Guidance on applications for COVID-19 medical device clinical trials under the Regulations: Application guidelines and process

On this page

• Pre-clinical trial stage
• Submitting an application
• Issuing an authorization
• Terms and conditions

Pre‐clinical trial stage

Please email the Investigational Testing Division of the Medical Devices Directorate (MDD) at it-ee@hc-sc.gc.ca if you:

• have a general enquiry about conducting a COVID-19 medical device clinical trial
• want a pre-clinical trial meeting to ask specific questions about your COVID-19 medical device clinical trial application, especially if it involves novel Class III and IV devices
  • meetings are held via teleconference

Submitting an application

Manufacturers, importers, clinicians, academia, contract research organizations and others may submit an application for authorization to:

• import or sell a COVID-19 medical device that is to be tested in a clinical trial
• conduct a clinical trial using the COVID-19 device

For all applications, the applicant's senior official should complete, sign and date the application form for medical device clinical trials under the Clinical Trials for Medical Devices and Drugs Relating to COVID-19 Regulations (PDF).

You may submit the information electronically, in any format you choose.

Applicants are welcome to use any of the following formats:

• standard document submission guidelines (Health Canada's "non-eCTD electronic-only" format)
• the International Medical Device Regulators Forum table of contents format
• a "question and answer" format using the criteria specified below as headers

Email your application to devicelicensing-homologationinstruments@hc-sc.gc.ca.

In your cover letter accompanying the application, clearly indicate the device's direct use in relation to the SARS-CoV-2 virus. Direct use is the active role the device plays in diagnosing, treating, mitigating or preventing COVID-19, the disease caused by the virus. Be sure to include enough information to help us make our decision on whether to issue a clinical trial authorization.

When submitting an application, you must also provide all of the detailed information that is required as indicated in the Regulations. Please note that the information to be submitted depends on the risk of the device. However, for the purposes of these Regulations, you must submit all required information for Class II to IV COVID-19 medical devices unless otherwise stated in this guidance.

Applicants and qualified investigators must keep records of all of the information and documents required under the Regulations. These records should be kept for a minimum period of 15 years, which would begin with the last visit of the last trial participant in Canada.

Name and contact information of applicant and importer, if applicable

The name and the contact information of the applicant and importer (if different from the applicant) should include:

• the formal mailing address
• telephone number(s)
• the email address

Name and class of device

The device name is the name that appears on the labelling and for which the authorization is issued under the Regulations. It includes information that helps the user identify the device and distinguish it from similar devices.

The Regulations make clear that the class of device is established according to the rules set out in Schedule 1 of the Medical Devices Regulations (MDR). If a COVID-19 medical device can be classified into more than 1 class, the class representing the higher risk applies.

Description of device and materials used

A description of the device and the materials used in its manufacturing and packaging is required for Class III and Class IV COVID-19 medical devices. Although the description is optional for Class II COVID-19 medical devices, we may ask for one if the information in the submission is insufficient.

When describing the device, include information related to the components, physical and chemical properties, key specifications and performance, as applicable. Please supply photos and diagrams, if available. If the device is based on a previously authorized device, summarize the differences (preferably in a table), based on the applicable elements above, between the current device and the previous version.

List the materials used to manufacture and package the device.

Include information as to whether the material will come into contact with the patient or user for any period of time.

Discuss whether any components are manufactured using additive manufacturing (for example, 3D printing, laser sintering, bioprinting).

Description of device features

A description of the device's features is required for Class III and Class IV COVID-19 medical devices. Although the description is optional for Class II COVID-19 medical devices, we may ask for one if the information in the submission is insufficient.

Describe the features of the device that permit it to be used for the medical conditions and purposes for which it will be sold by the manufacturer.

Provide a brief description of the device's design philosophy and performance specifications. Be sure to make a connection between this and the objectives of the proposed clinical trial.

Device identifier

Provide the identifier of the device. This includes the identifier of any medical device that is part of a system, test kit, medical device group, medical device family or medical device group family.

Manufacturer information

Provide the name and address of the manufacturer as it appears on the device label, including the address where the device is manufactured, if different. This should be the legal manufacturer of the device.

Diagnosis, treatment, mitigation or prevention information for which the device is required

This information is required for Class III and Class IV COVID-19 medical devices. Although it's optional for Class II COVID-19 medical devices, we may ask for one if the information in the submission is insufficient.

Include the following information:

• intended purpose, mechanism of action, indications for use, conditions for which the device is used
  • the intended use statement should be verbatim as it appears on the device labelling
• patient population for which the device is intended, including age range, if applicable, and specific diagnoses
• anatomical and physiological details related to the patient using the device, if applicable

Marketing history

A marketing history is required for Class III and Class IV COVID-19 medical devices. Although it's optional for Class II COVID-19 medical devices, we may ask for one if the information in the submission is insufficient.

Provide details of the regulatory status of the device, including a list of countries where the device has been sold and the total number of units sold in those countries.

You should also provide:

• a summary of any reported problems with the device and any recalls of the device in those countries
• a history of incidents, along with a summary of each event and the manufacturer's response

Quality, safety and effectiveness information

Information on quality, safety and effectiveness is required for Class III and Class IV COVID-19 medical devices, but is optional for Class II COVID-19 medical devices. If the information is insufficient for us to grant an authorization, we will ask for more information.

We may also ask for:

• a risk assessment, including an analysis and evaluation of the risks, and
• the risk reduction measures that have been adopted for novel devices or Class III or IV devices

The following is a guide to information you should include. You should provide a:

• list of applicable standards used in the design, manufacture and/or testing of the device
• copy of the manufacturer's quality management system certificate, evidence of good manufacturing practices or other
• summary of any bench testing performed for the device
• summary of the software verification/validation testing performed, if the device is or includes software
• summary of electrical safety and electromagnetic compatibility (EMC) testing, if applicable
• summary of any animal testing and/or clinical investigations carried out with the device
• summary of any biocompatibility testing performed with the device, if applicable

You should also provide:

• evidence of biological safety if the device is manufactured from or incorporates animal or human tissue or their derivatives
• a description of the sterilization method used and a summary of sterilization validation testing performed, if the device is intended to be sold in a sterile condition
• a summary of the evidence of shelf-life and packaging validation testing, if applicable
• incidents with a discussion of each event and response from the manufacturer
• analytical validation studies if the medical device is or includes an in vitro diagnostic device, such as:
  • specimen validation testing
  • sample preparation validation
  • the limit of detection, when applicable
  • inclusivity
  • cross reactivity (in silico analysis and cross reactivity testing)
  • preliminary precision results, if applicable
  • stability of samples
  • preliminary reagent stability
  • clinical validity studies

If the in vitro diagnostic device involves serology, nucleic acid or antigen testing, please consult the following guidance document:

• Testing devices for COVID-19

Directions for use

Provide the directions for use, unless directions are not required for the device to be used safely and effectively. For some complex, active or powered devices, the directions for use may require a special surgeon's instruction manual, operator's manual or user's manual.

Clearly indicate the control or version number in the document.

Attestation for post-market oversight

The applicant must attest that documented procedures are in place for distribution records, handling complaints, reporting incidents and recalls. We have provided an example of an attestation form.

Device label

Provide copies of the device and package labels. The device label should be legible, permanent, displayed prominently and easily understood by users.

If a package is too small to display all of the required information, the directions for use must be included. They do not need to be on the outside of the package or visible.

You should also provide marketing materials if the device is being used at point of care or sold directly to a consumer.

Qualified investigator

For all device classes, provide the name of the qualified investigator and evidence of membership (licence number) in good standing with a health care professionals' regulatory body. Also, provide the name and address of the institution where the clinical trial will be conducted.

For Class III and Class IV COVID-19 medical devices, provide information on the qualifications of the qualified investigator, including their training and experience. An academic or clinical curriculum vitae is suitable.

If a team is conducting a clinical trial at a particular trial site, provide the name of the responsible leader (qualified investigator) of that site. You do not need to provide the names and credentials of the other investigators at that site.

Where there are multiple trial sites, please provide the name of the qualified investigator and the name and address of the institution for each trial site, if available at the time of submission. You must keep the names and credentials of all qualified investigators on record. We may ask for this information if there's a safety issue.

Institution information

Provide the name and contact information of the institution where the qualified investigator is conducting the clinical trial. The contact information should include the formal mailing address, telephone number(s) and email address.

Protocol

Also required is the protocol of the proposed clinical trial. This protocol should indicate the following:

• number of human subjects
• number of units of the device proposed to be used for the clinical trial
• hypothesis for and objective of the clinical trial
• period of time during which the clinical trial will be carried out

The applicant must also provide a copy of the informed consent form (refer to the section on informed consent).

Clearly indicate the version number and date on both documents.

Written undertaking

A written undertaking is required for Class III and Class IV COVID-19 medical devices, but is optional for Class II COVID-19 medical devices.

You must provide a written agreement from the lead qualified investigator to:

• conduct the clinical trial in accordance with the protocol provided by the applicant
• inform a clinical trial subject of any risks and benefits associated with the use of the device and obtain the subject's informed consent for its use
• not permit the device to be used by any other person except under the direction of the qualified investigator

Both the applicant and the lead qualified investigator should keep this information on hand but the applicant does not need to submit it.

Research ethics board contact information

The requirement to provide contact information for your research ethics board applies to Class III and Class IV COVID-19 medical devices.

For each trial site, you must provide the name and contact information of the research ethics board that approved the protocol and informed consent form, if known at the time of submitting the application.

Include the formal mailing address, telephone number(s) and email address.

Other pertinent information

Applicants should follow the principles of the Declaration of Helsinki and the tri‐council policy statement on the ethical conduct for research involving humans. The principles should also conform to good clinical practices as set out by ISO 14155, clinical investigation of medical devices for human subjects. The ISO 14155 standard is generally consistent with the definitions and requirements of the Regulations. Where there are inconsistencies, the Regulations take precedence.

For devices already authorized for investigation under a different study protocol, you may cross‐reference device-specific information in your application. If available at the time you submit your application, please provide the results of the previously authorized study.

For Class II, III and IV devices, the applicant and qualified investigator must keep records of all the information and documents required under the Regulations while the Regulations are in force. These records should be kept for a minimum of 15 years, beginning with the last visit of the last participant in Canada.

Note: Any application that was outstanding when IO No. 2 was repealed will still be deemed an application under the Regulations. Health Canada has the authority to request more information about a COVID-19 clinical trial submission at any time.

Labelling

The labelling must include the following information:

• name of device
• name and contact information of manufacturer
• identifier of device, including the identifier of any medical device that is part of a system, test kit, medical device group, medical device family or device group family
• control number, if a Class III or Class IV device
• indication of what the package contains, expressed in terms appropriate to the device, such as the size, net weight, length, volume or number of units, if the contents are not readily apparent
• indication that the device is sterile, if the manufacturer intends the device to be sold in a sterile condition
• expiry date, if applicable to be determined by the manufacturer on the basis of the component that has the shortest projected useful life
• medical conditions, purposes and uses for which the device is manufactured, sold or represented, as well as the performance specifications of the device if those specifications are necessary for proper use (unless self-evident to users)
• directions for use (unless directions are not required) for the device to be used safely and effectively
• special storage conditions
• indication that the device is an investigational device
• indication that the device is to be used by qualified investigators only
• indication that the performance specifications of the device have not been established, if an in vitro diagnostic device

Labelling information must be in both English and French. However, for review purposes, Health Canada only requires that you submit the labelling in 1 official language (your choice).

For more information on the labelling requirements for COVID-19 medical devices to be imported or sold for use in a clinical trial, please consult the following guidance document:

• Applications for medical device investigational testing authorizations

Issuing an authorization

Health Canada will aim to complete the review of clinical trial applications and clinical trial application amendments for COVID-19 medical devices within 30 days. If we request additional information and material, including samples, you are encouraged to submit these within 2 calendar days of the request.

For more information on the review/authorization process, please consult the following guidance document:

• Applications for medical device investigational testing authorizations

Authorization holders may not import or sell a COVID-19 medical device or conduct a clinical trial with that device unless they have the approval of a research ethics board. You must obtain this approval for each clinical trial site.

Note: A COVID-19 medical device authorization issued by Health Canada under IO No. 2 and not revoked in whole is authorized under the Regulations. Therefore, research ethics board approval received under IO No.2 is considered an approval under the Regulations.

Terms and conditions

At any time, Health Canada may impose or amend terms and conditions on the authorization for the importation or sale of COVID-19 medical devices for the purpose of clinical trials. This authority allows for flexibility in allowing a trial to proceed while attaching additional conditions or limitations on the authorization.

We will apply terms and conditions on a case-by-case basis and only to ensure appropriate oversight or to manage uncertainties or risks.

Examples of terms and conditions include:

• requiring additional reporting or safety measures, such as limiting the population tested based on emerging information
• monitoring specific populations because of potential increased risk (for example, children)
• requiring new information to characterize and mitigate new risk

Information on the fulfilment of terms and conditions that fall outside the amendment process should be submitted in the form of a notification. Be sure to include a cover letter and any supporting documentation. We will review the notification and documentation to determine if the conditions have been met.

Once we are satisfied that all the terms and conditions of the original authorization have been met, we will issue a letter indicating this.

Note: Any terms and conditions imposed under IO No. 2 will remain in effect.