As patents for innovative biologic drugs expire, Health Canada is working towards establishing a regulatory framework for approving the increasing development of biosimilars.

As patents for innovative biologic drugs expire, interest in the development of "generic" biologics (more appropriately called "biosimilars" or "subsequent entry biologics" (SEBs)) is increasing. Biosimilars are large complex molecules that are not bioequivalent to the innovator products, and require a regulatory framework distinct from the traditional generic approval pathway. It is not possible for biosimilar manufacturers to make identical copies, in part due to different cell lines, manufacturing processes, conditions, materials and formulations as compared to innovator products. As well, animal models are not sufficiently predictive of immunogenicity in humans. Clinical trial data is required for biosimilars though they do rely partly on clinical trial data generated by innovators.

Health Canada is working toward establishing a regulatory framework for approving biosimilars. A draft guidance document titled “Information and Submission Requirements for Subsequent Entry Biologics (SEBs)” was published in early 2008. Revised draft guidelines are targeted for release in September 2008. The draft guidance document states that: a) SEBs must demonstrate similarity to an approved reference biologic product in order to rely in part on publicly available safety and efficacy data; b) the existing regulatory framework is applicable to approval of SEBs; c) approval of an SEB does not mean that it will be substitutable with the reference biologic product; d) SEBs will not automatically be granted all indications of a reference biologic product - appropriate data is required to support each clinical indication; and e) SEBs will have a product monograph distinct from the reference biologic product.

The European Commission (EC) has established legislation on biosimilars and has approved subsequent-entry human growth hormone, epoetin alfa, epoetin zeta, and filgrastim. The US Senate and House have proposed several draft bills, which include provisions regarding data requirements, interchangeability, exclusivity and patent resolution. Although efforts are in progress, it is not clear when the US will implement legislation. The US FDA has approved a human growth hormone biosimilar, however the FDA noted that this approval did not create a pathway for other biosimilars, and that new legislation was still required.