Clinical Trial Approval Process In Canada

Clinical_Trials_Approvals_In_Canada_Credevo

Health Canada (HC) reviews, evaluates, and approves applications for clinical trials using authorized therapeutic products in Canada.

HC assesses clinical trial protocols to evaluate participant protection and safety; reviews drug quality; assures institutional ethics committee review; verifies principal investigator qualifications; and monitors and reviews adverse drug reactions.

HC also approves the sale or importation of drugs for use in clinical trials in Canada.

HC’s scope of assessment includes clinical trials using:

Drugs not authorized for sale in Canada in development and comparative bioavailability studies, and
Marketed drugs where the proposed use of the drug for one of the following is different: indication(s) and clinical use; target patient populations(s); route(s) of administration; or dosage regimen(s).

Thus, conducting clinical trials in Canada may require sponsors (individual, corporate body, institution, or organization) to file a Clinical Trial Application (CTA) depending upon the types of clinical trials.

Do Your Clinical Trials Need Approvals in Canada?

Types Of Clinical Trials	Need CTA?
Phases I – III clinical trials	Yes
Comparative bioavailability trials	Yes
Clinical trials involving marketed drugs, where the proposed trial is outside of the parameters of the authorized NOC or DIN application, e.g., one or more of the following is different – indication(s) and clinical use – target patient population(s) – route(s) of administration – dosage regimen(s)	Yes
Clinical trials in Canada with products that have received a Notice of Compliance with Conditions (NOC/c)	Yes
Phase IV clinical trials involving marketed drugs where the investigation is to be conducted within the parameters of the authorized NOC or DIN application

Whom Should You Apply To?

As a sponsor undertaking the research, you should get approval from

Health Canada (HC) and
Research Ethics Board (REB).

before the initiation of a clinical trial.

The CTA should be sent directly to the appropriate Directorate:

CTAs involving pharmaceutical drugs should be sent to the Therapeutic Products Directorate (TPD).
CTAs involving biologics and/or radiopharmaceuticals should be sent to the Biologics and Genetic Therapies Directorate (BGTD).
The sponsor of a natural health product applies through the Natural Health Products Directorate.

Quick points to consider before you apply

Clinical trial application language	ENGLISH OR FRENCH
Parallel regulatory and ethical review permitted	YES
Clinical trial registration required	NO
In-country sponsor presence/representation required	YES
Age of minors	DETERMINED BY PROVINCE
Specimens export allowed	YES

Pre-CTA Consultation Meeting

You may request a pre-CTA consultation meeting with HC. The pre-CTA consultation meeting provides an opportunity for the sponsor to present relevant data, discuss concerns, and resolve issues regarding drug development.
You may invite the investigator(s) who will be involved in the proposed trial(s) in Canada to attend the meeting.

Parallel Approval

EC review for each clinical trial site may occur in parallel with HC’s CTA review and approval.
Canada has a decentralized process for the ethical review of clinical trial applications and requires the sponsor to obtain institutional ethics committee (EC) approval for each participating trial site.

What Should Your Application Include?

a protocol which details the objectives, benefits, risks, methods, and conditions for the trial to function
Research Ethics Board Attestation
Clinical Trial Site Information Form
Clinical Trial Application (CTA)
Qualified Investigator Undertaking

The module of application for CTA

The CTA is composed of three Modules:

Module 1 – Contains administrative and clinical information about the proposed trial
Module 2 – Contains Quality (Chemistry and Manufacturing) information about the drug product(s) to be used in the proposed trial
Module 3 – Contains additional supporting Quality information

Each Module should be submitted in a separate binder.

Changes to a previously authorized CTA must be submitted to Health Canada either as a Clinical Trial Application – Amendment (CTA-A) or a Notification.

Qualified Investigator (QI)

There must be a Qualified Investigator (QI) for Phase I-III clinical trials involving a drug or natural health product.

The QI is responsible to the sponsor for the conduct of the clinical trial at the trial site and is entitled to provide health care under the laws of the province where the clinical trial site is located.

For a clinical trial involving a

Drug: the QI is a physician and member in good standing of a professional medical association,
Drug to be used for dental purposes only: the QI is a physician or dentist and a member in good standing of a professional medical or dental association
Natural health product: At present, the same qualifications apply for the QI of a clinical trial involving a natural health product.

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REB Approval (Regional Ethics Board)

Clinical trials should obtain institutional ethics committee (EC) approval for each participating trial site. Once HC completes its review, the department issues a No Objection Letter (NOL) if the CTA is approved.

Institutionally based ethics committees (ECs) may independently decide whether to charge fees to conduct protocol reviews

Ethics Board – Documents Requirement

Clinical protocol
Informed consent forms (ICFs) and participant information
Participant recruitment procedures
IB
Safety information
Participant payments and compensation
Investigator(s) current curriculum vitaes (CVs)
Additional required institutional EC documentation

Time for approval

Once a CTA has been submitted and reviewed, Health Canada notifies the Sponsor within 30 calendar days if the application is found to be acceptable or deficient.
If the application is deemed acceptable, a No Objection Letter (NOL) is issued by Health Canada.
The EC review and approval process timeline vary by institution.
The application first undergoes a screening phase to ensure that all submission components have been provided.
Once screened for acceptability, the application is processed for review, and an acknowledgment letter is issued to the sponsor to indicate the start of the review period.

Import

If a sponsor (Canadian or foreign) wants to import a drug into Canada to conduct a clinical trial, he/she must include a copy of HC’s clinical trial authorization (i.e., the No Objection Letter) with the drug shipment.

After Approval

No waiting period is required following the applicant’s receipt of these approvals.
While the Directorates can establish shorter administrative targets of seven (7) days for the review of bioequivalence trials, the 30-day default system remains the regulatory requirement.
Applications to conduct Phase I clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines, or reproductive and genetic technologies are not included in the seven-day target system.

Soon after HC issues an NOL, it will publish the following information about the clinical trial in HC’s publicly accessible database:

Protocol number
Protocol title
Drug name
Medical condition
Study population
Authorization date
Sponsor name
HC control number
Trial start and end dates, if known.

Before initiation

Before initiating the trial, the sponsor must sign an agreement between all involved parties, including

ECs,
Qualified Investigators (QIs),
contract research organizations, and
others,

to ensure full compliance with the regulatory requirements.

Insurance

The Canada Food and Drugs FDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. However, G-CanadaRecords and the Guidance for Industry: ICH Guidance E6 – Good Clinical Practice: Consolidated Guideline (CA-ICH-GCPs) guide sponsors on providing insurance.

Fee

There are no fees to submit a clinical trial application in Canada.
Institutionally based ethics committees (ECs) may independently decide whether to charge fees to conduct protocol reviews. For example, an institutional EC may require industry sponsors or other for-profit organizations to pay a fee.

Medical devices

The regulations governing medical devices are within the Canadian Food and Drugs Act.
Medical devices are classified into one of Classes I to IV.
The classification is based on the level of invasiveness and whether the device is active (i.e., depends on a source of energy for operation, a source other than the energy generated by the human body or gravity).
Class I represents the lowest risk medical devices while Class IV represents the highest risk.
If a medical device can be classified into more than one class, the class representing the highest risk applies.

Investigational testing authorization (ITA)

Human experimentation and development of medical devices are not always established by phased development as with drugs (i.e., Phase I – IV clinical trials).
Proposed medical device research with humans is evaluated through the Device Evaluation Division of the Medical Devices Bureau of Health Canada.
An application is submitted and evaluated according to the Investigational Testing Authorization program governing the use of Class II, III, and IV medical devices. Class, I medical devices do not require investigational testing authorization.
If the investigational testing of a device is in conjunction with a drug in a clinical trial then the sponsor must obtain authorization for the clinical trial and authorization for the use of the investigational medical device.
Following a favorable Health Canada review of the Application for Investigational Testing, a “No Objection Letter” (NOL) is sent to the Manufacturer/Sponsor indicating Health Canada’s agreement for the Manufacturer/Sponsor to conduct the research.

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