Health Canada has released a revised version of the draft guidance document “Information and Submission Requirements for Subsequent Entry Biologics.”1 The guidance document outlines the regulatory review process that Health Canada will implement for a Subsequent Entry Biologic (SEB). Comments on this draft may be submitted to Health Canada for consideration until May 26, 2009.  

It is noteworthy that SEB regulation will take place entirely through guidance documents, not through any amendments to the Food and Drug Regulations or to the Patented Medicines (Notice of Compliance) Regulations (PM(NOC) Regulations).  

This guidance document is an update of the draft guidance released by Health Canada on January 30, 2008.2 This guidance document now reflects comments received by Health Canada from stakeholders over the past year. The guidance document has been published concurrently with two notices proposing amendments to guidance documents for the Data Protection and PM(NOC) Regulations in view of SEB regulation.  

Biologics are drug products derived from biological sources and include gene therapies, vaccines, antibodies and other therapeutic products derived through biotechnology. An SEB is defined by Health Canada as “a biologic product that would enter the market subsequent to, and similar to, an innovator product authorized for sale in Canada.” The innovator product is termed the “reference product” because the SEB manufacturer may make reference to the information contained in an innovator’s biologic drug submission in order to reduce the amount of clinical data that is included in its own drug submission.  

The guidance document indicates that SEBs will be approved through the existing New Drug Submission pathway under the Food and Drug Regulations. An SEB will be approved if a submission demonstrates similarity based on a direct or indirect comparison to a reference product. In certain circumstances, a manufacturer may be permitted to use a foreign reference product to demonstrate similarity between an SEB and a product authorized for sale in Canada. If a non-Canadian reference product is used, the submission must clearly explain the link between the reference product and the product authorized for sale in Canada. The proposed amendments to the guidance documents state when a comparison to a reference product will trigger the rights afforded to innovators under the Data Protection and PM(NOC) regimes.  

Details regarding the choice of reference product, determination of similarity, standards for quality assessment, non-clinical and clinical requirements and risk management are also discussed in the guidance document. The guidance document affirms that the authorization of an SEB is not a declaration of pharmaceutical and/or therapeutic equivalence to the reference product.  

In consultations, Health Canada has clearly stated its intention to regulate SEB approvals via this guidance document, rather than by an amendment to the drug submission requirements under the Food and Drug Regulations. Nor will the government be amending the PM(NOC) Regulations or the data protection provisions of the Food and Drug Regulations to deal with SEBs.  

Health Canada has indicated that there are SEB submissions currently under regulatory review and that the review process will proceed before the draft guidance document is finalized.