Health Canada has released a draft revision to its biosimilar guidance document that proposes eliminating the requirement for comparative Phase III clinical trials, representing a fundamental shift in the country's regulatory approach to biosimilar drug approvals. The consultation period for these proposed changes runs until September 8, 2025.
Major Policy Reversal on Clinical Requirements
The draft amendments to the Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs mark a significant departure from current policy. Under existing guidelines, biosimilar sponsors are generally expected to conduct comparative Phase III clinical studies involving hundreds of patients to establish lack of clinically meaningful differences between the biosimilar and the Canadian Reference Biologic Drug (CRBD).
The proposed guidance states that "in most cases, a comparative clinical efficacy and safety trial(s) is not required," reversing the current policy that considers such trials "important to rule out clinically meaningful differences in efficacy and safety between the biosimilar and reference biologic drug."
Streamlined Clinical Program Focus
Under the new framework, biosimilar clinical programs would be "generally limited" to comparative pharmacokinetic trials conducted to demonstrate pharmacokinetic equivalence. The draft guidance specifies that clinical programs should "primarily include a comparative pharmacokinetic study, and if feasible, a comparative evaluation of pharmacodynamics."
The purpose of this streamlined clinical program would be to "support a demonstration of a high degree of similarity derived from the comparative analytical assessments of the physicochemical characteristics, functional properties, and stability profiles between the biosimilar candidate and the CRBD."
Emphasis on Analytical Similarity
The revised guidelines shift focus toward requiring "extensive comparative quality studies to demonstrate a high degree of similarity" rather than the current approach that bases similarity determination "on all relevant data from structural, functional, non-clinical and clinical studies."
This change reflects a growing confidence in analytical methods to establish biosimilarity without extensive clinical validation.
Simplified Indication Authorization
The proposed guidance also removes requirements for detailed scientific rationales when authorizing biosimilar indications. Current guidelines require "a detailed rationale that scientifically justifies authorization of the biosimilar in each indication," including generating "additional clinical data" when necessary. The revised guidelines would require only demonstration of a "high degree of similarity" for indication authorization.
Global Regulatory Alignment
Health Canada's proposed changes align with similar developments in other major regulatory jurisdictions. The European Medicines Agency published a draft reflection paper on April 1, 2025, questioning the need for biosimilar comparative clinical studies. The EMA stated that "waiving certain clinical data requirements would simplify the development and evaluation process" while "maintaining the highest standards of safety and efficacy."
In the United States, regulatory discussions have already influenced industry behavior. Formycon announced in February 2025 that it terminated a Phase 3 study for its KEYTRUDA biosimilar candidate after the FDA determined that a Phase 3 study is no longer necessary. Similarly, Sandoz indicated on April 30, 2025, that it would be "minimizing" its Phase 3 trial of its KEYTRUDA biosimilar candidate following FDA discussions.
Industry Impact and Next Steps
The proposed changes could significantly accelerate biosimilar development timelines and reduce costs for manufacturers. Current comparative Phase III trials typically involve hundreds of patients and represent substantial time and financial investments for biosimilar developers.
Health Canada is actively seeking feedback from industry stakeholders, academics, health system partners, and the public during the consultation period. The agency has emphasized that the published guidance is for consultation purposes only and will not be implemented until the consultation process is complete.
The outcome of this consultation may have lasting impacts on Canada's biosimilar landscape, potentially making the country more attractive for biosimilar development while maintaining regulatory standards through enhanced analytical requirements.
