Summary of changes: Guidance on information and submission requirements for biosimilar biologic drugs
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Background
Health Canada has revised the Guidance on Information and Submission Requirements for Biosimilar Biologic Drugs (biosimilars guidance).
The guidance, for which the last comprehensive review was conducted in 2016, provides information and submission requirements to sponsors to assist them in meeting the requirements of the Food and Drug Regulations for the authorization of biosimilars. It was revised to better align with the current state of science and international developments in the regulation of biosimilars. The review also drew upon Health Canada's cumulative experience in reviewing biosimilars since 2016.
A draft of the revised guidance was posted on the Canada.ca website for stakeholder consultation from June 10, 2025, to September 8, 2025. Health Canada received comments from 15 stakeholders, representing biopharmaceutical companies, industry associations, patient organizations and a member of the general public. All comments were reviewed and considered in finalizing the guidance.
Key updates to the guidance
Comparative clinical efficacy studies
- The guidance was amended to indicate that comparative clinical efficacy studies are not typically required for a biosimilar candidate to a Canadian Reference Biologic Drug (CRBD) when the biosimilar can be compared and extensively characterized through appropriate analytical studies.
- The guidance now specifies that, if comparative clinical efficacy studies are included, sponsors should explain the role of the studies and the value of the results in the context of the submission.
Removal of scientific rationale for indications
- The guidance was amended to remove the requirement for a detailed scientific rationale to justify authorization of the biosimilar for each indication. The change aligns with and expands on guidance provided by the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA), which explains why a scientific rationale for each indication is no longer required, provided that:
- the biosimilar candidate has been shown to be highly similar to the CRBD, allowing all indications granted to the CRBD can be claimed without further justification
- the biosimilar is able to deliver the same dosage as the CRBD for each indication (for example, pediatric dosing)
Quality data requirements
- Quality sections were expanded to:
- emphasize that quality data must be robust and comprehensive to support the establishment of a high degree of similarity
- highlight that structural and functional studies are generally considered more sensitive than clinical studies for detecting differences between a biosimilar candidate and its CRBD, and that the comprehensive characterization is the primary driver for establishing similarity
- further explain the types of data (that is, physicochemical, functional, and stability studies) sponsors are expected to submit to demonstrate similarity between the biosimilar candidate and its CRBD
Clinical and non-clinical data requirements
- Consolidated requirements previously set out under subsections for pharmacokinetic (PK) and pharmacodynamic (PD) studies, as well as safety and immunogenicity.
- Emphasized the role of clinical studies to support the demonstration of similarity derived from comparative analytical assessments. Clinical studies should primarily include a comparative pharmacokinetic study, and if feasible, may include a comparative evaluation of pharmacodynamics.
Data requirements to address immunogenicity
- Provided additional information on immunogenicity in the quality and clinical data requirement sections, including new subsections that emphasize the shift toward using analytical and functional data to demonstrate comparable immunogenicity.
- Clarified that clinical PK studies remain descriptive and supportive, rather than serving as primary evidence for establishing comparable immunogenicity.
Comparative bioavailability (clinical studies)
- Recommended standards for comparative bioavailability studies were updated to align with international standards.
Risk management plan
- Replaced the text in the Risk management plan section with the following:
- "For details on the submission of risk management plans for biosimilars, refer to: Submitting risk management plans guidance document"
- This update ensures that sponsors are directed to the most current guidance as it evolves.
Change to terminology
- Changed "reference biologic drug" to "Canadian Reference Biologic Drug (CRBD)" to align with the text on notices of compliance (NOC) for biosimilars.
- Updated the "Sponsor Attestation: SNDS for Biosimilar Products – Addition of Indication to the Product Monograph to Align with the Canadian Reference Biologic Drug" template to reflect the new CRBD terminology introduced in the guidance.
Definition of "highly similar"
- Included a definition of the term "highly similar" in the context of biosimilars 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."
New sections and other revisions
- Introduced new sections:
- "Principles of the regulatory approach for biosimilars", which combines concepts from the now removed "1.3 Policy statements"
- "Scientific considerations and principles of demonstrating similarity in the authorization of biosimilars", to align with MHRA's biosimilars guidance
- Removed section "2.2 Information requirements for clinical trial applications (CTA)"
- Included a reference to the policy on low molecular weight heparins (LMWHs), clarifying that LMWHs are regulated as biologic drugs due to their biologic origin, despite not being listed on Schedule D of the Food and Drugs Act
- Clarified that short polypeptide drugs may be regulated as pharmaceutical or biologic drugs; chemically synthesized products may be authorized as generics via the abbreviated new drug submission (ANDS) pathway, while products manufactured using recombinant DNA procedures are considered biologic drugs and may be authorized as biosimilars
Contact us
Centre for Policy, Pediatrics and International Collaboration
Biologic and Radiopharmaceutical Drugs Directorate
Health Products and Food Branch
Health Canada
Email: brdd-cppic_brdd-cppci@hc-sc.gc.ca