Health Canada has proposed a substantial change to the regulation of biosimilar drugs in Canada that may result in earlier applications for marketing authorization and earlier litigation under the Patented Medicines (Notice of Compliance) Regulations (PMNOC Regulations). Specifically, under proposed new guidance, Health Canada would no longer require biosimilar manufacturers to provide clinical evidence of efficacy, which typically involves a large, phase 3 clinical trial. The proposed new guidance has other notable clarifications and regulatory shifts related to polypeptide drugs, animal studies, and indications for biosimilar drugs.

Background on biosimilar drugs

Biosimilar and generic drugs are both follow-ons of originator drugs; however, they have fundamental differences that have resulted in their approval being regulated differently in Canada.

  • The active ingredient in a generic drug is a chemically-synthesized small molecule with identical molecular structure to the active ingredient in the originator drug. Generic drugs are approved for sale through the Abbreviated New Drug Submission (ANDS) pathway.
  • By contrast, the active ingredient in a biosimilar drug is a biologically-manufactured large molecule that is highly similar – but not identical – to the active ingredient in the originator drug. Biosimilar drugs are approved for sale through the New Drug Submission (NDS) pathway.

Proposed revisions to biosimilar guidance

On June 10, 2025, Health Canada launched a consultation on proposed revisions to its Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs (Biosimilar Guidance). Since 2010, the Biosimilar Guidance has set out Health Canada’s standard practices for biosimilar drug approvals. The last comprehensive revision to the Biosimilar Guidance was in 2016.

Eliminating requirement for large clinical trials

In Health Canada’s new proposed revisions to the Biosimilar Guidance, the most substantial change relates to clinical trial evidence. Under the current Biosimilar Guidance, a comparative clinical trial is required in “most cases… to rule out clinically meaningful differences in efficacy and safety between the biosimilar and the reference biologic drug” (i.e., the originator drug).  Such comparative clinical trials are typically phase 3 trials that involve treating hundreds of patients with either the biosimilar or originator drug. The proposed new Biosimilar Guidance, by contrast, states: “In most cases, a comparative clinical efficacy and safety trial(s) is not required” (emphasis added). Instead, the clinical evidence would be generally limited to a comparative pharmacokinetic (PK) study. This PK study is also expected to collect data on the safety and immunogenicity of the biosimilar drug, and, if feasible, compare the pharmacodynamics of the biosimilar and originator drugs. 

In proposing these changes to the Biosimilar Guidance, Health Canada appears to be aligned with the European Medicines Agency, which on April 1, 2025, published a reflection paper suggesting that biosimilar drugs can be approved without clinical evidence of efficacy. 

In practical terms, no longer requiring phase 3 clinical studies may make it faster and cheaper to bring biosimilar drugs to market. For instance, according to a 2021 estimate, biosimilar phase 3 trials had a median length of 55 weeks and a median cost of $28 million USD. If so, Health Canada’s proposed changes to the Biosimilar Guidance may result in NDSs for biosimilar drugs being filed earlier in Canada. This in turn may trigger earlier patent infringement proceedings against biosimilar manufacturers under the PMNOC Regulations. 

Other proposed changes to the Biosimilar Guidance

Health Canada has proposed other notable changes to the Biosimilar Guidance:

  • Polypeptide drugs: The new guidance would state: “Short polypeptide drugs are classified as either a biologic or a pharmaceutical depending on the method of manufacture. When manufactured by recombinant DNA procedures, short polypeptides are considered biologic drugs and are eligible for authorization as a biosimilar. When chemically synthesized, they are considered pharmaceutical drugs and are eligible for authorization as a generic drug via the Abbreviated New Drug Submission (ANDS) pathway.”
  • Animal studies: The new guidance would confirm that in vivo non-clinical studies (i.e., animal studies) are generally not needed where a high degree of similarity is established through extensive in vitro studies.
  • Indications: The new guidance would no longer require justifications for why the biosimilar drug should be authorized for each of the originator drug’s approved indications.

Consultation is open

Health Canada is currently accepting comments on the proposed changes to the Biosimilar Guidance.  The consultation closes on September 8, 2025.

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