Upcoming Changes to Health Canada Regulations

In a major regulatory shift, Health Canada is adopting global standards for bioequivalence. Starting December 27, 2025, Health Canada will implement the ICH M13A guideline, marking a significant step toward global harmonization in generic drug approvals. Under the new ICH M13A guideline, Health Canada is making a few key changes to how generic drug equivalence is assessed:

(1) Cmax Requirement: Previously, only the T/R ratio of a generic drug’s maximum concentration (Cmax) compared to the brand-name drug had to fall between 80–125%. Now, the entire 90% confidence interval for that ratio must be contained within the 80.00–125.00% range. This approach aligns with that of Europe and US, aiding harmonization with other major regulatory agencies. While the old approach focused primarily on average values, the new standard introduces tighter controls by accounting for variability, ensuring greater statistical certainty and a more robust demonstration of bioequivalence. The impact of this requirement is that a higher number of volunteers need to be enrolled in studies in order to meet the more stringent requirement on Cmax, which is typically a more variable parameter which drives the sample size requirements of a bioequivalence study.

(2) Highly Variable Drugs: Where the previous method applied a one-size-fits-all approach, considering that the highest variability for expansion of bioequivalence limits is 50% (with maximum 90% interval acceptance range of 66.7 - 150%), the new guideline introduces Scaled Average Bioequivalence (SABE) — a flexible, science-based method that allows a wider acceptance range for drugs with excessively high variability, while still maintaining rigorous statistical requirements. Previously, although Health Canada had a mechanism to account for high variability with the intention of limiting sample sizes for highly variable drugs, for some drugs exhibiting extreme variability (i.e 75%+) the methodology was insufficient making studies on such products excessively large. This may have prohibited companies from developing those products for the Canadian market due to the cost of development.

(3) Global Alignment: Canada is moving from a country-specific framework to one that is harmonized with global regulators including the US, Europe and Japan. This can help streamline international submissions and reduce regulatory duplication, especially in the case of products accepted through the foreign-sourced reference product pathway.

This update marks a piviotal step in Canada's commitment to scientific excellence and global regulatory alignment, but interpreting existing guidelines from Health Canada remain a challenge, as some of the ICH M13A guidelines supersede current guidances in effect, while other aspects of current guidances remain in effect. It would be helpful for industry if Health Canada updated all of their current guidances to clearly communicate requirements, so as to avoid the need to reference multiple guidance documents.