Biosimilar Update: Health Canada Reconsiders Requirement for Comparative Clinical Trials

Overview

Health Canada has released a draft version of an amended Guidance Document on biosimilar submission requirements (link here). In a significant reversal of policy, the draft guidance removes the requirement for biosimilar sponsors to conduct comparative safety and efficacy clinical trials. The published guidance is for consultation purposes only, and will not be implemented at this time. The consultation periods on September 8, 2025.

Key Changes: Shift Away from Comparative Clinical 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 uses them as guidelines when evaluating drug submissions.

Health Canada’s proposed amendments significantly change the guidelines on biosimilar drug submissions. The focus shifts towards qualitative similarity with the reference biologic product, while moving away clinical studies:

1. “High degree of similarity”: The current guidance states that a “determination of similarity will be based on all relevant data from structural, functional, non-clinical and clinical studies”. The revised guidelines focus on a requirement for “extensive comparative quality studies to demonstrate a high degree of similarity”.
2. Comparative Clinical Efficacy/Safety Studies Not Required: The current guidance states that “[i]n most cases, a comparative clinical trial(s) is important to rule out clinically meaningful differences in efficacy and safety between the biosimilar and reference biologic drug”. The amendments reverse this current policy, stating that “[in most cases, a comparative clinical efficacy and safety trial”(s) is not required”. According to the amendments, the only required biosimilar clinical studies will be “generally limited” to a “comparative pharmacokinetic trial conducted to demonstrate pharmacokinetic equivalence”.
3. No “Detailed Rationale” for Indication Authorization: The current guidelines require “a detailed rationale that scientifically justifies authorization of the biosimilar in each indication”, including generating “additional clinical data” for a particular indication” when necessary. The revised guidelines are silent on the type of rationale required, instead requiring just a “high degree of similarity” for indication authorization.
4. Revised Labelling Requirements: The current requirement to include “relevant safety and efficacy information” from the reference biologic remains. However, there is no longer a requirement to include comparative data generated by the biosimilar. The amendments also remove the current prohibition against including claims for bioequivalence or clinical equivalence – it is unclear whether this leaves room for biosimilars to include such claims in their monographs.

Biosimilar Developments in Europe/USA

Health Canada’s proposed amendments follow recent developments in Europe and the USA that appear to relax clinical requirements for biosimilar submissions:  

• On April 1, 2025, the European Medicines Agency (EMA) published a draft reflection paper questioning the need for biosimilar comparative clinical studies (link here). The EMA stated that “[w]aiving certain clinical data requirements would simplify the development and evaluation process” of biosimilars “while maintaining the highest standards of safety and efficacy”. Stakeholders are invited to provide comments on the EMA paper until September 30, 2025.
• In the US, 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 (link here). Instead, Formycon proposes to rely on data from its ongoing Phase 1 trial combined with “a comprehensive analytical program”. On April 30, 2025, Sandoz similarity indicated that it would be “minimizing” its Phase 3 trial of its KEYTRUDA^® biosimilar candidate following discussions with the FDA (link here).