Canada Gazette, Part I, Volume 155, Number 21: ORDERS IN COUNCIL

May 22, 2021

DEPARTMENT OF HEALTH

FOOD AND DRUGS ACT

Order Approving Interim Order No. 2 Respecting Clinical Trials for Medical Devices and Drugs Relating to COVID-19

P.C. 2021-402 May 14, 2021

His Excellency the Administrator of the Government of Canada in Council, on the recommendation of the Minister of Health, pursuant to paragraph 30.1(2)(a) ^{footnote a} of the Food and Drugs Act ^{footnote b}, approves the Interim Order No. 2 Respecting Clinical Trials for Medical Devices and Drugs Relating to COVID-19, made by the Minister of Health on May 3, 2021.

EXPLANATORY NOTE

(This note is not part of the Order.)

Proposal

The Order in Council approves interim order (IO) No. 2, which was made by the Minister of Health on May 3, 2021. IO No. 2 repeals and replaces the (ARCHIVED) Interim Order Respecting Clinical Trials for Medical Devices and Drugs Relating to COVID-19 (IO No. 1), which came into force on May 23, 2020.

Without the Order in Council, IO No. 2 would, in accordance with the Food and Drugs Act, cease to have effect 14 days after it was made.

Objective

IO No. 2 supports Canada's continued focus on dealing with the significant risk that COVID-19 continues to pose to the health and safety of Canadians.

Background

COVID-19

COVID-19 is a novel infectious respiratory disease caused by a strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first detected in December 2019. It is caused by a new strain of coronavirus never before seen in humans.

COVID-19 infection has been known to cause respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, it can cause pneumonia, acute respiratory distress syndrome, kidney failure and death.

The World Health Organization declared a global pandemic related to COVID-19 on March 11, 2020. COVID-19 has now affected most countries across the globe. According to the COVID-19 dashboard by the text-center for Systems Science and Engineering at Johns Hopkins University, there are now more than 120 million cases and over 2.5 million people have lost their lives. According to the outbreak update from the Government of Canada, the number of confirmed cases in Canada as of March 25, 2021, is over 900 000. The situation continues to evolve and change.

From the outset, the COVID-19 pandemic created an urgent need for drugs and devices used to diagnose, treat, mitigate or prevent COVID-19. The pandemic also created a need for a pathway to facilitate clinical trials for these potential COVID-19 drugs and medical devices.

Health Canada permits the importation and sale of drugs and devices in clinical trials if they meet safety requirements and if the trial is expected to meet its objectives. Among other requirements, Health Canada assesses available information about the drug or device. Health Canada also requires that a research ethics board review and approve a trial before it starts at each site.

While approved trials are ongoing, Health Canada monitors the emerging safety data by assessing serious unexpected adverse drug reactions, medical device incidents and other information. Health Canada may also carry out routine or for-cause inspections to verify that these clinical trials are taking place in accordance with the regulatory requirements.

Government of Canada's response

The health and safety of Canadians are the Government of Canada's top priority during the COVID-19 pandemic. Therefore, the Minister of Health took action to provide a more efficient way to conduct clinical trials related to COVID-19, while upholding strong patient safety requirements and validity of trial data.

IO No. 1 provided a new optional pathway for authorizing

• clinical trials for drugs such as pharmaceuticals and biologics; and
• clinical trials for Class II to IV medical devices.

Clinical trials authorized under this pathway could assess

• the use of existing, marketed products in Canada as COVID-19 – related therapies; or
• new COVID-19 – related therapies currently under development.

The authorization scheme in IO No. 1 also gave the Minister a greater ability to

• oversee clinical trials and intervene, as needed; and
• request additional information, or suspend/cancel parts of or an entire authorization.

Thirty-six clinical trial applications have been submitted under this pathway as of April 16, 2021.

Order in Council SI/2020-39 that accompanied IO No. 1 brought into force several subsections of the Budget Implementation Act, 2019, No. 1, including section 3.1 of the Food and Drugs Act. This section prohibits the conduct of a clinical trial unless the person holds an authorization to do so.

Implications

As a result of the Order in Council, IO No. 2 will, in accordance with the Food and Drugs Act, cease to have effect on the earliest of

• the day on which it is repealed;
• the day on which regulations having the same effect come into force; or
• one year after the day on which the Interim Order is made;

Flexible pathway

As with the previous Interim Order, IO No. 2 increases efficiencies and reduces the administrative burden caused by certain requirements. This authorization pathway, established in IO No. 1 and now continued in IO No. 2, is designed to better facilitate clinical trials during a public health emergency. It also makes it easier to set up and run multi-site trials.

The pathway increases flexibility by, for example, expanding the scope of the definition of “qualified investigator” for clinical trials for drugs. This expanded scope permits additional licensed health care professionals, such as nurse practitioners, to fill that role. Only a physician or dentist may conduct a clinical trial under the pre-existing pathway in the Food and Drug Regulations.

This increased flexibility will help to facilitate trials

• across multiple sites; and
• in locations, such as remote Northern communities, where there are fewer physicians available to oversee them.

Through the pathway, an applicant for a medical device clinical trial authorization is not limited to a manufacturer and importer. An applicant may also be an investigator, such as researcher, clinician or health care facility. Under IO No. 1 and now IO No. 2, an investigator in a medical device clinical trial, independent of the medical device manufacturer, can also apply for an authorization.

The pathway also provides two other means of obtaining informed consent when prospective clinical trial participants are unable to consent in person or in writing:

1. permits remote, written informed consent of a prospective participant when they cannot be in the same location as the qualified investigator; and
2. permits non-written informed consent when a prospective participant cannot provide written informed consent.

These measures will also continue to reduce barriers to the provision of consent given the restrictions that are in place due to COVID-19. For instance, the infection control practices in most hospitals may prohibit people who are in isolation from accessing paper.

Other changes from the Food and Drug Regulations and Medical Devices Regulations introduced by the IO No. 1 pathway include

• reducing the requirements around communicating with Health Canada on changes that occur over the course of a trial;
• requiring amendment applications only for significant changes that carry potentially higher risks; and
• reducing the application, labelling and record-keeping requirements for marketed drugs already authorized in Canada for other uses and that are being used in COVID-19 – related clinical trials within the standard of medical practice.

Under IO No. 2, the Minister also continues to have the ability to partially suspend or revoke a trial authorization. This allows her to suspend a single treatment group of a randomized trial if needed, while allowing the rest of the trial to continue so that other participants may continue to receive a promising therapy. This ability offers increased flexibility for the type of innovative trial designs being pursued for COVID-19 drugs and devices.

Oversight of clinical trials

The health and safety of clinical trial participants are as important as ever. As with the previous interim order, IO No. 2 continues to provide the Minister with certain abilities to oversee and intervene in clinical trials, as needed, in the best interest of clinical trial participants.

These abilities include the use of terms and conditions on clinical trial authorizations, which may be applied on a case-by-case basis to address uncertainties and mitigate risks. Terms and conditions may include

• requiring more frequent safety reporting;
• monitoring specific populations because of potential increased risk (for example children); and
• requiring additional information to characterize and mitigate newly identified risks.

Another oversight ability permits the Minister to request additional information about a clinical trial application or authorization. This information may be considered necessary to enable the Minister to determine whether to issue, amend, suspend or cancel (in whole or in part) the authorization.

As with all clinical trials conducted in Canada, Health Canada will monitor the safety of the drugs and devices used under IO No. 2. If required, Health Canada will take immediate action, including the suspension or cancellation of authorizations, to protect the health and safety of Canadians.

IO No. 2 also includes provisions to ensure that all authorizations and suspensions for clinical trials issued under IO No. 1, including any terms and conditions, will remain in effect. Further, any applications made under IO No. 1 that are outstanding at the time of its repeal will be considered as applications made under IO No. 2.

As was the case under IO No. 1, the new authorization pathway is optional. The existing pathways in the Food and Drug Regulations and the Medical Devices Regulations continue to be available. Authorization holders continue to hold their existing authorizations under the regulatory framework for which they were approved.

IO No. 2 also addresses two concerns that were raised by the Standing Joint Committee for the Scrutiny of Regulations. These changes include

• correcting an inconsistency in the French text, with an amendment made to use only “précis” for the word “accurate”,
  • the French text used both “exacts” and “précis” for the word “accurate” in the English text in IO No. 1; and
• clarifying that informed consent can be obtained in accordance with applicable laws governing consent, which includes remotely as provided for in IO No. 2.

Consultation

Information gathered from the consultations held in the spring of 2020 for IO No. 1 helped to inform IO No. 2. Consultation sessions sought input on some of the concepts from key stakeholders, including

• research ethics boards across Canada;
• provincial and territorial governments;
• industry associations in the drug, medical device and biotechnology sectors; and
• Canadian Institutes of Health Research (CIHR).

Many aspects of IO No. 2 have leveraged elements from the forthcoming broader clinical trials modernization initiative. To date, outreach and other engagement activities have involved in-person and online consultations.

Health Canada continues to engage with the CIHR, the Canadian Association of Research Ethics Boards and other research ethics boards that review clinical trials in Canada. Engagement sessions on clinical trial oversight and implementation are held every month. Through this initiative, policymakers, regulators, funders and oversight bodies are collaborating and sharing information on clinical trials.

In December 2020, Health Canada informed industry, health care practitioners, hospital and university researchers, research institutes and academia, and health care partners about IO No. 2, including holding webinars. Written stakeholder feedback was encouraged between December 10, 2020, and January 25, 2021. There were no comments or questions related to IO No. 2.

Contact

Bruno Rodrigue
Executive Director
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Products and Food Branch
Health Canada
Holland Cross, Suite 14
11 Holland Avenue
Address locator: 3000A
Ottawa, Ontario
K1A 0K9
Email: hc.lrm.consultations-mlr.sc@canada.ca