline rhinotracheitis virus. Blood samples shall be drawn and individual serum samples tested. The cats shall be considered suitable for use if all swabs are negative for virus isolation and if all serums are negative for feline rhinotracheitis virus antibody at the 1:2 final dilution in a 50 percent plaque reduction test or other SN test of equal sensitivity. (2) A geometric mean titer of the dried vaccine produced from the highest passage of the Master Seed Virus shall be established before the immunogenicity test is conducted. The 20 cats used as vaccinates shall be administered a predetermined quantity of vaccine virus by the method to be recommended on the label and the remaining 10 cats shall be held as controls. To confirm the dosage calculations, five replicate virus titrations shall be conducted on a sample of the vaccine virus dilution used. If two doses are used, five replicate confirming titrations shall be conducted on each dose. (3) Twenty-one or more days after the final dose of vaccine, the vaccinates and controls shall each be challenged i… | |||||
| 9:9:1.0.1.5.51.0.80.101 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.316 Canine Parainfluenza Vaccine. | APHIS | [50 FR 436, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Canine Parainfluenza Vaccine shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.300 and the requirements in this section. (b) Each lot of Master Seed shall be tested for immunogenicity. The selected virus dose shall be established as follows: (1) Twenty-five canine parainfluenza susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Nasal swabs shall be collected from each dog on the day the first dose of vaccine is administered and individually tested on susceptible cell cultures for the presence of canine parainfluenza virus. Blood samples shall also be drawn and individual serum samples tested for neutralizing antibody. Dogs shall be considered susceptible if all swabs are negative for virus isolation and if all serums are negative for canine parainfluenza antibody at a 1:2 final dilution in a constant virus-varying serum neutralization test using 50 to 300 TCID 50 of canine parainfluenza virus. (2) A geometric mean titer of vaccine produced at the highest passage from the Master Seed shall be established before the immunogenicity test is conducted. The 20 dogs used as vaccinates shall be administered a predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on a sample of the vaccine virus dilution used to confirm the dosage administered. If two doses are used, five replicate confirming titrations shall be conducted on each dose. (3) Three to 4 weeks after the final dose of vaccine, all dogs shall be bled for serum antibodies and nasal swabs shall be collected for canine parainfluenza virus isolation. On the same day, all vaccinates and controls shall be challenged with canine parainfluenza virus furnished or approved b… | |||||
| 9:9:1.0.1.5.51.0.80.102 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.317 Parvovirus Vaccine (Canine). | APHIS | [50 FR 436, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Parvovirus Vaccine recommended for use in dogs shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.300 and the requirements in this section. (b) The Master Seed shall be tested for reversion to virulence in dogs using a method acceptable to Animal and Plant Health Inspection Service. If a significant increase in virulence is seen within five backpassages, the Master Seed is unsatisfactory. (c) Each lot of Master Seed shall be tested for immunogenicity. The selected virus dose shall be established as follows: (1) Twenty-five canine parvovirus susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood samples drawn from each dog shall be individually tested for neutralizing antibody against canine parvovirus to determine susceptibility. Dogs shall be considered susceptible if there is no neutralization at a 1:2 final serum dilution in a constant virus-varying serum neutralization test in cell culture using 50 to 300 TCID 50 of canine parvovirus. (2) A geometric mean titer of the vaccine produced at the highest passage from the Master Seed shall be established before the immunogenicity test is conducted. The 20 dogs used as vaccinates shall be administered a predetermined quantity of vaccine virus by the method recommended on the label. To confirm the dosage calculations, five replicate virus titrations shall be conducted on a sample of the vaccine virus dilution used. If two doses are used, five replicate confirming titrations shall be conducted on each dose. (3) Fourteen days or more after the final dose of vaccine the vaccinates and the controls shall be challenged with virulent canine parvovirus furnished or approved by Animal and Plant Health Inspection S… | |||||
| 9:9:1.0.1.5.51.0.80.103 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.318 Pseudorabies Vaccine. | APHIS | [50 FR 437, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Pseudorabies Vaccine shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.300 and the requirements in this section. (b) Each lot of Master Seed shall be tested for immunogenicity. The selected virus dose shall be established as follows: (1) Twenty-five pseudorabies susceptible pigs (20 vaccinates and 5 controls) of the youngest age for which the vaccine is recommended, shall be used as test animals. Blood samples shall be taken from each pig and the serums inactivated and individually tested for neutralizing antibody against pseudorabies virus. Pigs shall be considered susceptible if there is no neutralization at a 1:2 final serum dilution in a constant virus-varying serum neutralization test using 50 to 300 TCID 50 pseudorabies virus. (2) A geometric mean titer of the vaccine produced at the highest passage from the Master Seed shall be established before the immunogenicity test is conducted. The 20 pigs used as vaccinates shall be administered a predetermined quantity of vaccine virus by the method recommended on the label. To confirm the dosage administered, five replicate virus titrations shall be conducted on a sample of the vaccine virus dilution used. (3) Fourteen to 28 days postvaccination, the vaccinates and controls shall be challenged with virulent pseudorabies virus furnished or approved by Animal and Plant Health Inspection Service and observed each day for 14 days. (i) If at least four of the five controls do not develop severe central nervous system signs or die, the test is a No Test and may be repeated. (ii) If at least 19 of the 20 vaccinates in a valid test do not remain free of signs of pseudorabies, the Master Seed is unsatisfactory. (4) An Outline of Productio… | |||||
| 9:9:1.0.1.5.51.0.80.104 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | §§ 113.319-113.324 [Reserved] | APHIS | |||||||
| 9:9:1.0.1.5.51.0.80.105 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.325 Avian Encephalomyelitis Vaccine. | APHIS | [39 FR 44723, Dec. 27, 1974, as amended at 40 FR 18405, Apr. 28, 1975; 40 FR 41089, Sept. 5, 1975; 42 FR 43617, Aug. 30, 1977; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007; 79 FR 55969, Sept. 18, 2014] | Avian Encephalomyelitis Vaccine shall be prepared from virus-bearing tissues or fluids from embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300 and the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the test may be repeated and if the repeat test is inconclusive for the same reason, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. (c) Each lot of Master Seed Virus shall be tested for immunogenicity and the selected virus dose to be used shall be established as follows: (1) Avian encephalomyelitis susceptible chickens, all of the same age (eight weeks or older) and from the same source, shall be used. Twenty or more chickens shall be used as vaccinates for each method of administration recommended on the label. Ten additional chickens of the same age and from the same source shall be held as unvaccinated controls. (2) A geometric mean titer of the vaccine produced from the highest passage of the Master Seed Virus shall be established before the immunogenicity test is conducted. Each vaccinate shall receive a predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on an aliquot of the vaccine virus to confirm the amount of virus administered to each chicken used in the test. At least three appropriate (not to exceed tenfold) dilutions shall be used and the test conducted as follows: (i) For each dilution, inoculate at least 10 embr… | |||||
| 9:9:1.0.1.5.51.0.80.106 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.326 Avian Pox Vaccine. | APHIS | [39 FR 44724, Dec. 27, 1974, as amended at 40 FR 18406, Apr. 28, 1975; 40 FR 41089, Sept. 5, 1975; 44 FR 33051, June 8, 1979; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300 except paragraph (c) of this section and shall meet the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken inoculation test prescribed in § 113.36. (c) Each lot of Master Seed Virus shall be tested for immunogenicity and the selected virus dose to be used shall be established as follows: (1) Fowl pox susceptible birds all of the same age and from the same source, shall be used as test birds. Twenty or more birds shall be used as vaccinates for each method of administration recommended on the label. Ten additional birds of the same age and from the same source as the vaccinates shall be held as unvaccinated controls. (2) A geometric mean titer of the dried vaccine produced from the highest passage of the Master Seed Virus shall be established before the immunogenicity test is conducted. Each vaccinate shall receive a predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on an aliquot of the vaccine virus to confirm the amount of virus administered to each bird used in the test. At least three appropriate (not to exceed tenfold) dilutions shall be used and the test conducted as follows: (i) For each dilution, inoculate at least five embryos, 9 to 11 days old, on the chorioallantoic membrane with at least 0.2 ml each. Disregard all deaths during the first 24 hours post-inoculation. To be a valid test, at least four embryos in each dilution shall remain viable… | |||||
| 9:9:1.0.1.5.51.0.80.107 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.327 Bronchitis Vaccine. | APHIS | [39 FR 44724, Dec. 27, 1974, as amended at 40 FR 18406, Apr. 28, 1975; 40 FR 41089, Sept. 5, 1975; 42 FR 43617, Aug. 30, 1977; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 64 FR 43045, Aug. 9, 1999; 72 FR 72564, Dec. 21, 2007] | Bronchitis Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300 and the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the test may be repeated and if the repeat test is a No Test for the same reason, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. (c) Each lot of Master Seed Virus used for vaccine production shall be tested for immunogenicity and the selected virus dose to be used shall be established as follows: (1) Bronchitis susceptible chickens, all of the same age and from the same source, shall be used in the virus-recovery test. For each method of administration recommended on the label for each serotype against which protection is claimed, twenty or more chickens shall be used as vaccinates. Ten additional chickens for each serotype against which protection is claimed shall be held as unvaccinated controls. (2) A geometric mean titer of the dried vaccine produced from the highest passage of the Master Seed Virus shall be established before the immunogenicity tests are conducted. Each vaccinate shall receive a predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on an aliquot of the vaccine virus to confirm the amount of virus administered to each chicken used in such tests. At least three approved (not to exceed tenfold) dilutions shall be used and the… | |||||
| 9:9:1.0.1.5.51.0.80.108 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.328 Fowl Laryngotracheitis Vaccine. | APHIS | [39 FR 44726, Dec. 27, 1974, as amended at 40 FR 18407, Apr. 28, 1975; 40 FR 41089, Sept. 5, 1975; 41 FR 44359, Oct. 8, 1976; 42 FR 43617, Aug. 30, 1977; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Fowl Laryngotracheitis Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300 and the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of vaccine virus override, the test may be repeated and if the repeat test is a No Test for the same reason, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. Each lot shall also be tested for safety as follows: (1) Each of at least ten 3 to 4 week old susceptible chickens obtained from the same source and hatch as those used in the immunogenicity test prescribed in paragraph (c) of this section shall be injected intratracheally with 0.2 ml of the virus as used in the vaccine and the chickens observed each day for 14 days. (2) If more than 20 percent of the chickens die during the observation period, the virus is unsatisfactory. (c) Each lot of Master Seed Virus used for vaccine production shall be tested for immunogenicity and the selected virus dose to be used shall be established as follows: (1) Fowl laryngotracheitis susceptible chickens all of the same age and from the same source shall be used. Twenty or more chickens shall be used as vaccinates for each method of administration recommended on the label. Ten additional chickens of the same age and from the same source shall be held as unvaccinated controls. (2) A geometric mean titer of the dried vaccine produced from the highest passage of th… | |||||
| 9:9:1.0.1.5.51.0.80.109 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.329 Newcastle Disease Vaccine. | APHIS | [39 FR 44727, Dec. 27, 1974, as amended at 40 FR 18407, Apr. 28, 1975; 40 FR 23721, June 2, 1975; 40 FR 41090, Sept. 5, 1975; 42 FR 43618, Aug. 30, 1977; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 72 FR 72564, Dec. 21, 2007] | Newcastle Disease Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300, except § 113.34, and the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the test may be repeated and if the repeat test is a No Test for the same reason, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. (c) Each lot of Master Seed Virus used for vaccine production shall be tested for immunogenicity and the selected virus dose to be used shall be established as follows: (1) Newcastle Disease susceptible chickens, all of the same age and from the same source, shall be used. Twenty or more chickens shall be used as vaccinates for each method of administration recommended on the label. Ten additional chickens of the same age and from the same source shall be held as unvaccinated controls. (2) A geometric mean titer of the dried vaccine produced from the highest passage of the Master Seed Virus shall be established before the immunogenicity test is conducted. Each vaccinate shall receive a predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on an aliquot of the vaccine virus to confirm the amount of virus administered to each chicken used in the test. At least three appropriate (not to exceed tenfold) dilutions shall be used and the test conducted as follows: (i) For each dilution, inject at le… | |||||
| 9:9:1.0.1.5.51.0.80.110 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.330 Marek's Disease Vaccines. | APHIS | [61 FR 33841, July 1, 1996] | Marek's disease vaccine shall be prepared from virus-bearing tissue culture cells. Only Master Seed Virus which has been established as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300, and the requirements prescribed in this section. The identity test required in § 113.300(c) shall be conducted in a serotype-specific manner by a method acceptable to APHIS. Each lot of Master Seed Virus shall also be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. (b) Safety test. The Master Seed Virus shall be nonpathogenic for chickens as determined by the following procedure: (1) Specific pathogen free chickens or embryos, negative for Marek's disease virus antibodies, and from the same source, shall be isolated into the following groups: (i) Group 1. At least 50 test subjects shall be inoculated with 10 times as much viable virus as will be contained in one dose of vaccine, by the route recommended for vaccination. (ii) Group 2. At least 50 test subjects shall be injected with a very virulent Marek's disease virus provided or approved by APHIS, at a dosage level that will cause gross lesions of Marek's disease in at least 80 per cent of the chickens within 50 days. (iii) Group 3. Fifty uninoculated controls. For in ovo studies, this group should receive a sham inoculation of diluent. (iv) Group 4. For studies evaluating Serotype 1 Master Seed Viruses, a group of 50 uninoculated control chickens shall be housed in contact with the group 1 vaccinated chickens. (2) At least 40 chickens in each group shall survive to 5 days of age. All chickens that die shall be necropsied and examined for lesions of Marek's disease and cause of death. The test shall be jud… | |||||
| 9:9:1.0.1.5.51.0.80.111 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.331 Bursal Disease Vaccine. | APHIS | [44 FR 60263, Oct. 19, 1979, as amended at 44 FR 67087, Nov. 23, 1979; 48 FR 33473, July 22, 1983. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 64 FR 43045, Aug. 9, 1999; 72 FR 72564, Dec. 21, 2007] | Bursal Disease Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed Virus which has been established as pure, safe, and immunogenic in accordance with the requirements in paragraphs (a), (b), and (c) of this section shall be used for preparing the production seed virus for vaccine production. All serials shall be prepared from the first through the fifth passage from the Master Seed Virus. (a) The Master Seed Virus shall meet the applicable requirements prescribed in § 113.300 and the requirements prescribed in this section. (b) Each lot of Master Seed Virus shall be tested for pathogens by the chicken embryo inoculation test prescribed in § 113.37, except that, if the test is a No Test because of a vaccine virus override, the chicken inoculation test prescribed in § 113.36 may be conducted and the virus judged accordingly. Each lot of Master Seed Virus used in the preparation of modified live virus vaccines shall also be nonpathogenic to chickens as determined by the following procedures: (1) Each of twenty-five 1-day-old bursal disease susceptible chickens (vaccinates) shall be injected subcutaneously with 10 times the recommended dose of vaccine virus and observed for 21 days. Fifteen chickens of the same source and hatch shall be kept isolated as controls. (i) Seventeen days postvaccination, each of five controls shall be administered at least 10 2.0 EID 50 of a virulent bursal disease virus by eye-drop, isolated, and used as positive controls. The remaining controls shall be used as negative controls. (ii) If the vaccinates do not remain free of clinical signs of bursal disease, the Master Seed Virus is unsatisfactory. If unfavorable reactions which are not attributable to the Master Seed Virus occur in more than two of the vaccinates, the test shall be declared a No Test and may be repeated. (iii) Twenty-one days postvaccination, the vaccinates and the controls shall be necropsied and examined for gross lesions of bursal disease. If more th… | |||||
| 9:9:1.0.1.5.51.0.80.112 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.332 Tenosynovitis Vaccine. | APHIS | [50 FR 438, Jan. 4, 1985. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66784, 66786, Dec. 26, 1991; 64 FR 43045, Aug. 9, 1999; 72 FR 72564, Dec. 21, 2007] | Tenosynovitis Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed which has been established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed. (a) The Master Seed shall meet the applicable general requirements prescribed in § 113.300, except (a)(3)(ii) and (c), and the special requirements in this section. (b) Each lot of Master Seed shall be tested for: (1) Pathogens by the chicken inoculation test prescribed in § 113.36. (2) Lymphoid leukosis virus contamination as follows: (i) Each of at least 10 3-week-old or older lymphoid leukosis free chickens from the same source and hatch shall be injected intra-muscularly with an amount of Master Seed equal to 100 label doses of vaccine. At least 15 chickens of the same source and hatch shall be used as controls; 5 or more shall be unvaccinated and serve as negative controls; 5 or more shall be injected with subgroup A lymphoid leukosis virus; and 5 or more with subgroup B lymphoid leukosis virus. Each group of control chickens shall be held isolated from each other and from the vaccinates. (ii) Twenty-one to 28 days postinoculation, blood samples shall be taken from each chicken and the serum separated using a technique conducive to virus preservation. These serums shall be used as inocula in the complement fixation for avian lymphoid leukosis (COFAL) test prescribed in § 113.31. (iii) Serums from the vaccinates shall be tested separately, but serums within each control group may be pooled. A valid test shall have positive COFAL reactions from each virus inoculated group and negative reactions from the uninoculated controls. If any of the chickens injected with the Master Seed have positive COFAL test reactions in a valid test, the Master Seed is unsatisfactory. (3) Identity using the following agar gel immunodiffusion test. The undiluted Master Seed may be used… | |||||
| 9:9:1.0.1.5.51.0.80.86 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.300 General requirements for live virus vaccines. | APHIS | [39 FR 27430, July 29, 1974, as amended at 43 FR 49528, Oct. 24, 1978; 50 FR 1042, Jan. 9, 1985; 54 FR 19352, May 5, 1989. Redesignated at 55 FR 35562, Aug. 31, 1990; 60 FR 24549, May 9, 1995; 68 FR 57608, Oct. 6, 2003] | When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a live virus vaccine shall meet the applicable requirements in this section. (a) Purity tests —(1) Bacteria and fungi. Final container samples of completed product and comparable samples of each lot of Master Seed Virus shall be tested for bacteria and fungi in accordance with the test provided in § 113.27. (2) Mycoplasma. Final container samples of completed product and comparable samples of each lot of Master Seed Virus shall be tested for mycoplasma in accordance with the test provided in § 113.28. (3) Avian Origin Vaccine. Samples of each lot of Master Seed Virus and bulk pooled material or final container samples from each serial shall also be tested for: (i) Salmonella contamination as prescribed in § 113.30; and (ii) Lymphoid leukosis virus contamination as prescribed in § 113.31; and (iii) Hemagglutinating viruses as prescribed in § 113.34. (4) Extraneous viruses. Each lot of Master Seed Virus used to prepare live virus vaccine recommended for animals other than poultry shall meet the requirements for extraneous viruses as prescribed in § 113.55 (b) Safety tests. Samples of each lot of Master Seed Virus and final container samples of completed product from each serial or first subserial of live virus vaccine recommended for animals other than poultry shall be tested for safety in at least one species for which the vaccine is intended using methods prescribed in §§ 113.39, 113.40, 113.41, 113.44, and 113.45 or in a filed Outline of Production. The mouse safety test prescribed in § 113.33(a) shall also be conducted unless the virus or agent in the vaccine is inherently lethal for mice. (c) Virus identity test. At least one of the virus identity tests provided in this paragraph or a suitable identity test prescribed in the filed Outline of Production shall be conducted on the Master Seed Virus and final container samples from each serial or first subserial of biological product. (1) Fluorescen… | |||||
| 9:9:1.0.1.5.51.0.80.87 | 9 | Animals and Animal Products | I | E | 113 | PART 113—STANDARD REQUIREMENTS | § 113.301 Ovine Ecthyma Vaccine. | APHIS | [39 FR 27430, July 29, 1974. Redesignated at 55 FR 35562, Aug. 31, 1990, as amended at 56 FR 66786, Dec. 26, 1991] | Ovine Ecthyma Vaccine shall be prepared from tissue culture fluids or virus-bearing tissues obtained from sheep that have developed ovine ecthyma following inoculation with virulent ovine ecthyma virus. Ovine Ecthyma Vaccine is exempt from the requirements prescribed in §§ 113.27 and 113.300(a), (b), and (c). Each serial shall meet the moisture requirements in § 113.300(e) and the special requirements prescribed in this section. Any serial found unsatisfactory by a prescribed test shall not be released. (a) Safety tests. (1) Bulk or final container samples of completed product from each serial shall be tested for safety as prescribed in § 113.38. (2) The prechallenge period of the potency test shall constitute a safety test. If unfavorable reactions attributable to the vaccine occur in either of the vaccinates during the observation period, the serial is unsatisfactory. (b) Potency test. Final container samples of completed product from each serial and each subserial shall be tested for potency using susceptible lambs. The vaccine shall be prepared as recommended for use on the label. (1) Each of two lambs (vaccinates) shall be vaccinated by application of the vaccine to a scarified area on the medial surface of the thigh and observed each day for 14 days. (2) The immunity of the two vaccinates and one or more unvaccinated lambs (controls) shall be challenged in the same manner as for vaccination, using the opposite thigh. (3) If typical signs of ovine ecthyma, such as hyperemia, vesicles, and pustules do not develop on the controls during the first 2 weeks following challenge and persist for approximately 30 days, the test is a No Test and may be repeated. (4) If the vaccinates do not show a typical immune reaction, the serial is unsatisfactory: Provided, That, an initial active reaction with hyperemia which resolves progressively and disappears within 2 weeks, may be characterized as a typical immune reaction. |
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