Veterinary Biologics Guideline 3.15E:
Guideline for Reporting Suspected Adverse Events Related to Veterinary Biologics

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Table of Contents

1. Introduction
2. Legal Authority
3. General Guidance
4. Required Information
5. Definitions
6. References

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I. Introduction

The following provides guidance to veterinary biologics manufacturers and importers, veterinarians, animal owners and diagnostic laboratories for reporting and investigating suspected adverse events (SAE) related to veterinary biologics.

The Canadian Food Inspection Agency (CFIA) is responsible for licensing veterinary biologics, including veterinary vaccines, colostrum, antibody products and diagnostic kits, manufactured and/or used in Canada. The licensing program operates under the Health of Animals Act and Regulations, and is administered by the Canadian Centre for Veterinary Biologics (CCVB).

To meet Canadian licensing requirements, each veterinary biologic manufactured in or imported into Canada must be shown to be pure, potent, safe and efficacious when used according to the label recommendations. The Health of Animals Regulations require all holders of product licences and import permits to report all "serious expected" or "serious unexpected" SAE, including lack of efficacy, to CCVB within 15 days of receiving notice of the event from a veterinarian or animal owner. This includes complaints regarding all veterinary biologics (including autogenous vaccines) manufactured or imported for commercial, research or emergency use in Canada or those manufactured for export only. While holders of import permits are not required to report each separate SAE that has occurred in another country, they are required to report any information or adverse event which may indicate a significant deficiency in the purity, potency, safety or efficacy of a product.

Veterinarians and animal owners should notify CCVB of SAE related to veterinary biologics that occur in animals, including both vaccinated and in-contact animals. This can be done by notifying CCVB directly or through the licensed vaccine manufacturer or importer. Form CFIA/ACIA 2205 - Notification of Suspected Adverse Events to Veterinary Biologics - PDF (290 kb) for reporting SAE is available through CCVB, the CFIA Web site, or the Compendium of Veterinary Products.

When CCVB receives an SAE complaint, the manufacturer or designated importer is notified and requested to investigate the problem and prepare a report for the CFIA. Depending on the nature of the complaint, the manufacturer may be required to submit samples of the product to CFIA's laboratories for testing, or to conduct additional studies. If the adverse event rate for a particular serial (batch) or product is excessive, the manufacturer may be ordered to temporarily stop sale of the affected serial, recall the serial or withdraw the product from the market. When a product is withdrawn from the market, or a specific serial is recalled, the manufacturer is required to provide written notice to product users at the level of the recall (i.e. distributors or end-users). This notification is done through a letter that has been reviewed and approved by CCVB.

The CFIA is subject to Canadian legislation including the Access to Information Act and the Privacy Act. The CFIA will treat all information that it receives in accordance with such legislation.

II. Legal Authority

Health of Animals Regulations, Part XI

135.1 Every holder of a licence or permit issued under this part shall report to the Minister, in writing, any information concerning or any evidence of, a significant deficiency in safety, potency or efficacy of a veterinary biologic within 15 days after the date on which that information or evidence is known to the holder or is generally known to the industry.

III. General Guidance

Members of the public, including veterinarians and animal owners, can report SAE to veterinary biologics-Contacts directly or using the Form CFIA/ACIA 2205 - Notification of Suspected Adverse Events to Veterinary Biologics - PDF (290 kb), or through the product manufacturer/importer.

As stipulated by Section 135.1 of the Health of Animals Regulations, all reports that indicate "serious expected" or "serious unexpected" adverse events related to the use of a veterinary biologic, including lack of efficacy, must be reported to CCVB within 15 days of that information becoming known to the permit or licence holder. Follow-up reports, including case conclusions, must be submitted to CCVB in a timely manner. All other reports should be investigated by the licence/permit holder, summarized in a summary update report (SUR) and submitted to CCVB every six months. Summary update reports should be submitted within 60 days of the end of the reporting period.

SAE related to veterinary biologics are categorized as one of the following: Adverse Event (AE), Serious AE, Unexpected AE, and Lack of Efficacy. The definitions for Adverse Event (AE), Serious AE, and Unexpected AE can be found in the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)'s Guideline 24: Pharmacovigilance of veterinary medicinal products: management of adverse event reports (AERs), as well as in Section V of this guideline.

A causality assessment should also be assigned to each SAE. Each case should be classified as Probable, Possible, Unlikely, or Unknown.

The preferred method for permit/licence holders to submit SAE to CCVB is using a Microsoft Excel spreadsheet saved on a compact disc (CD). A copy of the Excel template can be obtained directly from CCVB. Accompanying supporting documentation (diagnostic test results, pathology reports, etc.) can be submitted in hard copy, or electronically on the same CD.

IV. Required Information

These requirements apply to manufacturers/importers preparing individual SAE reports and SUR.

Individual SAE Reports

1. Reporting company name and individual case number assigned by the company
2. Attending veterinarian and clinic name
3. Province in which the SAE occurred
4. Species of animal affected
5. Trade names and CCVB product file numbers of all veterinary biologics administered. Also include the trade names of all concurrently administered products.
6. Serial number(s)
7. Expiry date(s)
8. Report narrative: include animal characteristics (age, breed, sex), number vaccinated/affected, time of reaction onset, clinical signs, treatment, diagnostic tests performed, time to recovery, and all persistent sequelae
9. Causality assessment
10. Case status (initial or follow-up, ongoing or closed)

Summary Update Report

Information should be summarized in tabular form and can be submitted as a hard copy or on a CD.

1. Period of time summarized in the report
2. Manufacturer/importer information
3. Product information
   1. Assigned and trade names
   2. CCVB product file numbers
   3. United States Department of Agriculture (USDA) product codes (if applicable)
   4. Relative frequency of reports for time period covered, listed as number of SAE reports / 10 000 doses sold per product, including a concise analysis of presenting complaints and seriousness of reactions
4. Manufacturer case number
5. Date report received by reporter
6. Serial number
7. Expiry date
8. Species
9. Number treated/reacted/died
10. Product used as recommended
11. Clinical presentation (e.g. vomiting, facial edema, anaphylaxis, injection site reaction, etc.). Use of correct scientific terminology is strongly recommended.
12. Concurrently administered products
13. Treatment administered (yes/no)
14. Recovered (yes/no)
15. Manufacturer/importer causality assessment/conclusions

V. Definitions

Adverse Event (AE): Any observation in animals, whether or not it is considered to be product related, that is unfavourable and unintended and that occurs after any use of veterinary biologic(s).

Lack of Efficacy: Any AE whereby the veterinary biologic does not provide the expected level of efficacy based on the product label claims, including a diagnostic test kit that fails to provide the level of sensitivity and specificity described on the product label.

Summary Update Report: The document submitted to the regulatory authority to support the continued marketing and the adequacy of the approved labelling of the veterinary biologic, which will include an analysis of all AE received during the interval.

Possible: The administration of the vaccine is one of the possible and equally plausible explanations for the SAE. This category may be used when several products or antigens are given to an animal simultaneously and it is not known which product caused the AE.

Probable: There should be a reasonable association in time between the administration/use of the veterinary biologic and the SAE, the clinical signs or pathological lesions should be plausible given the veterinary biologic ingredients and expected AE, and there should be no other equally plausible cause for the SAE.

Serious AE: Any AE which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect.

Unexpected AE: Any AE of which the nature, severity or outcome is not consistent with the approved labelling describing expected AE for veterinary biologics.

Unknown: Reliable data is either unavailable or is insufficient to make an assessment.

Unlikely: Sufficient information must exist to establish that the described AE was not likely to be associated with the administration of the veterinary biologic, or another more plausible explanation exists.

VI. References

1. Access to Information Act, last accessed: 2009-01-05
2. Health of Animals Regulations, last accessed: 2009-01-05
3. Compendium of Veterinary Products (2007), Hensall, ON: North American Compendiums Ltd., ISBN: 978-1-896674-16-2.
4. Form CFIA/ACIA 2205 - Notification of Suspected Adverse Events to Veterinary Biologics - PDF (290 kb), last accessed: 2009-01-05
5. VICH Guidelines, last accessed: 2009-01-05