BIOSIMILARS AND THEIR APPROVAL IN CANADA
Biosimilars are regulated as innovative pharmaceuticals in Canada under Food and Drugs Act and Part C of the Food and Drugs Regulations. Health Canada has created a strong, science-based regulatory framework for approving the marketing of biosimilars. Biosimilars are approved for sale by Health Canada after a careful comparison to a reference biologic drug. A biosimilar may reach the market after the reference biologic drug's patents and data protection have expired (1)
Biosimilar drugs advantage more patients by allowing them to access biologic treatments earlier in the therapy cycle, while also offering healthcare professionals with a spectrum of treatment options and creating a more competitive market with a broader range of cost-effective treatment options. Biosimilar drugs have the potential to give health-care systems significant savings for the same results. In 2018, the total savings from the usage of etanercept, filgrastim, infliximab, and insulin glargine biosimilars in Canada was $94 million CAD (2). Moving ahead, a biosimilar can be approved for all or part of the indications that its reference biologic drug is approved. Moreover, the indications for a particular biosimilar are governed by characteristics such as Indications, which might be patented at various period. Indications protected by intellectual property cannot be allowed until the protection expires, and the biosimilar manufacturer decides which indications to seek for the product. Health Canada does not compel manufacturers to apply for indications that they do not want to have in Canada.
Part C, Division 8 of the Food and Drug Regulations establishes the standards for the sale of new drugs in Canada, including biosimilars, and prohibits the sale of new drugs unless the producer files an acceptable submission to the Minister containing sufficient information and data to allow the Minister to assess the new drug's safety and efficacy. The prerequisites for an new drug submission (NDS) are outlined in Section C.08.002 of the Food and Drug Regulations. To obtain authorization to sell a biosimilar, manufacturers must independently demonstrate the quality of the drug product and perform comparative studies to demonstrate the highly similar structure, function, efficiency, and safety to the reference biologic drug. Any statements made by the biosimilar sponsor must be backed up by appropriate scientific facts. Proposals for indications and uses not supported by clinical data particular to the biosimilar may still be considered for authorization. Clinical data should be developed depending on the product being sought for market authorization. Changes in chemistry and manufacturing introduced throughout the clinical development phase or at the conclusion of the clinical development programme may necessitate the collection of extra bridging data. For more information, sponsors should refer to ICH Q5E and consult with Biologics and Radiopharmaceutical Drugs Directorate (BRDD). While conducting the clinical programs the goal should be to demonstrate that there are no clinically relevant differences between the biosimilar and the reference biologic medication. The clinical programme should start with a PK/PD study (or studies), which may be followed by another clinical trial (s). Differences in immunogenicity detected between the biosimilar and reference biologic medicine should be addressed. If the discrepancies cannot be resolved, the sponsor should assess whether the biosimilar submission approach is still acceptable or if the regular new drug submission process is more appropriate (1).
The biosimilar product monograph should be prepared in accordance with the principles, methods, and processes indicated in the Product Monograph Guidance (3) and sponsors should follow the appropriate template (4). Appropriate safety and efficacy information from the product monograph of the biologic drug approved in Canada to which a provision is made, including warnings and precautions, Adverse Drug Reactions/Adverse Drug Effects, and key post-market safety information for all indications for which the biosimilar is authorized.
Author: Dr Nidhisha Bhalla
References:
- Guide to Guidance document: Information and submission requirements for biosimilars biologics drugs https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/information-submission-requirements-biosimilar-biologic-drugs-1.html
- Guide to the Benefits of Biosimilar Medicines https://biosimilarscanada.ca/wp-content/uploads/2020/12/Module5_final_EN.pdf
- Guidance document- product monograph https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/product-monograph/product-monograph.html
- Guide to Product monograph template schedule D biosimilar biologic drug https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/product-monograph/product-monograph-template-schedule-biosimilar-biologic-drug.html