What we heard: Consultation on a proposed regulatory framework for clinical trials on foods for a special dietary purpose

Consultations held spring and summer 2021

On this page

• About the modernization of clinical trial regulations
• About the consultations and who participated
• What we heard
• Next steps

About the modernization of clinical trial regulations

The Government of Canada's Regulatory Innovation Agenda for health products and food was developed in response to stakeholder feedback received during the 2018 Health and Biosciences Sector Regulatory Review consultations. One of the key pillars of the agenda is the modernization of clinical trial regulations. This pillar will benefit people living in Canada.

Technology is advancing quickly, with new types of promising health products and foods for a special dietary purpose (FSDP) being developed. We are also seeing new clinical trial types and designs.

In light of such advances, there's a need to modernize Canada's clinical trials regulatory framework.

A modernized regulatory framework for clinical trials in Canada would support the adoption of promising novel safe and effective health care therapies. It would also support innovations that can improve people's health. For example, the current regulatory framework does not allow clinical trials on FSDPs that do not comply with the Food and Drug Regulations (FDR).

With this initiative, we also want to ensure that people have access to the information they need to make informed decisions about their health.

As we stated in the Forward Regulatory Plan for 2021-2023, Health Canada is committed to modernizing the clinical trials framework. We intend to: 

• introduce a coherent risk-based approach
• offer greater flexibility in the safe development of innovative FSDPs
• authorize clinical trials for non-compliant foods for a special dietary purpose
• streamline processes to achieve greater efficiency and clarity
• align with international best practices on matters related to oversight and public access to information

For the Clinical Trials Regulatory Modernization Initiative as it relates to FSDP, we consulted selected stakeholders across Canada. We are using their feedback to help develop the proposed policy and regulatory framework.

We thank all the stakeholders across Canada who took part in the consultation process. They came from various sectors, including academia, industry and professional associations.

About the consultations and who participated

Health Canada conducted a targeted consultation on the proposed Clinical Trials Regulatory Modernization Initiative relating to FSDP. We consulted stakeholders for their feedback between April and June 2021.

As part of this process, we emailed a consultation paper to key stakeholders and invited them to comment in writing. The following summarizes their feedback.

Written submissions

From April 28 to June 12, 2021, we invited stakeholders to submit their comments and input by email. We received 5 written responses as follows:

• 3 from industry (or industry association) stakeholders
• 1 academic stakeholder
• 1 professional association, from its expert panel consisting of:
  • 10 Canadian nutrition experts from hospitals, academia, consultancies, a contract research organization, and a food industry association

Webinar sessions

We also held 1 interactive webinar session in May 2021, to clarify any questions.

What we heard

The consultation document included 13 questions for stakeholders on the proposed regulatory framework. Overall, most respondents supported the Clinical Trials Modernization Initiative relating to FSDP. We have summarized their comments in the following sections.

Scope

Stakeholders had questions about whether the scope included ingredients added to FSDP. They also wanted to know whether the subject population could be healthy subjects and if a list of FSDP food categories incorporated by reference (IBR) would be appropriate.

ICH definitions

Most stakeholders agreed that the international definitions distinguish a "qualified physician" from a "qualified investigator". The definitions are in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice.

One stakeholder indicated that the principal investigator should be a regulated health professional only, such as a medical doctor or a registered dietitian.

All stakeholders agreed with using the ICH definition of a clinical trial sponsor. They also said it would be appropriate to include the definition as well as the roles and responsibilities of the contract research organization in the proposed regulatory framework for FSDP clinical trials.

Information requirements

Most stakeholders asked that the purpose of the information requirements be clearer. They said the requirements appeared to be more burdensome compared to other jurisdictions.

Some stakeholders asked for clarification on the purpose of Health Canada's assessment. If the purpose is to assess the safety of the formulation used in the clinical trial, the information to be submitted should focus on the formulation.

One stakeholder also recommended that a cover letter and table of contents be included. Other items that should be included are the product's stability and shelf life and the name and address of the qualified investigator at each site.

Two stakeholders said that protocols and other information submitted to Health Canada should be final. The reasoning is that the clinical study's research ethics board/institutional review board would have already reviewed and approved the protocols and other information for each site. These stakeholders asked for clarity on the intent of Health Canada's assessment and expected outcomes.

Authorization conditions

Most stakeholders agreed with the proposed list of conditions for receiving an authorization from Health Canada to sell an FSDP and conduct the clinical trial on the FSDP.

Other suggestions were that Health Canada:

• endorse only good quality randomized trials that are designed and conducted using the CONSORT guidelines
• ask for and retain any published information and appropriate clinical or pre-clinical data for the products under investigation
• define the meaning and purpose of the authorization and establish service standard timelines and expectations, if an authorization process is maintained

Post-authorization commencement notice, change notifications and amendments

Most stakeholders asked for clearer information on the post-authorization commencement notice, change notifications and amendments.

Two stakeholders pointed out that a commencement notice and amendment notices sent to the institutional review board (IRB) for information and approval should be enough. They did not agree with approval being required by Health Canada if the IRB was aware and had approved.

Obligations and responsibilities

Adhering to good clinical practice

All stakeholders agreed with the need to adhere to good clinical practice. One stakeholder asked for clarity on 2 things:

1. the scope of Health Canada's review
2. the process if recommendations on the proposed clinical trial differ between the researchers/contract research organization and Health Canada reviewers

Labelling the investigational product

Health Canada provided details on what should be on the label. It was suggested that the regulatory framework should include provisions for exempting clinical products from the FDR's labelling requirements.

Record keeping

Most agreed with this requirement. One stakeholder suggested replacing the need to keep versions of the investigator's brochure with versions of the clinical study protocol and associated documents.

Storing records

One stakeholder felt 15 years was a long time to keep records. This could be reduced to 10 or 7 years.

Serious adverse event reporting

Stakeholders mostly supported the approach for serious adverse event reporting.

One stakeholder recommended replacing "any adverse occurrence in the health of a clinical trial participant" with "any untoward medical occurrence in participant." This participant said new wording would include accidents and abnormal lab test findings. Another suggestion was to include congenital anomalies in the definition of "serious adverse event".

A third stakeholder did not think that serious adverse events observed during clinical trials on FSDP should be reported to Health Canada. There are already requirements in place for reporting these events to the trial sponsor.

Post-authorization information

Everyone agreed it was appropriate for the sponsor to provide post-authorization information or samples upon request as part of the proposed regulations for FSDP clinical trials.

Registration

There was general agreement on the use of the databases listed. In addition, stakeholders referenced the clinical trial registration platforms of the European Union or Australia-New Zealand. They also suggested choosing the registries that are consistent with the criteria set out by the World Health Organization's International Clinical Trials Registry Platform. The Canadian Institutes of Health Research has endorsed this platform.

Discontinuance, suspension, revocation

Stakeholders found it appropriate for FSDP clinical trial regulations to reflect the same approach as clinical trials for drugs and natural health products when it comes to discontinuing, suspending or revoking authorization. They indicated that these measures should be taken only after prior notice has been given and the sponsor has an opportunity to rebut. The exception is cases of potential injury to clinical trial participants.

Missing elements and additional comments

One stakeholder recommended that trials be designed to examine only 1 intervention at a time compared to either a control intervention or the current standard of care. Ensuring there is sufficient follow-up in order to detect differences in outcomes that occur after an intervention was another recommendation.

A participant asked how novel food ingredients could be clinically tested in Canada, including those not intended to be added to FSDPs. "Would Health Canada's authorization be required in such cases?" Another question was, "Will an additional clinical trial be required if the matrices, dosages or processing of a food are being changed (ingredients are the same)?"

Regarding Health Canada's proposed guidance on FSDP clinical trials, stakeholders asked for flexibility in adjusting their protocol based on the expertise of the qualified researcher, the study's objective or specific considerations relating to the formulation.

Stakeholders questioned the need for this type of regulatory process as similar regulations are also absent in other countries. In fact, in other countries a clinical trial of food of this type typically requires an application for approval as a drug clinical trial. The proposed Canadian approach differentiates FSDP from drugs by applying a risk-based approach to the regulatory oversight of clinical trials. This approach is consistent with the recommendations by the Organisation for Economic Co-operation and Development on the oversight and management of clinical trials.

Stakeholders pointed out the FDR currently does not require human clinical evidence for foods intended for the general population or those regulated under Division 24.

Stakeholders said the regulatory framework should not introduce the requirement for conducting clinical studies with products regulated under Division 24 of the FDR. This goes for products in compliance with the current regulatory framework or those that are to be reviewed through temporary marketing authorization (TMA) applications. Compliance with current composition criteria, along with TMA reviews, provide enough assurance that the product will be safe for its intended use.

A suggestion was made to require that the clinical study:

• be registered in a publicly available database
• be conducted based on a protocol developed according to good clinical practices and positively reviewed by the site's own ethics and review board
• use a FSDP product labelled for clinical use

Next steps

Health Canada appreciates the comments and input from the various stakeholders involved in clinical trials in Canada.

The feedback received during the consultation process will help us refine the policy and develop regulations to modernize the clinical trials framework.

We will continue to engage stakeholders and subject matter experts as this initiative progresses.