Memorandum 2018-02: Criteria to waive target animal batch safety testing for veterinary vaccines

59 Camelot Drive
Ottawa, Ontario K1A 0Y9
Telephone: 613-773-7786
Facsimile: 613-773-7115

Date: February 16, 2018

To: Manufacturers and Importers of Licensed Veterinary Biologics

This memorandum serves to inform you that the Canadian Centre for Veterinary Biologics (CCVB), Canadian Food Inspection Agency, will consider requests for a waiver to the target animal batch safety test (TABST) for inactivated and live veterinary vaccines licensed in Canada.

Background

The International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) Steering Committee recently finalized guidelines "Harmonisation of Criteria to Waive Target Animal Batch Safety Testing for Inactivated Vaccines for Veterinary Use" (VICH GL 50) and "Harmonisation of Criteria to Waive Target Animal Batch Safety Testing for Live Vaccines for Veterinary Use" (VICH GL 55).

The target animal batch safety test (TABST) for inactivated or live veterinary vaccines is normally performed by administering an overdose of each batch or serial of the vaccine to the intended target species by the recommended route in accordance with the Canadian Health of Animals Regulations, Section 120.4(1)(e) or similar regulatory framework, and Section V.B of the approved Outline of Production. Testing is required for each batch or serial and, as such, veterinary vaccine manufacturers use a significant number of animals. The VICH guidelines outline a process by which the TABST may be waived for a veterinary vaccine meeting specific criteria and, thereby, reducing the use of animals.

The Canadian Centre for Veterinary Biologics is committed to the 3Rs (replacing, refining and reducing the number of animals in testing) and has adopted these VICH guidelines for implementation in Canada.  The CCVB will consider a request for a waiver to the TABST for fully licensed veterinary vaccines with a documented history of safe use.

Applying for a Waiver to the TABST

The CCVB will consider requests for a waiver if the following are met:

1. The product has a documented history of acceptable safety.
2. The product is manufactured and tested following recognized quality principles in a consistent and appropriate manner.
3. The product is manufactured from approved master seed and/or cell stocks in a seed lot system.

Canadian and Foreign, Non-U.S. Manufactured Vaccines

Requests for waivers to TABST will be reviewed on a product-by-product basis. Each request for a waiver to the TABST should include the following information:

• A summary of the manufacturing controls for maintaining serial-to-serial consistency in purity, potency, safety and efficacy.
• A summary of at least 10 consecutive recently-manufactured serials since licensing, and the total number of serials failed and reasons for failure. A justification is required should 10 consecutively-manufactured serials not be available.
• A summary of pharmacovigilance data, including frequency and severity of the suspected adverse events, to demonstrate consistent safe performance of the vaccine in the field.
• Revised pages of the Outline of Production with a revision to Section V.B.
• An Application for Services form (CFIA/ACIA 4720) and fees for a revision to the Outline of Production.

U.S. Manufactured Vaccines

For veterinary vaccines manufactured by a U.S. manufacturer and fully licensed for use and distribution in Canada the CCVB will recognize waivers to the TABST issued by the USDA Center for Veterinary Biologics as per USDA Veterinary Services Memorandum N^o. 800.116.

Canadian Manufactured Vaccines, For Export Only

A request for a waiver to the TABST for a Canadian-manufactured vaccine, licensed for export only, must first be granted by the importing country's regulatory authority. The application package should include the following information:

• Correspondence from the regulatory authority of the importing country granting the TABST waiver. If the product is exported to more than one country, then a letter from each country's regulatory authority must be filed with the CCVB.
• Revised pages of the Outline of Production with a revision to Section V.B.
• An Application for Services form (CFIA/ACIA 4720) and fees for a revision to the Outline of Production.

Exceptions to the Application Process

The CCVB will not consider waivers to the TABST for:

• Conditionally licensed veterinary vaccines,
• Autogenous vaccines or
• Aquaculture vaccines with a safety test as a precursor to a potency test.

Suspension of Waivers to the TABST

The CCVB may suspend a waiver to the TABST for a product in the following situations:

• Assessment of pharmacovigilance data for the product raises safety concerns.
• Observations of non-conformances during on-site inspection of the manufacturer.
• Observations of non-conformances during the review of batch release documentation.
• Any changes to product manufacturing such as, but not limited to, changes to master seed, site transfers, processes or equipment, that CCVB assesses as at risk of compromising the product safety.

Please contact our office if you have any questions about this Memorandum.

Surinder Saini, DVM, MVSc, PhD
National Manager
Canadian Centre for Veterinary Biologics
Animal Import/Export Division
Animal Health Directorate