How should MAHs interpret Health Canada guidelines when it comes to compiling aggregate reports?
Health Canada mandates foreign and local MAHs marketing their medicinal products in Canada to maintain the safety profile of a drug throughout its lifecycle. Cumulative or ‘aggregated’ safety information is gathered into reports on a periodic basis over time based on ICH guidelines. Aggregate reports could be in the form of Annual Summary Reports (ASRs), Periodic Safety Updated Repots (PSURs), and PBRERs among others. The purpose of ASRs is to enable an understanding of the Benefit-Risk profile of a product, and how it changes over time as more real-world data becomes available at different development and post-marketing stages. The end goal is to identify new risks to patients over time.
In this article we are mainly discussing ASRs as they constitute a critical step of product safety analysis, in addition to requiring major resources commitments on MAHs end.
To perform such analysis, maintenance of accurate records including AE line listings of all post-marketing reported adverse events (AEs) and adverse drug reactions (ADRs) is important. The source of those AEs and ADRs must include all possible channels including but not limited to spontaneous cases, cases identified during performance of literature screening and Canada vigilance database screening and cases reported during post-marketing studies. While the safety analysis is to assess brand name products, MAHs must assume cases that concern the active ingredient of their brand name products as their own and include it in the aggregate report compilation and safety analysis.
The common trap most MAHs fall into when preparing those aggregate reports is having to compile all AEs and ADRs including sections that may not be relevant to perform the analysis. While case tabulation is required according to Health Canada guidelines, compilation and case analysis must be performed in such a way allowing identification of changes to the overall benefit-risk profile of the product as well as early detection of signals that require further investigation. Therefore, MAHs are invited to increase the focus on discussing relevant safety signals and avoid elements that may have been already performed during daily case processing tasks- so long as it does not alter the overall assessment.
In drafting ASRs, MAHs should provide a global overview for a particular active substance through a comprehensive cumulative and interval analysis of safety and efficacy data for all strengths, indications, and/or formulations in the preceding 12 months. Failure to comply to the objective of those reports may result in compliance issues and observations during a GVP inspection.
Different ASR formats may be followed as indicated in the Health Canada guidelines1, however, critical analysis of the safety profile of a drug is necessary to allow MAHs make informed decisions in a timely manner and ensure efficient use of its resources at all times.
If you have concerns about the quality and compliance level of your ASRs, talk to a Zenith PV partner today to discuss how our expertise will help you stay fully compliant with all the requirements. Our experts can support you with all stages of your ASR planning, preparation- including medical writing, submission, and follow-up.
References:
- Preparing and Submitting Summary Reports for Marketed Drugs and Natural Health Products – Guidance Document for Industry The Preparing and Submitting Summary Reports for Marketed Drugs and Natural Health Products – Guidance Document for Industry – Canada.ca