Health Canada Removes Phase III Trials for Biosimilars: What It Means for Patent Enforcement

On May 19, 2026, Health Canada published its finalized revised guidelines on biosimilar submission requirements: Guidance on Information and Submission Requirements for Biosimilar Biologic Drugs. The final guidance document follows stakeholder consultations on Health Canada’s draft guidelines, which were published on June 13, 2025. In a significant reversal of policy on biosimilar drug submissions, Health Canada’s draft and final guidance signal a shift away from comparative clinical studies conducted in patient populations toward an analytical-comparability-driven framework.

Key Changes: Shift Away from Biosimilar Clinical Efficacy Studies

Health Canada's “guidance documents” are intended to assist drug sponsors in meeting regulatory requirements. Although these documents are administrative and do not carry the force of law, Health Canada generally applies them as guidelines when evaluating drug submissions.

Health Canada’s amendments are largely similar to the draft guidance published on June 13, 2025, with a few changes. Our analysis of the draft guidance can be found here. The newly implemented guidance shifts the focus of biosimilar approval towards qualitative similarity, while moving away from biosimilar clinical studies:

1. Expanded Focus on Quality and Analytical Data: The revised guidance expands the quality sections, emphasizing that quality data are central to establishing a “high degree of similarity” with the Canadian Reference Biologic Drug (i.e., the innovator biologic). “Highly similar” is defined as:

"A determination, based on robust and appropriately designed comparative analytical studies, that the proposed biosimilar and the reference biologic drug 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."

Additionally, while the 2025 draft guidance listed “the nature of the drug product” as a factor impacting the studies necessary to demonstrate a high degree of similarity, the final guidance expressly adds that this will depend on “the nature and composition of the drug product, including inactive ingredients and excipients and their impact on safety and immunogenicity”.

2. Clinical Efficacy Studies Generally Not Required: The revised guidance provides more detail than the draft guidance on the need (or lack thereof) for comparative clinical studies. The revised guidance confirms that comparative clinical efficacy studies are not typically required where biosimilarity can be established through analytical and clinical pharmacology data. Where such studies are included, sponsors are expected to explain their role and value within the overall submission.

The clinical program should primarily include a comparative pharmacokinetic (“PK”) study and may include a comparative evaluation of pharmacodynamics (“PD”). Unlike the draft guidance, the final guidance states that a PD endpoint may serve as a surrogate for PK in cases where drug concentrations cannot be measured reliably.

3. Updated Approach to Immunogenicity: The guidance introduces additional detail on immunogenicity, including new subsections addressing data expectations. These updates were not included in the draft guidance. The revised guidance clarifies that analytical and functional data are the primary foundation for assessing comparative immunogenicity risk, while anti-drug antibody data collected in comparative pharmacokinetic studies are descriptive and supportive.

4. Elimination of Indication‑Specific Scientific Rationale: Consistent with the draft guidance, the final guidance eliminates the requirement for a detailed scientific rationale to support each indication sought by a biosimilar. Authorization across indications may be supported where the biosimilar is shown to be highly similar to the Canadian Reference Biologic Drug and that it can deliver the same dosage across indications. The final guidance also explicitly states that all indications granted to the Canadian  Reference Biologic Drug may be applied to the biosimilar “without further justification” where the candidate has been shown to be highly similar in terms of both analytical characteristics and functional properties related to the mechanism of action.

Health Canada’s newly adopted guidance reflects a broader international trend, consistent with the draft guidance from the U.S. Food and Drug Administration (“FDA”) and the recently approved guidance from the European Medicines Agency (“EMA”).^[1] Similar to Health Canada, the EMA will no longer require comparative efficacy studies to approve biosimilars that can be characterized using analytical methods. The EMA specifies that comparative efficacy studies may still be important in cases where a biologic is not well-characterizable or has an unknown or poorly understood mechanism of action or structure-function relationship. The FDA similarly proposes to accept comparative analytical assessment in place of clinical efficacy studies. Our analysis of the FDA draft guidance can be found here.

Potential Implications for Biosimilar Litigation in Canada

With these changes, biosimilar development is poised to become more attractive. Innovative pharmaceutical and biotechnology companies will likely see:

• Increased biosimilar filers. Lower development costs will lower the barrier to entry, encouraging more sponsors—including smaller entrants previously deterred by clinical trial risk—to pursue Canadian submissions. For high-value biologics, innovative companies should anticipate not just earlier challenges under Canada’s patent linkage regime, the Patented Medicines (Notice of Compliance) Regulations, but also a higher number of concurrent challengers, each potentially advancing distinct invalidity and non-infringement theories.
• Compressed enforcement windows. With more biosimilar challengers, innovator companies should reassess patent enforcement timelines and litigation budgets.
• Impact on skinny label strategy. The guidance explicitly provides that all Canadian Reference Biologic Drug indications may be applied to a biosimilar “without further justification” once high analytical and functional similarity is established. Innovators that have structured their enforcement strategy around indication-specific patents should model how this regulatory posture may affect infringement exposure and the practical scope of skinny label arguments going forward.
• Portfolio assessment and pre-filing preparedness. The acceleration of the biosimilar regulatory pathway narrows the window for pursuing additional prosecution and patent register listings before challengers arrive.

^[1] European Medicines Agency, Reflection paper on tailored clinical approach in biosimilar development, adopted March 16, 2026; U.S. Food and Drug Administration, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, October 2025.