On May 19, 2026, Health Canada published the final version of its Guidance on information and submission requirements for biosimilar biologic drugs. This Guidance Document, which applies to all biosimilar drug submissions in Canada, introduces significant changes to the data required for submission and approval. Most notably, comparative clinical efficacy studies (typically Phase III clinical trials) will no longer be required in most cases.

Instead, a sponsor can rely on data establishing the biosimilar is “highly similar” to a Canadian Reference Biologic Drug (typically Phase I clinical trials). This data alone is sufficient to allow the biosimilar to seek approval of all indications of the reference product, without further justification.

Context

Before this Guidance Document, biosimilar sponsors were generally required to file a New Drug Submission providing comparative clinical data against a reference biologic product, which generally required extensive and costly clinical trials. Further, since such comparative data were often treatment-specific, biosimilar sponsors may have been required in some cases to conduct multiple trials to get multiple indications, despite similarity or effective equivalence to the reference product.

In recent years, as biosimilar products have become more widespread and seen as a means of managing public health costs relating to the high cost of biologic drugs, jurisdictions around the world including the UK, US, and the European Union have begun reducing the regulatory burden on biosimilar sponsors.

The new Health Canada Guidance Document is explicitly modelled after and aligns with updated regulations from the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA).

New Requirements

The new Guidance Document no longer requires comparative clinical data to establish “similarity” between a proposed biosimilar and a reference biologic drug (potentially for each indication depending on the comparative endpoint).

Instead, sponsors now need to show that the biosimilar candidate is “highly similar” to the Canadian Reference Biologic Drug, which 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.”

Importantly, the new definition of “highly similar” focuses on analytical data, quality attributes, and variability limits, which is similar to demonstration of bioequivalence for small molecule generic drugs.

In terms of non-clinical data, the Guidance Document highlights that structural and functional studies are considered more sensitive than clinical studies for detecting differences between the biosimilar and the Canadian Reference Biologic Drug, and that comprehensive characterization (i.e. analytical characterization rather than clinical efficacy) will be the “primary driver” for establishing similarity.

Health Canada will look for studies comparing:

• physicochemical characteristics (structure, post-translational modifications, heterogeneity, purity, impurities)
• functional properties (biological activity, immunochemical binding properties, etc.) and
• stability profile (stress, accelerated, forced degradation profiles)

As for clinical data, the Guidance Document notes that the clinical studies required are generally limited to a comparative pharmacokinetic trial to demonstrate pharmacokinetic equivalence.

If a “high degree of similarity” is demonstrated through these data, then the biosimilar sponsor can rely on the non-clinical and clinical data generated for the Canadian Reference Biologic Drug, and the safety and efficacy can also be “inferred to be relevant” to the biosimilar candidate.

The biosimilar sponsor can seek approval for every indication/condition that is approved for the reference drug based solely on “high degree of similarity” without separate clinical justification.

However, the Guidance Document notes that due to potential differences between biosimilars and the reference product, the information required to address any differences will be considered on a “case-by-case basis” depending on the specific difference observed. The sponsor can submit evidence or scientific justification to demonstrate that the differences have no impact on safety and efficacy.

A comprehensive list of updates is available from Health Canada.

Impact

Removal of a general requirement for comparative clinical efficacy data will significantly streamline the submission requirements for biosimilar sponsors. Generally, Phase I equivalence studies paired with sufficient analytical data can be expected to meet Health Canada’s requirements.

These changes are expected to materially reduce the amount of time and cost required before a sponsor can submit their NDS, and are in line with the Government of Canada’s stated mandate of speeding up regulatory approval and availability of biosimilar drugs.

It should be noted that the Guidance Document does not alter the intellectual property rights and the patent linkage regime. Sponsors who make reference to an originator biologic submission may still need to address the requirements under the Patented Medicines (Notice of Compliance) Regulations.

Sponsors should also carefully consider product labelling requirements, which have not been specifically changed in the new Guidance Document, but which may be materially different in practice due to the potential absence of comparative clinical efficacy data for new submissions.

If you have further questions, please contact a member of our team for assistance.