Health Canada consulting on new biosimilar guidance document
Health Canada has published a draft amended guidance document covering information and submission requirements for biosimilar biologic drugs. If implemented, Health Canada will use the draft guidance in evaluating drug submissions. The consultation period for the draft guidance ends September 8, 2025.
A key component of this guidance documents is the elimination (in most cases) of the need to do comparative clinical efficacy and safety trials between the biosimilar and the Canadian reference biologic drug (CRBD).
Under the draft guidance, the decision to authorize a biosimilar for requested indications is dependent on the biosimilar sponsor demonstrating a “high degree of similarity” between the biosimilar candidate and the CRBD based on data derived from comparative quality, non-clinical, and clinical pharmacology studies.
The comparative quality studies will compare attributes of the biosimilar candidate and CRBD, including physicochemical characteristics (structure, post-translational modifications, heterogeneity, purity, impurities), functional properties (biological activity, immunochemical binding properties, etc.), and stability profile (stress, accelerated, forced degradation profiles).
The draft guidance highlights the following four criteria as key points when demonstrating a high degree of similarity via comparative quality studies:
- Physicochemical Characteristics: Testing should include a determination of the composition, physical properties, and primary structure of the desired product. The molecular heterogeneity of the biosimilar candidate should also be considered.
- Purity and Impurities: Testing should provide data to allow for evaluation of relevant differences in purity and product-related impurity profiles. Differences in purity and product-related impurity profiles should be evaluated to assess their potential impact on safety and efficacy.
- Functional Properties: Multiple functional assays should be performed as part of the similarity assessment, reflecting the mechanism(s) of action to the extent possible.
- Stability: Comparative stability studies (e.g., accelerated, stressed, and forced degradation studies) should be conducted to compare degradation profiles.
Where a high degree of similarity is established via comparative quality studies, and where in vitro mechanistic studies also indicate a high degree of similarity, in vivo non-clinical studies are generally not required.
Though the currently implemented guidance document states that “in most cases, a comparative clinical trial(s) is important to rule out clinically meaningful differences in efficacy and safety between the biosimilar and reference biologic drug”, the draft guidance removes the requirement for biosimilar sponsors to conduct comparative clinical efficacy and safety trials. The draft guidance specifies that “in most cases, a comparative clinical efficacy and safety trial(s) is not required.” Biosimilar sponsors need only conduct a comparative clinical pharmacokinetic (PK) trial to demonstrate PK equivalence between the biosimilar and CRBD.
As well, if a clinically relevant pharmacodynamic (PD) marker exists and is measurable, it should also be evaluated and can be incorporated into a combined comparative PK/PD study.
Safety and comparative immunogenicity data are still required and should be collected within the comparative clinical pharmacology studies.
The final determination of whether a biosimilar candidate is “highly similar” to its CRBD is based on all relevant data from the comparative quality, non-clinical, and clinical pharmacology studies with the weight of evidence being provided by the comparative quality studies.
With respect to product labelling, the draft guidance removes the current requirement to include comparative data generated by the biosimilar sponsor in its product monograph. The product monograph should include the following information:
- A statement indicating the drug is a biosimilar to the CRBD; and
- Relevant safety and efficacy information from the product monograph of the biologic drug authorized in Canada to which a reference is made.
The draft guidance also removes the current prohibition against including claims for bioequivalence or clinical equivalence.
