Veterinary Biologics Guideline 3.22E: Requirements for master seed stocks, master cell stocks and veterinary biologic serials
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- I. Introduction
- II. Legal authority
- III. Requirements for master seed and master cell stocks
- IV. Requirements for pre-licensing serials
- V. Post-licensing requirements
The purpose of this guideline is to inform veterinary biologics (VB) manufacturers and Canadian importers of the Canadian regulatory requirements for master seed stocks, master cell stocks, and veterinary biologic serials of VB licensed, distributed or sold in Canada.
II. Legal authority
Health of Animals Regulations
Section 129. (1)
Every holder of a product licence shall
(a) keep and make available for inspection by a veterinary inspector records with respect to the preparation, manufacture, preservation, storage, testing, sale and distribution of every veterinary biologic manufactured under the product licence and any diluent to be used therewith.
No person shall sell a veterinary biologic or any diluent to be used therewith if the veterinary biologic or diluent has been prepared, manufactured, preserved, packed, labelled or tested otherwise than in the manner described in the product outline.
Where the Minister is satisfied from tests of a veterinary biologic, or otherwise, that a veterinary biologic is unsafe to use, is likely to cause communicable disease in animals or is contaminated or ineffective, he may, by order, prohibit the importation, manufacture, sale or distribution of the veterinary biologic.
III. Requirements for master seed and master cell stocks
Master seed and master cell stocks used in the production of a VB must be prepared in a consistent and well-documented manner, thoroughly characterized, and demonstrated to be free of contamination or extraneous agents.
As part of the licensing submission, manufacturers are required to provide a separate, detailed report containing the following information for each master seed or master cell stock:
- origin and source of the master seed or master cell
- detailed passage history
- conditions for growth, storage and propagation; growth, passaging and freezing /preservation media; expected titres; identification of any ingredients of animal origin
- identity test results for the master seed (morphology, biochemical, serotyping, etc.), for the master cell (species, cell type, karyology, etc.) and/or for any antigens that are important for immunogenicity (restriction enzyme profile, PCR, Western blot, etc.)
- purity test results to confirm absence of bacterial or fungal contamination
- tests to confirm absence of extraneous agents specific for the source species of the master stock and for the intended species of the final product
- for biotechnologically-derived seeds, genetic characterization and demonstration of genetic and phenotypic stability for at least five passages
- for modified live viral seeds, backpassage studies to confirm lack of reversion to virulence
- for live ruminant viral seeds, tests to confirm freedom from bluetongue virus contamination
- for live swine viral seeds, tests to confirm freedom from pseudorabies (Aujeszky's disease) and Seneca Valley virus contamination
For VB manufactured in Canada or in foreign countries other than the United States of America (USA), the Canadian Centre for Veterinary Biologics (CCVB) may require additional confirmatory testing of master seed and master cell stocks at a CFIA- approved laboratory. Should testing be required, the CCVB will instruct the manufacturer on the sample submission procedures. The CCVB does not require confirmatory testing of VB manufactured in authorized facilities in the USA, as these activities are done by the Center for Veterinary Biologics of the United States Department of Agriculture (CVB-USDA). An exception to this is a VB manufactured in the USA under the Food and Drugs Administration Export Reform and Enhancement Act of 1996 (FDA-EREA). Further information about the requirements for FDA-EREA VB will be provided, as required, by the CCVB evaluator.
IV. Requirements for pre-licensing serials
VB serials must be prepared in a consistent manner, according to the approved Product Outline, and shown to be safe for use in the intended species, efficacious, and free of contamination or extraneous agents.
Manufacturers must provide summary test results from three consecutive pre-licensing serials to verify uniformity, and serial-to-serial consistency of production serials. In the case of a smaller component VB of an already licensed combination vaccine, the CCVB will require the results from at least one pre-licensing serial.
The test results must be submitted to the CCVB on a Manufacturer's Serial Release Test Report. For USA-manufactured VB the test results must be submitted on the APHIS Form 2008 – Veterinary Biologics Production and Test Report and clearly show the USDA-CVB disposition.
Canadian- and foreign-manufactured pre-licensing serials may be selected for further confirmatory testing. Should a serial be selected for testing, further instructions will be provided by the CCVB. The CCVB does not require confirmatory testing of VB manufactured in authorized facilities in the U.S., as these activities are done by the USDA-CVB.
For Canadian-manufactured VB prepared For Export Only, the manufacturer's summary test results from three consecutive pre-licensing serials may be required by the CCVB. There is no requirement for confirmatory testing of Canadian-manufactured For Export Only VB.
V. Post-licensing requirements
VB serials intended for sale or distribution in Canada must be prepared in a consistent manner, according to the approved Product Outline and demonstrated to be safe to use, efficacious, and free of contamination or extraneous agents. VB manufacturers in Canada, USA (manufacturing in accordance with FDA-EREA), and other foreign countries must submit serial test results for approval by the CCVB prior to distribution and sale in Canada. These serial-specific test results demonstrate the manufacturer's ability to consistently manufacture VB that meets the approved Product Outline section V specifications.
The test results must be submitted to the CCVB on a Manufacturer's Serial Release Test Report. Test references on the Test Report must cite the approved Product Outline and referenced procedures, as filed with the CCVB. Serials may be randomly selected for additional testing by a CFIA designated laboratory. In this situation, further instructions will be provided by the CCVB. For all serials sold or distributed in Canada, manufacturers must retain production records and at least two sample units of each serial for a minimum of 6 months post-expiry of the serial.
The CCVB recognizes the serial release process of the USDA-CVB; however, the CCVB will require additional confirmatory testing results for live viral vaccines for bovines or swine to confirm absence of bluetongue virus, pseudorabies virus and Seneca Valley virus respectively.
Any further questions may be directed to the CCVB.
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