Guidance on information and submission requirements for biosimilar biologic drugs: Overview

Health Canada revised this guidance document to update terminology and clinical and quality data requirements to support alignment with international approaches and evolving science. We made these edits before and after consulting stakeholders.

Refer to the summary of changes to learn more about the updates.

Date published: May 19, 2026

On this page

• Introduction
• Scope and application
• Policy objective
• Principles of the regulatory approach for biosimilars
• Background
• Scientific considerations and principles of demonstrating similarity in the authorization of biosimilars
• Note about guidance documents in general

Introduction

Health Canada, the federal regulatory authority that evaluates the safety, efficacy and quality of drugs for approval in Canada, recognizes that manufacturers may be interested in pursuing subsequent-entry versions of biologic drugs. The term 'biosimilar biologic drug', hereafter referred to as 'biosimilar', is used by Health Canada to describe a subsequent-entry version of a Canadian authorized originator biologic. It is demonstrated to be highly similar to the latter, referred to as the Canadian reference biologic drug (CRBD).

The Biologic and Radiopharmaceutical Drugs Directorate (BRDD) within the Health Products and Food Branch of Health Canada is the regulator of biologic drugs for human use. It provides regulatory oversight for biologics with its comprehensive reviews of biologic drug submissions covering quality, safety and efficacy.

Sponsors are encouraged to consult with BRDD for further guidance, if necessary.

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Scope and application

This guidance document applies to all biologic drug submissions for which the sponsor seeks authorization for sale based on a demonstrated high degree of similarity to a previously authorized biologic drug. These submissions rely on prior information regarding that biologic drug to support, in part, a reduced clinical package as part of the submission.

The following criteria determine the scope of drugs that are eligible to be authorized as biosimilars:

• a suitable CRBD exists that:
  • was originally authorized for sale based on a comprehensive quality, non-clinical and clinical data package
  • has a substantial body of evidence regarding quality, safety, efficacy and effectiveness of the CRBD, which has accumulated since market authorization
• the biosimilar and CRBD can be extensively characterized by a set of modern analytical methods
• the biosimilar, through extensive characterization and analysis, can be judged to be highly similar to the CRBD by meeting an appropriate set of pre-determined criteria

The demonstration of a high degree of similarity depends upon detailed and comprehensive drug characterization. This guidance applies to biologic drugs that contain, as their medicinal ingredient(s), well characterized proteins derived through modern biotechnological methods such as recombinant DNA and/or cell culture.

Short polypeptide drugs are classified as either a biologic or a pharmaceutical depending on the method of manufacture. When manufactured by recombinant DNA procedures, subsequent entry versions of short polypeptides are considered biologic drugs and are eligible for authorization as a biosimilar. When chemically synthesized, they are considered pharmaceutical drugs irrespective of the manufacturing process of the CRBD and could be eligible for authorization as a generic drug via the abbreviated new drug submission (ANDS) pathway on a case-by-case basis.

In Canada, low molecular weight heparins (LMWH) are regulated as biologic drugs because of their biologic origin, despite not being listed on Schedule D of the Food and Drugs Act (FDA). Sponsors of subsequent versions of LMWH products should use this guidance document together with the Policy Statement: Clarifying the Appropriate Regulatory Pathway for Subsequent Entry Low Molecular Weight Heparins for additional guidance.

Biosimilars manufactured using methods different than those used to produce the CRBD are eligible for authorization. Careful consideration should be given to expression system differences that may present challenges to demonstrating a high degree of similarity of the biosimilar candidate to the CRBD.

Policy statement: Clarifying the appropriate regulatory pathway for subsequent entry low molecular weight heparins

Policy objective

Health Canada has developed this guidance with the purpose of helping sponsors to meet the requirements of the FDA and the Food and Drug Regulations (FDR) when seeking a notice of compliance (NOC) for a biosimilar.

Principles of the regulatory approach for biosimilars

Biosimilars are regulated under the FDA and Part C of the FDR. The concepts and the scientific and regulatory principles within the existing regulatory frameworks for biologic, pharmaceutical and generic pharmaceutical drugs are used as the basis for the regulatory approach for biosimilars.

While biosimilars are conceptually similar to generic drugs, they are not eligible for authorization through the ANDS pathway under C.08.002.1, due to their inherent heterogeneity and complexity. Rather, biosimilar drug submissions are filed using the new drug submission (NDS) pathway in accordance with C.08.002. Health Canada's issuance of a NOC for a biosimilar is a confirmation of a high degree of similarity to the CRBD but is not a declaration of equivalence. A biosimilar sponsor is eligible to apply for the indication(s) and condition(s) of use that are held by the CRBD authorized in Canada.

A biosimilar drug submission leverages the safety and efficacy information of the CRBD. Paragraphs C.08.002(2)(g) and (h) can be satisfied by establishing a high degree of similarity to the CRBD through quality, clinical and non-clinical analyses described in this document. As such, the non-clinical package included in the biosimilar drug submission does not require certain information that is typically expected in a conventional submission for a biologic drug. The clinical package is also expected to be reduced relative to the content of a conventional submission for a biologic drug. A biosimilar candidate relies on establishing a high degree of similarity to the CRBD through comprehensive physicochemical and functional characterization data. This permits the submission for a biosimilar candidate to leverage clinical data that supported the authorization of the CRBD.

Background

Biologic drugs have contributed to the health of Canadians as diagnostic, treatment and preventative tools for various diseases and medical conditions. Unlike pharmaceutical drugs, biologic drugs are derived through the metabolic activity of living organisms and are heterogeneous and structurally complex. Biologics can be labile and sensitive to changes in manufacturing processes. Biological source materials, production cells or their fermentation media can present risks to patients, such as the presence of pathogens or the growth of adventitious agents (for example, viruses). Due to these risks, stringent processes are applied to raw materials and virus inactivation and/or clearance during product purification and product testing. Changes to source materials, manufacturing processes, equipment or facilities can result in important and unexpected changes to the intermediate and/or final product.

The term biosimilar is used by Health Canada to describe a biologic drug that receives market authorization subsequent to an originator biologic that has been authorized in Canada (referred to as the CRBD). It is demonstrated to be highly similar to the CRBD. Demonstration of a high degree of similarity enables the biosimilar sponsor to rely on relevant information about the CRBD.

Scientific considerations and principles of demonstrating similarity in the authorization of biosimilars

The purpose of a biosimilar development program is to establish a high degree of similarity between the biosimilar candidate and its CRBD based on a comprehensive comparability exercise. A biosimilar is highly similar to its CRBD in terms of physicochemical properties, functional properties and clinical pharmacology.

A biosimilar candidate requires extensive comparative analytical studies to demonstrate a high degree of similarity. It is recommended to use orthogonal analytical methods to increase confidence in the assessment of a given quality attribute. The chosen techniques should reflect current best practices and be state-of-the-art, where feasible. These studies compare the attributes of the biosimilar candidate and its CRBD, including:

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

The demonstration of a high degree of similarity does not signify that the quality attributes of the two drugs being compared are identical, but that they are highly similar with two consequences:

1. that non-clinical and clinical data previously generated with the CRBD are applicable to the biosimilar candidate
2. the demonstration of safety and efficacy via non-clinical and clinical data previously generated for the CRBD can be inferred to be relevant to the biosimilar candidate

Given the heterogeneous nature of biologic drugs, a biosimilar can exhibit differences compared to its CRBD. The information required to address such differences is considered on a case-by-case basis and will depend on the specific difference(s) observed. These differences between the biosimilar candidate and its CRBD may be acceptable if the sponsor can provide sufficient evidence and/or scientific justification that the differences have no impact on both safety and efficacy.

The clinical studies required to support the authorization of a biosimilar are generally limited to a comparative pharmacokinetic trial conducted to demonstrate pharmacokinetic equivalence between the biosimilar and the CRBD. The study is also expected to collect data on safety and immunogenicity. Pharmacodynamic endpoints may be included, if feasible. Comparative clinical efficacy studies are not typically required for a biosimilar candidate to a CRBD when the biosimilar can be compared and extensively characterized by appropriate analytical studies. If comparative clinical efficacy studies are included, the sponsor should explain the role of the studies and the value of results in the context of the submission.

Differences between a biosimilar candidate and its CRBD should be evaluated in terms of a potential effect on function and stability. If major differences are identified between a biosimilar candidate and its CRBD, it is unlikely that the drug would be considered a biosimilar. Clinical efficacy and safety studies cannot address major differences in quality attributes between a biosimilar candidate and its CRBD.

Note about guidance documents in general

Guidance documents provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material or define conditions not specifically described in this document, to help us adequately assess the safety, effectiveness or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the relevant sections of the regulations and other applicable guidance documents.

In this guidance document, "must" is used to express a requirement that the user is obliged to satisfy to comply with the regulatory requirements. "Should" is used to express a recommendation that is advised but not required, and "may" is used to express an option that is permissible within the limits of the guidance document.