[Table of Contents]

Volume: 26S1 - February 2000

Guidelines for Reporting Adverse Events Associated with Vaccine Products
Supplementary guidelines for the Canadian Pharmaceutical Industry

II. General Procedures For Reporting - Features Unique to Vaccines

Many of the procedures are consistent with the TPP Guidelines. This section highlights the features unique to vaccine products.

A. What Constitutes a VAAE Report

As stated in the TPP Guidelines, in making a report to a manufacturer, the practitioner is indicating that the observed event may have been caused by the drug or vaccine. For vaccine-related adverse events, the manufacturer should submit the report to LCDC. However, submission of such a report does not necessarily mean that the manufacturer accepts causality.

Follow-up information should be actively sought and submitted, as it becomes available, for any case on which information is not complete enough to adequately assess the adverse event and its relation to vaccination. VAAE reports submitted by the manufacturer to LCDC should be clearly labelled as "initial" or "follow-up" reports. In the follow-up report, specific reference should be made to the initial report, for example, by including the manufacturer number specific to the report. As well, a notation should be made if the case was also reported to the appropriate provincial/territorial public health authority, since it will, in turn, resubmit the report to LCDC.

The Regulations to be followed by manufacturers refer only to submitting cases to the HPB. Therefore, in order to avoid duplication of VAAE reports, it is extremely useful for reports submitted from manufacturers to be labelled as to whether they were received from a provincial/territorial public health agency, a practitioner or a member of the public, and whether a copy has been sent to the relevant province/territory.

B. Domestic VAAE Reports

Adverse reactions to vaccines occurring in Canada are considered "domestic" VAAE reports.

Priority (15-day) Reports

All reports of serious VAAEs must be forwarded to LCDC within 15 calendar days of the receipt of the report by the Canadian manufacturer. Although they are not explicitly covered under regulations, the Division of Immunization also considers as serious cases those that would fall under ACCA review criteria (see Appendix 2 for definition). These should also be forwarded under the 15-day criteria.

Reports to Regional Centres (managed by the Therapeutic Products Programme)

This provision applies only in cases in which a reporter has forwarded a vaccine-related report to a Regional Centre managed by the TPP. If a manufacturer becomes aware of a report that has been submitted by a practitioner to one of the TPP Regional Centres (listed on the reverse of the latest drug ADR reporting form - HC-4016), the manufacturer should still submit the report to LCDC in the appropriate fashion. Although the ADR Reporting Section of TPP is aware of the need to forward all vaccine-related cases to LCDC, it cannot be assumed that the reporter has indeed actually sent the case to the Regional Centre, or that it did not get lost or delayed for some other reason and thus was never submitted to LCDC.

Consumer Reports

On receiving reports from consumers, it is recommended that a manufacturer encourage consumers to report the reaction through their physicians or local public health department. The nature of the vaccine postmarket surveillance program in Canada, as outlined in these guidelines, should be explained to consumers in order to encourage reporting through public health departments. If vaccine recipients agree to report their VAAE to their provider or public health units, the manufacturer should still submit a 15-day (preliminary) report as required by the Regulations, in case consumers do not follow through. In order to avoid duplicate reporting, it would be helpful to note that the consumer may be reporting this case to the public health department. If reporting to their provider is unsatisfactory to the consumers, the manufacturer should then attempt to obtain as much information as possible from them, including the name of the physician and/or local public health unit.

Other Non-serious Reports

Since the monitoring of adverse reactions to vaccines includes both a search for rare, serious and unexpected events as well as lot-by-lot monitoring and surveillance for programmatic errors, which rely often on case reports that may describe more minor reactions, manufacturers are asked to submit all VAAE reports that come to their attention to LCDC. VAAE reports are defined as any vaccine adverse event that is communicated, for example, by telephone, e-mail, fax, or letter, to a manufacturer and that is duly recorded as a VAAE report by the manufacturer under its standard operating procedures.

Although not covered under the Regulations for expedited reporting (only as reportable on request or within annual summaries), LCDC nevertheless requests that minor reaction reports be forwarded as soon as practical to its monitoring program, but at least within 30 days. In the same way as for priority (15-day) reports, the Division will forward the cases to the appropriate provincial/territorial public health authority.

C. Foreign Adverse Reaction Reports Priority (15-day) Reports - Foreign Cases

VAAEs occurring outside Canada for vaccines in use outside Canada, when a product with the same composition is licensed and distributed in Canada, are considered "foreign" reports and are to be forwarded as outlined in the TPP Guidelines.

D. Unusual Failure in Efficacy - Domestic Reports

Lack of efficacy has been considered an adverse reaction for many years in the Canadian Food and Drug Regulations. For all vaccines, LCDC monitors effectiveness from time to time through epidemiologic investigations of outbreaks of vaccine-preventable disease. There will always be individuals who do not respond serologically to the administration of a vaccine, and therefore vaccine failures are anticipated. Thus, failures in efficacy of vaccines are not as important as for other drug products. The requirement for reporting lack of efficacy under the Regulations, which in fact pertain only to new drugs according to the definition in Section C.08.001, need not be applied to vaccines. From time to time, however, LCDC may still place certain vaccines under special surveillance to monitor lack of efficacy for a limited period of time. In those cases a request will be made in writing to the manufacturer or distributor of the product involved to ask that it applies the Regulations, monitors the vaccine and submits reports to the LCDC.

E. Summary Reports or Periodic Safety Update Reports (PSURs)

As is the case for drugs, the summary report is to be prepared annually and upon special request by the Director. The summary report is to be maintained on site (or be easily accessible) and, WHEN REQUESTED, it is to be submitted to the monitoring program for VAAEs at LCDC within 30 calendar days of the request.

In general, the summary report will consist of three sections: a summary line listing of VAAE reports received during the review period, a critical analysis of them, and recommended actions.

The summary report should be prepared as outlined in the TPP Guidelines. It is recognized that the line listing that includes non-serious reports represents some duplication of reporting in the case of vaccines. This situation is acknowledged and accepted.

Should a manufacturer feel that it has insufficient direct VAAE reporting, and that international reports from the parent company are inadequate to conduct the proper critical analysis, LCDC can be contacted for the data that was submitted directly to the Division. Summary line listings of VAAE reports stripped of all vaccine recipient and reporter identifiers can be provided to the manufacturer in order to facilitate meeting the requirements of the Regulations.

F. Reports from Studies on Marketed Vaccines

Manufacturer Sponsored Studies

For studies conducted on marketed vaccines that are not subject to the Investigational New Drug (IND) Regulations (C.08.005 and C.08.005.1) the TPP Guidelines should be followed for all serious, domestic VAAEs; serious, unexpected foreign VAAEs are reported to the manufacturer by the investigator(s) so that the manufacturer can provide such reports to the Division of Immunization, LCDC within the 15-day period specified in the Regulations (see Appendix 2for a summary of the reporting requirements).

Studies conducted on marketed products that are subject to the IND Regulations (e.g. studies on new age groups) are to be sent to the TPP Bureau overseeing the IND Submission (usually the Bureau of Biologics and Radiopharmaceuticals) through the central office of the Submission and Information Policy Division (see Appendix 4 for address).

Blinded Reports

As is the case for adverse drug reactions, if the manufacturer receives a report from the investigator that is blinded to individual vaccine recipient treatment, the code must be broken before submitting the report to LCDC.

Non-Manufacturer Sponsored Studies

Follow the TPP Guidelines.

G. Audit

Same as the TPP Guidelines.

H. Forms

Acceptable Forms

The use of either the "Report of a Vaccine Associated Adverse Event" form (HC/SC 4229 (03-96)) or the CIOMS I form is the acceptable method of reporting VAAEs to LCDC. A copy of the first form is included in Appendix 5 . If a report is received on an individual form from an association, hospital, pharmacy or other source, it is not necessary for the manufacturer to transcribe the report onto one of the above-mentioned forms.

Key Data Elements

The minimum information required for reporting purposes is an identifiable vaccine recipient, a suspect medicinal product, an identifiable reporting source, and an adverse event. For vaccines, the lot number is very important. The reporting form included in Appendix 5 can serve as a model to guide the collection of items that enhance the quality of a VAAE report. Attempts should be made to obtain information on as many listed items as are pertinent to the case, and in sufficient detail to allow for independent causality assessment of the case.

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