Best Practices
| By Bradley J. Scott
Clinical considerations for the authorization of
biosimilar biologic drugs in Canada A summary of the pathway to authorization for biosimilars in Canada
14 BIOTECHNOLOGY FOCUS August/September 2017
B
iologic medicines have been invaluable in the treatment of diseases ranging from cancer to autoimmune disease. The expiry of patents for many successful biologic medicines has fostered a high degree of interest in the development of subsequent entry versions, known as biosimilar biologic drugs or, simply, biosimilars. Biosimilars have the potential to increase competition and decrease the substantial costs often associated with biologic treatment. In 2013, data published regarding the number of biosimilars in development signaled a high level of activity in this area. For example, over 40 programs were reported to be underway for biosimilar versions to three of the most successful biologics: the TNF inhibitors known as Humira, Enbrel, and Remicade[1]. Since then, a number of biosimilars have been approved and have come to market in Canada. This article is intended to provide a summary of the pathway to authorization for biosimilars in Canada with a focus on clinical aspects as outlined within Health Canada’s
recently updated guidance document: Information and Submission Requirements for Biosimilar Biologic Drugs.[2] Biologics are structurally complex and more difficult to replicate than small molecule pharmaceuticals. This is partially due to their large size, in comparison to pharmaceuticals, but also due to their production, which is accomplished by harnessing the productive capabilities of living cells. Due to the complexity of both the product and the manufacturing process, it is not possible to make an exact copy of a biologic product, and therefore the regulations that specify the requirements for demonstrating that a generic small molecule drug is pharmaceutically equivalent to its reference product do not apply. To address this, and to provide a framework for the authorization of biosimilars, Health Canada has published guidance on the information required to support submissions for biosimilar biologic drugs. Health Canada’s guidance, originally published in 2010 and revised in 2016, provides recommendations to guide sponsors through the development of a biosimilar. Importantly, a biosimilar submission must make reference to a product that is currently authorized for sale in Canada. It is acceptable for sponsors to compare to reference product sourced from another jurisdiction, so long as the product can be justified to be a reasonable surrogate for the product that is authorized in Canada. Following the guidance should allow the sponsors of biosimilars to fulfill the requirements of the Food and Drugs Act and regulations that apply to all new drugs. Importantly, the guidance emphasizes the need for extensive side-by-side chemistry and manufacturing comparisons. By laying the foundation for the demonstration of similarity, this extensive comparative characterization of critical quality attributes, including assessments of biological function, facilitates a reduced clinical data package. Clinical components, discussed below, are required to address the residual uncertainty that exists due to the fact that minor differences will always exist between a biosimilar
