In Canada, biosimilar products are approved by way of a new drug submission, following Health Canada guidance first released in 2010 and significantly revised in 2016. Such guidance had, in most cases, required comparative clinical efficacy and safety trials between the biosimilar and reference product. In 2025, Health Canada consulted on a revised draft guidance document for biosimilar submissions, which notably proposed removing the requirement for comparative clinical efficacy and safety trials. On May 19, 2026, Health Canada released its final Guidance on information and submission requirements for biosimilar biologic drugs implementing this change.
According to Health Canada, the Guidance was revised to “better align with the current state of science and international developments in the regulation of biosimilars” and drew upon Health Canada’s cumulative experience reviewing biosimilar submissions since the last comprehensive review of the Guidance in 2016. Health Canada received input from 15 stakeholders before finalizing the Guidance but has not yet posted the input or its typical “What we heard” summary.
Key updates, new sections and other revisions are summarized by Health Canada, including:
- Scope of drugs that may be “biosimilars”: A biologic drug suitable for use as a Canadian Reference Biologic Drug (CRBD) is a drug originally authorized based on a comprehensive quality, non-clinical and clinical data package, with a substantial body of evidence regarding quality, safety, efficacy and effectiveness since market authorization. Additionally, both the proposed biosimilar and the CRBD must be extensively characterized by a set of modern analytical methods through which the biosimilar can be judged to be “highly similar” to the CRBD by meeting an appropriate set of predetermined criteria.
- Definition of “highly similar”: “A determination, based on robust and appropriately designed comparative analytical studies, that the proposed biosimilar and the [CRBD] demonstrate analytical concordance in structural and functional characteristics, with critical quality attributes falling within prospectively justified, pre-defined ranges informed by reference product variability, and that any observed differences have been assessed and determined not to have a meaningful impact on safety or efficacy."
- Removal of requirement for comparative clinical efficacy studies: The Guidance has been finalized as proposed in the draft, noting that such studies “are not typically required for a biosimilar candidate to a [CRBD] when the biosimilar can be compared and extensively characterized through appropriate analytical studies.” If such studies are included, the biosimilar manufacturer should “explain the role of the studies and the value of the results in the context of the submission.”
- Indication-specific scientific rationale not required: A biosimilar can be approved for all indications granted to the CRBD without requiring additional justification, provided the biosimilar is highly similar in analytical and functional characteristics related to the mechanism of action of the CRBD and can deliver the same dosages for the relevant indications.
- Clarification on classification as biosimilars or generics: Low molecular weight heparins are regulated as biologic drugs, and the Guidance applies to their subsequent versions. In contrast, short, chemically synthesized polypeptide drugs could be eligible for authorization as a generic drug through an Abbreviated New Drug Submission even if the original reference product is a biologic drug; the Guidance would not apply in such cases.
International context: Health Canada’s Guidance is broadly consistent with recent developments in biosimilar approval frameworks in the UK, Europe and the United States:
- UK: The Medicines and Healthcare products Regulatory Agency (MHRA)’s Guidance on the licensing of biosimilar products (last updated February 2025) states that, in most cases, a comparative efficacy trial may not be necessary if appropriately justified by sound scientific rationale. Exceptions may arise, particularly “where there is a lack of understanding of the biological functions of the [reference biologic] related to its clinical effects or where the relevant [critical quality attributes] may not be sufficiently characterised due to analytical limitations.”
- Europe: On March 16, 2026, the European Medicines Agency (EMA) adopted a reflection paper, concluding that comparative efficacy studies “may not be required for well characterized biological substances where the analytical comparability exercise provides a more sensitive determination of biosimilarity, in conjunction with [pharmacokinetic] and appropriate safety studies.”
- United States: The FDA’s October 2025 draft guidance, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, states that comparative analytical assessments are generally more sensitive than comparative efficacy studies and supports a streamlined development approach in which comparative efficacy studies may not be necessary.
ICH, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, has also established the M18 expert working group to develop a new multidisciplinary guideline that will outline the factors to consider when determining the utility of comparative efficacy studies in biosimilar development programs intended to support regulatory approval (see the M18 Concept Paper).
Should you have any questions, please do not hesitate to contact a member of the Life Sciences Regulatory & Compliance Group or the Pharmaceutical Litigation Group.
The preceding is intended as a timely update on Canadian intellectual property and life sciences regulatory law. The content is informational only and does not constitute legal or professional advice. To obtain such advice, please communicate with our offices directly.