On June 10, 2025, Health Canada issued a draft of the new "Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs" (the "draft Guidance Document"). It aims to guide sponsors in meeting the regulatory requirements for biosimilar authorization under the Food and Drugs Act and the Food and Drug Regulations. A consultation period is open until September 8, 2025.
The draft Guidance Document suggests eliminating the need for biosimilar sponsors to demonstrate the safety and efficacy of their products through phase III clinical trials.
Background
A biosimilar is a biologic drug developed to be highly similar to an already authorized biologic drug, known as the Canadian Reference Biologic Drug ("CRBD"). Due to the complex and variable nature of biologic drugs, biosimilars cannot be made pharmaceutically equivalent to the CRBD, thus distinguishing them from generic drugs. As a result, biosimilars must be submitted for approval through the New Drug Submission pathway, requiring that they demonstrate a high degree of similarity to the CRBD.[1] This allows manufacturers to use a reduced clinical and non-clinical package for their submissions, thereby potentially speeding up the approval process, but still maintaining a regulatory process more onerous than that applicable to generic drugs.
Scope of Application of the Draft Guidance Document
The draft Guidance Document is an update to the Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs, issued for consultation purposes only. While it is not to be implemented at this time and its effective date is unknown, consultations are open.
The draft Guidance Document applies to sponsors seeking authorization for a biosimilar based on the demonstration of a "high degree of similarity" to a CRBD. Namely, it applies to biologic drugs containing well-characterized proteins derived through modern biotechnological methods such as the use of recombinant DNA and/or cell culture, short polypeptides manufactured by recombinant DNA procedures, and low molecular weight heparin.
Significant Changes Brought by the Draft Guidance Document
The Suppression of Clinical Efficacy Trials
Under existing guidelines, sponsors developing biosimilars are typically expected to perform a comparative phase III clinical study to demonstrate the lack of clinically meaningful differences between the biosimilar and the CRBD in terms of efficacy, safety or immunogenicity.
While comparative data is still required under the draft Guidance Document, comparative clinical efficacy and safety trials would no longer be necessary. Instead, data could be gathered from comparative clinical pharmacology studies and supplemented with data from other trial designs, such as studies specifically focused on safety or immunogenicity.
If the new guideline is adopted, it would represent a major shift in the regulation of biosimilars in Canada, potentially fast-tracking the approval process of biosimilar candidates.
The Demonstration of a "High Degree" of Similarity
Under the proposed guidelines, instead of demonstrating the clinical safety and efficacy of the drug through clinical trials to show "similarity" to a CRBD, sponsors of biosimilars would need to establish a "high degree" of similarity to a CRBD.
Although the draft Guidance Document does not define those terms, it suggests that a high degree of similarity depends upon detailed and comprehensive drug characterization and is established through quality, clinical, and non-clinical analyses and comparison studies.
A high degree of similarity between a biosimilar candidate and its CRBD does not mean their quality attributes are identical. Instead, it signifies that they are highly similar, such that the knowledge of both drugs sufficiently predicts that any differences will not adversely affect the safety or efficacy of the biosimilar, and that non-clinical and clinical data about the CRBD is applicable to the biosimilar. The determination of similarity relies on comprehensive data from physicochemical, functional, stability, and non-clinical and clinical studies.
Key criteria for demonstrating this similarity include evaluating the physicochemical characteristics, functional properties, and stability profiles of both the biosimilar and the CRBD. If a high degree of similarity cannot be established by such comparative quality studies, the drug cannot be considered biosimilar.
Pharmacokinetic and Pharmacodynamic Clinical Information
While the requirement for non-clinical studies remains unchanged under the draft Guidance Document, clinical study requirements have slightly evolved. The draft Guidance Document provides that clinical studies—aiming to support the demonstration of high similarity through comparative assessments of physicochemical characteristics, functional properties, and stability profiles between the biosimilar and the CRBD—should primarily include comparative pharmacokinetics studies, and if feasible, pharmacodynamics evaluations.
Previously, Health Canada recommended that the clinical studies begin with pharmacokinetic and pharmacodynamic studies, potentially followed by additional trials. Such trials were necessary to rule out clinically meaningful differences in efficacy and safety between the biosimilar and the reference biologic drug.
As mentioned above, the draft Guidance Document aims to eliminate the general requirement for biosimilar sponsors to conduct clinical trials, leaving the possibility of comparative clinical efficacy and safety trials in exceptional circumstances. This major shift in the regulatory approval approach, paired with the requirement to conduct pharmacodynamic studies only if feasible, rather than automatically, could potentially accelerate the approval of biosimilar candidates.
Other Considerations
The draft Guidance Document has not modified the labelling requirements and the need for a risk management plan. Insofar as post-market requirements are concerned, these still relate to adverse drug reaction reporting and post-notice of compliance changes.
However, certain changes stem from the removal of the requirement of clinical trial data. For instance, biosimilar monographs may need to be modified to no longer contain the comparative clinical data. As well, Health Canada highlights that the biosimilar may request authorization for all indications held by the CRBD based on the safety and efficacy data from both pre- and post-market settings, rather than a detailed scientific rationale.
Conclusion
Health Canada's draft Guidance Document provides a streamlined approach for biosimilar approval, emphasizing quality assessments over clinical trials. By focusing on establishing a high degree of similarity through comprehensive quality assessments rather than extensive clinical trials, the document facilitates a faster approval process for biosimilar drugs.
Stakeholders have until September 8, 2025, to submit their comments to the Biologic and Radiopharmaceutical Drugs Directorate.
Fasken's Life Sciences group remains available to assist in navigating these upcoming changes.
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