Questions and Answers Regarding the Adoption of Periodic Benefit Risk Evaluation Report (PBRER) Review at Health Canada

1. What is the purpose of the Notice Regarding the Adoption of the International Conference on Harmonisation (ICH) Guidance on Periodic Benefit Risk Evaluation Report- ICH Topic E2C(R2)?

The purpose of the Notice is to notify Market Authorization Holders (MAHs) that Health Canada will accept annual summary reports in the Periodic Safety Update Report (PSUR) or PBRER format and content as outlined in the ICH E2C(R1) and ICH E2C(R2) guidances, respectively, in fulfillment of the requirements under C.01.018 to prepare annual summary reports.

2. What is a Periodic Benefit Risk Evaluation Report (PBRER)?

A PBRER is intended to present a periodic, comprehensive, concise and critical analysis of new or emerging information on the risks of the health product, and on its benefits in approved indications, to enable an appraisal of the product's overall benefit-risk profile.

3. What is the International Conference on Harmonisation?

The International Conference on Harmonisation (ICH) is a project that brings together regulatory bodies and research-based industry from three regions (United States, Europe, and Japan) where most new medicines are currently developed. The purpose of ICH is to harmonize regulatory requirements in order to avoid duplication during the development of medicine. This is carried out via the development and implementation of harmonized technical guidelines and standards for the development, registration and surveillance of pharmaceutical products. As an official observer to, and active participant in the ICH, Health Canada is committed to the adoption and implementation of ICH guidances.

4. Why is Health Canada adopting ICH E2C(R2)?

Health Canada is committed to the adoption and implementation of ICH guidances. The adoption of the ICH E2C(R2) guidance will allow Health Canada and MAHs to:

• align product vigilance with international best practices;
• support the life cycle approach to product vigilance;
• strengthen the link between risk assessment and regulatory actions to minimize risk;
• minimise international regulatory burden and improve reviewing efficiency of submissions; and,
• increase accountability.

5. Which products and/or product lines will follow the PBRER format and content? How will they be managed?

The PBRER will only apply to human drugs with an active Drug Identification Number (DIN) specific to the following product lines:

• Pharmaceuticals;
• Biologics;
• Biotechnology products;
• Radiopharmaceuticals;
• Preventative vaccines; and,
• Therapeutic vaccines.

PBRERs will be received, processed, and tracked, using a single window approach using the Drug Submission Tracking System (DSTS) through the Office of Submissions and Intellectual Property (OSIP).

6. How is this tool used to enhance pharmacovigilance activities at Health Canada?

PBRERs will enhance Health Canada pharmacovigilance activities because they:

• will include updates and summaries of important new safety information that may lead to identifying new safety concerns within the context of any pertinent efficacy/effectiveness information;
• will incorporate an analysis of changes in the benefit-risk profile;
• will support risk communication activities by regulatory authorities; and,
• could provide an early indication on the need for additional risk management initiatives.

7. How will PBRERs submitted to Health Canada be reviewed, once this Notice is in effect?

The emphasis of Health Canada reviews will continue to be on the safety and risks aspects of the PBRER, until such time as a methodology and approach to the review of Benefit and Benefit-Risk sections of the PBRER have been developed.

8. Which guidance documents will be affected by this Notice?

If MAHs submit a PBRER, the Notice Regarding the Adoption of the International Conference on Harmonisation (ICH) Guidance on Periodic Benefit Risk Evaluation Report- ICH Topic E2C(R2) will supersede Section 5 of the Guidance Document for Industry - Reporting Adverse Reactions to Marketed Health Products. Health Canada guidance documents that are affected by the Notice Regarding the Adoption of the International Conference on Harmonisation (ICH) Guidance on Periodic Benefit Risk Evaluation Report- ICH Topic E2C(R2) include, but are not limited to, the following:

• Guidance Document for Industry - Reporting Adverse Reactions to Marketed Health Products;
• Guidance Document: Notice of Compliance with Conditions (NOC/c);
• Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format;
• Guidance Document for Industry - Issuance of Health Professional Communications and Public Communications by Market Authorization Holders;
• Good Pharmacovigilance Practices (GVP) Guidelines (GUI-0102); and,
• Any other applicable Health Canada guidance documents related to PSUR.

Please follow the procedures outlined in the Notice until otherwise notified.

9. Are MAHs required to submit a PBRER to Health Canada?

MAHs are expected to prepare annual summary reports for all their health products, with an active DIN, including generic drugs. However, annual summary reports, which may be prepared in either PSUR or PBRER format, are only required to be submitted if notifying Health Canada of a significant change in what is known about the risks and benefits, or upon request.

10. What is the time interval between the Data Lock Point (DLP) and solicited PBRER submissions?

As a result of the expanded scope of the PBRER, the time interval between the data lock point (DLP) and submission of solicited PBRERs should be as follows:

• PBRERs covering intervals of 6 or 12 months: within 70 calendar days;
• PBRERs covering intervals in excess of 12 months: within 90 calendar days;
• ad hoc PBRERs: 90 calendar days, unless otherwise specified in the ad hoc request.

The day of DLP is day 0 of the 70- or 90-calendar day interval between the DLP and report submission of the report.

11. What if in preparing the annual summary report, it is concluded that there has been a significant change in what is known about the risks and benefits of the health product?

In preparing the annual summary report and in accordance with the Food and Drug Regulations, if the MAH concludes that there has been a significant change in what is known about the risks and benefits of the health product, the MAH must inform Health Canada in writing without delay^{Footnote 1}. Potential reasons for notification include, but are not limited to, a significant change in the frequency or severity of a known risk or the identification of a previously unknown risk.

The notification should include the most recent complete annual summary report, which may be provided in either PSUR or PBRER format, the Annual Summary Report Checklist and a cover letter indicating that the information is being sent pursuant to the reporting requirements detailed in C.01.018(4).

12. Where do I submit the PBRER?

All PBRER submissions will be processed and tracked using the Drug Submissions Tracking System (DSTS) managed by the Office of Submissions and Intellectual Property (OSIP). MAHs are required to submit PBRERs and related information directly to OSIP at the following address:

Office of Submissions and Intellectual Property (OSIP)
Therapeutic Products Directorate
Health Canada
Postal Locator: 0201A1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9