Veterinary Biologics Guideline 3.6E
Guideline for Bluetongue Virus Exclusion Testing of Veterinary Biologics

I. Introduction

To prevent the transmission of bluetongue virus (BTV) through veterinary biologics, the Canadian Centre for Veterinary Biologics (CCVB) requires manufacturers to conduct BTV exclusion tests on live virus vaccines which are intended for use in ruminants. Other products such as live bacterial vaccines intended for use in ruminants will require BTV exclusion tests, if significant quantities of ruminant serum are used in the manufacturing process.

II. Legal Authority

Section 64.(1)
The Governor in Council may make regulations for the purpose of protecting human and animal health through the control or elimination of diseases and toxic substances and generally for carrying out the purposes and provisions of this Act, including regulations

Section 64.(1)(s)
prohibiting or regulating the importation, preparation, manufacturing, preserving, packing, labelling, storing, testing, transportation, sale, conditions of sale, advertising for sale, use and disposal of veterinary biologics and regulating their purity, potency, efficacy and safety.

Health of Animals Regulations

Section 121.(1)
No person shall import a veterinary biologic into Canada unless he does so under and in accordance with a permit issued by the Minister.

Section 122.(1)
Subject to subsection (2), every applicant for a permit to import a veterinary biologic into Canada shall include with his application

Section 122.(1)(c)
the results of such tests of the veterinary biologic as will enable the Minister to analyse the veterinary biologic;

Section 122.(1)(h)
any information the Minister may require in order to determine, in the course of assessing the safety of the veterinary biologic, whether the introduction of the veterinary biologic into the environment could result in the spread within Canada of a vector, disease or toxic substance that would have a harmful effect on human or animal health.

Section 124.
No person shall manufacture a veterinary biologic unless he does so under and in accordance with a product licence issued by the Minister.

Section 126.
Subject to section 127, every applicant for a product licence shall include with his application the material and information referred to in subsection 122 (1).

III. Guidance

A. Testing Requirements

For live vaccines, which are intended for use in ruminants and are produced using either non-irradiated ruminant serum or primary ruminant cells, manufacturers are required to conduct BTV exclusion testing. Tests may be carried out on raw materials or on finished serials as described below. The test option and test method must be pre-approved by CCVB:

Option 1
Testing of raw material of ruminant origin which is not subjected to a sterilization process: Test all ruminant serum used at the premises, whether used in production, quality control or research. Test all seeds and all primary ruminant cells used at the premises. Utilize satisfactory in-process controls to prevent BTV contamination during manufacture. Document the test procedure in the Production Outline for each product.

Option 2
Testing of each serial of the final product: The laboratory's test results must be reviewed and signed off by the importing company's authorized regulatory official. A signed memorandum (see attached template) must accompany each shipment being imported into Canada. Documents must be retained on file by the importing company.

B. Conditions for a waiver of testing requirements

The BTV exclusion testing may be waived if all of the following conditions are met and are documented in the Production Outline:

  1. Either ruminant serum is not used in the manufacture of the vaccine, or all of the ruminant serum used at the manufacturing facility is gamma irradiated at a level which has been demonstrated to inactivate BTV.
  2. Primary ruminant cells are not used in the manufacture of the vaccine. Only established cell lines or non-ruminant primary cells are used.
  3. All master seeds and master cell stocks have been tested for BTV with negative results.

IV. Related Guidelines and References

Veterinary Biologics Guideline 3.1E. Summary of Requirements and Guidelines for New Product Submissions of Veterinary Biologics in Canada
Veterinary Biologics Guideline 3.21E. Guidelines for the Importation of Veterinary Biologics for Research or Emergency Use

V. For further information

Any further questions or clarification regarding the regulations and requirements pertaining to BTV exclusion testing of veterinary biologics may be directed to the Canadian Centre for Veterinary Biologics.

Memorandum

[Date]

To: [Manufacturer name and address]

From: [Importer name and address]

Subject: List of serials eligible for importation under the [importer-manufacturer company names] Permit to Import Veterinary Biologics

This will confirm that I have reviewed the test results for the product serial(s) listed below, and verified that they conform with the testing requirements and permit conditions as described on the current Permit To Import Veterinary Biologics.

A copy of this memorandum must accompany the shipment. It will be retained on file at [Importer name]

  1. [CCVB file number] [USDA product code]
    [Assigned name] [trade name];
    [Serial No]; [Expiration date - yyyy-mm-dd]
    [Serial No]; [Expiration date - yyyy-mm-dd]
  2. [CCVB file number] [USDA product code]
    [Assigned name] [trade name];
    [Serial No]; [Expiration date - yyyy-mm-dd]
    [Serial No]; [Expiration date - yyyy-mm-dd]

[Signature, importer's authorized representative] [Date]
[Name, importer's authorized representative]
[Position]
[Importer company name]