According to USDA Document Number: CVB-SOP-0078 <Adjuvants and Excipients>, Section/Area: CVB-SOP-PEL-REV, The Food Safety and Inspection Service (FSIS) transferred the official responsibility to evaluate adjuvants and excipients used in Veterinary Biologies back to the Animal and Plant Health Inspection Service (APHIS) in 2006. Center for Veterinary Biologies (CVB) Notice 06-13 provides details regarding this transfer. FSIS had been providing chemical, toxicological, and pathologic evaluations of new adjuvants/excipients, but APHIS now has the scientific resources necessary to conduct these evaluations. Resuming adjuvant reviews eliminates a step in the approval process that industry must follow and requires contact only with APHIS.

All new product licensing packages should include a thorough description and the composition of any adjuvants. Veterinary Services Memorandum 800.5] provides guidance regarding appropriate data that should be submitted for adjuvants. In general, all new product license applications should contain the following information:

1. Generic name of adjuvant (and Trade Name if applicable)
2. Chemical composition of adjuvant (list all ingredients and proportions)
3. Amount of completed/total adjuvant per dose of product
4. Dose volume of product
5. Animal species in which the product is to be used
6. Route of administration (and specific anatomical site, if designated)
7. Information regarding source, grade, quality of tests performed (if any) on each lot
8. Slaughter withdrawal period proposed [at least 21 days is required as per title 9, Code of Federal Regulations (9 CFR), section 112.2(a)(8)]
9. Other products for which the adjuvant/excipient has been approved (if applicable)

Reviewers should compare the additive description and composition with historic data regarding adjuvants and excipients on file at the CVB. A spreadsheet containing ^proved adjuvants is available to facilitate review of historic data (see adjuvant spreadsheet). The spreadsheet contains information regarding adjuvants and miscellaneous additives that have been approved for use by the CVB. Please note that not all of the products that these approved additives are to be used in are currently licensed. Some products are in the pre-license stage. Some products listed have been licensed but may not be currently manufactured. The adjuvant spreadsheet may not contain all of the adjuvants approved by the CVB. It is simply meant to be used as a tool for reviewers to use when reviewing adjuvant submissions. Reviewers are encouraged to contact the Adjuvant Coordinated Review Team (CRT) chair if revisions or updates to this spreadsheet are identified. Additional data regarding previously approved adjuvants are filed in the adjuvant folder for each firm, located in the file

Additional data and evaluation may be required fbr previously approved adjuvants that are to be included in products in unique ways. The reviewer should consist with the Adjuvant CRT if any questions arise regarding adjuvants. The purpose of the Adjuvant CRT is to generate useful and timely information for the reviewer in order to facilitate scientific review of adjuvants. In order to achieve this purpose, goals of the Adjuvant CRT include:

1. The CRT will strive to provide a response to adjuvant-related questions within 4 weeks of initial consultation.

2. Pathologist on the adjuvant CRT is also available for the specific questions related to pathology at any time.

The reviewer should consult the Adjuvant CRT prior to approval of new adjuvants, or to approval of previously approved adjuvants to be used at increased levels, in different routes of administration, or with different withdrawal periods. Results of an injection site study in the host animal may be required to complete evaluation of the adjuvant.

3. Considerations for an Injection Site Study

The following guidelines should be considered when reviewing an injection site study:

3.1 A protocol should be submitted by the firm prior to conducting the study to ensure the study design is adequate. The proposed dates of conducting the study should be included to allow observation by CVB personnel if deemed necessary.

3.2 At least 10 animals of the minimum age should be included fbr adjuvants used in food-producing species other than fish and poultry:

1. The firm should compare the injection site of the new adjuvant to a product matched placebo by injecting the new product on one side of the animal, and the placebo on the other side of the animal. In certain instances, a placebo other than a product-matched placebo may be considered. Justification for using other types of placebos should be included in the protocol submitted fbr review.
2. The injection sites should be examined grossly by a veterinarian or board certified veterinary pathologist. The veterinarian or veterinary pathologist should also collect the tissues to be analyzed histologically. The results of gross pathologic examination should be included in the report. High resolution pictures of any gross pathology should be included.
3. Histopathology of tissue samples taken from all injection sites should be analyzed by a board certified veterinary pathologist who has no knowledge regarding the products used in the study, and photographs of the histopathologic sections of the injection site should be included in the final report. The same pathologist should evaluate all the slides. The slides should be submitted to the CVB fbr Adjuvant CRT evaluation if requested.