Notice to stakeholders – Clarification of requirements under the Food and Drug Regulations when conducting clinical trials with cannabis

March 9, 2023
Our file number: 23-101308-988

Health Canada is issuing this notice to clarify the requirements for clinical trials with cannabis under the Food and Drug Regulations (FDR).

Health Canada recognizes that conducting clinical trials (i.e., research carried out on humans) with cannabis is critical to generating high-quality evidence that can be used to better understand the health risks and benefits of cannabis use, inform health policies and protect the health and safety of Canadians. Clinical research also supports the development of cannabis-based drug products that are safe, effective and of high quality.

Sponsors interested in conducting clinical trials with cannabis must also meet certain requirements under the Cannabis Act and its regulations. Authorization to conduct research with cannabis must be obtained by applying for a federal cannabis research licence from the Controlled Substances and Cannabis Branch of Health Canada. The Cannabis Licensing Application: Research Licence webpage provides more information on how to obtain a research licence from Health Canada under the Cannabis Act and its regulations.

Sponsors who are considering undertaking a clinical trial to investigate cannabis are encouraged to request a pre-Clinical Trial Application (CTA) meeting with the Office of Clinical Trials to discuss their specific circumstances and requirements. Pre-CTA meeting requests should be submitted via email to: oct.pre.cta-dec.bec@hc-sc.gc.ca.

Table of contents

• General requirements for clinical trials with cannabis
  • Quality requirements
  • Investigator's brochure
• Compliance and enforcement
• Contact information

General requirements for clinical trials with cannabis

For the purposes of this document, a clinical trial is defined as a study designed to discover or verify certain effects, safety, or efficacy of a drug, in a therapeutic setting (i.e., treating a medical disease or condition).

Any research with cannabis that meets the definition of a clinical trial in the FDR is subject to Part C, Division 5 of those regulations.

This definition only applies to clinical trials that are interventional. The application of this definition does not depend on how data generated from a clinical trial will be used. This means that research that is not intended to support the development of an authorized drug product could still meet the definition of a clinical trial, if the criteria set out in the definition above are met.

Division 5 of the FDR sets out the federal requirements for the sale and importation of drugs used in human clinical trials in Canada.

Clinical trials must be administered in accordance with national and international ethical, medical and scientific standards. These standards serve to protect the rights, safety and well-being of clinical trial participants and other persons.

Approval from a Research Ethics Board (REB), which provides additional oversight to protect participants' health and safety and ethical interests, must also be obtained before starting a clinical trial. Information on Clinical Trial Application (CTA) requirements for drug products can be found in the Guidance Document For Clinical Trial Sponsors: Clinical Trial Applications.

The sponsor is required to submit an application, which includes, but is not limited to, a study protocol, statement of the risks and benefits as outlined in the informed consent form, an Investigator's Brochure (IB), chemistry and manufacturing information, along with other pertinent information.

Sponsors must report to Health Canada all serious unexpected adverse drug reactions (ADRs) that occur during a clinical trial. Information on ADR reporting can be found at Clinical Trials - Adverse Drug Reaction (ADR) Reporting.

Quality requirements

Quality (chemistry and manufacturing) requirements for CTAs involving cannabis are the same as for any drug being tested in a clinical trial. The scope and detail of information submitted in support of the quality portion of a CTA should be sufficient to enable Health Canada to make an adequate assessment as to whether the use of the drug for the purposes of the clinical trial is in the best interests of the participants, and whether its use could endanger the health of clinical trial participants or other persons. As the drug progresses in its development, sponsors are expected to submit progressively more detailed quality information. Information on quality requirements can be found in the Guidance Document - Quality (Chemistry and Manufacturing) Guidance: Clinical Trial Applications (CTAs) for Pharmaceuticals.

Under the FDR (Section C.05.001), every sponsor is required to ensure that a clinical trial is conducted in accordance with internationally accepted principles of Good Clinical Practices (GCP). As part of GCP, drugs used in clinical trials must meet Good Manufacturing Practices (GMP), which is a requirement under C.05.010(j) of the FDR. Consequently, the sponsor will need to provide an attestation that the investigational product is manufactured in a facility that is compliant with GMP. Health Canada is aware that it may be challenging for some sponsors to obtain GMP-grade cannabis for research, but this requirement is necessary to ensure the consistency of the investigational product throughout the clinical trial(s). It is important to note that Good Production Practices (GPP) and GMP are not interchangeable standards.

Investigator's brochure

Researchers have informed Health Canada that a product-specific IB is not always feasible for cannabis, and acts as an impediment to cannabis research in Canada. In early phase trials, Health Canada may consider that the absence of the full set of product-specific pre-clinical studies in the IB is acceptable if the clinical trial involves a cannabis product that is produced under GMP conditions, and for which there is sufficient evidence of safe human use. Health Canada expects that the sponsor will be developing a product-specific IB, aligned with the requirements of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) M3(R2), for trials designed to assess the efficacy and safety of the cannabis product, and that the IB will be updated as new information accumulates. See table below for a summary.

Some flexibility may be acceptable for cannabis products where a similar product has received market authorization either in Canada or another member state of the ICH. In this situation, Health Canada may consider the absence of a full set of product-specific pre-clinical studies acceptable in early phase trials if the sponsor can provide information that establishes the similarity of the chemical and physical properties of the investigational product to the marketed product. Synthetic products that are not duplicates of naturally occurring phytocannabinoids, or where a similar product has not received market authorization either in Canada or in an ICH member state, requires product-specific pre-clinical studies, even for early phase trials.

Please see below for a tabular summary of the approach to various types of clinical trials with cannabis in a therapeutic setting submitted under the FDR.

Compliance and enforcement

As part of its regulatory responsibilities, Health Canada promotes, monitors and enforces compliance. As such, Heath Canada inspectors may conduct inspections of clinical trials under the authority of Section 23 of the Food and Drugs Acts (FDA). The purpose of these inspections is to verify compliance with Part C, Division 5 of the FDR, which include the requirement to comply with GCP. For more information on compliance and enforcement, please refer to the Compliance and Enforcement Policy for Health Products (POL-0001) and to the various guidance documents available on the Health Canada Good Clinical Practices webpage.

Contact information:

Office of Clinical Trials – Pharmaceuticals Drugs Directorate
Health Products and Food Branch
General Enquiries
E-mail: oct.enquiries-requetes.bec@hc-sc.gc.ca

Pre-CTA Meeting Request
Email: oct.pre.cta-dec.bec@hc-sc.gc.ca

Licensing and Medical Access Directorate
Controlled Substances and Cannabis Branch
E-mail: sp-licensing-cannabis-licences-sp@hc-sc.gc.ca

Clinical Trial Compliance Program
Regulatory Operations and Enforcement Branch
E-mail: gcp_bpc@hc-sc.gc.ca