Summary:

On March 8, 2010, Health Canada released the finalized version of its Guidance Document on the approval of Subsequent Entry Biologics ("SEBs"). The finalized Guidance Document follows the original and revised draft Guidance Documents, released on January 30, 2008 and March 30, 2009 respectively. Health Canada's revised draft Guidance Document was the subject of a March 31, 2009 Pharma in brief.

An SEB is defined as "a biologic drug that enters the market subsequent to a version previously authorized in Canada and with demonstrated similarity to a reference biologic drug. An SEB relies in part on prior information regarding safety and efficacy that is deemed relevant due to the demonstration of similarity to the reference biologic drug and which influences the amount and type of original data required." An SEB is not a "generic biologic".

HEALTH CANADA GUIDANCE DOCUMENT FOR SEBs - KEY PROVISIONS:

The finalized Guidance Document is substantially similar to the revised draft Guidance Document. Key provisions and some notable additions include:

  • Approval for a SEB is sought by way of a New Drug Submission (not an Abbreviated NDS)
  • An SEB will only be approved if the submission demonstrates similarity to a reference biologic drug that has been previously approved for sale in Canada.
  • Health Canada will allow a reference product that is not authorized for sale in Canada to be used in the demonstration of similarity provided that certain criteria are satisfied. Comparator studies must include characterization studies that are conducted in a side-by-side format
  • The determination of similarity does not signify that the quality attributes of the two products being compared are identical, nor is it a declaration of pharmaceutical and/or therapeutic equivalence. Instead, a finding of similarity means that:
  • The existing knowledge of both products is sufficient to predict that any differences in quality attributes should have no adverse impact on the safety or efficacy of the SEB; and
  • Non-clinical and clinical data previously generated with the reference biologic drug is relevant to the SEB.
  • A final determination of similarity can include analytical testing, biological assays, and non-clinical and clinical data; however, the majority of evidence should be based on analytical and biological characterization.
  • Although the majority of SEB submissions require comparative clinical trials to demonstrate efficacy and safety, some submissions may only require a comparative clinical safety study (e.g., recombinant human soluble insulin products)
  • An SEB product sponsor may apply for one or more clinical indications granted to the reference biologic drug in Canada. While any claims made by the SEB sponsor should be supported by suitable scientific data, proposals for additional indications held by the reference biologic drug may also be granted in the absence of clinical data (e.g., the use of comparative pharmacokinetic/pharmacodynamic data to bridge two indications).
  • A product using a clearly different manufacturing process compared to the reference biologic drug may not be suitable for authorization as an SEB. An SEB should not be used as a reference biologic drug for another SEB submission.
  • As proposed in the revised draft Guidance Document, Health Canada's Guidance Document for Data Protection under C.08.004.1 of the Food and Drug Regulations has been amended (Update to Guidance Document for Data Protection). Specifically, a submission for an SEB comparing to an innovative drugmay not be filed until six years after the first approval for the innovative drug.
  • As proposed in the revised draft Guidance Document, Health Canada's Guidance Document for the Patented Medicines (Notice of Compliance) Regulations ("PM(NOC) Regulations") has also been amended (Update to Guidance Document for the PM(NOC) Regulations). Specifically:
  • Section 5 of the PM(NOC) Regulations applies to SEB submissions that seek approval based on a direct or indirect comparison to a reference product that has patents listed on the Patent Register. Accordingly, SEB sponsors will be required to fulfill the requirements for second persons under the PM(NOC) Regulations.
  • SEB submissions that rely on a non-Canadian biologic drug as a proxy for the Canadian biologic drug, will be considered to contain a comparison with, or reference to, the Canadian biologic drug as contemplated by section 5 of the PM(NOC) Regulations.
  • Sponsors of SEBs are not permitted to copy the Product Monograph of the reference biologic drug in its entirety
  • The required contents of a SEB Product Monograph are outlined in the Guidance Document
  • The Guidance Document is effective as of March 5, 2010.

LINK TO GUIDANCE DOCUMENT:

Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs)