Canada – Statement on the Investigational Use of Marketed Drugs in Clinical Trials

This statement provides guidance to clinical trial applicants about the investigational use of marketed drugs within clinical trials in Canada. It will serve as interim interpretive guidance until amendments can be made to the Food and Drug Regulations. The objective of the statement is to explain how the requirements of Part C, Division 5 of the Food and Drug Regulations apply in relation to the off-label use of a drug that is authorized for sale in Canada. The guidance describes when a marketed drug used off-label in a clinical trial is not considered to be investigational within the meaning of the definition of “drug” in section C.05.001 of the Food and Drug Regulations.

2) Background

Section C.05.001 of the Food and Drugs Regulations defines “drug” as “a drug for human use that is to be tested in a clinical trial”(Regulations Amending the Food and Drug Regulations (1024—Clinical Trials), SOR/2001-203). Clinical trial is defined for the purposes of these regulations as “an investigation in respect of a drug for use in humans that involves human subjects and that is intended to discover or verify the clinical, pharmacological or pharmacodynamic effects of the drug, identify any adverse events in respect of the drug, study the absorption, distribution, metabolism and excretion of the drug, or ascertain the safety and efficacy of the drug”. The clinical trial regulations prohibit the sale of a marketed drug for a purpose that falls outside the recommended uses and conditions of use of the drug for which it has been authorized for sale (i.e. an “on-label” use).

Clinical trials often involve the off-label use of a marketed drug (i.e. a use not in accordance with the labelled uses or conditions of use for which the drug has received market authorization). Health Canada has taken the view that any drug sold for off-label use in a clinical trial is a study drug that must be identified as an investigational drug in a CTA. As the off-label uses of an authorized drug can often be supported by well-established clinical practice overseen by provincial bodies that govern medical practice, this interpretation may be creating an unnecessary barrier to clinical research.

Considering the above, the following considerations will inform whether the off-label use of a marketed drug in a clinical trial is investigational or not…