Author: Bhavesh Patel, Chartered Chemist
On November 24, 2017 Health Canada published the Guidance Document “Use of a Foreign-sourced Reference Product as a Canadian Reference Product”, for sponsors who are seeking to demonstrate pharmaceutical equivalence and bioequivalence with a Canadian Reference Drug under paragraph (c) of C.08.001.1 of the Food and Drug Regulations. The Guidance Document replaces previous guidance which had been in place since 1995.
The objective of the Guidance Document is to provide sponsors of an Abbreviated New Drug Submission or Abbreviated Extraordinary Use New Drug Submission with guidance on how to demonstrate that the reference drug is acceptable to the Minister of Health as a Canadian reference product.
The purpose of demonstrating pharmaceutical equivalence and bioequivalence against the Canadian Reference Product (“CRP”) is to provide evidence that the safety and efficacy profiles of the subsequent-entry (generic) product will be equivalent to that of the innovative product which is marketed in Canada and for which safety and efficacy has been demonstrated clinically. In order to determine the acceptability of this evidence, the Minister must be satisfied that a reference product proposed under paragraph (c) appears to be the same as the innovative product marketed in Canada and that any potential undocumented differences between these two products would not be therapeutically significant.
Many reference products are manufactured for other countries with the same formulations and under the same conditions as the Canadian market. On occasion, these products are manufactured in only one location for worldwide distribution. In this situation, acceptance by the Minister of a reference drug marketed in another country as a CRP can avoid repetition of comparative studies in human subjects and thereby reduce the risks for study participants and the cost to manufacturers. This is most relevant for drug submissions which involve demonstration of bioequivalence based upon bioavailability studies, pharmacodynamics studies, clinical studies, or a combination thereof.
However, detailed information regarding the formulation and manufacture of products marketed outside of Canada is not generally available to Health Canada. In respect of these products, the Guidance Document sets out a list of requirements, which, if satisfied, will render the product acceptable to the Minster for use as a Canadian Reference Product. Some examples of the requirements include, approval and marketing abroad, reporting of undocumented differences between the foreign and domestic products, and requirements based on the dosage form of the foreign product. The complete list of all requirements can be found in Section 2 of the Guidance Document.
Health Canada will be consulting with stakeholders on potential future revisions to the Guidance Document. An additional Notice to be posted in the near future will invite stakeholders to provide comments and recommendations for future updates to the Guidance Document.
Thank you for reading Regulated Affairs, the CAPRA Blog. CAPRA is a non-profit organization dedicated to providing professional development opportunities in Regulatory Affairs. Feel free to share our blog posts and join us on social media.
Reference:
Health Canada guidance document: Use of a Foreign-sourced Reference Product as a Canadian Reference Product, dated 2017-11-24 https://www.canada.ca/content/dam/hc-sc/documents/services/drug-health-product-review-approval/drug-products/guidance-documents/canadian-reference-product-guidance-eng.pdf