Canada Gazette, Part I, Volume 159, Number 51: Clinical Trials Regulations

December 20, 2025

Statutory authority
Food and Drugs Act

Sponsoring department
Department of Health

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the regulations.)

Executive summary

Issues

Clinical trial regulations safeguard participant safety and ensure the collection of reliable trial-related data, while upholding ethical principles for health-product testing involving human participants. The existing primary regulatory framework for clinical trials involving drugs under Part C, Division 5 of the Food and Drug Regulations (FDR) — which Health Canada administers — not only facilitates the development of important pharmaceutical and biologic drugs^{footnote 1} but also protects participant safety and supports broader economic goals as well as the continual development of the scientific knowledge base pertaining to drugs.

However, the current framework under the FDR oversees the conduct of clinical trials indirectly through regulating the importation and sale of drugs for the purpose of testing in humans. Prior to the 2019 amendments to the Food and Drugs Act (the Act), there was no explicit authority to make regulations for the conduct of clinical trials. This lack of direct oversight over the conduct of trials has limited Health Canada’s ability to regulate clinical trials with the flexibility and efficiency needed in today’s dynamic research environment. Advances in technologies, promising new therapeutic products, and innovative trial designs,^{footnote 2} as well as the increasingly global nature of clinical trials, have further exposed the limitations of the current framework.

For example, this lack of clarity in the case of master protocol trials^{footnote 3} — which may involve, under a single clinical trial authorization, multiple sub-studies^{footnote 4} testing different drugs for the same condition or a single drug for different conditions — creates inefficiencies for sponsors and hinders Health Canada’s ability to review and track the complexities of these trials. The current framework also lacks provisions for flexible, targeted oversight of clinical trials, especially for complex designs, such as adaptive or multiphase trials. These trials pose unique risks that could be mitigated through modern regulatory tools, including terms and conditions on clinical trial authorizations. The current inflexibilities can delay or hinder clinical trials involving innovative drugs or trial designs, especially where uncertainties exist.

In addition, the current framework presents several challenges that could limit or discourage the use of decentralized trials (i.e. trials that leverage digital health technology, remote monitoring, and telemedicine to conduct some or all trial activities outside traditional in-person trial sites). These challenges include the requirement for “written informed consent,” the requirement that investigators be physicians or dentists and members in good standing of a professional medical or dental association, and the lack of a clear definition of a “trial site” that encompasses both the main location and remote locations.

The current framework may also, in some cases, place a disproportionate and unnecessary burden on sponsors of certain types of clinical trials, such as lower-risk trials involving authorized drugs.^{footnote 5,footnote 6} Authorized drugs used outside of their approved conditions of use in a trial are currently subject to all of the clinical trial rules due to the inflexibility of the existing requirements under Part C, Division 5 of the FDR. Authorized drugs used as authorized are also subject to some of these rules. For example, even if a drug being tested in a clinical trial has already received authorization, its labelling must still comply with the requirements set out in Part C, Division 5 of the FDR, rather than those for authorized drugs.

The above-mentioned limitations ultimately affect the number of clinical trials being conducted in Canada, and limit Canadians’ access to these trials, particularly those with rare diseases or those living in remote areas.

In addition to the above-noted limitations, the FDR do not provide for direct oversight of third-party service providers, such as contract research organizations, which are increasingly prevalent in the conduct of clinical trials. Additionally, the current framework lacks flexibility in adapting compliance and enforcement actions to risk levels. For example, under the current framework, actions such as suspension or revocation for safety-related reasons apply to an entire trial or trial site, even if closing parts of the trial (such as suspending one arm of the trial) would have been more appropriate. Further, in instances where a sponsor, investigator, or service provider is involved in multiple, independent trials, and where their conduct is suspected of non-compliance, which may create systemic issues, the Act allows Health Canada to take compliance and enforcement actions without the need to inspect each trial site. However, the FDR do not explicitly provide the Minister of Health (the Minister) with the authority to suspend or revoke multiple clinical trial authorizations.

Canada’s regulatory framework for clinical trials involving drugs must keep pace with the dynamic field of drug development, to support the adoption of promising new therapeutic products in the Canadian health care system and to improve the health of people living in Canada. Although Health Canada amended the Act to provide the authority for the direct regulation of the conduct of clinical trials, which would support the modernization of the clinical trial regulatory framework, new regulations have yet to be developed to implement these amendments to the Act.

Background

A clinical trial is a research study involving human participants that is used to evaluate the safety, effectiveness, and quality of new medical treatments, drugs, or procedures.^{footnote 7} Clinical trials are crucial for advancing medical research, improving patient care, and developing more targeted and personalized treatments for people in Canada. Clinical trials also provide early access to promising therapies for individuals who may not have effective treatment options.

Current clinical trial regulatory regimes for drugs

In Canada, clinical trials involving human participants are regulated under the Act. The current regulatory frameworks for clinical trials involving drugs under the Act include Part C, Division 5 of the FDR and Part 2 of the Clinical Trials for Medical Devices and Drugs Relating to COVID-19 Regulations (COVID-19 CT Regulations). Part C, Division 5 of the FDR is the primary framework governing most clinical trials involving drugs, whereas Part 2 of the COVID-19 CT Regulations represents an optional framework for sponsors of clinical trials involving COVID-19 drugs, as an alternative to the FDR.

Under both frameworks, Health Canada assesses available information about a drug intended to be used in a clinical trial as well as ensures that the trial is scientifically sound and that it is not contrary to the best interests of trial participants. Both frameworks also require that a research ethics board (REB) review and approve the trial before it is initiated at each clinical trial site. Further, while trials are ongoing, Health Canada monitors and assesses the emerging safety data and other information to ensure the health of trial participants.

Recent legislative and regulatory developments

Health Canada is committed to enhancing regulatory flexibility to support innovation and economic growth, while protecting the health of people living in Canada. The Department of Health (the Department) has recognized that the limitations of Canada’s current oversight model for clinical trials may discourage some trials from coming to Canada, thereby limiting access to innovative trials and new therapeutic products. To address these regulatory barriers, the Department has proposed the Clinical Trials Modernization initiative, aimed at modernizing Canada’s clinical trial regulations.

In 2019, the Budget Implementation Act, 2019, No. 1 (BIA 2019) amended the Act to provide the legislative powers necessary to support the Clinical Trials Modernization initiative. These amendments to the Act provided the legal authorities necessary for the oversight of the conduct of clinical trials for drugs (which, at the level of the Act, includes natural health products [NHPs]), medical devices, and prescribed foods for a special dietary purpose (FSDP).^{footnote 8} This shift to regulating the conduct of a clinical trial, in addition to the importation and sale of a drug for use in a clinical trial, is intended to allow for more flexible, responsive, and targeted oversight throughout the life cycles of increasingly complex clinical trials. Achieving this shift in oversight through the development of modern regulations would better support the conduct of innovative clinical trials and facilitate access to these clinical trials and the associated health products in Canada. The BIA 2019 also introduced new regulation-making authorities regarding clinical trials. These include authorities to make regulations for the conduct of clinical trials, the issuance, amendment, suspension, and revocation of authorizations, the imposition of terms and conditions on authorizations, and the Minister’s authority to require sponsors (clinical trial authorization holders) to provide safety information after trial completion or discontinuance.

The amendments to the Act described above were brought into force on May 23, 2020, in advance of developing any new clinical trial regulations under the Clinical Trials Modernization initiative. At the time, this allowed the Minister to quickly respond to the COVID-19 pandemic by making an interim order to enable an optional regulatory framework for clinical trials involving COVID-19 drugs and medical devices.^{footnote 9} This interim order, issued on May 23, 2020, was replaced by a second interim order, which was then replaced with the COVID-19 CT Regulations on February 27, 2022. These COVID-19 CT Regulations were designed to sustain the optional framework until new regulations for all trials could be developed under the Clinical Trials Modernization initiative.^{footnote 10}

The interim orders and subsequent COVID-19 CT Regulations have demonstrated the value and feasibility of many elements of this proposal that Health Canada was already considering as part of the Clinical Trials Modernization initiative. The amendments to the Act, along with other flexibilities, obligations, and oversight mechanisms in the COVID-19 CT Regulations, enabled a broader range of COVID-19 drug trials during the COVID-19 pandemic. These changes provided Health Canada with the ability to address uncertainties and mitigate risks more effectively. Without them, Health Canada might not have otherwise been able to authorize these trials under the FDR. One of the flexible oversight tools introduced under this optional framework was the Minister’s ability to impose terms and conditions on clinical trial authorizations. As of July 30, 2025, out of the 47 drug clinical trials authorized under this new pathway, 9 were authorized with terms and conditions.

Phased approach to clinical trials modernization

While issues exist with the current clinical trial frameworks for drugs, medical devices and NHPs and there is an acknowledged need for a clinical trial framework for prescribed FSDPs, Health Canada is proposing to address the breadth of products through a phased approach. Phase I of the Clinical Trials Modernization initiative would be limited to clinical trials involving drugs. This first phase aims to bring about immediate improvements for more people living in Canada, as there is a larger number of clinical trials involving drugs compared to clinical trials involving other health products. Therefore, by prioritizing drug trials, the initiative is anticipated to provide notable near-term benefits for people living in Canada, such as enhancing access to innovative trials and therapeutic products, and potentially offering a broader range of timely and effective treatment options for those in need. Establishing a new clinical trial framework for drugs would also set a robust foundation for the entire Clinical Trials Modernization initiative. In future phases, the modernized framework could be amended to encompass other product lines, while still accounting for those product lines’ unique characteristics.

Objective

The objective of this proposal is to establish a modernized regulatory framework for the flexible oversight of clinical trials involving drugs throughout their life cycle. The proposed framework is expected to better support complex and innovative trials, allowing people in Canada to benefit from new drug therapies and innovative trial designs. The proposal also aims to better protect participants’ safety, ensure the reliability of trial-related data, facilitate participants’ access to clinical trials through the use of decentralized trials, enhance proportional oversight, and further international alignment. The proposed framework is also expected to help sustain economic growth in Canada’s health research sector by increasing the volume and diversity of clinical trials, thereby attracting direct investments, improving national health outcomes, and strengthening Canada’s position as a global leader in clinical research.

Description

The proposed Regulations would establish a new, stand-alone regulatory framework under the Act for clinical trials involving drugs for human use. This proposed framework would replace the existing clinical trial regulatory schemes for drugs in Part C, Division 5 of the FDR and Part 2 of the COVID-19 CT Regulations. The proposed Regulations would also make several consequential amendments to the FDR, the COVID-19 CT Regulations and related regulations.

Proposed Clinical Trials Regulations

Scope and application

The proposed Regulations would apply to clinical trials involving drugs for human use, including pharmaceutical and biologic drugs, radiopharmaceuticals, and cannabis. In accordance with the definition of clinical trial in the Act, the proposed Regulations would apply to a study involving human participants^{footnote 11} for the purpose of discovering or verifying the effects of a drug. Further, the scope of drugs to which the proposed Regulations would apply would include those being tested in a clinical trial (i.e. the main focus of the study), as well as comparator drugs used as reference products (including placebos), and any other drugs used in accordance with the protocol (such as background treatments,^{footnote 12} rescue medications,^{footnote 13} and drugs used to assess trial end-points^{footnote 14}).

However, the proposed Regulations would not apply to concomitant drugs (i.e. authorized drugs for sale in Canada that trial participants take simultaneously with the drugs used for the purposes of a clinical trial, but unrelated to the trial design). In addition, the proposed Regulations would not apply to (1) clinical trials of positron-emitting radiopharmaceuticals used in basic research studies and for which the importation and sale are authorized under Part C, Division 3 of the FDR, for the purposes of those studies; (2) non-therapeutic research on cannabis, as defined in subsection 1(2) of the Cannabis Regulations; and (3) clinical trials of NHPs regulated under Part 4 of the Natural Health Products Regulations (NHPR).

The proposed Regulations would apply to both authorized drugs (i.e. drugs for which the Minister has issued a notice of compliance [NOC] and/or a drug identification number [DIN] under the FDR) and drugs that are not currently authorized in Canada (including foreign-sourced versions of authorized drugs) for use in clinical trials. The proposed Regulations would tailor certain requirements based on this distinction, as well as whether an authorized drug is used in a clinical trial as authorized.

Except for certain provisions of the FDR,^{footnote 15} provisions under the FDR concerning various drug-related activities would not apply to (1) drugs that are not currently authorized and (2) authorized drugs not used as authorized, when those drugs are used for the purposes of a clinical trial that has been authorized under the proposed Regulations. The provisions of the FDR that would continue to apply to all drugs used in a clinical trial include those related to good manufacturing practices. In contrast, the FDR rules that apply to authorized drugs would continue to apply to authorized drugs used in a clinical trial where such use is in accordance with their authorization under the FDR. To avoid regulatory duplication, many provisions of the proposed Regulations would not apply to these authorized drugs, as they would already be subject to the requirements of the FDR.

Parties involved in the conduct of clinical trials

The proposed Regulations would define sponsor, investigator, and service provider and establish obligations for these parties.

Definitions

“Sponsor” would mean the person who conducts a clinical trial and, in the case where they conduct it in combination with other persons, takes responsibility for the overall conduct of the clinical trial. In contrast, the definition of “sponsor” in Part C, Division 5 of the FDR does not acknowledge the possibility of other persons conducting trial-related activities for or on behalf of the sponsor.

“Investigator” would mean the person responsible to the sponsor for the conduct of the clinical trial at a clinical trial site,^{footnote 16} which may consist of multiple locations,^{footnote 17} including the main location where the investigator is based and other associated remote locations. The investigator would be responsible for leading the clinical team that is conducting the clinical trial at a clinical trial site’s main location and all of its associated remote locations. A clinical trial may be conducted at more than one clinical trial site. Each clinical trial site would be overseen by one investigator,^{footnote 18} who would be responsible for trial-related activities at the entire site, including the main location, as well as any locations remote from the main location where trial activities take place. In some cases, the investigator may also be the sponsor. Given that a clinical trial may be conducted at more than one clinical trial site, more than one investigator may be involved in the trial. Further, an “investigator” must be a health care practitioner licensed in the province or territory in which the main location of the clinical trial site under their purview is situated;^{footnote 19} they would also need to have relevant clinical expertise within their regulated scope of practice to exercise their duties in the trial. The proposed definition of “investigator” would allow a broader range of regulated health professionals to conduct a trial as investigators, similar to the COVID-19 CT Regulations. This change would remove the current limitation in the definition of “qualified investigator” in Part C, Division 5 of the FDR, which restricts this role to licensed physicians and dentists. Under the proposed framework, other licensed or registered health care professionals, such as nurse practitioners, may also serve as investigators. In all cases, however, their training, expertise and experience would need to be appropriate to the objectives of the clinical trial. Expanding the scope of investigators would provide greater flexibility in selecting main locations, thus better enabling decentralized trials.

“Service provider” would mean a person (other than a sponsor, an investigator or team members under the oversight of the investigator) who provides a service to or on behalf of the sponsor or investigator to conduct one or more trial-related activities. A service provider may be an individual or a commercial, academic, or other organization, such as a contract research organization, site management organization, academic health centre, research institute, or clinical trial network conducting trial-related activities. A service provider may also be any contracted laboratory conducting testing activities that generate key clinical data for the clinical trial (e.g. data used for analysis in bioequivalence studies in healthy volunteers). Guidance would provide additional clarity on the types of persons that Health Canada would consider service providers.

Obligations

Under the proposed Regulations, a sponsor would be required to hold an authorization to conduct a clinical trial, unless the sponsor is exempt from section 3.1 of the Act. This exemption applies to trials involving only authorized drugs, provided that those drugs are used as authorized within the conditions outlined in the drugs’ respective authorizations.

Service providers and investigators involved in the conduct of a clinical trial on behalf of a sponsor would not be required to hold an authorization. Further, members of a clinical team under the oversight of an investigator (e.g. physicians or dentists responsible for medical decisions, researchers, nurses, and/or other health professionals) would not be required to hold an authorization. As such, when an authorization is issued for a clinical trial, the sponsor would be the sole holder of that authorization; therefore, they would also be referred to as the “authorization holder.”

The proposed Regulations would permit all of the above-mentioned persons to conduct trial-related activities if the trial is authorized or if they conduct a trial exempt from section 3.1 of the Act (while still following any applicable requirements). However, they would not be permitted to conduct trial-related activities if the authorization is suspended or revoked (at least in relation to the suspended or revoked part of the authorization), or if the Minister has directed a sponsor to cease conducting the trial.^{footnote 20} Furthermore, although the proposed Regulations would recognize that clinical trial activities may be performed by other parties (service providers, investigators, etc.), the sponsor would remain ultimately responsible for ensuring that the trial is conducted in accordance with the proposed Regulations.

In addition, all persons conducting trial-related activities would be required to do so in accordance with good clinical practices, as applicable to the activities they are conducting. This approach would address an existing compliance and enforcement gap under the FDR, where Health Canada currently has direct regulatory oversight only over sponsors.

Research ethics board

Under the proposed Regulations, an REB would retain the same principal mandate described in Part C, Division 5 of the FDR of approving the initiation of biomedical research involving participants and of conducting periodic reviews of such research to ensure the protection of participants’ rights, safety and well-being. However, the following changes would be introduced to the composition of an REB:

• (1) Currently, the majority of members of an REB must be Canadian citizens or permanent residents under the Immigration and Refugee Protection Act; the proposed Regulations would also include persons registered as Indians under the Indian Act as eligible members of that majority;
• (2) Currently, an REB must include at least one member who is from a community or is a representative of an organization interested in the areas of research to be approved; the proposed Regulations would also allow this member to be a member of a community affected by any of the areas of research to be approved;^{footnote 21} and
• (3) Part C, Division 5 of the FDR indicates that an REB is a body that is not affiliated with the sponsor; the proposed Regulations would further clarify that each member, except the one described in item (2), must have no affiliation with the sponsor that could compromise, or be perceived to compromise, their ability to fulfill the board’s principal mandate.

The proposed Regulations would also permit the use of a national research ethics board (national REB). A national REB would be defined as an REB designated on the List of National Research Ethics Boards, which would be established by the Government of Canada and published on its website, and incorporated by reference into the proposed Regulations. A national REB would still have to meet the above-mentioned general requirements for all REBs. Enabling the use of a national REB is intended to reduce duplicative REB reviews across multiple sites, by allowing a national REB to approve the protocol and informed consent form for the trial as a whole in a way that is not site-specific. Not obtaining site-specific approvals would reduce the burden on sponsors and facilitate the opening of multiple trial sites across Canada, extending the reach of clinical trials and enhancing access for participants. The introduction of national REBs is not intended to impact how an REB conducts its substantive review of clinical trials; rather, it would enable a sponsor to seek fewer REB approvals in circumstances where there are multiple clinical trial sites. According to the proposed Regulations, the decision to seek approval from a national REB would be voluntary for sponsors. The proposed Regulations would include a general interpretation clause indicating that certain provisions can be read without references to “the clinical trial site” or “for each clinical trial site.” This, for example, would allow an authorized clinical trial to begin at any site as long as the sponsor has, among other things, obtained approval of the protocol and informed consent form from a national REB.

The use of a list incorporated by reference would allow for updates in a timely and flexible manner. The list would be developed, reviewed, maintained, and amended in accordance with the guiding principles set out in Health Canada’s Incorporation by Reference Policy.

Shift to regulating the conduct of clinical trials

The proposed Regulations would provide oversight over the conduct of clinical trials involving drugs, in addition to the importation and sale of drugs used in clinical trials. Specifically, section 3.1 of the Act prohibits a person from conducting a drug clinical trial unless they hold an authorization issued under the applicable regulations. The proposed Regulations would create a scheme enabling the Minister to authorize the conduct of clinical trials.

Under the proposed scheme, a person would have to obtain an authorization to conduct a clinical trial involving drugs, except for trials that only involve authorized drugs where their use adheres to the purposes and conditions of use set out in those drugs’ authorizations. Sponsors of clinical trials that involve only these types of drugs would be exempt from section 3.1 of the Act; however, they would still need to comply with certain requirements under the proposed Regulations, such as the good clinical practices provisions.

Importation and sale of drugs for the purposes of clinical trials

Similar to the FDR, the proposed Regulations would prohibit persons from importing or selling a drug for use in a clinical trial, unless the sponsor of the clinical trial holds an authorization to conduct the trial or is exempt from section 3.1 of the Act. Additionally, if a drug is to be imported for such a trial, the sponsor/authorization holder must have a representative in Canada who is responsible for the importation of the drug and a representative in Canada who is responsible for the sale of the drug. These representatives could be the sponsor, a person working for the sponsor or a person working for a third party acting on the sponsor’s behalf, and they could be the same person. Where the Minister has suspended or revoked an authorization, or directed a sponsor exempt from section 3.1 of the Act to cease conducting a trial, the prohibitions on importation and sale (and the prohibition on conduct) would reapply to the respective drug(s) and trial as soon as these persons have been notified.^{footnote 22}

Provisions applicable only to clinical trials requiring an authorization

Application

Under the proposed Regulations, a sponsor of a clinical trial would have to submit an application for authorization to the Minister to conduct the trial, unless they are exempt from section 3.1 of the Act. The proposed Regulations would streamline requirements, including by consolidating and modernizing the application requirements under the FDR and the COVID-19 CT Regulations, and allow sponsors to file a single application for authorization for a master protocol trial. An application would have to contain sufficient information for the Minister to determine whether the sponsor should be authorized to conduct the clinical trial.

Application requirements common to all clinical trials that require an authorization, subject to certain exceptions discussed below, would include

• administrative information such as the sponsor’s name and contact information (and for foreign sponsors, the name and contact information of their representative in Canada; if the drug is to be imported, the name and contact information of the sponsor’s representative in Canada responsible for the importation of the drug and the name and contact information of the sponsor’s representative in Canada responsible for the sale of the drug);
• the clinical trial protocol;
• the title of the protocol and the protocol code;
• a statement of anticipated benefits and risks to the health of participants of the clinical trial as outlined in each informed consent form; and
• an attestation, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, that the sponsor will take responsibility for the overall conduct of the trial, that the trial will be conducted in accordance with good clinical practices and the proposed Regulations, and that the application is complete and the information in the application is not false or misleading.

The proposed Regulations would also require certain information as part of an application if such information is available at the time of submitting the application and at any time before a determination is made concerning the application. This information would include

• the name and contact information of the investigator for each clinical trial site and any service provider;^{footnote 23}
• the name and contact information of the REB that approved the protocol and the informed consent form for each trial site, or, where the REB is a national REB, the name of the REB that approved the protocol and the informed consent form for the entire trial;
• the name and contact information of any REB that has previously refused to approve the protocol (including its reasons for doing so and the date on which it gave the refusal);
• the proposed start date of the trial for each site; and
• a description (including reasons) of any of the following decisions or measures taken by foreign regulatory authorities:
  • any refusal to authorize the conduct of a trial, any refusal to authorize an amendment to an authorized trial, and any suspension or revocation of a trial authorization in whole or in part;
  • any terms and conditions imposed by any foreign regulatory authorities;
  • any other measures taken by any foreign regulatory authority regarding a trial to protect the health of trial participants or other persons; and
  • any refusal by a foreign REB (i.e. a body outside Canada whose mandate is equivalent to that of a Canadian REB, including the authority to approve clinical trial protocols) to approve the protocol or any other protocol prepared for the trial.^{footnote 24}

This information would allow the Minister to make a more informed decision as to whether the sponsor should be authorized to conduct the clinical trial, and it would enable better oversight, including during the trial.

In addition, to allow the Minister to determine whether the authorization criteria have been met, if the protocol involves enrolling any participant in the clinical trial without their prior documented informed consent or before their documented informed consent is obtained, the application would have to include sufficient information to establish that it meets the medical emergency criteria for an exception to prior documented informed consent (as detailed in the subsection “Documented informed consent”).

Further, similar to the existing application requirements under the FDR and the COVID-19 CT Regulations, the proposed Regulations would also require the submission of drug-specific information for each drug to be used in the trial, such as chemistry and manufacturing information, and non-clinical and clinical information — including risk information — that is necessary to support the use of the drug in the trial. Certain information, such as chemistry and manufacturing information, would not be required for authorized drugs, as it would already have been submitted to the Minister when market authorization was sought for these drugs.

Where a sponsor proposes to implement a selective approach to maintaining records of adverse events^{footnote 25} related to a drug to be used in a clinical trial, their application would have to include sufficient evidence to support the conclusion that the safety profile of the drug is sufficiently characterized to justify the selective approach. In addition, they would have to specify in the protocol: (1) the types of adverse events — other than serious unexpected adverse drug reactions^{footnote 26} — for which a record will not be created or will be created less frequently; and (2) how the selective approach will be implemented (e.g. for all participants, for a subset of participants, or after an initial trial period).^{footnote 27}

This information would allow the Minister to make a more informed decision as to whether the sponsor should be authorized to conduct the clinical trial, and it would enable better oversight, including during the trial. The Minister would also be able to request that the sponsor who submitted an application for an authorization submit — within two business days after the day on which the request is made or any longer period specified by the Minister — any additional information or material (including samples) that is necessary to enable the Minister to determine whether the sponsor should be authorized to conduct the clinical trial.

Obtaining an authorization

The proposed authorization scheme differs from the current approach under Part C, Division 5 of the FDR, where the sale and importation of a drug to be tested in a clinical trial are permitted by default within 30 days after the Minister receives the application, unless the Minister notifies the sponsor otherwise. Specifically, the new scheme would require the Minister to issue a contingent authorization and a written notice to the sponsor within 7 days of the sponsor submitting a complete application. This written notice would indicate the day on which the complete application was submitted. A contingent authorization would not authorize a sponsor to conduct a clinical trial or to import or sell a drug for use in a clinical trial. Its only effect would be that it would have the potential to become an authorization, which would then authorize the sponsor to conduct a clinical trial. By default, a contingent authorization would become an authorization after the expiry of a 30-day period beginning the day on which the sponsor submitted a complete application — unless the Minister takes one of the following actions within those 30 days:

• (1) The Minister sends the sponsor a written notice indicating that
  • (i) the application does not meet the application content requirements and, if applicable, the requirements for adopting a selective approach to maintaining records of adverse events; or
  • (ii) the Minister has reasonable grounds to believe that the sponsor should not be authorized to conduct the clinical trial for any of the following reasons:
    • the conduct of the clinical trial, including the use of any drug in it, is likely to result in unacceptable risks to the health of its participants or other persons;
    • if a drug to be used in the clinical trial contains a certain substance referred to in any of sections C.01.036,^{footnote 28} C.01.037,^{footnote 29} C.01.038^{footnote 30} or C.01.040^{footnote 31} of the FDR, or a colouring agent other than one listed in subsections C.01.040.2(3) and (4) of the FDR,^{footnote 32} the drug does not have the potential to result in a therapeutic benefit for human beings;^{footnote 33}
    • the clinical trial is contrary to the best interests of its participants; and
    • the objectives of the clinical trial are not achievable.
• (2) The Minister sends the sponsor a written notice indicating that no grounds exist for the Minister to send the sponsor the notice referred to in item (1) above, in which case the contingent authorization would become an authorization the day on which the Minister sends such notice (i.e. before the expiration of the 30-day period).
• (3) The Minister sends the sponsor a written notice indicating that they did not comply with the Minister’s request for additional information in relation to the application.

These conditions for authorization are similar to those currently in place under Part C, Division 5 of the FDR and the COVID-19 CT Regulations, and only a single authorization would be obtained by a sponsor for a clinical trial involving one or more drugs, including a trial designed with multiple sub-studies under a master protocol trial.

However, the Minister may also, within 30 days after the sponsor submitted the application, send a notice to the sponsor indicating that more time is needed to review the application. If this notice is sent, the Minister would have an additional 30 days to review the application. This potential 30-day extension would have to be based on one or more of the following factors:

• the degree of complexity of the trial, including (i) the potential need to impose terms and conditions on the authorization to address that complexity; (ii) the extent to which the trial has a complex design, including whether it is a master protocol trial; or (iii) the extent to which the drug represents an emerging or innovative technological, scientific or medical development, or the manufacturing of the drug or the controls to be used in its manufacture involve an emerging or innovative process; or
• whether further assessment is needed to protect a particular vulnerability of the study population or any part of it.

If such a notice is sent to the sponsor, the 30-day period (after which a contingent authorization would become an authorization) would be extended to 60 days.

Terms and conditions

As part of the proposed risk-based approach, the Minister would be able to impose terms and conditions on an authorization and amend them on a case-by-case basis at any time from the day the trial is authorized until its completion or discontinuation, including where an entire authorization or part of it has been suspended and is being reinstated. Terms and conditions would enable the Minister to authorize trials that may not have otherwise satisfied the authorization criteria, by enabling targeted oversight to mitigate specific risks or uncertainties throughout a trial’s life cycle.

Under the proposed Regulations, the Minister could only impose terms and conditions on an authorization after considering the sufficiency of other requirements under the Act to meet the following objectives: (i) mitigating the risks concerning the conduct of the trial, including the drug(s) being used in the trial; and (ii) collecting information to enable the management of the uncertainties relating to the risks. Further, the Minister would also have to assess whether the proposed terms and conditions are feasible, whether complying with them may contribute to meeting the intended objectives, and whether less burdensome means exist in achieving those objectives.

Examples of potential terms and conditions that the Minister could impose include

• submitting more frequently safety and/or efficacy reporting (e.g. copies of development safety update reports (DSUR), data and safety monitoring board (DSMB) reports) and/or safety review committee reports;
• submitting updated versions of the informed consent form that reflect changes made to the study protocol and require re-consent of trial participants before resuming dosing;
• adjusting inclusion and/or exclusion criteria for further recruitment to the trial to mitigate a risk or potential safety signal;
• adapting the study population throughout the trial (e.g. limiting the number of participants prior to expanding to additional participants);
• monitoring of specific study populations because of potential increased risk;
• submitting additional information to characterize and mitigate a newly identified risk or safety signal; and
• submitting final results from ongoing studies (clinical trial or post-market) in other jurisdictions.

In accordance with section 3.2 of the Act, the sponsor would be required to comply with any terms and conditions imposed by the Minister on an authorization.

A term and condition imposed or amended by the Minister post-authorization could necessitate a change to the protocol by the sponsor. Depending on the specific term and condition, the sponsor may need to submit either a notification or an application to the Minister to amend the authorization.

Requirements for authorization holders prior to conducting a clinical trial at a site

Similar to the FDR and the COVID-19 CT Regulations, the proposed Regulations would permit the conduct of a clinical trial (for which an authorization has been obtained) at a specific trial site only if the following conditions are met at that site:

• the sponsor has obtained the approval by an REB for the protocol and the informed consent form (which may include a national REB approval in respect of all sites), and the approval has not been withdrawn; and
• the sponsor has submitted to the Minister the following information (if it was not included in their clinical trial application): (1) the name and contact information of the investigator, and the address of the main location of the clinical trial site if it is different from the investigator’s address; (2) the name and contact information of the REB that approved the protocol and the informed consent form for the clinical trial site, or the name of the national REB that approved the protocol and the informed consent form for the entire trial; and (3) the proposed start date of the trial at the site.

Further, if these requirements were met in respect of a site and the trial was conducted and the site was subsequently closed, the trial can only restart at the site if the sponsor notifies the Minister of any change to the information described above in (1) and, if applicable, in (2), as well as the proposed restart date.

Post-authorization changes

Similar to the FDR, the proposed Regulations would require sponsors to inform the Minister of certain changes to previously submitted information by submitting a notification or an application to amend the authorization, depending on the nature of the change.

Notifications

A sponsor would be able to make the following changes to previously submitted information, if they notify the Minister within 15 days of such changes, and if the proposed Regulations do not require the sponsor to amend their authorization for such changes:

• a change to the protocol that does not alter the risk to the health of trial participants or other persons; and
• a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug.

In addition, the proposed Regulations would require a sponsor to notify the Minister within 15 days after becoming aware of

• any decision (including reasons) by a foreign regulatory authority, including refusing to approve the protocol that was included in the application for authorization, refusing to authorize a trial, refusing to authorize amendments to an authorized trial, suspending or revoking an authorization, imposing terms and conditions on an authorization, and any other measures taken by any foreign regulatory authority regarding a trial to protect the health of trial participants or other persons;
• an REB’s refusal to approve the protocol of the trial; or
• an REB’s withdrawal of its approval of the protocol or informed consent form statement for a trial site, unless it is a national REB.

Further, the proposed Regulations would require a sponsor to notify the Minister of the following changes to previously submitted information within 15 days of such changes:

• any change to the name or contact information of the sponsor or, in the case of a foreign sponsor, their representatives in Canada; or, in the case where a different person becomes the foreign sponsor’s Canadian representative, or the representative responsible for importing or selling the drug in Canada, that person’s name and contact information;
• any change to the name or contact information of an investigator, or to the address of the clinical trial site’s main location^{footnote 34} if it is different from the investigator’s contact information; or, in the case where another person becomes the investigator at the clinical trial site, that other person’s name and contact information;

In addition, the proposed Regulations would require a sponsor to notify the Minister of the following changes to previously submitted information within 15 days after the day on which they become aware of them:

• any change to the name and contact information of a service provider who conducts the trial; and
• any change to the name and contact information of an REB that approved the protocol and the informed consent form, except where the REB is a national REB.

In addition, the sponsor would be required to notify the Minister of the name and contact information of any service provider that conducts trial activities, within 15 days after the day the service provider begins to conduct those activities, if the sponsor did not provide that information earlier.

Amendments

A sponsor would be prohibited from conducting an authorized clinical trial or importing or selling a drug for use in the clinical trial if the trial is subject to any of the changes listed below, unless the authorization is amended accordingly.^{footnote 35} The proposed Regulations would require a sponsor to submit an application to amend an authorization for the following changes:

• an amendment to the protocol that affects the selection, monitoring or dismissal of a trial participant, including the number of participants;
• an amendment to the protocol that affects the evaluation of the clinical efficacy of the drug;
• an amendment to the protocol that alters the risk to the health of trial participants or other persons;
• an amendment to the protocol that affects the safety evaluation of the drug;
• an amendment to the protocol that changes the duration of the clinical trial;
• in the case of a master protocol trial, an amendment to the protocol to add a sub-study;
• an amendment to the protocol to add or modify a selective approach to maintaining records of adverse events associated with a drug used in the clinical trial; and
• a change to the chemistry and manufacturing information submitted as part of the clinical trial application that may affect the safety or quality of the drug.

Further, if the protocol or the informed consent form are amended following a change listed in this section, the conduct of the trial in accordance with the amended protocol and/or informed consent form would be prohibited at a clinical trial site, unless the sponsor has obtained approval for the amended protocol and/or the amended informed consent form, either from an REB for that site, or from a national REB for the entire trial, and the approval has not been withdrawn.

However, if the continued conduct of a clinical trial or the use of a drug in the trial poses a risk to the health of any trial participant or other person, the sponsor would be permitted to make a change immediately to protect their safety and conduct the trial in accordance with that change. In these situations, the sponsor would be required to submit an amendment application within 30 days of making the change, and include in the application the reasons for making the change and a description of any risks to the health of participants or other persons. If the application for an amendment has not yet been submitted within seven days after making the change, the sponsor would also have to notify the Minister of the change within that seven-day period, and the notification must include a description of the change and the reasons for making it, including any risks to the health of participants or other persons.

An amendment application must contain sufficient information and material to enable the Minister to determine whether the authorization should be amended, including information and material similar to that required in an initial clinical trial application that is relevant to the change, and attestations that (1) the trial will be conducted in accordance with good clinical practices and the proposed Regulations; and (2) all information contained in or referred to in the application is complete, and not false or misleading.

While reviewing the application, the Minister would be able to request the sponsor to submit — within two business days or any longer period specified by the Minister and in the form and manner specified by the Minister — any additional information or material (including samples) that is necessary to determine whether the authorization should be amended. The threshold for amending an authorization would be the same as the initial authorization threshold. Further, comparable to the initial review process, the proposed Regulations would enable the Minister to consider other available information when making such determinations. In addition, as with the initial review process, the Minister may take into account terms and conditions to be imposed on the authorization when making such decisions.

Unless the Minister takes one of the following actions within 30 days of the sponsor submitting an application to amend an authorization, the authorization would be amended accordingly upon the expiration of that time period:

• (1) the Minister sends the sponsor a written notice indicating that
  • (i) the application does not contain sufficient information and material to determine whether the authorization should be amended; or
  • (ii) at least one of the requirements of the authorization threshold for the amendment is not met.
• (2) the Minister sends the sponsor a written notice indicating that no grounds exist for the Minister to send the sponsor the notice referred to in item (1) above, in which case the authorization is amended accordingly the day on which the Minister sends such notice (i.e. before the expiration of the 30-day period).
• (3) the Minister sends the sponsor a written notice indicating that they did not comply with the Minister’s request for additional information in relation to the application.

Transfer of authorization

An authorization to conduct a clinical trial would be transferred from its current sponsor to another person (i.e. its new sponsor) if the following conditions are met:

• the current sponsor notifies the Minister in writing of their intention to transfer the authorization to the other person;
• the Minister receives from the other person a written acknowledgement that they agree to become the sponsor of the clinical trial upon transfer of the authorization; and
• the Minister receives from the other person an attestation, signed and dated by the person’s senior medical or scientific officer in Canada and senior executive officer, confirming that (i) the person will take responsibility for the overall conduct of the clinical trial; and (ii) the clinical trial will be conducted in accordance with good clinical practices and the proposed Regulations.

Under the proposed Regulations, obligations on the former holder of a clinical trial authorization (i.e. a sponsor whose authorization was revoked in whole), related to (1) post-trial reporting of serious adverse drug reactions and serious unexpected adverse drug reactions; and (2) record retention, would apply to the sponsor who held the authorization on the day on which it was revoked in whole. In the case of an authorization transfer, these post-trial obligations would apply to the new sponsor.

Reporting of adverse drug reactions by sponsors

Reporting of serious unexpected adverse drug reactions

The proposed Regulations would require sponsors to report to the Minister any serious unexpected adverse drug reaction that has occurred inside or outside Canada. Under the proposed Regulations, “adverse drug reaction” would mean any adverse and unintended occurrence in the health of a participant who is administered a drug in a clinical trial for which there are reasonable grounds to believe that the occurrence could be a noxious response to any dose of the drug. This definition of “adverse drug reaction” is similar to the definition of “adverse drug reaction” under the FDR, with the addition of “for which there are reasonable grounds to believe,” to better align with the language in the International Council for Harmonisation of Technical for Pharmaceuticals for Human Use (ICH) E6 guideline for Good Clinical Practice (ICH E6 guideline). This addition would clarify the types of reports on serious unexpected adverse drug reactions to be submitted to Health Canada.

Specifically, where a serious unexpected adverse drug reaction is fatal or life-threatening, the sponsor who holds the authorization for the clinical trial would have to notify the Minister in writing within seven days after becoming aware of the information. Subsequently, the sponsor would have to submit a complete report for the serious unexpected adverse drug reaction, including an assessment of the importance and implication of any findings made, within eight days after notifying the Minister. When a serious unexpected adverse drug reaction is neither fatal nor life-threatening, the sponsor who holds the authorization for the clinical trial would have to notify the Minister in writing within 15 days after becoming aware of the information. Subsequently, the sponsor would not have to submit a complete report.

Case reports and issue-related summary reports

The proposed Regulations would also introduce new provisions to enable the Minister to request, on a discretionary basis, case reports and issue-related summary reports relating to adverse drug reactions and serious adverse drug reactions to the drug used in a clinical trial.

A “case report” would mean a detailed record of all relevant data associated with the use of a drug in a participant.

An “issue-related summary report” would have to contain

• a concise, critical analysis of the adverse drug reactions and serious adverse drug reactions to a drug; and
• case reports of all or specified adverse drug reactions and serious adverse drug reactions to the drug that the Minister directs the sponsor to analyze in the report.

The Minister may request such reports to assess the safety of a drug that is used in a clinical trial and require that such reports be submitted in the time, form, and manner specified by the Minister. Circumstances that may prompt such requests would include safety signals from foreign jurisdictions, published literature, and the receipt of information regarding one or multiple related serious unexpected adverse drug reactions.

Exceptions to serious unexpected adverse drug reaction, and case and issue-related summary, reporting

The two requirements above relating to serious unexpected adverse drug reaction and case and issue-related summary reports would not apply to an authorized drug used in a clinical trial in accordance with its authorization. However, similar requirements under the FDR would apply to these authorized drugs due to the manufacturer’s reporting obligations for authorized drugs under the FDR.

Post-trial reporting

Under the FDR and the COVID-19 CT Regulations, the Minister does not have the authority to require sponsors to submit any safety information for unauthorized drugs used in clinical trials once the trials are completed or discontinued. Therefore, Health Canada’s ability to identify, assess, and mitigate risks associated with these drugs post-trial is limited. To address this gap, the proposed Regulations would allow the Minister to require a former sponsor who was a holder of an authorization to report to the Minister any serious adverse drug reactions or serious unexpected adverse drug reactions related to drugs used in a trial inside or outside Canada that come to the sponsor’s attention following the completion or discontinuation of the trial. This reporting requirement would apply for a period of up to 15 years (ending earlier if the drug were to become authorized under the FDR during that period). The Minister could only rely on this authority where the Minister has reasonable grounds to believe that there could be a risk of health consequences for participants associated with the use of the drug in the clinical trial that could arise over the long term. Further, post-trial reporting would only apply to drugs used in a clinical trial that were not authorized under the FDR at the time of the imposition of this reporting requirement; the sponsor would only have to report such a reaction where reasonable grounds exist to suggest the reaction originated from the use of the drug in the trial inside or outside Canada (i.e. not based on its use on the market after the trial). Therefore, this reporting would only be required in rare cases.

Similar to reporting during a trial, post-trial reporting would be required where a serious adverse drug reaction or a serious unexpected adverse drug reaction is fatal or life-threatening; the former sponsor would have to notify the Minister in writing of this adverse drug reaction within seven days after becoming aware of the information. Subsequently, the sponsor would have to submit to the Minister a complete report, including an assessment of the importance and implication of any findings made, within eight days after submitting the original report. Where a serious adverse drug reaction or serious unexpected adverse drug reaction is neither fatal nor life-threatening, the sponsor would have to notify the Minister in writing within 15 days after becoming aware of the information. Subsequently, the sponsor would not have to submit a complete report.

Discontinuance or completion of a clinical trial for which an authorization has been issued

Discontinuation of a trial

Similar to the FDR and the COVID-19 CT Regulations, the proposed Regulations would require a sponsor to notify the Minister if they discontinue a trial (in whole or in part), within 15 days of the discontinuation. The notification would need to include the reasons for the discontinuation. The sponsor would also be required to advise the Minister of its impact on any other clinical trial involving drug(s) used in the discontinued trial for which an authorization has been issued to the sponsor, including any potential risks to the health of participants or other persons. The sponsor would also have to inform all investigators and, if applicable, the national REB that approved the protocol of the discontinuation without delay and provide them with the reasons for discontinuation and any potential risks to participants or other persons. Finally, except for an authorized drug used as authorized, the sponsor would have to stop importing or selling the drug used at the discontinued trial site and take reasonable measures to recover any unused quantities of the drug.

Immediately after being informed of the discontinuation of the clinical trial (in whole or in part) by the sponsor, an investigator whose site is discontinued accordingly would be required to inform both the relevant clinical trial participants and the relevant REB (if it is not a national REB) of the discontinuation, provide them with the reasons for the discontinuation, and advise them, in writing, of any potential risks to the health of participants or other persons.

The proposed Regulations would also require the Minister to revoke the sponsor’s authorization (in whole or in part) upon receiving the sponsor’s notice. To note, if the sponsor were to seek to restart a clinical trial discontinued in whole, then they would have to submit a new clinical trial application; or if they were to seek to restart a clinical trial discontinued in part, then they would have to submit an application to amend the protocol to reintroduce the part that was discontinued.

Closure of a clinical trial site

Similar to the FDR and the COVID-19 CT Regulations, the proposed Regulations would require a sponsor who holds an authorization to notify the Minister, in writing, that a clinical trial site is closed within 15 days after the day on which it is closed (whether the trial conduct was discontinued or completed at that site). A clinical trial site is considered to be closed when the last visit of the last participant at the last of the locations of the clinical trial site is finished.

Clinical trial completion

The proposed Regulations would codify current guidance on notifications for trial completion, providing regulatory clarity and certainty for stakeholders. Specifically, a sponsor who holds an authorization would be required to notify the Minister in writing and every investigator and service provider who conducts the clinical trial within 15 days of the trial completion date. In the case where the clinical trial includes a sub-study, the sponsor would also be required to notify the Minister, and every investigator and service provider who conducts the sub-study of the date for completion of the sub-study within the master protocol trial (i.e. completion in part), as well as the date for completion of the entire clinical trial (i.e. completion in whole), no later than 15 days after each completion. The proposed Regulations would deem the authorization revoked either in whole or in part 15 days after the completion of the trial in whole or in part.

Suspension and revocation of an authorization

Suspension

The proposed Regulations would enable the Minister to suspend, in whole or in part, an authorization to conduct a clinical trial if the Minister has reasonable grounds to believe that

• the conduct of the clinical trial, including the use of any drug in it, is likely to result in unacceptable risks to the health of its participants or other persons; if a drug to be used in the clinical trial contains a certain substance^{footnote 36} or colouring agent,^{footnote 37} the drug does not have the potential to result in a therapeutic benefit for human beings; the clinical trial is contrary to the best interests of its participants; or the objectives of the clinical trial are not achievable;
• the sponsor, investigator, service provider or person who conducts the clinical trial has contravened, in relation to the clinical trial, any provision of the Act or the proposed Regulations, any applicable provision of the FDR, or any order made under the Act;
• the sponsor has failed to comply with a term and condition imposed on the authorization;
• any information submitted by or on behalf of the sponsor about the clinical trial, including the drug(s) used in the clinical trial, is false or misleading; or
• the sponsor, investigator, service provider or person who conducts the clinical trial has failed to comply with good clinical practices.

The ability of the Minister to suspend part of an authorization would allow for more risk-based and flexible oversight. For example, Health Canada would have the ability to suspend an arm, or treatment group, of a multi-arm trial. This would allow the Department to suspend the part of the trial that poses an unacceptable health risk to participants or other persons while allowing the rest of the trial to proceed, ensuring that other participants can continue to take part in the trial without interruption.

The proposed Regulations would also allow the Minister to suspend multiple authorizations, in whole or in part, where the Minister has reasonable grounds to believe that any of the above circumstances — other than the first — are met and the issue or circumstances are present in multiple clinical trials involving the same person (e.g. the same sponsor, service provider, or investigator). This ability to address systemic issues would enable more efficient post-authorization actions as well as compliance and enforcement actions.

If the Minister intends to suspend an authorization in whole or in part, they would have to send the sponsor a written notice, outlining the extent of (i.e. in whole or in part) and reasons for the intended suspension. The sponsor would then be given an opportunity to respond in writing concerning the intended suspension. If the sponsor provides information or material (including samples) within 30 days demonstrating that the authorization thresholds are met, or that the situation giving rise to the intended suspension did not exist or has been corrected, the Minister would not be able to proceed with the suspension. If no such information is received within the 30-day period, the Minister could suspend the authorization, in whole or in part, and would have to notify the sponsor of the date, the extent (in whole or in part) of the suspension and the reasons for it. However, these requirements would not apply if an immediate suspension is required (see below).

Immediate suspension

The proposed Regulations would allow the Minister to suspend an authorization (or multiple authorizations involving the same person) in whole or in part if they have reasonable grounds to believe that such action is necessary to prevent injury to the health of a clinical trial participant or other person. In these circumstances, the proposed Regulations would require the Minister to notify the sponsor of the date, the extent (in whole or in part) of the suspension and the reasons for the suspension. Although the sponsor would not be given an opportunity to be heard prior to the suspension, they would have an opportunity to be heard prior to the revocation of the authorization (described below).

Notification of suspension to third parties

If a clinical trial authorization is suspended, in whole or in part, the sponsor would be required to notify without delay all affected investigators, service providers, persons conducting the trial under the sponsor’s oversight, and persons who import or sell the drug for use in the trial. The sponsor would also be required to ensure that persons conducting the trial under the oversight of affected investigators and service providers are notified of the suspension as soon as feasible.

Reinstatement and revocation

The proposed Regulations would require the Minister to reinstate a suspended authorization, in whole or in part, if the sponsor provides information or material (including samples) demonstrating that the authorization thresholds are met, or that the situation giving rise to the suspension did not exist or has been corrected.

If the sponsor does not submit to the Minister such information or material within 60 days of an immediate suspension, or within 30 days of a suspension with a prior opportunity to be heard, or if the submitted information or material is insufficient, then the Minister would be able to revoke the authorization, in whole or in part.

Finally, where the Minister has revoked an authorization, in whole or in part, the proposed Regulations would require the Minister to notify the sponsor of such revocation, setting out the reason for the revocation, its effective date, and whether the authorization is revoked in whole or in part. Further, if the authorization is revoked in whole or in part, the sponsor would be required to notify all investigators and service providers who conduct the affected part of the trial and persons who import or sell the drug for use in the trial as soon as is feasible. These notification requirements for sponsors would also apply in cases of automatic revocation of an authorization — whether in whole or in part — due to the discontinuation of a trial (in whole or in part) or the completion of a trial or a sub-study.

Request for information and material

To determine whether to suspend or revoke an authorization, the Minister would be able to request that a sponsor submit any relevant information or material (including samples) that is necessary to enable the Minister to make that determination. In such a case, the sponsor would be required to submit the requested information or material in the time, form, and manner specified by the Minister.

Provisions applicable only to clinical trials not requiring an authorization

Under the proposed Regulations, certain clinical trials would not require prior authorization by the Minister (e.g. the sponsor of these trials would be exempt from section 3.1 of the Act). However, these trials would still have to meet all applicable requirements outlined in the proposed Regulations.^{footnote 38} These trials would only involve authorized drugs being used as authorized. Since these trials would not require prior authorization, the Minister would not be able to suspend or revoke the authorization to address an issue or non-compliance. Additional authorities and compliance and enforcement tools are required to address issues or non-compliance in circumstances where there could be an impact on the health or safety of trial participants or data integrity.

Under the proposed Regulations, the Minister would have the authority to direct a sponsor exempt from section 3.1 of the Act to cease the conduct of a trial, in whole or in part, if the Minister has reasonable grounds to believe that

• the conduct of the clinical trial, including the use of any drug in it, is likely to result in unacceptable risks to the health of its participants or other persons; the clinical trial is contrary to the best interests of its participants; or the objectives of the clinical trial are not achievable;
• the sponsor, investigator, or service provider has contravened any provision of the proposed Regulations, any provision of the Act, any applicable provision of the FDR, or any order made under the Act;
• any information submitted about a drug used or the clinical trial is false or misleading; or
• there has been a failure to comply with good clinical practices.

The proposed Regulations would also allow the Minister to direct one or more sponsors to cease the conduct of several clinical trials, in whole or in part, where the Minister has reasonable grounds to believe that any of the above circumstances — other than the first — are present in multiple clinical trials due to the act or omission of the same person (e.g. the same sponsor, service provider, or investigator).

The Minister would be required to provide the sponsor with a notice of intent to issue a direction to cease the conduct of a trial in whole or in part, including the reasons for the intended direction, giving the sponsor an opportunity to be heard concerning the intended direction. After receiving the notice, the sponsor would have 30 days to submit information or material (including samples) demonstrating that the applicable requirement is met, or the situation giving rise to the intended direction did not exist or has been corrected.

Similar to the immediate suspension authority, the Minister would not have to notify a sponsor or provide them with an opportunity to be heard prior to directing the sponsor to cease conducting the trial, in whole or in part, if the Minister has reasonable grounds to believe such action is necessary to prevent injury to the health of a clinical trial participant or other person.

In either case, where the Minister directs a sponsor to cease the conduct of a trial in whole or in part, the Minister would have to notify the sponsor of such a direction and include in that notice the reasons for the direction and its effective date. Following the Minister’s direction, the sponsor would be required to notify, without delay, all affected investigators, service providers, persons conducting the trial under the sponsor’s oversight, and persons who import or sell the drug for use in the trial. The sponsor would also be required to ensure that persons conducting the trial under the oversight of affected investigators and service providers are notified of the direction to cease conduct as soon as feasible. Further, the proposed Regulations would require the Minister to lift a cease conduct direction, in whole or in part, if the sponsor submits sufficient information or material (including samples) demonstrating that the applicable requirement is met, or the situation giving rise to the direction did not exist or has been corrected within

• 30 days following a direction to cease conduct with prior opportunity to be heard; or
• 60 days following a direction to cease conduct without prior opportunity to be heard.

If the Minister does not lift the direction within 15 days after the applicable 30- or 60-day period ends, the direction would become permanent, and the sponsor would be required to notify all investigators and service providers who conduct the affected part of the trial and persons who import or sell the drug for use in the trial as soon as feasible.

Similar to the suspension or revocation authority, to determine whether to direct the sponsor to cease the conduct of the clinical trial, the Minister would be able to request that a sponsor submit any relevant information or material (including samples) that is necessary to enable the Minister to make that determination. In such a case, the sponsor would be required to submit the requested information or material in the time, form, and manner specified by the Minister.

Requirements for all clinical trials

Good clinical practices

The proposed Regulations would require that all persons conducting a clinical trial apply the applicable good clinical practices. “Good clinical practices” would be defined in the proposed Regulations to mean generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of clinical trial participants and other persons and the reliability of the trial results. In accordance with current practices, Health Canada guidance would refer to the ICH E6 guideline as the standard to follow.^{footnote 39}

Sponsors, who retain overall responsibility for a trial, would be required to take all reasonable measures to ensure that the trial is conducted in accordance with good clinical practices, which include, but are not limited to ensuring that a clinical trial is scientifically sound and clearly described in a detailed protocol; ensuring adherence to the protocol, the proposed Regulations, and any applicable clinical trial authorization (including any terms and conditions); managing risks to the health of participants and other persons appropriately (including that medical care and decisions are under the supervision of a physician or dentist, as appropriate) and ensuring the reliability of trial results; obtaining approval of the protocol and informed consent form, either from an REB for each clinical trial site or from a national REB for the entire trial; ensuring that all personnel are qualified to perform their respective duties; obtaining documented informed consent as set out in the proposed Regulations; and ensuring compliance with standards for drug manufacturing, handling and storage.

The proposed requirements pertaining to good clinical practices are similar to those set out in the FDR and the COVID-19 CT Regulations,^{footnote 40} with some modifications, including, but not limited to (1) introducing the notion of the above-mentioned “reliability of results”; (2) adding the clarification that the population to be studied in the trial must be consistent with the study’s objectives; (3) requiring compliance with any terms and conditions imposed on the clinical trial authorization, if applicable (a new requirement); (4) requiring the identification of a qualified physician or, when appropriate, a qualified dentist, as the individual with the overall responsibility for the medical care given to, and medical decisions made for, trial participants throughout the trial at a clinical trial site (a new requirement as a result of introducing greater flexibility in the types of health professionals who can conduct a trial as an investigator); (5) requiring documented informed consent, rather than written informed consent, from every trial participant before they participate in the trial, and allowing certain exceptions to such requirements (a modification to current requirements, as discussed below); and (6) incorporating certain other terminology changes.

Documented informed consent

As part of good clinical practices, sponsors would be required to obtain documented informed consent from every person before they participate in a clinical trial in accordance with applicable laws. This consent can only be obtained after the person has been informed of the risks and anticipated benefits to their health arising from trial participation, as well as all other aspects of the trial necessary for them to make an informed decision to participate in the trial. The introduction of the notion of “documented informed consent” is intended to provide additional flexibility for participants or prospective participants in providing informed consent in remote and/or virtual trial environments, facilitating the conduct of decentralized trials. This shift from “written” informed consent, as in the FDR, toward “documented” informed consent would permit consent through electronic signatures and/or the documentation of informed consent when participants provide it orally, either in person or remotely, live or recorded.

Further, the proposed Regulations would permit an exception to documented informed consent, provided that all of the following conditions are met:

• the objectives of the clinical trial relate to persons experiencing a medical emergency that is described in the protocol;
• the protocol indicates that it is not necessary to obtain documented informed consent from a participant before their participation, only in circumstances in which it is impossible to do so; and
• in respect of the medical emergency to which the trial relates:
  • either no standard of care exists, or the trial offers a potential direct benefit to the participant that is greater than the potential direct benefit of the standard of care, and
  • either the risks to the health of the participant are no greater than those posed by the standard of care, or the risks are justified by the potential direct benefit to their health.

The exception to documented informed consent is intended to address a medical emergency situation in which all of the following factors are present: (1) the prospective participant is experiencing severe suffering or is at risk of sustaining serious bodily harm that requires immediate intervention; (2) a delay in treatment could result in risking the effectiveness of the drug or result in the treatment being provided outside of the therapeutic window; (3) the prospective participant lacks the capacity to consent to the proposed intervention; and (4) consent cannot be obtained from a substitute decision-maker on behalf of the prospective participant in a timely manner.

This exception would allow clinical trials involving prospective participants experiencing the aforementioned medical emergencies to proceed without their prior informed consent (or that of their authorized third party), while still complying with the proposed Regulations. However, this would have to be conducted in accordance with applicable laws governing consent. In circumstances where any applicable law does not permit the exception, the trial could not proceed without the prior informed consent from participants (or their authorized third party) despite the emergency situation.

Further, under this exception, documented informed consent would have to be obtained from every person before they continue to participate in the clinical trial when possible and, if so, as soon as feasible, but only after they have been informed of (1) the risks and anticipated benefits to their health arising from participation in the trial; and (2) all other aspects of the trial necessary for them to decide whether to continue to participate in the trial.

Together, these requirements would mean that even in trials relating to medical emergencies, where prior documented informed consent is impossible in respect of a prospective participant, the sponsor would be required to ensure that documented informed consent is eventually obtained in accordance with the proposed Regulations.^{footnote 41}

Labelling

The proposed Regulations would prohibit persons from conducting a clinical trial involving a drug unless each drug’s label meets the requirements of the proposed Regulations.

Specifically, under the proposed Regulations, each drug’s label would have to set out the following information, in both English and French, in a legible and prominent manner, using plain language, and in a format that does not impede comprehension:

• a statement indicating that the drug is for use only in a clinical trial by an investigator (or other statements that convey that meaning);
• the brand name, code or chemical name of the drug or a number or identifying mark assigned to the drug for the purposes of the clinical trial;
• the expiration date of the drug, if any;
• the recommended storage conditions for the drug;
• the lot or batch number of the drug;^{footnote 42}
• the sponsor’s name and contact information that enable a person in Canada to contact the sponsor;
• the protocol code; and
• if the drug is a radiopharmaceutical as defined in section C.03.201 of the FDR, the radiation warning as required by subparagraph C.03.202(1)(b)(vi) of the FDR.

In addition, if the drug is contained in a container described in subsection A.01.061(1) or A.01.062(1) of the FDR, the label must meet the applicable requirements of sections A.01.061 to A.01.063 of the FDR.

However, to reduce unnecessary burden, any authorized drug (under the FDR) used in a clinical trial, whether it is used in the trial as authorized or outside of its authorized purpose and conditions of use, would not have to be labelled in accordance with the proposed Regulations if its label already complies with the FDR and its Canadian authorization. Optionally, a sponsor could still choose to label such drugs in accordance with the proposed Regulations, in which case labelling in accordance with the FDR would not be required for the purpose of the use of the drug in the clinical trial.

Maintenance of records

Sponsors would be required to ensure, by taking all reasonable measures, that all information regarding the clinical trial is recorded, handled, and stored in a manner that allows for the complete and accurate reporting of the information as well as the interpretation and verification of the information, including in relation to service providers on whom the proposed Regulations would also impose direct record-related obligations.

Sponsors would also be required to ensure, by taking all reasonable measures, that complete and accurate records are maintained to establish that the clinical trial is conducted in accordance with good clinical practices and the proposed Regulations, including the following:

• (a) In the case where a sponsor holds an authorization, for each drug used in the clinical trial, as applicable, a copy of all versions of the document that includes, among other information, any non-clinical and clinical data to support the use of the drug in the clinical trial, such as an investigator’s brochure or equivalent document;
• (b) Records of each change made to the document or information referred to in paragraph (a) above, including the rationale for each change and documentation that supports each change;
• (c) Subject to certain exceptions discussed below, records of all adverse events from the drug that have occurred inside or outside Canada, including the indication for use and the dosage form of the drug at the time of the adverse event;
• (d) Information about the enrollment of participants, including information that allows all participants to be identified and contacted in the event that the conduct of the clinical trial may endanger the health of participants or other persons;
• (e) Except for authorized drugs, whether or not used as authorized, records about the shipment, receipt, disposition, return and destruction of the drug;
• (f) The lot or batch number of the drug used in the clinical trial;
• (g) A copy of the protocol, informed consent form, and any amendment to the protocol or informed consent form that has been approved either by an REB for each clinical trial site, or by a national REB for the entire trial; and
• (h) An attestation, signed and dated either by an REB for each clinical trial site or by a national REB for the entire trial, stating that it has reviewed and approved the protocol and informed consent form, and that the REB or the national REB carries out its functions in a manner consistent with good clinical practices.^{footnote 43}

Importantly, paragraphs (a) and (b) above would not apply to authorized drugs used in a clinical trial as authorized, since sponsors would not be required to include the information in (a) in their application for clinical trial authorization.

In addition, paragraph (c) above would carry over the current requirement to maintain records of all adverse events; however, this requirement would be subject to two exceptions:

• clinical trials for which an authorization has been issued with a version of the protocol that describes a selective approach to maintaining records of adverse events, in which case the following records would be required to be maintained:
  • records about all serious unexpected adverse drug reactions that occur inside or outside of Canada, and
  • records about any other adverse events that occur inside or outside Canada, as described in the approach outlined in the protocol.
• clinical trials for which the sponsor is exempt from section 3.1 of the Act would require that only records about all serious expected and unexpected adverse drug reactions that occur inside or outside Canada be maintained.

Service providers would also be directly required to record, handle, and store all information concerning the clinical trial in a manner that allows for the complete and accurate reporting of the information as well as the interpretation and verification of the information. Similarly, service providers would also be required to maintain complete and accurate records — including the information in paragraphs (a) to (h) above that are relevant to the service they provide to or on behalf of a sponsor or investigator — to establish that the service provider conducts the clinical trial in accordance with good clinical practices and the proposed Regulations. Further, those service providers would be subject to the same exceptions and requirements as sponsors relating to (1) selective approaches to adverse event reporting and (2) clinical trials for which the sponsor is exempt from section 3.1 of the Act. Again, these exceptions and additional requirements would only apply to the service provider if they are relevant to the service that they provide to or on behalf of the sponsor or investigator.

Record retention period

Similar to the FDR and the COVID-19 CT Regulations, the sponsor would have to retain all clinical trial records for at least 15 years after the end of the trial. In the case where the sponsor is a former holder of an authorization, this period would begin the day on which the authorization is revoked in whole. In the case where the sponsor conducted a trial only involving authorized drugs used as authorized, this period would begin on the day on which the trial is completed in whole, or the earliest of the day on which the trial is discontinued in whole by the sponsor or the day on which a direction to cease the conduct of the trial in whole becomes permanent.

Transition

This section outlines how applications under review and ongoing clinical trials authorized under the current regulatory framework would transition to the new scheme.^{footnote 44} Applications and clinical trials transitioned to the new scheme would be subject to the proposed Regulations once they come into force. For example, sponsors of all ongoing trials would have to comply with the requirements for good clinical practices, documented informed consent, labelling, and other obligations set out in the proposed Regulations. Additionally, terms and conditions could be imposed on authorizations of clinical trials that were previously authorized under Part C, Division 5, of the FDR and Part 2 of the COVID-19 CT Regulations and are still ongoing, in accordance with the authority set out in the proposed Regulations. Further, specific transitional provisions are introduced to clarify how applications under review, ongoing clinical trials, and other related administrative actions would proceed under the proposed Regulations.

Transitional provisions applicable to clinical trials involving unauthorized drugs and/or authorized drugs used outside authorized purpose and conditions of use

Applications for authorization under review

When the proposed Regulations come into force, some applications for authorization filed in the preceding 30 days under Part C, Division 5, of the FDR or filed under Part 2 of the COVID-19 CT Regulations, including applications for new trials and those seeking amendments to existing authorizations, could still be under review by Health Canada. Such an application would be deemed submitted under the proposed Regulations.

If a clinical trial application for authorization was submitted under Part C, Division 5, of the FDR at least seven days before the day on which the proposed Regulations come into force and the Minister determines it to be complete, then the Minister would be required to send the sponsor a written notice indicating the submission date and issue a contingent authorization for the trial on the day the proposed Regulations come into force.^{footnote 45} For any other deemed application submitted under Part C, Division 5, of the FDR or Part 2 of the COVID-19 CT Regulations, if the Minister determines it to be complete, the Minister would be required to send the sponsor a written notice indicating the submission date and issue a contingent authorization for the trial within seven days after the application was submitted. All deemed applications for new authorizations would be subject to the new authorization scheme under the proposed Regulations; however, the submission date for complete applications, submitted prior to the coming into force of the proposed Regulations, would remain the date on which they were submitted under the previous schemes. And, similarly, the submission date for complete amendment applications would remain the date on which they were submitted under the previous schemes. In both cases, the submission date would be used to determine the start of the 30-day review period.^{footnote 46}

If a deemed application — whether for a new authorization or for amendment(s) to an existing authorization — does not include all required information under the proposed Regulations, then Health Canada would inform the sponsor that information is missing so that the sponsor could submit a complete application in accordance with the proposed Regulations. Health Canada intends to operationalize such transitions in a manner so as to minimize disruptions and additional burden on stakeholders.

Ongoing clinical trials

For an ongoing clinical trial involving more than just authorized drugs used as authorized, the sponsor would be deemed to hold an authorization under the proposed Regulations if the clinical trial falls into one of the following two categories:

• The sponsor is authorized under Part C, Division 5, of the FDR to sell or import a drug used in the trial, provided that the trial was not completed or discontinued in whole, immediately before the day on which the proposed Regulations come into force;^{footnote 47} or
• A COVID-19 drug clinical trial authorization has been issued or reinstated under the COVID-19 CT Regulations, provided that the authorization was not revoked in whole, and the trial was not completed or discontinued in whole, immediately before the day on which the proposed Regulations come into force.

Investigators, team members, service providers, and other persons who conducted the trial immediately before the proposed Regulations come into force would be permitted to continue these activities once the proposed Regulations are in effect. This would be enabled under the exemptions described above in the section “Parties involved in the conduct of clinical trials,” which would allow these persons to conduct trial-related activities without holding an authorization. Although a sponsor is not required to provide the name and contact information of service providers who began conducting the trial under the current regulatory framework, they would be required to submit this information to the Minister within six months after the proposed Regulations come into force. Failure to do so would prohibit these service providers from conducting the trial after this six-month period.^{footnote 48}

In addition, the following transitional provisions would apply to such a trial.

Terms and conditions

If any terms and conditions were imposed on a COVID-19 drug authorization under the COVID-19 CT Regulations before the proposed Regulations come into force, that authorization would be deemed an authorization subject to the same terms and conditions imposed under the proposed Regulations.

Amendments

If an authorization^{footnote 49} was amended under Part C, Division 5, of the FDR or Part 2 of the COVID-19 CT Regulations before the proposed Regulations come into force, it would be deemed amended to the same extent under the proposed Regulations.

Suspension

If an authorization is suspended in whole or at a clinical trial site under Part C, Division 5, of the FDR, or suspended in whole or in part under the COVID-19 CT Regulations, immediately before the day on which the proposed Regulations come into force, the authorization would be deemed suspended to the same extent under the proposed Regulations. Any subsequent steps toward reinstatement or revocation would occur in accordance with the proposed Regulations.

Revocation in part

If an authorization was cancelled at a clinical trial site under Part C, Division 5, of the FDR or revoked in part under the COVID-19 CT Regulations before the proposed Regulations come into force, it would be deemed revoked in part to the same extent under the proposed Regulations.

Transitional provisions applicable to clinical trials involving only authorized drugs used as authorized

Ongoing clinical trials

If an ongoing clinical trial previously authorized under Part C, Division 5, of the FDR or the COVID-19 CT Regulations only involves authorized drugs used as authorized, the sponsor would be exempt from holding an authorization under the proposed Regulations. However, the sponsor and other persons conducting the trial would still be subject to the proposed Regulations, unless specifically exempted from a provision.

Direction to cease

If, immediately before the day on which the proposed Regulations come into force, an authorization to sell or import a drug for a clinical trial involving only authorized drugs used as authorized is suspended in its entirety or at a clinical trial site under Part C, Division 5, of the FDR, the sponsor of the trial would be deemed subject to a direction to cease the conduct of the trial imposed under the proposed Regulations to the same extent. Any subsequent steps toward lifting the direction or its becoming permanent would occur in accordance with the proposed Regulations.

Permanent direction to cease

If, before the proposed Regulations come into force, an authorization to sell or import a drug for a clinical trial involving only authorized drugs used as authorized was cancelled in its entirety or on a clinical trial site, after having been suspended, under Part C, Division 5, of the FDR, the sponsor of the trial would be deemed subject to a permanent direction to cease the conduct of the trial imposed under the proposed Regulations to the same extent.

Transitional provisions applicable to all clinical trials

The Minister’s request for information, material or samples

If the Minister previously requested any information, material, or samples under Part C, Division 5, of the FDR or Part 2 of the COVID-19 CT Regulations, related to a clinical trial application under review or an ongoing clinical trial, and the trial was not completed or discontinued in whole prior to the proposed Regulations having come into force, the request would be deemed made under the proposed Regulations.

Continuation of record retention obligations

If a sponsor was required to retain records for a clinical trial that had been completed, discontinued, cancelled or revoked in whole under Part C, Division 5, of the FDR or Part 2 of the COVID-19 CT Regulations before the proposed Regulations came into force, they would still be required to retain those records as they had been required to do so under the applicable provisions of Part C, Division 5, of the FDR or Part 2 of the COVID-19 CT Regulations once the proposed Regulations come into force.

Coming into force

The proposed Regulations would come into force 12 months after the day on which they are published in the Canada Gazette, Part II.

Regulations Amending Certain Regulations Relating to Clinical Trials

The proposed Regulations Amending Certain Regulations Relating to Clinical Trials would repeal Part C, Division 5 of the FDR and Part 2 of the COVID-19 CT Regulations. In addition, these regulations would include consequential amendments to the following instruments:

• Food and Drug Regulations (Part C Division 1, Part C Division 1A, Part C Division 3, Part C Division 8);
• Natural Health Products Regulations;
• Cannabis Exemption (Food and Drugs Act) Regulations;
• Clinical Trials for Medical Devices and Drugs Relating to COVID-19 Regulations (to ensure that these regulations apply exclusively to COVID-19 medical devices by revising or repealing provisions that pertain to COVID-19 drugs, as necessary);
• Patented Medicines Regulations;
• Certificate of Supplementary Protection Regulations;
• Regulations Excluding Certain Vaping Products Regulated Under the Food and Drugs Act from the Application of the Tobacco and Vaping Products Act;
• Cannabis Regulations; and
• Regulations Amending Certain Regulations Concerning Cannabis Research and Testing and Cannabis Beverages.

These regulations would come into force on the day on which the proposed Clinical Trials Regulations come into force.

Health Canada is assessing consequential amendments to the Blood Regulations and the Safety of Human Cells, Tissues and Organs for Transplantation Regulations and any potential related proposals under the new clinical trials framework for these drugs. Targeted consultations will take place to this effect.

Regulatory development

Consultation

Consultations on agile regulations, COVID-19 interim orders, and the COVID-19 CT Regulations

Over the course of consultations held in 2019 and early 2020, stakeholders raised concerns relating to the current regulations for clinical trials. These comments arose in consultations with a broad range of stakeholders through regulatory innovation road shows, online consultation on agile regulations for advanced therapeutic products and clinical trials, and various other forums. Stakeholders indicated that the current regulations are reducing Canada’s competitiveness in attracting clinical trials, and constraining the sector’s growth in various ways across the business lines of prescription and non-prescription drugs, medical devices, NHPs, veterinary drugs and foods. They confirmed that a flexible, enabling clinical trial framework would attract key companies and investments, and support research and innovation in Canada.

Additionally, between spring 2020 and winter 2020, Health Canada held various consultations and stakeholder engagement sessions to seek stakeholders’ input on a more flexible pathway for clinical trials involving COVID-19 drugs and medical devices. In general, stakeholders were supportive of the resulting optional regulatory framework under the COVID-19 interim orders and COVID-19 CT Regulations. This framework allowed Health Canada to pilot many of the potential flexibilities that are being considered under the Clinical Trials Modernization initiative.

Consultation on the proposed Clinical Trials Modernization initiative

In spring and summer 2021, Health Canada consulted stakeholders on the proposed Clinical Trials Modernization initiative. Through a consultation paper, the Department invited stakeholders to submit written feedback between May 20, 2021, and July 4, 2021. Health Canada received 122 submissions encompassing a diverse array of contributors, including industry (43%), academic research institutes (34%), participant advocacy groups (11%), health care practitioners (4%), health care organizations (2%), REBs (1%), and other stakeholders (5%). During this period, Health Canada also organized eight interactive webinars tailored to different stakeholder groups. In total, close to 1 000 stakeholders participated in the webinars. These included stakeholders from research institutes, academia and contract research organizations (350), the medical devices sector (205), the pharmaceutical, biologic and over-the-counter medicines sector (150), patients and patient groups (100), biologic and radiopharmaceutical drugs sectors (84), national research organizations (80), and the NHP sector (22).

Health Canada then published a What We Heard Report, which detailed descriptions of the submissions and stakeholder feedback received on the Clinical Trials Modernization initiative. Overall, stakeholders expressed support for the initiative. Of the stakeholders who responded to the question of whether the proposals in the consultation paper would meet Health Canada’s goal of enabling innovative clinical trials in Canada, 75% believed that the proposals would accomplish that goal, while 18% were uncertain and 7% disagreed. This view was reflected across the three key respondent categories — academics/research institutions, industry, and patient advocacy — each of which showed a majority in favour. The majority of the respondents also expressed that the proposed modernized framework would improve participants’ access to innovative clinical trials and new health technologies, while enabling greater clinical trial efficiency throughout those trials’ life cycles without compromising participant safety.

Additionally, stakeholders emphasized that the proposed initiative could facilitate and attract innovative clinical trials in Canada. They also stated that it could reduce burden to industry, contingent upon regulatory alignment with major regulators, such as the United States Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA), predictable regulations and application requirements, and reasonable review timelines.

Stakeholders also suggested improvements to the proposed clinical trials framework, including increasing harmonization, collaboration, and alignment across global regulators such as the United States (U.S.) and the European Union (EU). While the majority of the respondents favoured international alignment, some also stressed the importance of learning from other regulators’ challenges. In developing the proposed Regulations, the Department reviewed several international regimes and guidelines (such as the ICH E6 guideline) and examined relevant international standards and recommendations. Many aspects of the proposed Regulations would further align with international best practices and recommendations regarding clinical trial oversight. In particular, the proposed provisions regarding conduct, terms and conditions, service providers, description of population to be studied, and a risk-based approach would be comparable to those of Health Canada’s international counterparts, such as the U.S. FDA and the EMA. Additionally, the proposed Regulations would introduce requirements for sponsors to submit information regarding any negative decisions by foreign regulatory authorities, terms and conditions imposed by foreign regulatory authorities, any other measures taken by foreign regulatory authorities regarding a trial to protect the health of trial participants or other persons, and refusals by a foreign REB.

Furthermore, stakeholders emphasized the paramount importance of safety in any innovation and urged the Department to consider the needs and issues of high-risk populations, such as children and individuals living with rare or fatal diseases. Patients and patient groups also suggested increasing patient involvement and engagement when designing studies to ensure the inclusion of patient-relevant outcomes (e.g. by setting research priorities and defining research questions). Health Canada is committed to protecting the health of people living in Canada while facilitating access to innovative clinical trials and therapeutic products. The proposed Regulations would be expected to support advanced study designs for high-risk populations, while mitigating the inherent risks associated with such trials through enhanced oversight tools, including terms and conditions that can be specifically tailored to address the level of risk to participants.

With respect to the proposed approach to facilitating the use of decentralized clinical trials (DCTs) in Canada, most respondents expressed support.^{footnote 50} However, respondents also highlighted the need for additional details and clarity to better define DCTs. Stakeholders from research institutes, academia, and contract research organizations stressed that oversight requirements must be clearly outlined in a guidance document to facilitate implementation and help to ensure compliance. They also requested more information on how Health Canada would ensure safety for trial participants through adverse event reporting. In addition, academic and research institute respondents expressed that the lack of clarity on how remotely generated data would be accepted could lead to sponsors’ hesitancy to adopt novel technologies. Respondents also suggested that Health Canada provide further clarification on technological requirements for supporting DCTs.

Health Canada took the comments into consideration in developing the proposed Regulations. The proposed framework would be expected to better enable DCTs by introducing greater flexibility regarding the types of regulated health professionals who can serve as investigators, and by clarifying the definition of a trial site to include both main and remote locations. Furthermore, sponsors would have the added flexibility of obtaining documented informed consent, instead of written informed consent, which would help to facilitate the recruitment of participants in remote locations. To further address stakeholder concerns, guidance documents would be developed to clarify the technological and safety requirements for DCTs. Additionally, sponsors would be encouraged to request a pre-clinical trial application (CTA) meeting with Health Canada to discuss any questions regarding the acceptability of remotely generated data for future drug submissions.^{footnote 51} With respect to adverse events reporting requirements, Health Canada is not proposing any significant changes. The existing reporting requirements, combined with the additional oversight tools to be introduced by the proposed Regulations, would provide Health Canada with the necessary information to determine if additional measures are required to address unexpected events. For example, Health Canada could potentially address the issue giving rise to the event by imposing terms and conditions to more closely monitor risks once the trial is underway. The proposed Regulations would also enable the Minister to request, on a discretionary basis, case reports and issue-related summary reports relating to adverse drug reactions and serious adverse drug reactions for a drug used in a clinical trial. Additionally, Health Canada already has a risk-based inspection program in place for clinical trials involving drugs. The safety of trial participants remains a top priority for Health Canada, and the proposed new ability to impose terms and conditions would provide the Department with the flexibility to better tailor oversight according to the level of risk.

In addition, from the sponsors’ perspective, respondents supported the proposed regulatory oversight of service providers. They stated that it would help clarify expectations between sponsors and service providers involved in a clinical trial, and increase the quality of outsourced activities, since service providers would be legally accountable for their regulated activities. However, some respondents expressed concerns about the potential increase in the costs of clinical trials, given that service providers would assume more legal risks. These comments were considered during the development of the proposed Regulations. Under the proposed Regulations, Health Canada would have direct oversight of the conduct of service providers, allowing the Department to address instances of non-compliance directly with those responsible, thereby protecting the health of trial participants or other persons. As noted in the “Regulatory cooperation and alignment” section below, this would better align with the approach adopted by the U.S. FDA, despite some differences. Health Canada would include information specifically for service providers when modifying existing guidance to help them understand how to comply with the proposed Regulations. Additionally, although sponsors would retain the ultimate responsibility over clinical trials, service providers would benefit from increased clarity regarding their responsibilities (e.g. reporting and compliance with good clinical practices).

Consultation on the cost-benefit analysis

Health Canada sent a costing survey to over 8 000 stakeholders on January 4, 2022, requesting feedback by March 29, 2022. Stakeholders included businesses, associations, research institutes and academics. Health Canada received 22 responses from stakeholders that conduct clinical trials involving drugs: 13 out of 22 responses were from businesses, 2 responses were from associations, and 7 responses were from research institutes and academics.

Indigenous engagement, consultation and modern treaty obligations

As required by the Cabinet Directive on the Federal Approach to Modern Treaty Implementation, a detailed assessment of modern treaty implications was conducted on the proposed Regulations. The assessment did not identify any modern treaty implications or obligations. In addition, a United Nations Declaration on the Rights of Indigenous Peoples (UN Declaration) consistency analysis was conducted on the proposed Regulations. The assessment did not identify potential intersections between the proposed Regulations and the rights and interests of First Nations, Inuit and Métis, and no inconsistencies with the UN Declaration are apparent.

Instrument choice

Health Canada considered the following regulatory and non-regulatory options.

Option 1: Maintain status quo

Under the status quo, Health Canada would not meet the commitment to establish a modernized regulatory framework for the oversight of clinical trials involving drugs made in the BIA 2019. Regulatory changes are necessary for Health Canada to fully implement the recent amendments to the Act, which enable the direct regulation of the conduct of clinical trials in addition to the sale and importation for sale of drugs for use in clinical trials. In the absence of a modernized clinical trial framework, Health Canada’s current lack of regulatory flexibility would impede innovative types of clinical trials and prevent wider access to participation in trials, and could hinder Canada’s clinical research ecosystem and impact access to innovative drugs.

Option 2: Propose amendments to Part C, Division 5 of the FDR

Modernizing the regulatory framework for drug clinical trials by amending Part C, Division 5 of the FDR would pose challenges for future regulatory proposals that would modernize clinical trial frameworks for other health products. For example, this approach would likely necessitate subsequent and significant amendments to other regulations, such as the NHPR and the Medical Devices Regulations (MDR). It follows that this approach would also pose challenges in aligning clinical trial regulations across different health products, particularly for trials involving combination products or multiple types of health products. Interactions between multiple regulations (i.e. the FDR, the NHPR, and the MDR) during both regulatory development and implementation could duplicate efforts, increase regulatory complexity, and increase the burden on industry and Government.

Option 3: Propose new regulations to replace the current regulatory frameworks for clinical trials involving drugs, including Part C, Division 5 of the FDR and Part 2 of the COVID-19 CT Regulations

Creating new, stand-alone regulations would be the most efficient approach to modernizing the drug clinical trial regulatory framework. This approach would better facilitate the integration of other product lines into these stand-alone regulations through subsequent phases. It aims to build a robust foundation for achieving the ultimate goal of establishing a single, coherent regulatory framework aligned across product lines, while still accounting for their differences.

Regulatory analysis

Benefits and costs

The cost-benefit analysis aims to quantify the benefits and costs of the proposed Regulations.

The incremental costs for industry are estimated at $7.3 million present value (PV) over a 10-year period. It is expected to cost Health Canada $15.7 million PV to review and manage additional clinical trial applications, terms and conditions, additional notifications, case reports and issue-related summary reports, and to undertake additional training and compliance promotion. As a result, the total anticipated costs of the proposed Regulations would be $23 million PV.

The quantitative benefits include an estimated $23.3 million PV in savings for industry, resulting from not having to relabel authorized drugs used in clinical trials, and not having to retain records of non-serious adverse drug reactions for drugs used in clinical trials.

The total anticipated net monetized benefit of the proposal is $313,926 PV over a 10-year period or an annualized average of approximately $44,696.

In addition, the proposed Regulations are anticipated to yield some tangible benefits to the economy through research and development (R&D) investments during clinical trial stages. It is estimated that approximately five new additional clinical trials would be approved each year, increasing investment in Canada’s clinical trial ecosystem; it is estimated that about $3.3 billion PV would be invested as a result of new clinical trials over the 10-year analysis.

The full cost-benefit analysis report is available upon request by email at lrm.consultations-mlr@hc-sc.gc.ca.

Baseline versus regulatory scenario

The baseline reflects current business and review processes and is used as the basis for the analysis when accounting for any incremental costs and benefits.

The existing primary regulatory framework for clinical trials involving drugs is under the FDR. The COVID-19 CT Regulations represent an optional pathway for sponsors of clinical trials involving COVID-19 drugs. Under both frameworks, Health Canada assesses available information about a drug to be used in a clinical trial, ensures that the trial is scientifically sound and is not contrary to the best interests of the trial participant, and requires that an REB reviews and approves the trial before it is initiated at each clinical trial site. While trials are ongoing, Health Canada monitors and assesses the emerging safety data and other information to ensure the health of trial participants or other persons. The Department currently receives, on average, approximately 1 306 clinical trial applications and 2 760 clinical trial application amendments involving drugs each year. Health Canada’s drug submissions performance annual reports show that the 5-year average clinical trial application approval rate is about 93%, as some are either rejected or cancelled by sponsors during the review or at the processing stage.

Regulatory scenario

The proposed Regulations would shift from regulating the importation and sale of a drug that is to be tested in a clinical trial to also regulating the conduct of a clinical trial involving drugs. Under the proposed Regulations, there would be additional costs to industry to comply with terms and conditions; to provide service provider’s contact information; and to submit additional notifications, case reports and issue-related summary reports to the Minister. The costs to Government would include reviewing additional clinical trial applications; issuing terms and conditions; reviewing additional notifications, amendments, case reports and issue-related summary reports; and additional training and compliance promotion.

It is anticipated that industry would benefit from reduced labelling requirements for clinical trials involving the use of authorized drugs and reduced record retention of adverse events for clinical trials that do not require an authorization.

Key assumptions

• The proposed Regulations would come into force 12 months after the day on which they are published in the Canada Gazette, Part II, allowing sufficient time for stakeholders to establish processes and compliance readiness with the proposed Regulations.
• The analytical time frame is 10 periods, each period spanning 12 months, starting when the proposed Regulations are registered (period one).
• No growth is assumed during the analytical period.
• Present values are calculated from period one at a discount rate of 7%.
• All costs and benefits start to be realized in the second period of the analysis, and all monetary values are reported in 2024 Canadian dollars, unless otherwise stated.

Benefits

Labelling exemption for industry

Under the current regulations, labelling requirements can impose unnecessary burdens on sponsors of clinical trials involving drugs that are already authorized under the FDR. The proposed Regulations include a flexible option for the labelling of an authorized drug used in a clinical trial where sponsors would not have to label authorized drugs in accordance with the proposed Regulations, if the label already complies with the FDR and its Canadian authorization. However, the sponsor could still choose to label the authorized drug in accordance with the proposed Regulations. It is assumed that sponsors would opt for an alternative that would reduce their costs. Through the costing survey, sponsors have identified that about 40% of the active clinical trials involved the use of an authorized drug with off-label uses, which translates to about 524 trials per period. Additionally, there are approximately 70 clinical trials that would not require authorization (i.e. exempt from section 3.1 of the Act); this was estimated using a 10-year average (2013 to 2023) of clinical trials registered on ClinicalTrials.gov that use authorized drugs with on-label uses as authorized for phase IV clinical trials.^{footnote 52} Therefore, it is estimated that a total of 594 clinical trials, per period, would no longer need to label an authorized drug in accordance with the proposed Regulations.

Based on a recent cost estimate outlined in the Regulations Amending the Natural Health Products Regulations, the cost to conduct a label change to include certain information on a product label was $6,410.^{footnote 53} Assuming, conservatively, that there is one authorized drug used in a clinical trial, the total estimated savings would be approximately $3.8 million per period, or a total $23.2 million PV over the analytical period.

Records retention of adverse events exemption for industry

Currently, sponsors of trials authorized under the FDR are required to maintain records of all adverse events. Under the proposed Regulations, sponsors would no longer be required to maintain records for non-serious adverse drug reactions if they are able to demonstrate full understanding of the safety profile of their drug. Further, an application to conduct a clinical trial would outline what information would be retained (i.e. at minimum, information on all serious unexpected adverse drug reactions would still be retained), and Health Canada would assess the information provided to determine if the application meets the threshold for selective record retention.

In addition, under the proposed Regulations, sponsors of clinical trials that do not require an authorization (e.g. exempt from section 3.1 of the Act) would only be required to maintain records of expected and unexpected serious adverse drug reactions. It is assumed that sponsors of clinical trials only involving authorized drugs already on the market and used in accordance with their authorization would have a well-characterized safety profile for the drugs as a result of their approved marketing status and history of use, and would, therefore, not need to retain records of non-serious adverse events.

It is estimated that there are approximately 70 new clinical trials that would be exempted from section 3.1 of the Act per year, and would no longer be required to retain these records. These 70 trials are estimated based on a 10-year average (2013 to 2023) of clinical trials registered on ClinicalTrials.gov that use authorized drugs with on-label uses as authorized for phase IV clinical trials.^{footnote 52} For each of these clinical trials, sponsors would be estimated to save approximately $52 per year, assuming organizations would no longer spend one hour of an employee’s time conducting regulatory affairs activities on retaining records and would no longer purchase one gigabyte of digital storage. This represents an estimated savings of $95,204 PV over a 10-year period. This is expected to reduce the administrative burden for industry and is outlined in the “One-for-One rule” section below.

Costs

Increased number of clinical trial applications

It is expected that the proposed framework would encourage more clinical trials in Canada through the flexibilities that would enable the Minister to take risk-based regulatory actions along with other proposed elements. Based on an internal analysis assessing previously withdrawn clinical trial applications, four to six of withdrawn applications could have had a different outcome to move forward in Canada with the use of terms and conditions. It is assumed that, starting in the second period, there would be an average of five new clinical trials per period that are direct results of the proposed Regulations. The analysis does not assume any growth in the number of clinical trial applications nor does it take into account the potential for additional new trials from elements on decentralized clinical trials or international regulatory alignment due to limited evidence.

Costs of additional clinical trials to Government

Health Canada would require additional resources to review applications, communicate with the sponsor, and authorize the five additional clinical trials. It costs the Department approximately $5,820 to process and review an application. This would amount to approximately $28,923 per period, beginning in period two. The Department estimates that these costs would total $176,110 PV.

Costs of additional clinical trial amendments to Government

Having more clinical trial applications would also mean an increase in the number of clinical trial application amendments. Data from the drug submission performance reports^{footnote 54} indicated the ratio of amendments to clinical trial applications ranges from 1.3:1 for pharmaceutical to 3:1 for biologics with an average of 2:1. It is anticipated that the proposed Regulations would allow for the sponsors of innovative trials such as master protocol trials to amend the protocol for a sub-study instead of submitting a new application. For these reasons, the higher ratio (3:1) is used as a proxy to calculate the cost of reviewing the new amendments. This translates to an average of 15 additional amendments per period being submitted to Health Canada. It costs the Department about $2,890 to screen, review, track, and monitor a submission and to communicate with the sponsor about it. It is estimated that, starting in the second period, the cost would be $43,842 per period. The estimated total cost to process and review clinical trial application amendments is $266,952 PV.

Costs of compliance and enforcement to Government for additional clinical trials

The increase in clinical trial applications would represent an additional workload for Health Canada to maintain the same level of enforcement, suggesting the number of clinical trial inspections would need to grow at the same rate as the increase in clinical trial applications. Therefore, to maintain the same level of enforcement, Health Canada would carry costs of $13,488 per period or an estimated cost of $82,129 PV.

Application requirements

In addition to existing application requirements under the FDR, the proposal would also require sponsors to submit the name and contact information of their trial’s service providers when submitting their clinical trial application to Health Canada, if the service provider is known at the time of application. If the service provider is not known at the time of application, the sponsor would be required to notify Health Canada of that service provider once it is known.

Costs of application requirements to industry

It is estimated that around 70% of clinical trial applicants use a service provider during their clinical trial, based on responses to the costing survey. It is assumed that sponsors would already have the contact information of their service provider readily available, resulting in a minimal cost to include this information in their application. It is assumed that searching and writing the contact information on an application would take approximately five minutes of a regulatory affairs officer’s time. It is assumed the average hourly wage of a regulatory affairs officer, including overhead, is $51 resulting in a reporting cost of approximately $4 per application.

It is estimated that of the 1 311 clinical trials per period, there would be approximately 918 that would use a service provider. As a conservative assumption, Health Canada assumes that all applicants would know the contact information of one of their service providers at the time of application. Therefore, the annual cost for sponsors to submit service provider contact information is estimated to be around $3,920 per year or an estimated total cost of $23,869 PV over the analytical period. The proposed provision would impose an administrative burden onto industry, which is outlined in the “One-for-One rule” section below.

Obtaining an authorization

Currently, authorization permits the sale and importation of a drug to be tested in a clinical trial by default within 30 days after the Minister receives the application, unless the Minister notifies the sponsor otherwise. Under the proposed Regulations, the Minister would issue a contingent authorization within 7 days of the sponsor submitting a complete application. As explained under the “Description” section above, the Minister could also, within 30 days after the sponsor submitted the application, send a notice to the sponsor indicating that more time is needed to review the application for more complex clinical trials. If such a notice is sent to the sponsor, the initial 30-day review period would be extended to 60 days in total.

Cost of reviewing complex clinical trial applications to Government

The proposed Regulations would allow Health Canada to extend the review period to 60 days for trial applications considered as complex or if further assessment is needed to protect a particular vulnerability of the study population or any part of it. Currently, the Department receives approximately 1 311 clinical trial applications per period. Internal analysis indicated about 20–30% of these are considered as complex trials. This translates to an average of 320 complex trial applications Health Canada has to review each year. The incremental cost for Health Canada to review these complex trial applications is estimated to be about $1,400 per application. Therefore, the annual cost to the Department is estimated to be $445,749 or a total PV of $2,714,168.

Terms and conditions

Under the proposed Regulations, the Minister would have the ability on a case-by-case basis to impose and amend terms and conditions on an authorization. When imposing terms and conditions, the Minister would have to consider whether compliance with the proposed terms and conditions could contribute to meeting the intended objectives and whether there is less burdensome means of achieving those objectives. Examples of some of the terms and conditions that could be imposed on an authorization include, but are not limited to, increasing safety and efficacy reporting, monitoring specific populations, providing additional information on how to characterize and mitigate identified risks, and submitting information that was not available at the time of the application.

Cost of terms and conditions to industry

Currently, under the COVID-19 CT Regulations, the Minister can impose terms and conditions on authorizations of clinical trials involving COVID-19 drugs. Some of the terms and conditions imposed on these authorizations remained in place for several months, while others remained in place for the entire length of the trial. With the proposed Regulations, it is difficult to estimate the exact time frame for each term and condition that would be imposed on clinical trial authorizations; however, similar to the COVID-19 CT Regulations, it is expected that most would last for the duration of the clinical trial.

According to a 2019 study, the median duration of a clinical trial was found to be 5.9 to 7.2 years, and the median duration of oncology clinical trials was around 13.1 years.^{footnote 55} More recent research from Deloitte found that the average clinical trial duration in 2022 increased to 7.1 years compared to 6.15 years in 2014.^{footnote 56} For the purpose of the cost-benefit analysis, this latest finding of 7.1 years is used as the average duration of a clinical trial.

Internal analysis suggests that approximately 15% of clinical trial applications would have reporting terms and conditions imposed annually resulting in 196 terms and conditions on 1 306 clinical trials. Further, the proposed Regulations would allow for five additional trials to be authorized with a term and condition, resulting in the Minister imposing an estimated 201 terms and conditions on the approximate 1 311 clinical trial applications each period. Based on the costing survey, the cost to fulfill a reporting term and condition ranged from $700 to $9,000 with an average of $4,311, distributed evenly over the assumed seven years. Therefore, the estimated cost for industry in the second period is $123,798 and is expected to increase each period to an estimated $866,586 in the eighth period and would remain stable for the rest of the analytical period. The anticipated total is $3.2 million PV over the analytical period.

Cost of terms and conditions to Government

The average cost for Health Canada to impose terms and conditions per authorization is estimated to be $2,400, including costs associated with drafting, reviewing, and issuing those terms and conditions. The total cost to Health Canada to impose the estimated 201 terms and conditions per year is estimated to be $483,440 annually. Further to these costs, Health Canada would require an analytics tool to properly monitor and track terms and conditions as well as a dedicated staff to develop and perform tasks. Additional fixed costs include licences to use the tool and one equivalent full-time employee; this amounts to approximately $133,657 per year beginning in the second period. The total cost of imposing terms and conditions is estimated to be $3.8 million PV over the analytical period.

Costs of compliance and enforcement to Government for terms and conditions

The introduction of terms and conditions would also impact inspections of clinical trials that have a term and condition on their authorization. The length of an inspection of a clinical trial with a term and condition is estimated to increase by approximately two days due to additional time spent on planning, preparation, on-site verification, and reporting activities. The additional length of an inspection for a single clinical trial with a term and condition is estimated to cost Health Canada $1,250. Assuming that 15% of clinical trials would have a term and condition on their authorization, the proposal would result in an estimated cost of $31,588 PV over a 10-year period.

Every term and condition would also need to be reviewed and placed within the current risk-based approach to clinical trial inspections. The cost of analyzing, reviewing, and categorizing all terms and conditions based on their risk is estimated to cost Health Canada approximately $50,000 per period. This would result in an estimated cost of $307,984 PV over the analytical period.

Notifications

The proposal would introduce new notification requirements, as outlined in the “Description” section above, for sponsors who must notify the Minister within 15 calendar days of becoming aware of

• any negative decision from a foreign regulatory authority, as well as any refusal by a foreign REB;
• an REB’s refusal to approve the protocol of a trial; or
• an REB’s withdrawal of its approval of the protocol or informed consent form statement for a trial site, unless it is a national REB.

A sponsor must also provide any change to the name and contact information of an REB that approved the protocol and the informed consent form, except where the REB is a national REB.

Cost of notifications to industry

On average, Health Canada receives about 8 000 notifications per year. The Department expects to receive an increase of approximately 15% or 1 234 notifications annually under the proposed Regulations. Responses to the costing survey for filing an administrative notification to submit foreign decision information to Health Canada ranged from $50 to $1,395; the average used in this analysis is $523 per notification. Therefore, it is anticipated to cost $645,742 annually, or a total of $3.9 million (PV) over the analytical period. The proposed provision would impose an administrative burden onto industry, which is outlined in the “One-for-one rule” section below.

Cost of notifications to Government

Health Canada would need to screen, review, track, monitor, and communicate with sponsors on these notifications, which is estimated to cost $515 per notification. With the expectation that there would be approximately 1 234 additional notifications per period, the annual expected cost to the Department is $635,762, or a total of $3.9 million (PV) over the analytical period.

Case reports and issue-related summary reports

As noted in the “Description” section, under the proposed Regulations, the Minister would be able to request case reports and issue-related summary reports relating to adverse drug reactions and serious adverse drug reactions for the drugs used in a clinical trial.

Cost of case reports and issue-related summary reports to industry

Health Canada estimates that there could be between 7 and 15 reports, collectively, requested per period, an average of 11 reports annually across industry. The cost for industry to provide a case report or an issue-related summary report is estimated to be $1,350 per report, according to responses to the costing survey. In total, it is estimated to cost $14,900 per year, or $90,487 (PV) over the analytical period. Providing case reports and issue-related summary reports would impose an administrative burden on authorization holders, and its calculation is outlined in the “One-for-one rule” section below.

Cost of case reports and issue-related summary reports to Government

It is assumed that the costs to review, follow-up, screen, and process these new reports would be about $500 per report; therefore, it is estimated to cost $5,556 annually to review, screen, and process 11 case reports and issue-related summary reports, resulting in a cost of $33,828 (PV) over the analytical period.

Training, implementation, and compliance promotion

Costs of implementation to Government

Health Canada would incur costs to prepare for the implementation of the proposed Regulations, including developing new standards of operation and training staff. It is expected that the cost would be incurred in the first two periods of the analysis at an estimated $1 million per period.

Costs of compliance promotion to Government

Health Canada is also expected to incur implementation costs within the first two periods after the proposed Regulations are registered. These costs would include training inspectors, assistance to transition active clinical trials, conduct of compliance promotions and updating procedures. These activities are expected to cost Health Canada approximately $1.7 million in the first period and $1.1 million in the second period.

The expected total cost to develop new standards of operation, training of staff (inspectors), assistance to transition active clinical trials, conduct of compliance promotions and updating procedures is $4.5 million (PV) over the analytical period.

Qualitative impacts

The full cost-benefit analysis report includes a more comprehensive list of qualitative impacts of the proposal.

Overall impacts on the number of clinical trials

Impacts on industry

The process of developing a drug for a new treatment or finding a cure for a disease can be lengthy and costly for industry. Despite high costs and uncertainties, there are financial benefits for industry to take these risks. A recent report showed that the average return on investment in pharmaceutical R&D for the 20 largest pharmaceutical companies in the world was 4.1% in 2023.^{footnote 57} Worldwide, it is anticipated that prescription drug revenue will grow to US$1.7 trillion by 2030 from US$1.1 trillion in 2023.^{footnote 58} Moreover, sponsors could benefit from market exclusivity, which could be the key incentive for innovators as well. However, it is not possible to estimate the benefit from the return on investment to industry generated from the proposal. Another added benefit for industry is that they would have the opportunity to advance their knowledge of diseases and treatments for the Canadian population.

Impacts on Government

In 2022, over 9 100 new medicines were undergoing clinical evaluation globally — a sharp increase of almost 60% from 2018.^{footnote 59} In the same year, 4% of global clinical trials occurred in Canada, and Canada was fourth globally in the number of clinical trial sites.^{footnote 60} There is a continuing need to develop new and innovative treatments to better address emerging and existing pathogens and diseases such as cancer, Alzheimer’s disease, and diabetes. The proposed Regulations are expected to support and encourage the attraction of additional innovative clinical trials in Canada. The anticipated additional clinical trials would not only continue to have a positive economic impact, but they would be fulfilling Health Canada’s commitment to strengthen the infrastructure of clinical trials in the country to make Canada a more attractive destination for biomanufacturing and life sciences ecosystem companies, and to protect Canadians against future health emergencies.^{footnote 61} Furthermore, the data collected from clinical trials could be used to support the approval of drugs for Canadians.

Impacts on Canadians

Clinical trials not only allow researchers to discover new insights into diseases and treatments, but they offer increased accessibility for patients with limited treatment options. Having more clinical trials conducted in Canada could mean earlier access to new drug therapies for Canadians. The insights gained from these trials are specific to the Canadian population. Furthermore, having more clinical trials in Canada would provide Canadians with more opportunities for medical care and close monitoring, improving health outcomes for Canadian participants.

Terms and conditions

Impacts on industry

A study published in the Journal of the American Medical Association in 2016 that examined 640 phase III trials found that 17% of the trials failed due to safety concerns.^{footnote 62} It has been suggested that safety concerns are often found with larger populations in phase III studies.^{footnote 63} Terms and conditions could allow the Minister to authorize trials that might not otherwise meet the authorization criteria and would enable targeted oversight throughout the life cycle of a trial. Additionally, imposing terms and conditions would help to address uncertainties and mitigate risks related to the conduct of the trial. This would potentially allow for industry to conduct trials that otherwise may have been suspended or rejected at the application stage.

Impacts on Government

The ability to impose terms and conditions would allow for greater flexibility in Health Canada’s role as a regulator, as the level of oversight would be tailored to the level of risk associated with the clinical trial. Terms and conditions would also enable targeted oversight throughout the life cycle of the trial.

Impacts on Canadians

The use of terms and conditions is expected to mitigate risks and uncertainties associated with clinical trials, which, in turn, would make clinical trials safer for Canadian participants. Terms and conditions could facilitate the conduct of clinical trials that would enable more innovative designs for clinical trials and increase treatment options for Canadians.

Research ethics board

Impacts on industry

The proposed Regulations would permit the use of a national REB, which is expected to reduce the burden on industry by not having to seek separate approval from an REB for each individual trial site. Depending on how many trial sites, the potential savings could be significant, as they would not only reduce the burden, but they could also reduce the delays in starting a clinical trial. A single review process is likely to be more efficient and faster than a multiple approvals process.

Impacts on Government

Enabling the use of a national structure for REBs would standardize ethics review, which would help ensure consistency in protocols. This would reduce the burden on Government by reducing duplicative REB reviews across multiple sites.

Oversight over service providers

Impacts on industry

The proposed Regulations would require service providers to comply with specific obligations, as applicable to the activities they are conducting, including good clinical practices, labelling, records, and reporting of adverse drug reactions. While the proposed Regulations would add regulatory requirements for service providers, imposing specific obligations on service providers would not change the sponsor-service provider contractual relationship, and therefore there would be no impact on service providers or sponsors.

Impacts on Government

Service providers would be able to better understand their specific obligations, as clarified through the proposed Regulations, and there would be some gains in efficiency for Health Canada by working directly with service providers instead of relying on sponsors to relay requests for corrective actions to service providers.

Decentralized clinical trials

Impacts on industry

Decentralized trials could allow sponsors to recruit and screen a wide pool of potential participants online, allowing sponsors to ensure the most appropriate participants are enrolled.^{footnote 64} According to one study, around 19% of phase II and III trials registered as closed in 2011 were terminated due to a lack of participants.^{footnote 65} Decentralized trials have been found to attract more participants while also having higher retention rates for participants.^{footnote 66} Therefore, decentralized trials could allow for clinical trials to continue that would have otherwise closed due to a lack of participants.

Further, a study examining the possible financial returns of phase II and III decentralized trials found a substantial net financial return on decentralized trial investments due to the shorter trial duration per phase, lower mean trial costs, and fewer substantive protocol amendments as a result of the ability to attract and retain more participants.^{footnote 67} Although Health Canada does not know how many sponsors would decide to conduct decentralized trials, sponsors could potentially have a sevenfold return on investment per drug from conducting decentralized trials for both phases II and III.^{footnote 67} Integrating decentralized elements into clinical trials can enhance efficiency and inclusivity, ultimately accelerate drug development and research, and bring more new therapies to the market.^{footnote 68}

Impacts on Canadians

Decentralized trials improve health equity, as it allows Canadians living in rural areas more opportunities to participate in clinical trials, allowing for greater diversity in participation that could improve the generalizability of results.^{footnote 69} Individuals in rural areas would be more likely to gain access to potential treatments for their health conditions, including treatments for participants with rare diseases and treatments that are not yet available to the public.

Decentralized trials have been found to increase satisfaction for participants in comparison to conventional site models.^{footnote 70} They may allow participants to participate in trials from the comfort of their home and continue their normal daily routine, potentially improving participant adherence to the protocol and increasing overall retention rates.^{footnote 71}

Overall, the proposed Regulations remove the challenges for sponsors to conduct decentralized trials, leading to an increase in diverse study populations, an increase in participant satisfaction, improved participant adherence to the study protocol, increased retention rates, and a reduction in travel time and costs.

Benefits to the economy

Data from the United Kingdom demonstrates that investments in clinical trials not only benefit patients but also have significant economic benefits. Their data indicated that for every £1 the Government spends on R&D, via the National Institute for Health Research, they generate over £19 in economic returns.^{footnote 72} In 2021, R&D in the pharmaceutical sector accounted for 0.7% of Canada’s gross domestic product, while contributing $16 billion to the economy.^{footnote 73} It is expected that the country’s economy would further benefit from having new R&D investments as a result of this proposal. In this analysis, the benefit to the economy is the amount of new investment sponsors would be spending in the clinical testing stage, which is solely looking at phases I to III of the drug development stages. The estimates below only focus on the direct spending on incremental clinical trials in each phase using data from recent studies. Costing data are scaled to Canada’s average number of clinical trial participants. Following are the outlines of each variable in the calculation:

• Weighted average cost (xÌ„): A study (Sertkaya et al.)^{footnote 74} estimated the mean cost of developing a drug is US$879.3 million or equivalent to approximately $1.4 billion Canadian (in 2024 dollars). This includes the cost of failures and capital cost, which accounts for the duration of the development process and the opportunity cost of capital. The study also indicated that clinical stages (phases I to III) accounted for about 68% of total mean costs. Hence, the estimated cost of developing a drug during the clinical stages is approximately $981 million ($1.4 billion x 68%). This cost is further broken down to determine the weighted average of phases I to III, as the cost to conduct the clinical trial increases as a clinical trial progresses to the next phase. The proportion of costs for each phase is 6%, 20% and 74%, respectively. It is estimated that the weighted average cost is $327 million.
• Scaling factor (SF): Sertkaya et al. used a per-patient cost approach; however, the data used in this study were data from the United States. In this study, the average number of patients in the clinical stage was 916. This is considerably different from a Canadian study in 2023, where it was found that the median number of patients per trial in Canada between 2019 and 2021 was 305.^{footnote 75} Therefore, the clinical stage costs obtained from Sertkaya et al. study are adjusted to near one third (305/916).

Anticipated benefits to the Canadian economy:

• Impacts on economy = xÌ„ x SF x 5 additional clinical trials = $544,456,811

The increased annual R&D investment spending in the clinical trial ecosystem from five additional trials in a given year is estimated to be approximately $544,456,881. The benefits to the Canadian economy, as estimated here, are the direct R&D investment in phases I to III. There are other impacts that Health Canada has not taken into account due to limited data, such as preclinical investment, impacts on jobs and local economies, and the potential reduction in long-term health care costs as a result of new drugs or treatments.

Cost-benefit statement

• Number of periods: 10 periods (2027–2036)
• Price year: 2024
• Present value base year: Period 1 (2027)
• Discount rate: 7%

Table 1: Monetized benefits
Figures may not add up to totals due to rounding.

Impacted stakeholder	Description of benefit	Period 1	Period 2	Period 3	Final Period	Total (PV)	Annualized value
Industry	Labelling	$0	$3,810,262	$3,810,262	$3,810,262	$23,200,694	$3,303,257
	Records retention	$0	$3,640	$7,280	$25,480	$95,204	$13,555
All stakeholders	Total benefits	$0	$3,813,902	$3,817,542	$3,835,742	$23,295,898	$3,316,812

Table 2: Monetized costs

Impacted stakeholder	Description of cost	Period 1	Period 2	Period 3	Final Period	Total (PV)	Annualized value
Industry	Application requirements	$0	$3,920	$3,920	$3,920	$23,869	$3,398
	Terms and conditions	$0	$123,798	$247,596	$866,586	$3,237,927	$461,008
	Notifications	$0	$645,742	$645,742	$645,742	$3,931,925	$559,818
	Case/Issue-related summary reports	$0	$14,861	$14,861	$14,861	$90,487	$12,883
Government	New clinical trial applications	$0	$28,923	$28,923	$28,923	$176,110	$25,074
	New clinical trial application amendments	$0	$43,842	$43,842	$43,842	$266,952	$38,008
	Compliance and enforcement for new clinical trial applications	$0	$13,488	$13,488	$13,488	$82,129	$11,693
	Obtaining of authorizations	$0	$445,749	$445,749	$445,749	$2,714,168	$386,436
	Terms and conditions	$0	$617,097	$617,097	$617,097	$3,757,506	$534,984
	Compliance and enforcement for terms and conditions	$0	$55,768	$55,768	$55,768	$339,572	$48,347
	Notifications	$0	$635,762	$635,762	$635,762	$3,871,157	$551,166
	Case/Issue-related summary reports	$0	$5,556	$5,556	$5,556	$33,828	$4,816
	Training, implementation, and compliance promotion	$2,769,644	$2,138,548	$0	$0	$4,456,343	$634,483
All stakeholders	Total costs	$2,769,644	$4,773,053	$2,758,303	$3,377,293	$22,981,972	$3,272,116

Table 3: Summary of monetized costs and benefits

Impacts	Period 1	Period 2	Period 3	Final Period	Total (PV)	Annualized value
Total benefits	$0	$3,813,902	$3,817,542	$3,835,742	$23,295,898	$3,316,812
Total costs	$2,769,644	$4,773,053	$2,758,303	$3,377,293	$22,981,972	$3,272,116
NET IMPACT	−$2,769,644	−$959,151	$1,059,239	$458,449	$313,926	$44,696

Qualitative impacts

In terms of qualitative benefits:

• Aside from the estimated five additional clinical trials, it is expected that there would be even more trials conducted as a result of decentralized clinical trials and international regulatory alignment.
• More clinical research would provide more opportunities for Canadians to gain access to potential treatments for their health conditions.
• Terms and conditions could allow the Minister to authorize trials that might not otherwise meet the authorization criteria and would enable targeted oversight throughout the life cycle of a trial.
• The proposed Regulations would provide service providers with a better understanding of specific obligations, which would likely lead to greater compliance.
• Sponsors of clinical trials only involving authorized drugs already on the market and used in accordance with their authorization would no longer be required to retain records of non-serious adverse drug reactions. This could lead to Health Canada having fewer records to review during a clinical trial inspection.
• More decentralized trials could lead to an increase in more diverse participants, as well as increased participant satisfaction and retention rates. Decentralized trials could also provide a greater return on investment for sponsors.

In terms of qualitative costs:

• There could be upfront costs to industry for setting up an electronic platform and developing security measures to protect participants’ information for sponsors with regard to the flexibility of documented informed consent; however, this remains as an option for sponsors.

Small business lens

According to the Policy on Limiting Regulatory Burden on Business of the Treasury Board Secretariat, a small business is defined as a company with fewer than 100 employees or less than $5 million in annual gross revenue.^{footnote 76} The small business lens would apply to some stakeholders who are conducting clinical trials involving drugs for human use. Internal data suggests that approximately 4% (a total of four) of all impacted stakeholders would meet the definition of small business in Canada. Health Canada’s internal small business database was used to define what stakeholders fit the criteria of small business.

Although the proposed Regulations do not contain any specific exemptions or processes for small businesses, outside of what already exists in regulation and in practice, the Department considered the needs of small business when developing the proposal. For example, the proposed Regulations would require the Minister to consider whether the proposed terms and conditions are feasible and whether the sponsor could reasonably achieve the objectives of the terms and conditions. The Minister would also consider whether there are less burdensome means than imposing terms and conditions that would achieve the objectives.

Small business lens summary

• Number of small businesses impacted: 4
• Number of years: 10
• Price Year: 2024
• Present value base year: 2027
• Discount rate: 7%

Table 4: Benefits

Administrative or compliance	Description of benefit	Present value	Annualized value
Administrative	Record retention for non-serious adverse events exemption	$3,967	$565
Compliance	Labelling exemption	$966,721	$137,639
Total	Total benefits	$970,688	$138,204

Table 5: Costs

Administrative or compliance	Description of cost	Present value	Annualized value
Administrative	Notifications	$163,833	$23,326
	Case reports and issue-related summary reports	$3,770	$537
	Application requirements	$994	$141
Compliance	Terms and conditions	$134,934	$19,212
Total	Total costs	$303,530	$43,216

Table 6: Net impacts

Amount	Present value	Annualized value
Net impact on all impacted small businesses [Total benefits minus total costs]	$667,157	$94,988
Average net impact on each impacted small business [Net impact divided by number of impacted small businesses]	$166,789	$23,747

One-for-one rule

The one-for-one rule applies since there is an incremental increase in administrative burden on business. The proposal is considered burden IN under the rule, and a new regulatory title (title in) is introduced.

As per the Red Tape Reduction Regulations, the assessment of administrative impacts was conducted for a period of ten years commencing from registration. All values listed in this section are presented in 2012 dollars, discounted to 2012 at a rate of 7%.

Notifications

The proposed Regulations would require authorization holders to send additional notifications each year to the Minister. These activities require authorization holders to spend, on average, an estimated 12 hours for each notification that they send to Health Canada at a rate of $34.22 (including overhead, in 2012 dollars),^{footnote 77} and it is assumed that there would be approximately 1 234 additional notifications per year.

Case reports and issue-related summary reports

Further, under the proposed Regulations, authorization holders would now be required to provide case reports and issue-related summary reports relating to adverse drug reactions and serious adverse drug reactions at the request of the Minister. On average, an authorization holder spends an estimated 30 hours per case report or issue-related summary report at a rate of $34.22 (including overhead, in 2012 dollars), and it is assumed that there would be approximately 11 reports per year.

Application requirements

Under the proposed Regulations, sponsors would be required to submit the name and contact information of the trial’s service providers when submitting their clinical trial application to Health Canada, if the service provider is known at the time of application. Sponsors would spend an estimated 0.8 hours per year at a rate of $38.57 (including overhead, in 2012 dollars).

Record retention for non-serious adverse drug reactions

Under the proposed Regulations, clinical trials for which the sponsor is exempt from section 3.1 of the Act would no longer have to retain records of non-serious adverse events. It is estimated that 70 new clinical trials would be exempted from section 3.1 of the Act each year and, therefore, no longer be required to retain records. Sponsors would no longer spend an estimated 1 hour per year to retain records of non-serious adverse events at a rate of $39.33 (including overhead, in 2012 dollars).

Research ethics board

While there would be an administrative burden reduction associated with the national REB, Health Canada does not regulate how sponsors would seek approvals from REBs. This administrative burden cost is outside of the control of Health Canada and independent of regulatory design. Regarding the process of submitting evidence of an REB’s approval to Health Canada, while the proposed regulatory change has the potential to reduce the number of REB approvals required and lower costs to stakeholders, information submitted to Health Canada about clinical trial sites would remain the same and thus no administrative burden is removed or added.

Summary

The annualized anticipated increase in the administrative burden on business is estimated at $154,219 or $1,606 per business.

The objective of imposing terms and conditions would be to manage the uncertainties and mitigate risks regarding the conduct of clinical trials. This requirement would be directly related to ensuring the health of trial participants. Therefore, the costs of fulfilling terms and conditions are not considered an administrative burden as defined by the Red Tape Reduction Act, as their primary purpose is not for demonstrating compliance. Further, exempting sponsors from labelling requirements for those conducting clinical trials that use authorized drugs would be compliance savings as labelling is considered a compliance activity under the Red Tape Reduction Act. This reduction would significantly reduce the compliance burden on industry.

Regulatory cooperation and alignment

International obligations

In developing the proposed regulatory framework, Health Canada reviewed several international regimes and models, including the clinical trial regulatory frameworks in the United States and the EU. Health Canada has also examined relevant international standards and recommendations made through multilateral organizations or working groups including the Organisation for Economic Co-operation and Development and the ICH.

The analysis revealed that a single standard does not exist for clinical trial regulations across jurisdictions. Differences persist due to the unique regulatory landscape of each jurisdiction. Alignment, however, is sought through various jurisdictions’ adoption of recognized international standards (e.g. various ICH standards for drug clinical trials), which enables key regulators to more easily collaborate and work together in the areas of compliance and enforcement. The ICH E6 guideline, which focuses on the conduct of clinical trials, provides principles that all ICH member countries, including Canada, are expected to implement. Health Canada’s involvement in the 2025 update of the guideline has helped to ensure that the proposed Regulations would be aligned with the latest international consensus.

Given the global nature of health care and technological innovation, Canada is not alone in recognizing a need to modernize clinical trial oversight. As a country with a relatively small patient population, Canada strives to harmonize internationally with other trusted regulators, to the extent possible under existing legal frameworks, to ensure that patient access to safe and effective drugs would not be impeded by regulatory barriers. While different international approaches to authorizing and regulating clinical trials exist, other international regulators are increasingly recognizing the need to adopt a more internationally aligned, flexible, and risk-based approach that could better accommodate innovative clinical trials and health products. For example, in March 2019, the U.S. FDA Commissioner released a statement^{footnote 78} on new strategies to modernize clinical trials. The statement noted that the U.S. FDA “has worked closely with stakeholders, including the Clinical Trial Transformation initiative, to identify innovative clinical trial designs, evaluate the role of decentralized clinical trials and mobile technologies, and help validate novel endpoints that can enable clinical trials to generate reliable evidence needed to assess product safety and efficacy more efficiently.” The statement also points to several new guidance documents for industry that were released to help stakeholders achieve these goals while navigating the regulatory landscape. Similarly, in March 2020, the EMA published a forward-looking strategic document, the EMA Regulatory Science to 2025: Strategic Reflection (PDF), which, among other topics, explores different ways to foster innovation in clinical trials and to develop a regulatory framework for emerging clinical data generation. Additionally, the EMA implemented new clinical trial regulations in January 2022 that provide a risk-based approach. Swissmedic, the Swiss Agency for Therapeutic Products, published a position paper in September 2021, updated in December 2022.^{footnote 79} Medicines and Healthcare products Regulatory Agency (MHRA) is also aiming to modernize the United Kingdom’s clinical trial regulations following public consultation in 2023.^{footnote 80}

Many aspects of the proposed Regulations would further be aligned with international best practices and recommendations regarding clinical trial oversight, potentially reducing regulatory differences with other jurisdictions. In particular, the proposed provisions regarding conduct, terms and conditions, service providers, description of population to be studied in protocols, and a risk-based approach would be comparable to those of Health Canada’s international counterparts, such as the U.S. FDA and EMA. For example, regulating conduct in addition to the sale and importation for sale of drugs for use in clinical trials would align with some international regulators such as the EMA and Swissmedic. In addition, the proposed Regulations’ risk-based oversight would further align Canada with the EMA. Comparable to the proposal’s oversight over service providers, U.S. FDA regulations allow for a formal transfer of responsibility from the sponsor to the service provider (e.g. a contract research organization), which allows the U.S. FDA to directly regulate service providers’ actions as they relate to a clinical trial. While the proposal would not allow for such a formal transfer of responsibilities in Canada, the proposed regulatory framework would provide Health Canada with oversight over service providers’ actions as they relate to the conduct of a clinical trial.

National obligations

In Canada, provinces and territories are responsible for health care delivery, including licensing health care providers and overseeing the delivery of health care services, which are often involved in the conduct of clinical trials. Provinces and territories may also establish requirements related to REBs and the collection and privacy of clinical data. The proposed Regulations are designed to complement these provincial and territorial responsibilities rather than overlap with them.

Effects on the environment

In accordance with the Cabinet Directive on Strategic Environmental and Economic Assessment, a Climate, Nature and Economy Lens analysis was conducted, and it was concluded that there would be no expected important environmental effects, either positive or negative; therefore, a detailed environmental assessment is not required, and an economic assessment was not required as the proposal is subject to the Cabinet Directive on Regulation.

Gender-based analysis plus

The proposed framework aims to reduce barriers to access and participation in clinical trials for individuals with various sex, gender, and other identity characteristics. This would be accomplished by leveraging technology and enabling decentralized clinical trials, permitting documented rather than written informed consent, and broadening the scope of persons who may be an investigator. These flexibilities may allow for greater participation in clinical trials by certain individuals, such as individuals in rural areas, individuals with rare diseases, and individuals with different socio-economic statuses. Other elements of the proposal, such as safety monitoring and terms and conditions that require regulated parties to continue to generate, analyze, and/or submit data, may also help to collect and improve data broken down by demographic factors. This could ultimately lead to more equitable health outcomes. In turn, such data may allow for enhanced monitoring and consideration for how clinical trials are designed to accommodate various under-represented populations.

Further, the proposed Regulations would clarify that a sponsor, through their good clinical practices obligations, must ensure that the population to be studied in the clinical trial is consistent with the study’s objectives. This clarification would ensure that sponsors carefully define the clinical trial population to be recruited depending on the stage of drug development, the objective of the trial and the epidemiology of the disease to be studied. Therefore, populations to be recruited could vary in scope. A narrower scope may be chosen to reduce risks to participants if there are known adverse outcomes for certain populations, or to maximize the sensitivity of the study to detect certain effects in certain populations. In contrast, a broader scope is crucial when looking for dosing, safety, and efficacy data. Trial participants should be representative of those who will use the health product. Drugs can impact populations with varying demographic factors differently, and populations underrepresented in trials tend to have increased adverse events and decreased efficacy.

Implementation, compliance and enforcement, and service standards

Implementation

The proposed Regulations would come into force 12 months following their publication in the Canada Gazette, Part II. This delay is intended to provide industry with sufficient time to adapt to the new regulatory requirements. It also accounts for Health Canada’s operational readiness, including stakeholder outreach and internal process implementation.

Health Canada would develop guidance documents to provide assistance to the sponsors and persons involved in the conduct of clinical trials of drugs on how to comply with the proposed Regulations. The documents would also assist sponsors seeking authorization to import or sell a drug for a clinical trial in Canada. In addition, communications would clarify the transition process for applications under review and ongoing trials by the time the proposed Regulations come into force.

Health Canada is developing several new guidance documents to support implementation of the proposed Regulations. These guidance documents cover various topics, including suggested gender-based analysis plus considerations, decentralized trials, remote activities, clinical trial sites, the submission of a complete clinical trial application, and adherence to regulatory timelines.

Further, the Department would modify several existing guidance documents to support the implementation of the proposed Regulations.

The draft versions of these new and revised guidance documents are available on Health Canada’s website for public consultation, at the same time as the proposed Regulations are prepublished in the Canada Gazette, Part I. Health Canada intends to publish final versions of both new and revised guidance documents on its website when the proposed Regulations are published in the Canada Gazette, Part II.

Compliance and enforcement

Health Canada would carry out compliance and enforcement activities for the proposed Regulations using a risk-based approach. This approach would align with existing departmental policies, including compliance promotion and monitoring and enforcement activities in accordance with the Department’s Compliance and enforcement policy for health products (POL-0001). Additionally, to modernize Health Canada’s risk-based approach to the oversight of clinical trials, the proposed Regulations would provide new compliance and enforcement tools and authorities. A key element would be expanding oversight to include service providers to whom clinical trial activities are outsourced. This would allow Health Canada to take action with the party directly responsible when an issue of non-compliance arises. These modernization efforts would support Health Canada’s ongoing commitment to protecting the safety and well-being of trial participants, helping to safeguard the integrity of trial data, and strengthening public confidence in trial outcomes, while ensuring that Canada remains globally competitive in the sector.

Compliance promotion

Health Canada would strengthen compliance promotion activities, such as updating/developing and publishing guidance and training materials, to improve overall compliance with regulatory requirements. This would include guidance and training materials on records retention and good clinical practices.

Compliance monitoring

Compliance monitoring would include international collaboration and coordination, routine inspections, and other compliance verification activities — such as inspections triggered by suspected non-compliance related to data integrity or adherence to good clinical practices. In selecting clinical trial sites for inspection, Health Canada would apply a risk-based approach to optimize compliance and enforcement actions, aiming to protect trial participants and increase confidence in the reliability of trial results.

Enforcement

In terms of enforcement actions, the proposed Regulations would enable the Minister to suspend clinical trial authorizations in whole or in part. This would allow Health Canada to take more targeted action to suspend the conduct of only the non-compliant parts of a trial, while enabling the compliant parts to continue. Similarly, to address significant non-compliance of trials that do not require prior authorization under section 3.1 of the Act, the proposed Regulations would enable the Minister to direct a sponsor to cease conducting such a trial, in whole or in part, if required. While sponsors of these trials would be exempt from requiring an authorization, they would still be required to comply with the proposed Regulations. Health Canada would conduct the appropriate oversight of these trials to verify compliance and take appropriate enforcement measures when required in accordance with Compliance and Enforcement Policy for Health Products (POL-0001).

Service standards

The proposed Regulations include service standards for the new proposed clinical trial authorization process (e.g. contingent authorization within 7 days of the sponsor submitting a complete application, followed by confirmation of authorization, denial of authorization or extension of the review period within 30 days of the sponsor submitting a complete application) as set out in the “Description” section above. No user fees are proposed relating to the proposed Regulations.

Contact

Debra Haltrecht
Acting Executive Director
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Products and Food Branch
Health Canada
Holland Cross, Suite P2108
11 Holland Avenue
Ottawa, Ontario
K1A 0K9
Address locator: 3001
Email: lrm.consultations-mlr@hc-sc.gc.ca

PROPOSED REGULATORY TEXT

Notice is given that the Governor in Council proposes to make the annexed Clinical Trials Regulations under section 30^{footnote a} of the Food and Drugs Act ^{footnote b}.

Interested persons may make representations concerning the proposed Regulations within 90 days after the date of publication of this notice. They are strongly encouraged to use the online commenting feature that is available on the Canada Gazette website but if they use email, mail or any other means, the representations should cite the Canada Gazette, Part I, and the date of publication of this notice, and be sent to Debra Haltrecht, Acting Executive Director, Office of Legislative and Regulatory Modernization, Health Products and Food Branch, Department of Health, Address Locator: 3001, 11 Holland Avenue, Suite P2108, Ottawa, Ontario K1A 0K9 (email: lrm.consultations-mlr@hc-sc.gc.ca).

Ottawa, December 15, 2025

Janna Rinaldi
Acting Assistant Clerk of the Privy Council

TABLE OF PROVISIONS

Clinical Trials Regulations

Interpretation

• 1 Definitions
• 2 Interpretation — clinical trial site
• 3 Research ethics board — characteristics

Application

• 4 Application
• 5 Non-application — authorization issued

Exemptions

• 6 Exemptions — drug used as authorized
• 7 Exemptions — authorization issued

Importation and Sale of Drugs

• 8 Prohibition — import or sale
• 9 Prohibition — suspension
• 10 Prohibition — direction to cease

Authorizations to Conduct Clinical Trials

Application for Authorization

• 11 Application — requirements
• 12 Selective approach — records of adverse events
• 13 Request by Minister

Obtaining an Authorization

• 14 Contingent authorization
• 15 Conversion of contingent authorization
• 16 Extension

Commencement of Conduct of Clinical Trial at Clinical Trial Site

17 Prohibition — commencement

Terms and Conditions

18 Terms and conditions

Amendments

• 19 Prohibitions — amendment of authorization
• 20 Application for amendment
• 21 Request by Minister
• 22 Amendment of authorization
• 23 Prohibitions — approval of research ethics board
• 24 Immediate change

Transfer of Authorization

25 Requirements for transfer

Suspension and Revocation

• 26 Suspension — opportunity to be heard
• 27 Immediate suspension
• 28 Notification of third parties — suspension
• 29 Mandatory reinstatement
• 30 Discretionary revocation
• 31 Mandatory revocation — notice of discontinuation
• 32 Automatic revocation — completion of sub-study
• 33 Automatic revocation — completion of clinical trial
• 34 Notification of third parties — revocation
• 35 Request by Minister

Direction to Cease

• 36 Application
• 37 Prohibition — direction to cease
• 38 Direction to cease — opportunity to be heard
• 39 Direction to cease — immediate
• 40 Notification of third parties — direction to cease
• 41 Mandatory lifting of direction
• 42 Permanent direction to cease
• 43 Notification of third parties — permanent direction to cease
• 44 Request by Minister

General

National Research Ethics Boards

45 Interpretation

Good Clinical Practices

• 46 Good clinical practices — requirements
• 47 Exception — clinical trial involving medical emergency
• 48 Exception — drug used as authorized

Provision of Information

• 49 Notification after change made — authorization issued
• 50 Provision of information after becoming aware — authorization issued
• 51 Service providers commencing service — authorization issued
• 52 Serious unexpected adverse drug reactions — authorization issued
• 53 Case reports and summary report — authorization issued
• 54 Exception — drug used as authorized
• 55 Discontinuation of clinical trial — authorization issued
• 56 Notification of discontinuation by investigator — authorization issued
• 57 Closure of clinical trial site — authorization issued
• 58 Notification of completion of sub-study — authorization issued
• 59 Notification of completion of clinical trial — authorization issued
• 60 Direction to notify — former holder

Records

• 61 Records — sponsor
• 62 Records — service providers
• 63 Records — selective approach to adverse events
• 64 Exception — exempt sponsor
• 65 Exception — authorized drug
• 66 Retention period after end of clinical trial

Labelling

• 67 Prohibition on conduct — without required label
• 68 Non-application — prohibition

Transitional Provisions

Interpretation

69 Definitions

Applications for Authorization

• 70 Deeming — applications for authorization
• 71 Applications in queue
• 72 Deeming — applications to amend authorization

Authorizations

• 73 Deeming — Budget Implementation Act, 2019, No. 1
• 74 Deeming — certain drugs
• 75 Deeming — COVID-19 drugs
• 76 Revocation of authorization — Budget Implementation Act, 2019, No. 1

Other Matters

• 77 Service providers — notification by sponsor
• 78 Deeming — requests
• 79 Deeming — direction to cease
• 80 Deeming — permanent direction to cease
• 81 Records — continuation of obligation

Coming into Force

82 First anniversary of publication

Clinical Trials Regulations

Interpretation

Definitions

1 (1) The following definitions apply in these Regulations.

Act

means the Food and Drugs Act. (Loi)

adverse drug reaction

means any adverse and unintended occurrence in relation to the health of a participant who is administered a drug in a clinical trial, for which there are reasonable grounds to believe that the occurrence could be a noxious response to any dose of the drug. (réaction indésirable à une drogue)

adverse event

means any adverse occurrence that is in relation to the health of a participant who is administered a drug in a clinical trial and that may or may not be caused by the administration of the drug. It includes an adverse drug reaction. (incident thérapeutique)

authorization

means, unless the context otherwise requires, a contingent authorization issued under paragraph 14(1)(b) that, under section 15, has ceased to be a contingent authorization and has become an authorization that authorizes the sponsor to conduct a clinical trial in respect of a drug. (autorisation)

business day

means a day other than

• (a) a Saturday; or
• (b) a Sunday or other holiday. (jour ouvrable)

drug

means a drug for human use. (drogue)

good clinical practices

means generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of participants and other persons and the reliability of results, including the practices referred to in paragraphs 46(1)(a) to (l). (bonnes pratiques cliniques)

investigator

means a person who, in respect of a clinical trial,

• (a) is entitled to provide health care under the laws of the province in which the main location of a clinical trial site is situated;
• (b) possesses relevant clinical expertise, within their scope of practice, to exercise their profession in the course of the clinical trial given its objectives;
• (c) if the person is not also the sponsor of the clinical trial, is responsible to the sponsor for the conduct of the clinical trial at the clinical trial site; and
• (d) if the clinical trial is conducted at the clinical trial site by a team, is the responsible leader of the team. (chercheur)

List of National Research Ethics Boards

means the List of National Research Ethics Boards that is published by the Government of Canada on its website, as amended from time to time. (Liste des comités nationaux d’éthique de la recherche)

master protocol trial

means a clinical trial in respect of which the following criteria are met:

• (a) it includes one or more sub-studies;
• (b) the research questions of the sub-studies fall within the scope of those of the clinical trial; and
• (c) a framework exists to support a common organizational approach for the sub-studies and the other parts of the clinical trial as well as to support the sharing of research infrastructure, such as clinical trial sites, resources and personnel. (essai basé sur le protocole maître)

material

includes samples, except in subsections 11(2), 20(2) and 61(2). (matériel)

national research ethics board

means a research ethics board that is set out in the List of National Research Ethics Boards. (comité national d’éthique de la recherche)

participant

means a human subject who participates in a clinical trial. (participant)

protocol

means a document that describes the objectives, design, methodology, study population, statistical considerations and organization of a clinical trial. (protocole)

research ethics board

means a body that has the characteristics described in section 3. (comité d’éthique de la recherche)

serious adverse drug reaction

means an adverse drug reaction that requires in-patient hospitalization or prolongation of existing hospitalization, causes congenital malformation, results in persistent or significant disability or incapacity, is life threatening, results in death or requires medical intervention to prevent any of those outcomes. (réaction indésirable grave à une drogue)

serious unexpected adverse drug reaction

means a serious adverse drug reaction that is not identified in nature, severity or frequency in the risk information set out in the document referred to in paragraph 11(2)(o) that pertains to the drug or on the label of the drug. (réaction indésirable grave et imprévue à une drogue)

service provider

means a person who conducts a clinical trial by providing a service to or on behalf of the sponsor or an investigator, but does not include an investigator or a person to whom the exemption provided for in subsection 6(3) or 7(2) applies. (fournisseur de service)

sponsor

means a person who

• (a) conducts a clinical trial solely or in combination with other persons; and
• (b) takes responsibility for the overall conduct of the clinical trial. (promoteur)

sub-study

means a study that

• (a) is or is proposed to be part of a clinical trial; and
• (b) is aimed at discovering or verifying the effects of one or more of the drugs used — or proposed by the study to be used — in the clinical trial. (sous-étude)

Words and expressions

(2) Unless the context otherwise requires, words and expressions used in these Regulations have the same meaning as in the Food and Drug Regulations.

Interpretation — clinical trial site

2 (1) In these Regulations, a reference to a clinical trial site is a reference to all of the following:

• (a) the main location of the clinical trial site
  • (i) at which an investigator conducts a clinical trial, and
  • (ii) from which the investigator oversees the conduct of the clinical trial at each of the locations referred to in paragraph (b), if any; and
• (b) any locations that are remote from the main location and at which persons conduct the clinical trial under the oversight of the investigator.

Interpretation — commencement

(2) For the purposes of these Regulations, a clinical trial is considered to commence at a clinical trial site when the clinical trial first begins to be conducted at any of the locations referred to in subsection (1).

Research ethics board — characteristics

3 For the purposes of these Regulations, a research ethics board must have the following characteristics:

• (a) its principal mandate is to approve the initiation, and conduct periodic reviews, of biomedical research involving participants in order to ensure the protection of their rights, safety and well-being;
• (b) it has at least five members, a majority of whom are Canadian citizens, permanent residents within the meaning of the Immigration and Refugee Protection Act or persons registered as Indians under the Indian Act;
• (c) it includes at least
  • (i) one man and one woman,
  • (ii) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the methods and areas of research to be approved and one of whom is from a medical discipline or, in the case of a clinical trial in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
  • (iii) one member knowledgeable in ethics,
  • (iv) one member knowledgeable in Canadian laws relevant to the research to be approved,
  • (v) one member whose primary experience and expertise are in a non-scientific discipline, and
  • (vi) one member who is one of the following persons and is not affiliated with the sponsor or the clinical trial site where the clinical trial is to be conducted:
    • (A) a member of a community of persons who are interested in or affected by any of the areas of research to be approved, or
    • (B) a representative of an organization interested in any of the areas of research to be approved; and
• (d) each member of the board, other than the member referred to in subparagraph (c)(vi), has no affiliation with the sponsor that could compromise the member’s ability to fulfil the board’s principal mandate or that could be perceived to do so.

Application

Application

4 These Regulations apply to

• (a) the importation and sale of a drug for use in a clinical trial; and
• (b) the conduct of a clinical trial in respect of such a drug.

Non-application — authorization issued

5 (1) Subject to subsection (2), the Food and Drug Regulations, other than the following provisions, do not apply to the importation or sale of a drug for use in a clinical trial or the conduct of a clinical trial in respect of such a drug if the sponsor holds an authorization in respect of the clinical trial:

• (a) the provisions of Part A; and
• (b) sections C.01.015, C.01.051, C.01.051.1, C.01.064 to C.01.067, C.01.070, C.01.131, C.01.133 to C.01.136 and C.01.435.

Application — drug used as authorized

(2) The Food and Drug Regulations apply to the importation and sale of a drug that is for use in a clinical trial and the conduct of a clinical trial in respect of such a drug if it is one of the following drugs:

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Non-application — labelling

(3) Despite subsections (1) and (2), except as provided for in section 68, the provisions of the Food and Drug Regulations as they apply in respect of labelling do not apply to the label of a drug to be used in a clinical trial.

Exemptions

Exemptions — drug used as authorized

6 (1) A sponsor who conducts a clinical trial that involves the use of only one or more of the following drugs is, in respect of the clinical trial, exempt from section 3.1 of the Act:

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Exemption — investigators and service providers

(2) If a sponsor is exempt under subsection (1) from section 3.1 of the Act in respect of a clinical trial, an investigator or service provider who conducts the clinical trial is, in respect of the clinical trial, also exempt from that section.

Exemption — other persons

(3) Any person — other than a sponsor, service provider or investigator — who conducts a clinical trial is, in respect of the clinical trial, exempt from section 3.1 of the Act if they are under the oversight of

• (a) the sponsor of the clinical trial, in the case where the sponsor is, in respect of the clinical trial, exempt from that section under subsection (1); or
• (b) an investigator or service provider who is, in respect of the clinical trial, exempt from that section under subsection (2).

Non-application — direction to cease in whole

(4) If a sponsor is subject to a direction imposed by the Minister under section 38 or 39 to cease the conduct of a clinical trial in whole,

• (a) the exemption provided for in subsection (1) does not apply to the sponsor as of the day on which the direction takes effect;
• (b) the exemption provided for in subsection (2) does not apply to an investigator or service provider as of the time when they are notified of the direction; and
• (c) the exemption provided for in subsection (3) does not apply to a person who is under the oversight of a person referred to in paragraph (3)(a) or (b) as of the time when they are notified of the direction.

Non-application — direction to cease in part

(5) If a sponsor is subject to a direction imposed by the Minister under section 38 or 39 to cease the conduct of a clinical trial in part,

• (a) the exemption provided for in subsection (1) does not apply to the sponsor in respect of the part of the clinical trial to which the direction applies as of the day on which the direction takes effect;
• (b) in the case where an investigator or service provider conducts the part of the clinical trial to which the direction applies, the exemption provided for in subsection (2) does not apply to the investigator or service provider in respect of that part as of the time when they are notified of the direction; and
• (c) in the case where a person who is under the oversight of a person referred to in paragraph (3)(a) or (b) conducts the part of the clinical trial to which the direction applies, the exemption provided for in subsection (3) does not apply to the person in respect of that part as of the time when they are notified of the direction.

Clarification

(6) For greater certainty, subsection (4) or (5), as the case may be, applies if a direction imposed by the Minister under section 38 or 39 becomes permanent under section 42.

Exemptions — authorization issued

7 (1) A service provider or investigator who conducts a clinical trial for which the sponsor holds an authorization is, in respect of the clinical trial, exempt from section 3.1 of the Act.

Exemption — other persons

(2) Any person — other than a service provider or investigator — who conducts a clinical trial for which the sponsor holds an authorization is, in respect of the clinical trial, exempt from section 3.1 of the Act if the person is under the oversight of

• (a) the sponsor; or
• (b) an investigator or service provider who is, in respect of the clinical trial, exempt from that section under subsection (1).

Non-application — suspension in whole

(3) If a sponsor’s authorization is suspended in whole,

• (a) the exemption provided for in subsection (1) does not apply to an investigator or service provider as of the time when they are notified of the suspension; and
• (b) the exemption provided for in subsection (2) does not apply to a person who is under the oversight of a person referred to in paragraph (2)(a) or (b) as of the time when they are notified of the suspension.

Non-application — suspension in part

(4) If a sponsor’s authorization is suspended in part,

• (a) in the case where an investigator or service provider conducts the part of the clinical trial to which the suspension applies, the exemption provided for in subsection (1) does not apply to the investigator or service provider in respect of that part as of the time when they are notified of the suspension; and
• (b) in the case where a person who is under the oversight of a person referred to in paragraph (2)(a) or (b) conducts the part of the clinical trial to which the suspension applies, the exemption provided for in subsection (2) does not apply to the person in respect of that part as of the time when they are notified of the suspension.

Non-application — revocation in part

(5) If the part of the sponsor’s authorization that was suspended is revoked,

• (a) the exemption provided for in subsection (1) does not apply to the investigator or service provider referred to in paragraph (4)(a) in respect of that part; and
• (b) the exemption provided for in subsection (2) does not apply in respect of that part to the person referred to in paragraph (4)(b) who is under the oversight of a person referred to in paragraph (2)(a) or (b).

Importation and Sale of Drugs

Prohibition — import or sale

8 (1) Subject to subsection (2), it is prohibited to import or sell a drug for use in a clinical trial unless

• (a) the sponsor holds an authorization in respect of the clinical trial; and
• (b) if the drug is to be imported, the sponsor has a representative in Canada who is responsible for the importation of the drug and a representative in Canada who is responsible for the sale of the drug.

Exception — exempt sponsor

(2) Subsection (1) does not apply if the sponsor is exempt, in respect of the clinical trial, under subsection 6(1) from section 3.1 of the Act.

Prohibition — suspension

9 (1) If an authorization in respect of a clinical trial is suspended, in whole or in part, and a person has been notified of the suspension, it is prohibited for the person to

• (a) in the case of a suspension in whole, import or sell a drug for use in the clinical trial; and
• (b) in the case of a suspension in part, import or sell a drug for use in the part of the clinical trial to which the suspension relates.

Prohibition — revocation in part

(2) If the part of an authorization that was suspended is revoked, it is prohibited to import or sell a drug for use in the part of the clinical trial to which the revocation relates.

Prohibition — direction to cease

10 If a sponsor is subject to a direction imposed by the Minister under section 38 or 39 to cease the conduct of a clinical trial, in whole or in part, and a person has been notified of the direction, it is prohibited for the person to

• (a) in the case of cessation in whole, import or sell a drug for use in the clinical trial; and
• (b) in the case of cessation in part, import or sell a drug for use in the part of the clinical trial to which the direction relates.

Authorizations to Conduct Clinical Trials

Application for Authorization

Application — requirements

11 (1) An application by a sponsor for an authorization to conduct a clinical trial in respect of a drug must be signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer and must be submitted to the Minister in the form and manner specified by the Minister.

Contents

(2) The application must contain sufficient information and material to enable the Minister to determine whether the sponsor should be authorized to conduct the clinical trial, including

• (a) the name and contact information of the sponsor and, in the case of a foreign sponsor, the name and contact information of the sponsor’s representative in Canada;
• (b) if a drug to be used in the clinical trial is to be imported, the name and contact information of the sponsor’s representative in Canada who is responsible for the importation of the drug and the sponsor’s representative in Canada who is responsible for the sale of the drug;
• (c) if known at the time of submission of the application, the name and contact information of the investigator for each clinical trial site and, if the investigator’s contact information specifies a civic address that differs from the civic address of the clinical trial site’s main location, the civic address of the main location;
• (d) if known at the time of submission of the application, the name and contact information of any service provider who is to conduct the clinical trial;
• (e) the protocol for the clinical trial;
• (f) the title of the protocol referred to in paragraph (e) and the protocol code;
• (g) a copy of the statement, as it will be set out in each informed consent form, of the risks and anticipated benefits to the health of participants that arise as a result of their participation in the proposed clinical trial;
• (h) if the protocol referred to in paragraph (e) provides for the enrolment of participants in the clinical trial without their prior documented informed consent, sufficient information to establish that the conditions set out in section 47 will be met;
• (i) subject to subsection (4) and if known at the time of submission of the application, for each clinical trial site, the name and contact information of the research ethics board that approved the protocol referred to in paragraph (e) and the informed consent form that contains the statement referred to in paragraph (g);
• (j) if applicable and known at the time of submission of the application, the name and contact information of any research ethics board that has previously refused to approve the protocol referred to in paragraph (e), its reasons for doing so and the date on which the refusal was given;
• (k) if applicable and known at the time of submission of the application, a description of any of the following decisions made or measures taken in respect of the clinical trial in the jurisdiction of any foreign regulatory authority, including the reasons for the decision or measure and, in the case of subparagraph (v), the text of terms and conditions or amended terms and conditions:
  • (i) a refusal, by a body that has a mandate similar to the one described in paragraph 3(a), to approve the protocol referred to in paragraph (e) or any other protocol prepared for the clinical trial,
  • (ii) a refusal by a foreign regulatory authority to authorize the conduct of the clinical trial,
  • (iii) a refusal by a foreign regulatory authority to authorize amendments to an authorization to conduct the clinical trial,
  • (iv) a suspension or revocation, in whole or in part, by a foreign regulatory authority of an authorization to conduct the clinical trial,
  • (v) the imposition of terms and conditions on an authorization to conduct the clinical trial — or any amendment of such terms and conditions — by a foreign regulatory authority, and
  • (vi) any other measure taken by a foreign regulatory authority in respect of the clinical trial for which there are reasonable grounds to believe that the purpose of the measure is to protect the health of participants or other persons;
• (l) if known at the time of submission of the application, for each clinical trial site, the proposed date for the commencement of the clinical trial;
• (m) an attestation, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, that confirms that
  • (i) the sponsor takes responsibility for the overall conduct of the clinical trial,
  • (ii) the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and
  • (iii) all information and material contained in, or referenced by, the application are complete and are not false or misleading;
• (n) subject to subsection (5), the following information in respect of each drug to be used in the clinical trial:
  • (i) the brand name, code or chemical name,
  • (ii) the therapeutic and pharmacological classifications,
  • (iii) the medicinal ingredients,
  • (iv) the non-medicinal ingredients, and
  • (v) the dosage form;
• (o) subject to subsection (5), for each drug to be used in the clinical trial, a document that contains all of the following information:
  • (i) the physical, chemical and pharmaceutical properties of the drug,
  • (ii) any non-clinical and clinical information, including risk information, that is necessary to support the use of the drug in the clinical trial, and
  • (iii) if the drug is a radiopharmaceutical, directions for its preparation as well as the radiation dosimetry of, and storage requirements for, the prepared radiopharmaceutical;
• (p) for each drug to be used in the clinical trial, other than a drug referred to in subparagraph (r)(i) or (ii), that contains a human-sourced excipient and, if applicable, for a placebo in which a human-sourced excipient is to be used,
  • (i) in the case where the excipient is a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, a statement to that effect,
  • (ii) in the case where the excipient is a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, a statement to that effect, and
  • (iii) in the case of any other excipient,
    • (A) details of the method of manufacture of the excipient and the controls to be used in its manufacture,
    • (B) sufficient information to support the characterization of the excipient, and
    • (C) information respecting the safety of the excipient;
• (q) for each drug to be used in the clinical trial that contains a novel excipient,
  • (i) details of the method of manufacture of the excipient and the controls to be used in its manufacture,
  • (ii) sufficient information to support the characterization of the excipient, and
  • (iii) information respecting the safety of the excipient;
• (r) for each drug to be used in the clinical trial that is not one of the following drugs, the chemistry and manufacturing information for the drug, including its site of manufacture:
  • (i) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, or
  • (ii) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled; and
• (s) for each drug to be used in the clinical trial that contains a substance referred to in any of sections C.01.036, C.01.037, C.01.038 and C.01.040 of the Food and Drug Regulations or contains a colouring agent other than those listed in subsections C.01.040.2(3) and (4) of those Regulations, scientific evidence that the drug may result in a therapeutic benefit for human beings.

Follow-up information

(3) If the sponsor becomes aware of a refusal referred to in paragraph (2)(j) or decision or measure referred to in paragraph (2)(k) after submitting the application but before the earliest of the following events, they must provide the information referred to in paragraph (2)(j) or (k) to the Minister within two business days after the day on which they became aware of it:

• (a) receipt by the sponsor of a notice referred to in paragraph 15(1)(a) or (b) or subsection 15(2); and
• (b) subject to section 16, the end of the 30-day period referred to in subsection 15(1).

Exception — national research ethics board

(4) Paragraph (2)(i) does not apply if

• (a) a national research ethics board approved the protocol referred to in paragraph (2)(e) and the informed consent form that contains the statement referred to in paragraph (2)(g); and
• (b) the sponsor indicates the name of the national research ethics board in the application.

Exception — drug used as authorized

(5) Paragraphs (2)(n) and (o) do not apply to a drug to be used in a clinical trial if

• (a) the drug is a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations and the proposed use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) the drug is a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled and the proposed use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Selective approach — records of adverse events

12 A sponsor may propose, in the application referred to in section 11, a selective approach to maintaining records of adverse events — other than serious unexpected adverse drug reactions — in respect of a drug to be used in the clinical trial if the following conditions are met:

• (a) the protocol referred to in paragraph 11(2)(e) includes
  • (i) a detailed description of the proposed selective approach, including of the types of adverse events for which a record will not be created or for which records will be created at a reduced frequency, and
  • (ii) a detailed description of how the selective approach will be implemented during the clinical trial; and
• (b) the application includes sufficient information to support the conclusion that the safety profile of the drug is sufficiently characterized to justify the selective approach to maintaining records.

Request by Minister

13 The Minister may request that a sponsor who submitted an application for an authorization submit to the Minister — within two business days after the day on which the request is made or any longer period specified by the Minister and in the form and manner specified by the Minister — any additional information or material that is necessary to enable the Minister to determine whether the sponsor should be authorized to conduct the clinical trial.

Obtaining an Authorization

Contingent authorization

14 (1) If a sponsor submits an application for an authorization under section 11 and the Minister determines that the application is complete, the Minister must, within seven days after the day on which the application was submitted, issue to the sponsor

• (a) a written notice that indicates the day on which the application was submitted; and
• (b) a contingent authorization in respect of the clinical trial.

Clarification

(2) For greater certainty, a contingent authorization does not authorize the sponsor to conduct the clinical trial.

Conversion of contingent authorization

15 (1) Subject to subsection (2) and section 16, unless the Minister takes one of the following actions within 30 days after the day on which a sponsor submits an application referred to in section 14, a contingent authorization issued to the sponsor under paragraph 14(1)(b) ceases, at the end of that period, to be a contingent authorization and becomes an authorization that authorizes the sponsor to conduct the clinical trial:

• (a) the Minister sends to the sponsor a written notice indicating that
  • (i) the application does not meet the requirements set out in section 11 and, if applicable, section 12, or
  • (ii) based on an assessment of the application and any information or material requested under section 13 and a review of any other information, if applicable, the Minister has reasonable grounds to believe that the sponsor should not be authorized to conduct the clinical trial for any of the following reasons:
    • (A) the conduct of the clinical trial, including the use of any drug in it, is likely to result in unacceptable risks to the health of its participants or other persons,
    • (B) if a drug to be used in the clinical trial contains a substance referred to in any of sections C.01.036, C.01.037, C.01.038 and C.01.040 of the Food and Drug Regulations or contains a colouring agent other than those listed in subsections C.01.040.2(3) and (4) of those Regulations, the drug does not have the potential to result in a therapeutic benefit for human beings,
    • (C) the clinical trial is contrary to the best interests of its participants, and
    • (D) the objectives of the clinical trial are not achievable; or
• (b) if the sponsor has not submitted to the Minister, in accordance with section 13, any additional information or material that was requested under that section, the Minister sends to the sponsor a written notice containing a statement to that effect.

Notice of no objection

(2) If the Minister sends to the sponsor a written notice indicating that the Minister has determined that no grounds exist for the Minister to send to them the notice referred to in paragraph (1)(a), the contingent authorization issued to the sponsor under paragraph 14(1)(b) ceases, on the day on which the Minister sends the written notice, to be a contingent authorization and becomes an authorization to conduct the clinical trial.

Extension

16 (1) The Minister may, within 30 days after the day on which a sponsor submits an application referred to in section 14 for which a contingent authorization is issued under paragraph 14(1)(b), send a notice to the sponsor that indicates that, based on one or more of the following factors, more time is needed for the review of the application:

• (a) the degree of complexity of the clinical trial, including
  • (i) any potential need for the Minister to impose terms and conditions on an authorization that would authorize the conduct of the clinical trial in order to address the complexity of the clinical trial,
  • (ii) the extent to which the clinical trial has a complex design, including whether it is a master protocol trial, or
  • (iii) the extent to which
    • (A) a drug to be used in the clinical trial represents an emerging or innovative technological, scientific or medical development, or
    • (B) the manufacturing of a drug to be used in the clinical trial or the controls to be used in its manufacture involve a process that is emerging or innovative; or
• (b) whether additional assessment is needed in order to protect a particular vulnerability of the study population of the clinical trial or any part of that population.

Interpretation — “30-day period” and “30 days”

(2) If the Minister sends the notice referred to in subsection (1) to the sponsor,

• (a) the reference in paragraph 11(3)(b) to “30-day period” is to be read as a reference to “60-day period”; and
• (b) the reference in subsection 15(1) to “30 days” is to be read as a reference to “60 days”.

Commencement of Conduct of Clinical Trial at Clinical Trial Site

Prohibition — commencement

17 (1) It is prohibited to commence, at a clinical trial site, the conduct of a clinical trial in respect of which the sponsor holds an authorization unless

• (a) the sponsor has obtained, for the clinical trial site, the approval by a research ethics board of the protocol referred to in paragraph 11(2)(e) and the informed consent form that contains the statement referred to in paragraph 11(2)(g) and the approval has not been withdrawn;
• (b) the sponsor has submitted to the Minister the information referred to in paragraphs 11(2)(c) and (l) in respect of the clinical trial site; and
• (c) the sponsor has
  • (i) if the research ethics board is a national research ethics board, notified the Minister in writing of the name of the national research ethics board, and
  • (ii) in any other case, submitted to the Minister the information referred to in paragraph 11(2)(i) in respect of the clinical trial site.

Prohibition — recommencement

(2) If the requirements of subsection (1) were met in respect of a clinical trial site, the clinical trial was conducted at that site and that site was subsequently closed, it is prohibited to recommence the conduct of the clinical trial at that site unless the sponsor notifies the Minister in writing of

• (a) any change in the information referred to in paragraph 11(2)(c) and, if applicable, paragraph 11(2)(i) that the sponsor previously submitted to the Minister in respect of the clinical trial site; and
• (b) the date on which conduct of the clinical trial at that site is proposed to recommence.

Terms and Conditions

Terms and conditions

18 The Minister may, at any time, impose terms and conditions on an authorization, or amend any such terms and conditions, after considering

• (a) whether the requirements under the Act are sufficient for the following objectives to be met:
  • (i) mitigating the risks associated with the conduct of the clinical trial, including in respect of the drugs used in it, and
  • (ii) collecting information to enable the management of the uncertainties relating to the risks;
• (b) whether the proposed terms and conditions may contribute to those objectives being met;
• (c) whether compliance with the proposed terms and conditions is technically feasible; and
• (d) whether there are less burdensome ways for those objectives to be met.

Amendments

Prohibitions — amendment of authorization

19 (1) It is prohibited to conduct a clinical trial in respect of which the sponsor holds an authorization or to import or sell a drug for use in the clinical trial if the clinical trial has been subject to any of the changes referred to in subsection (2), unless the authorization is amended accordingly.

Types of changes

(2) An amendment of an authorization is required for any of the following changes:

• (a) an amendment to the protocol that affects the selection, monitoring or dismissal of a participant or the number of participants;
• (b) an amendment to the protocol that affects the evaluation of the clinical efficacy of a drug used in the clinical trial;
• (c) an amendment to the protocol that alters the risk to the health of participants or other persons;
• (d) an amendment to the protocol that affects the safety evaluation of a drug used in the clinical trial;
• (e) an amendment to the protocol that changes the duration of the clinical trial;
• (f) in the case of a master protocol trial, an amendment to the protocol to add a sub-study;
• (g) an amendment to the protocol to add or modify a selective approach to maintaining records of adverse events in respect of a drug used in the clinical trial; and
• (h) in the case of a drug referred to in paragraph 11(2)(p), (q) or (r) for which information referred to in, as the case may be, subparagraph 11(2)(p)(iii) or paragraph 11(2)(q) or (r) was previously submitted to the Minister, a change to that information that may affect the safety or quality of a drug used in the clinical trial.

Application for amendment

20 (1) An application by a sponsor to amend an authorization must be signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer and must be submitted to the Minister in the form and manner specified by the Minister.

Contents

(2) The application must contain sufficient information and material to enable the Minister to determine whether the authorization should be amended, including

• (a) the information and material referred to in subsection 11(2) or section 12 that relates to the applicable change referred to in subsection 19(2); and
• (b) an attestation, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, that confirms that
  • (i) the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and
  • (ii) all information and material contained in, or referenced by, the application are complete and are not false or misleading.

Request by Minister

21 The Minister may request that a sponsor who submitted an application to amend an authorization submit to the Minister — within two business days after the day on which the request is made or any longer period specified by the Minister and in the form and manner specified by the Minister — any additional information or material that is necessary to enable the Minister to determine whether the authorization should be amended.

Amendment of authorization

22 (1) Subject to subsection (2), unless the Minister takes one of the following actions within 30 days after the day on which a sponsor submits an application under section 20 to amend an authorization, the authorization is amended accordingly at the end of that period:

• (a) the Minister sends to the sponsor a written notice indicating that
  • (i) the application does not meet the requirements set out in section 20 and, if applicable, section 12, or
  • (ii) based on an assessment of the application and any information or material requested under section 21 and a review of any other information, if applicable, the Minister has reasonable grounds to believe that any of the reasons set out in clauses 15(1)(a)(ii)(A) to (D) would exist in respect of the clinical trial if the amendment were to be approved; or
• (b) if the sponsor has not submitted to the Minister, in accordance with section 21, any additional information or material that was requested under that section, the Minister sends to the sponsor a written notice containing a statement to that effect.

Notice of no objection

(2) If the Minister sends to the sponsor a written notice indicating that the Minister has determined that no grounds exist for the Minister to send to them the notice referred to in paragraph (1)(a), the authorization is amended accordingly on the day on which the Minister sends the written notice.

Prohibitions — approval of research ethics board

23 (1) It is prohibited to conduct, at a clinical trial site, a clinical trial in respect of which the sponsor holds an authorization if the clinical trial has been subject to a change referred to in subsection 19(2) that results in an amendment to the protocol referred to in paragraph 11(2)(e), unless the sponsor has obtained, for the clinical trial site, the approval of a research ethics board in respect of the amendment and the approval has not been withdrawn.

Prohibition — statement

(2) It is prohibited to conduct, at a clinical trial site, a clinical trial in respect of which the sponsor holds an authorization if the clinical trial has been subject to a change referred to in subsection 19(2) that results in an amendment to the statement referred to in paragraph 11(2)(g), unless the sponsor has obtained, for the clinical trial site, the approval of a research ethics board in respect of the amendment and the approval has not been withdrawn.

Immediate change

24 (1) Despite sections 19 and 23, a sponsor may immediately make any of the changes referred to in subsection 19(2) — other than the change referred to in paragraph 19(2)(f) — if there are reasonable grounds to believe that the change is required because the clinical trial would otherwise endanger the health of participants or other persons.

Application to amend required

(2) The sponsor must, within 30 days after the day on which the sponsor makes a change referred to in subsection (1), submit an application under section 20 to amend the authorization and include in the application the reasons for making the change and a description of any risks to the health of participants or other persons.

Notification of change

(3) If the sponsor does not submit the application within seven days after the day on which the sponsor makes the change, the sponsor must notify the Minister in writing, before the end of that period, of the change and the reasons for making it and must include a description of any risks to the health of participants or other persons.

Application of prohibitions — section 19

(4) If the Minister sends to the sponsor a notice referred to in paragraph 22(1)(a) or (b), section 19 applies again in respect of the change as of the time when the sponsor receives the notice.

Application of prohibition — subsection 23(1)

(5) If the change results in an amendment to the protocol referred to in paragraph 11(2)(e) and a research ethics board refuses to approve the amendment, subsection 23(1) applies again in respect of the change as of the time when the sponsor is notified of the refusal.

Application of prohibition — subsection 23(2)

(6) If the change results in an amendment to the statement referred to in paragraph 11(2)(g) and a research ethics board refuses to approve the amendment, subsection 23(2) applies again in respect of the change as of the time when the sponsor is notified of the refusal.

Transfer of Authorization

Requirements for transfer

25 (1) An authorization to conduct a clinical trial is transferred from the sponsor who holds the authorization to another person and the other person becomes the sponsor of the clinical trial if the following requirements are met:

• (a) the sponsor notifies the Minister in writing that they intend to transfer the authorization to the other person;
• (b) the Minister receives from the other person an acknowledgement in writing that the person agrees to become the sponsor of the clinical trial on transfer of the authorization; and
• (c) the Minister receives from the other person an attestation, signed and dated by the person’s senior medical or scientific officer in Canada and senior executive officer, that confirms that
  • (i) the other person agrees to take responsibility for the overall conduct of the clinical trial on transfer of the authorization, and
  • (ii) the clinical trial will be conducted in accordance with good clinical practices and these Regulations.

Interpretation

(2) If an authorization is transferred under subsection (1), the reference in subsection 60(1) to “the former holder of an authorization in respect of a clinical trial” and the reference in paragraph 66(2)(a) to “the former holder of an authorization in respect of the clinical trial” are to be read as references to the sponsor who was the holder of the authorization on the day on which the authorization was revoked in whole.

Suspension and Revocation

Suspension — opportunity to be heard

26 (1) Subject to subsection (3), the Minister may suspend, in whole or in part, a single authorization to conduct a clinical trial if the Minister has reasonable grounds to believe that

• (a) any of the reasons set out in clauses 15(1)(a)(ii)(A) to (D) exist in respect of the clinical trial;
• (b) the sponsor, an investigator, a service provider or a person who is exempt from section 3.1 of the Act under subsection 7(2) has, in respect of the clinical trial, contravened any provision of the Act or these Regulations, any applicable provision of the Food and Drug Regulations or any order made under the Act;
• (c) the sponsor has failed to comply with the terms and conditions of the authorization;
• (d) any information submitted to the Minister by or on behalf of the sponsor, in respect of the clinical trial or a drug used in the clinical trial, is false or misleading; or
• (e) the sponsor, an investigator, a service provider or a person who is exempt from section 3.1 of the Act under subsection 7(2) has, in respect of the clinical trial, failed to comply with good clinical practices.

Suspension — several authorizations

(2) Subject to subsection (3), the Minister may suspend, in whole or in part, several authorizations to conduct a clinical trial if the Minister has reasonable grounds to believe that any of paragraphs (1)(b) to (e) applies in respect of each of the clinical trials to which those authorizations relate, or a drug used in each of those clinical trials, as the case may be, due to the same act or omission of any of the following persons:

• (a) in the case where the sponsor of each of those clinical trials is the same person,
  • (i) that sponsor, or
  • (ii) an investigator, service provider or person who is exempt from section 3.1 of the Act under subsection 7(2) who is conducting each of those clinical trials; or
• (b) in any other case, a person referred to in subparagraph (a)(ii).

Conditions

(3) The Minister may suspend an authorization under subsection (1) or (2) only if

• (a) the Minister has sent to the sponsor a notice that indicates whether the authorization is to be suspended in whole or in part and the reasons for the intended suspension; and
• (b) the sponsor does not, within 30 days after the day on which they receive that notice, provide the Minister with information or material that enables the Minister to determine that
  • (i) in the case of an intended suspension based on paragraph (1)(a), the applicable reason set out in any of clauses 15(1)(a)(ii)(A) to (D) does not exist in respect of the clinical trial, and
  • (ii) in the case of an intended suspension based on any of paragraphs (1)(b) to (e), the situation giving rise to the intended suspension did not exist or has been corrected.

Notice

(4) If the Minister suspends an authorization, the Minister must send to the sponsor a written notice that indicates the day on which the suspension takes effect, whether the authorization is suspended in whole or in part and the reasons for the suspension.

Immediate suspension

27 (1) The Minister may suspend a single authorization, in whole or in part, before giving the sponsor an opportunity to be heard if the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of participants or other persons.

Suspension — several authorizations

(2) The Minister may suspend, in whole or in part, several authorizations to conduct a clinical trial before giving any sponsor an opportunity to be heard if the Minister has reasonable grounds to believe, in respect of each of the clinical trials to which those authorizations relate, that it is necessary to do so to prevent injury to the health of participants or other persons due to the same act or omission of any of the following persons:

• (a) in the case where the sponsor of each of those clinical trials is the same person,
  • (i) that sponsor, or
  • (ii) an investigator, service provider or person who is exempt from section 3.1 of the Act under subsection 7(2) who is conducting each of those clinical trials; or
• (b) in any other case, a person referred to in subparagraph (a)(ii).

Notice

(3) If the Minister suspends an authorization, the Minister must send to the sponsor a written notice that indicates the day on which the suspension takes effect, whether the authorization is suspended in whole or in part and the reasons for the suspension.

Notification of third parties — suspension

28 (1) A sponsor whose authorization is suspended in whole or in part must, without delay, notify the following persons in writing of the suspension:

• (a) investigators and service providers who are conducting the clinical trial or, if the clinical trial is suspended in part, the part of the clinical trial that is suspended;
• (b) persons who are under the sponsor’s oversight, other than investigators and service providers, and who are conducting the clinical trial or, if the clinical trial is suspended in part, the part of the clinical trial that is suspended; and
• (c) persons who import or sell a drug for use in the clinical trial.

Notification of other persons

(2) The sponsor must ensure that persons who are under the oversight of investigators and service providers and who are conducting the clinical trial — or, if the clinical trial is suspended in part, the part of the clinical trial that is suspended — are notified of the suspension as soon as feasible.

Mandatory reinstatement

29 The Minister must reinstate an authorization that is suspended in whole or in part, as the case may be, if the sponsor provides the Minister with information or material that enables the Minister to determine that

• (a) in the case of a suspension based on paragraph 26(1)(a), the applicable reason set out in any of clauses 15(1)(a)(ii)(A) to (D) does not exist in respect of the clinical trial; and
• (b) in the case of a suspension based on any of paragraphs 26(1)(b) to (e) or subsection 27(1) or (2), the situation giving rise to the suspension did not exist or has been corrected.

Discretionary revocation

30 (1) The Minister may revoke, in whole or in part, an authorization that is suspended if the sponsor does not provide the Minister with information or material within the applicable period referred to in subsection (2) that enables the Minister to determine that

• (a) in the case of a suspension based on paragraph 26(1)(a), the applicable reason set out in any of clauses 15(1)(a)(ii)(A) to (D) does not exist in respect of the clinical trial; and
• (b) in the case of a suspension based on any of paragraphs 26(1)(b) to (e) or subsection 27(1) or (2), the situation giving rise to the suspension did not exist or has been corrected.

Period — information or material

(2) The period within which the sponsor is to provide information or material is

• (a) in the case of a suspension under section 26, 30 days after the day on which the suspension takes effect; and
• (b) in the case of a suspension under section 27, 60 days after the day on which the suspension takes effect.

Clarification

(3) For greater certainty, the Minister is not authorized under subsection (1) to revoke a larger part of the authorization than the part that is suspended.

Notice

(4) If the Minister revokes an authorization under subsection (1), the Minister must send to the sponsor a written notice that indicates the day on which the revocation takes effect, whether the authorization is revoked in whole or in part and the reasons for the revocation.

Mandatory revocation — notice of discontinuation

31 The Minister must revoke, in whole or in part, an authorization if the Minister has received a notice of discontinuation referred to in subparagraph 55(1)(c)(i).

Automatic revocation — completion of sub-study

32 The part of an authorization that relates to a sub-study is revoked 15 days after the day on which the sponsor notifies the Minister of the completion date of the sub-study under section 58.

Automatic revocation — completion of clinical trial

33 An authorization is revoked in whole 15 days after the day on which the sponsor notifies the Minister of the completion date of the entire clinical trial under section 59.

Notification of third parties — revocation

34 A sponsor whose authorization is revoked, in whole or in part, must, as soon as feasible, notify the following persons in writing of the revocation:

• (a) investigators and service providers who are conducting the clinical trial or, if the clinical trial is revoked in part, the part of the clinical trial that is revoked; and
• (b) persons who import or sell a drug for use in the clinical trial.

Request by Minister

35 (1) The Minister may request that a sponsor who holds an authorization submit to the Minister any information or material that is necessary to enable the Minister to determine whether to suspend or revoke the authorization.

Time, form and manner

(2) The sponsor must submit the information or material in the time, form and manner specified by the Minister.

Direction to Cease

Application

36 Sections 37 to 44 apply to a sponsor whose clinical trial involves the use of only one or more of the following drugs:

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Prohibition — direction to cease

37 It is prohibited for a sponsor to conduct the clinical trial, in whole or in part, if they are subject to a direction imposed by the Minister under section 38 or 39.

Direction to cease — opportunity to be heard

38 (1) Subject to subsection (3), the Minister may direct a sponsor to cease the conduct of a single clinical trial, in whole or in part, if the Minister has reasonable grounds to believe that

• (a) the direction should be imposed for any of the following reasons:
  • (i) the conduct of the clinical trial, including the use of any drug in it, is likely to result in unacceptable risks to the health of its participants or other persons,
  • (ii) the clinical trial is contrary to the best interests of its participants, and
  • (iii) the objectives of the clinical trial are not achievable;
• (b) the sponsor, an investigator, a service provider or a person who is exempt from section 3.1 of the Act under subsection 6(3) has, in respect of the clinical trial, contravened any provision of the Act or these Regulations, any applicable provision of the Food and Drug Regulations or any order made under the Act;
• (c) any information submitted to the Minister by or on behalf of the sponsor, in respect of the clinical trial or a drug used in the clinical trial, is false or misleading; or
• (d) the sponsor, an investigator, a service provider or a person who is exempt from section 3.1 of the Act under subsection 6(3) has, in respect of the clinical trial, failed to comply with good clinical practices.

Direction to cease — several clinical trials

(2) Subject to subsection (3), the Minister may direct one or more sponsors to cease the conduct of several clinical trials, in whole or in part, if the Minister has reasonable grounds to believe that any of paragraphs (1)(b) to (d) applies in respect of each of those clinical trials, or a drug used in each of those clinical trials, as the case may be, due to the same act or omission of any of the following persons:

• (a) in the case where the sponsor of each of those clinical trials is the same person,
  • (i) that sponsor, or
  • (ii) an investigator, service provider or person who is exempt from section 3.1 of the Act under subsection 6(3) who is conducting each of those clinical trials; or
• (b) in any other case, a person referred to in subparagraph (a)(ii).

Conditions

(3) The Minister may direct a sponsor to cease the conduct of a clinical trial under subsection (1) or (2) only if

• (a) the Minister has sent to the sponsor a notice that indicates whether the direction to cease is to apply to the clinical trial in whole or in part and the reasons for the direction; and
• (b) the sponsor does not, within 30 days after the day on which they receive that notice, provide the Minister with information or material that enables the Minister to determine that
  • (i) in the case of an intended direction based on paragraph (1)(a), the applicable reason set out in any of subparagraphs (1)(a)(i) to (iii) does not exist in respect of the clinical trial, and
  • (ii) in the case of an intended direction based on any of paragraphs (1)(b) to (d), the situation giving rise to the intended direction did not exist or has been corrected.

Notice

(4) If the Minister directs the sponsor to cease the conduct of a clinical trial, the Minister must send to the sponsor a written notice that indicates the day on which the direction takes effect, whether the direction applies to the clinical trial in whole or in part and the reasons for the direction.

Direction to cease — immediate

39 (1) The Minister may direct a sponsor to cease the conduct of a single clinical trial, in whole or in part, before giving the sponsor an opportunity to be heard, if the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of participants or other persons.

Direction to cease — several clinical trials

(2) The Minister may direct one or more sponsors to cease the conduct of several clinical trials, in whole or in part, before giving any sponsor an opportunity to be heard, if the Minister has reasonable grounds to believe, in respect of each of the clinical trials, that it is necessary to do so to prevent injury to the health of participants or other persons due to the same act or omission of any of the following persons:

• (a) in the case where the sponsor of each of those clinical trials is the same person,
  • (i) that sponsor, or
  • (ii) an investigator, service provider or person who is exempt from section 3.1 of the Act under subsection 6(3) who is conducting each of those clinical trials; or
• (b) in any other case, a person referred to in subparagraph (a)(ii).

Notice

(3) If the Minister directs a sponsor to cease the conduct of a clinical trial, the Minister must send to the sponsor a written notice that indicates the day on which the direction takes effect, whether the direction applies to the clinical trial in whole or in part and the reasons for the direction.

Notification of third parties — direction to cease

40 (1) If the Minister directs a sponsor to cease the conduct of a clinical trial under section 38 or 39, the sponsor must, without delay, notify the following persons in writing of the direction:

• (a) investigators and service providers who are conducting the clinical trial or, if the direction is to cease the clinical trial in part, the part of the clinical trial to which the direction relates;
• (b) persons who are under the sponsor’s oversight, other than investigators and service providers, and who are conducting the clinical trial or, if the direction is to cease the clinical trial in part, the part of the clinical trial to which the direction relates; and
• (c) persons who import or sell a drug for use in the clinical trial.

Notification of other persons

(2) The sponsor must ensure that persons who are under the oversight of investigators and service providers and who are conducting the clinical trial — or, if the direction is to cease the clinical trial in part, the part of the clinical trial to which the direction relates — are notified of the direction as soon as feasible.

Mandatory lifting of direction

41 (1) The Minister must lift a direction to cease the conduct of a clinical trial in whole or in part, as the case may be, if the sponsor provides the Minister with information or material within the applicable period referred to in subsection (2), that enables the Minister to determine that

• (a) in the case of a direction based on paragraph 38(1)(a), the applicable reason set out in any of subparagraphs 38(1)(a)(i) to (iii) does not exist in respect of the clinical trial; and
• (b) in the case of a direction based on any of paragraphs 38(1)(b) to (d) or subsection 39(1) or (2), the situation giving rise to the direction did not exist or has been corrected.

Period — information or material

(2) The period within which the sponsor is to provide information or material is

• (a) in the case of a direction imposed under section 38, 30 days after the day on which the direction takes effect; and
• (b) in the case of a direction imposed under section 39, 60 days after the day on which the direction takes effect.

Permanent direction to cease

42 A direction imposed by the Minister on a sponsor under section 38 or 39 becomes permanent if the Minister does not lift the direction within 15 days after the day on which the applicable period referred to in subsection 41(2) ends.

Notification of third parties — permanent direction to cease

43 If the Minister directs a sponsor to cease the conduct of a clinical trial under section 38 or 39 and the direction becomes permanent under section 42, the sponsor must, as soon as feasible, notify the following persons in writing that the direction has become permanent:

• (a) investigators and service providers who are conducting the clinical trial or, if the direction is to cease the clinical trial in part, the part of the clinical trial to which the direction relates; and
• (b) persons who import or sell a drug for use in the clinical trial.

Request by Minister

44 (1) The Minister may request that a sponsor submit to the Minister any information or material that is necessary to enable the Minister to determine whether to direct the sponsor to cease the conduct of the clinical trial.

Time, form and manner

(2) The sponsor must submit the information or material in the time, form and manner specified by the Minister.

General

National Research Ethics Boards

Interpretation

45 (1) Paragraph 17(1)(a), subsections 23(1) and (2) and paragraph 61(2)(g) are to be read without reference to the words “for the clinical trial site” if the research ethics board referred to in the applicable provision is a national research ethics board.

Additional interpretation

(2) Paragraphs 46(1)(f) and 61(2)(g) and (h) are to be read without reference to the words “for each clinical trial site” if the research ethics board referred to in the applicable provision is a national research ethics board.

Good Clinical Practices

Good clinical practices — requirements

46 (1) The sponsor of a clinical trial must ensure that the clinical trial is conducted in accordance with good clinical practices, including by ensuring that

• (a) the clinical trial is scientifically sound and clearly described in a detailed protocol;
• (b) the study population of the clinical trial is consistent with the objectives of the clinical trial;
• (c) the clinical trial is conducted, and each drug used in the clinical trial is used, in accordance with the protocol and these Regulations;
• (d) if the sponsor holds an authorization in respect of the clinical trial, the clinical trial is conducted in accordance with the terms and conditions imposed on the authorization, if any;
• (e) systems and procedures are implemented that are
  • (i) designed to ensure the protection of the health of participants and other persons,
  • (ii) proportionate to the risks to the health of participants and other persons, and
  • (iii) designed to ensure the quality of every aspect of the clinical trial and the reliability of its results;
• (f) for each clinical trial site, the approval of a research ethics board is obtained before the clinical trial begins;
• (g) for each clinical trial site, there is no more than one investigator;
• (h) for each clinical trial site, medical care and medical decisions in respect of the clinical trial are under the supervision of
  • (i) in the case of a clinical trial respecting a drug to be used for dental purposes only, a person who is entitled to practise medicine or dentistry under the laws of the province where the main location of the clinical trial site is situated, and
  • (ii) in any other case, a person who is entitled to practise medicine under the laws of the province where the main location of the clinical trial site is situated;
• (i) each person who conducts the clinical trial is qualified by education, training and experience to perform their respective tasks;
• (j) subject to section 47, documented informed consent, given in accordance with the applicable laws governing consent, is obtained from every prospective participant prior to their participation in the clinical trial, but only after they have been informed of
  • (i) the risks and anticipated benefits to their health arising from participation in the clinical trial, and
  • (ii) all other aspects of the clinical trial that are necessary for them to make the decision to participate in the clinical trial;
• (k) in the case of a clinical trial in respect of which the conditions set out in section 47 are met, documented informed consent, given in accordance with the applicable laws governing consent, is obtained — when possible and, if so, as soon as feasible — from every participant before they continue to participate in the clinical trial, but only after they have been informed of
  • (i) the risks and anticipated benefits to their health arising from participation in the clinical trial, and
  • (ii) all other aspects of the clinical trial that are necessary for them to decide whether they will continue to participate in the clinical trial; and
• (l) subject to section 48, each drug used in the clinical trial is fabricated, handled and stored in accordance with the applicable good manufacturing practices referred to in Divisions 2 to 4 of Part C of the Food and Drug Regulations, with the exception of sections C.02.019, C.02.025 and C.02.026 of those Regulations.

Other persons

(2) Any person who, in addition to the sponsor, conducts a clinical trial must do so in accordance with good clinical practices, including the practices set out in paragraphs (1)(a) to (l) that are relevant to their roles and responsibilities in the conduct of the clinical trial.

Exception — clinical trial involving medical emergency

47 Paragraph 46(1)(j) does not apply to a clinical trial if the following conditions are met:

• (a) the objectives of the clinical trial relate to persons experiencing medical emergencies that are described in the protocol;
• (b) the protocol provides that it is not necessary to obtain documented informed consent from a participant prior to their participation in the clinical trial, but only in circumstances in which it is impossible to comply with that paragraph; and
• (c) there are reasonable grounds to believe that the following conditions apply to the medical emergencies to which the clinical trial’s objectives relate:
  • (i) either no standard of care exists or participation in the clinical trial offers a potential direct benefit to the health of a participant that is greater than the potential direct benefit to their health offered by the standard of care, and
  • (ii) either the risks of participation in the clinical trial to the health of a participant are not greater than that those posed by the standard of care or the risks of participation to their health are justified by the potential direct benefit of participation to their health.

Exception — drug used as authorized

48 Paragraph 46(1)(l) does not apply to

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Provision of Information

Notification after change made — authorization issued

49 (1) A sponsor who holds an authorization in respect of a clinical trial must notify the Minister in writing of any of the following changes in respect of the clinical trial within 15 days after the day on which the change is made:

• (a) a change to the sponsor’s name or contact information;
• (b) in the case of a foreign sponsor, a change to the name or contact information of the sponsor’s representative in Canada;
• (c) if a drug to be used in the clinical trial is to be imported, a change to the name or contact information of the sponsor’s representative in Canada who is responsible for the importation of the drug or the sale of the drug;
• (d) a change to the name or contact information of the investigator at a clinical trial site;
• (e) if, in respect of a clinical trial site, the investigator’s contact information specifies a civic address that differs from the civic address of the clinical trial site’s main location, a change to the civic address of the main location other than a change to the civic address that results from a change to its physical location;
• (f) a change to the name or contact information of a service provider who is conducting the clinical trial;
• (g) a change to the name and contact information of a research ethics board referred to in paragraph 11(2)(i);
• (h) an amendment to the protocol referred to in paragraph 11(2)(e) that does not alter the risk to the health of participants or other persons, other than an amendment to the protocol for which an amendment to the authorization is required by section 19; and
• (i) a change to the chemistry and manufacturing information for a drug used in the clinical trial that does not affect the quality or safety of the drug.

Replacement of person

(2) If any of the following persons are replaced, the sponsor must provide the Minister with the name and contact information of the new person within 15 days after the day on which they begin to occupy the position:

• (a) in the case of a foreign sponsor, the sponsor’s representative in Canada;
• (b) if a drug used in the clinical trial is imported,
  • (i) the sponsor’s representative in Canada who is responsible for the importation of the drug, and
  • (ii) the sponsor’s representative in Canada who is responsible for the sale of the drug; and
• (c) in respect of a clinical trial site, the investigator.

Provision of information after becoming aware — authorization issued

50 (1) A sponsor who holds an authorization in respect of a clinical trial must provide the following information to the Minister in respect of the clinical trial within 15 days after the day on which they become aware of it:

• (a) any information referred to in paragraph 11(2)(j) or (k); and
• (b) the name and contact information of the research ethics board that, in respect of a clinical trial site, approved the protocol referred to in paragraph 11(2)(e) and the informed consent form that contains the statement referred to in paragraph 11(2)(g) but withdrew that approval, including its reasons for doing so and the date on which approval was withdrawn.

Exception — research ethics board information

(2) The requirement under paragraph (1)(b) to provide the name and contact information of a research ethics board does not apply if the research ethics board that withdrew its approval was a national research ethics board.

Service providers commencing service — authorization issued

51 A sponsor who holds an authorization in respect of a clinical trial must notify the Minister in writing of the name and contact information of a service provider who provides a service to or on behalf of the sponsor or an investigator in respect of the clinical trial within 15 days after the day on which the service provider begins to provide the service, if the information was not previously submitted to the Minister.

Serious unexpected adverse drug reactions — authorization issued

52 (1) If a serious unexpected adverse drug reaction occurs during the course of a clinical trial — regardless of whether the clinical trial is being conducted inside or outside Canada — the sponsor who holds the authorization in respect of the clinical trial must notify the Minister in writing of the serious unexpected adverse drug reaction:

• (a) if it is neither fatal nor life threatening, within 15 days after the day on which they become aware of it; and
• (b) if it is fatal or life threatening, within seven days after the day on which they become aware of it.

Complete report

(2) The sponsor must, within eight days after the day on which they notify the Minister under paragraph (1)(b), submit to the Minister a complete report in respect of the serious unexpected adverse drug reaction that includes an assessment of the importance and implications of any findings.

Case reports and summary report — authorization issued

53 (1) The Minister may, for the purposes of assessing the safety of a drug that is used in a clinical trial, request in writing that the sponsor who holds the authorization in respect of the clinical trial submit to the Minister any of the following reports in respect of the drug:

• (a) the case reports relating to any adverse drug reactions and serious adverse drug reactions that are known to the sponsor; or
• (b) an issue-related summary report.

Content of summary report

(2) A report referred to in paragraph (1)(b) must contain a concise, critical analysis of any adverse drug reactions and serious adverse drug reactions, as well as case reports of all or specified adverse drug reactions and serious adverse drug reactions that are known to the sponsor in respect of the issue that the Minister directs the sponsor to analyze in the report.

Time, form and manner

(3) The sponsor must provide any reports requested under subsection (1) in the time, form and manner specified by the Minister.

Definition of case report

(4) In this section, case report means a detailed record of all relevant data associated with the use of a drug in a participant.

Exception — drug used as authorized

54 Sections 52 and 53 do not apply to

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Discontinuation of clinical trial — authorization issued

55 (1) If a sponsor who holds an authorization in respect of a clinical trial discontinues the clinical trial in whole or in part, the sponsor must

• (a) without delay notify all investigators who are conducting the clinical trial in writing of the discontinuation, the reasons for it and any potential risks to the health of participants or other persons;
• (b) in the case where a national research ethics board approved the protocol referred to in paragraph 11(2)(e), without delay notify the national research ethics board in writing of the discontinuation, and the reasons for it and any potential risks to the health of participants or other persons;
• (c) within 15 days after the day on which the clinical trial is discontinued, notify the Minister in writing of
  • (i) the discontinuation and the reasons for it, and
  • (ii) any impact that the discontinuation may have on any other clinical trial that involves a drug used in the clinical trial and in respect of which the sponsor holds an authorization, including any potential risks to the health of participants or other persons; and
• (d) subject to subsection (2), in respect of each clinical trial site for which the trial is discontinued, stop the sale and, if applicable, importation of each drug used in the clinical trial as of the day on which the clinical trial is discontinued and take all reasonable measures to recover all quantities of those drugs that have been sold but remain unused.

Exception — drug used as authorized

(2) The requirement under paragraph (1)(d) to take all reasonable measures to recover all quantities of the drug that have been sold but remain unused does not apply to

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, if the use of the drug in the clinical trial is for a purpose — and falls within the conditions of use that relate to that purpose — for which the notice of compliance is issued; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled, if the use of the drug in the clinical trial falls within a use or purpose for which the drug identification number was assigned.

Notification of discontinuation by investigator — authorization issued

56 (1) Subject to subsection (2), an investigator who is notified by a sponsor under paragraph 55(1)(a) of the discontinuation of a clinical trial must, if the discontinuation affects the investigator’s clinical trial site, without delay,

• (a) notify the participants who are associated with the clinical trial site — and the research ethics board that approved the protocol for the clinical trial site — in writing of the discontinuation and the reasons for it; and
• (b) notify the participants and the research ethics board in writing of any potential risks to the health of participants or other persons that were communicated to the investigator by the sponsor under paragraph 55(1)(a).

Exception — national research ethics board

(2) If the research ethics board that approved the protocol is a national research ethics board,

• (a) paragraph (1)(a) is to be read without reference to the words “and the research ethics board that approved the protocol for the clinical trial site”; and
• (b) paragraph (1)(b) is to be read without reference to the words “and the research ethics board”.

Closure of clinical trial site — authorization issued

57 (1) A sponsor who holds an authorization in respect of a clinical trial must notify the Minister in writing of the closure of a clinical trial site within 15 days after the day on which it is closed.

Interpretation — closed

(2) For the purposes of subsection (1), a clinical trial site is considered to be closed when the last visit of the last participant at the last of the locations referred to in subsection 2(1) is finished.

Notification of completion of sub-study — authorization issued

58 A sponsor who holds an authorization in respect of a clinical trial that includes a sub-study must notify the Minister and every investigator and service provider who is conducting the sub-study in writing of the sub-study’s completion date within 15 days after that date.

Notification of completion of clinical trial — authorization issued

59 A sponsor who holds an authorization in respect of a clinical trial must notify the Minister and every investigator and service provider who is conducting the clinical trial in writing of the completion date of the entire clinical trial within 15 days after that date.

Direction to notify — former holder

60 (1) The Minister may direct a sponsor who is the former holder of an authorization in respect of a clinical trial to notify the Minister of any serious adverse drug reaction or serious unexpected adverse drug reaction in respect of a drug that was used in the clinical trial if the following conditions are met:

• (a) the drug is not
  • (i) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, or
  • (ii) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled; and
• (b) the Minister has reasonable grounds to believe that there could be a risk for participants of health consequences associated with the use of the drug in the clinical trial that could arise over the long term.

Obligation to notify

(2) A sponsor who is subject to a direction imposed under subsection (1) must notify the Minister in writing of any serious adverse drug reaction or serious unexpected adverse drug reaction that occurs after the completion of the entire clinical trial, regardless of whether the clinical trial was conducted inside or outside Canada:

• (a) if it is neither fatal nor life threatening, within 15 days after the day on which they become aware of it; and
• (b) if it is fatal or life threatening, within seven days after the day on which they become aware of it.

Complete report

(3) The sponsor must, within eight days after the day on which they notify the Minister under paragraph (2)(b), submit to the Minister a complete report in respect of the serious adverse drug reaction or serious unexpected adverse drug reaction that includes an assessment of the importance and implications of any findings.

Cessation of obligations

(4) Subsections (2) and (3) cease to apply to the sponsor on the earlier of

• (a) the day on which the 15-year period referred to in section 66, during which the sponsor is required to retain records in respect of the clinical trial, ends, and
• (b) the day on which
  • (i) in the case of a new drug, a notice of compliance has been issued in respect of the drug under section C.08.004 or C.08.004.01 of the Food and Drug Regulations, and
  • (ii) in the case of a drug, other than a new drug, a drug identification number has been assigned in respect of the drug under subsection C.01.014.2(1) of those Regulations.

Records

Records — sponsor

61 (1) The sponsor of a clinical trial must ensure that all information in respect of the clinical trial is recorded, handled and stored in a manner that allows for the complete and accurate reporting of the information as well as the interpretation and verification of the information.

Content of records

(2) The sponsor must ensure that complete and accurate records that include the following information and material are maintained to establish that the clinical trial is conducted in accordance with good clinical practices and these Regulations:

• (a) if the sponsor holds an authorization, a copy of all versions of the documents referred to in paragraph 11(2)(o) in respect of the drugs used in the clinical trial;
• (b) information respecting each change made to a document referred to in paragraph 11(2)(o), the rationale for each change and documentation that supports each change;
• (c) subject to subsections 63(1) and 64(1), information respecting any adverse event in respect of a drug used in the clinical trial that occurs inside or outside Canada, including the indication for use and the dosage form of the drug at the time of the adverse event;
• (d) information respecting the enrolment of participants, including information that allows all participants to be identified and contacted in the event that conduct of the clinical trial may endanger the health of participants or other persons;
• (e) subject to section 65, information respecting the shipment, receipt, disposition, return and destruction of each drug used in the clinical trial;
• (f) the lot or batch number of each drug used in the clinical trial;
• (g) for each clinical trial site, a copy of the protocol and informed consent form as well as any amendment to the protocol or informed consent form that has been approved for the clinical trial site by a research ethics board; and
• (h) for each clinical trial site, an attestation, signed and dated by a research ethics board, stating that it has reviewed and approved the protocol and informed consent form and that it carries out its functions in a manner consistent with good clinical practices.

Records — service providers

62 (1) Each service provider who conducts a clinical trial must record, handle and store all information in respect of the clinical trial in a manner that allows for the complete and accurate reporting of the information as well as the interpretation and verification of the information.

Content of records

(2) Subject to subsections 63(1) and 64(1), each service provider must maintain complete and accurate records that include the information and material referred to in paragraphs 61(2)(a) to (h) that are relevant to the service that they provide to or on behalf of the sponsor or an investigator, to establish that they conduct the clinical trial in accordance with good clinical practices and these Regulations.

Additional records to maintain — service provider

(3) If the sponsor of a clinical trial is required to maintain records referred to in subsection 63(2) or 64(2), a service provider who conducts the clinical trial must also maintain those records if they are relevant to the service that they provide to or on behalf of the sponsor or an investigator.

Records — selective approach to adverse events

63 (1) If, in the case where a sponsor holds an authorization in respect of a clinical trial, the protocol referred to in paragraph 11(2)(e) describes a selective approach to maintaining records of adverse events in respect of a drug used in the clinical trial,

• (a) paragraph 61(2)(c) does not apply, in respect of the drug, to the sponsor; and
• (b) subsection 62(2) does not apply, in respect of information referred to in paragraph 61(2)(c) as that paragraph pertains to the drug, to a service provider who conducts the clinical trial.

Records to maintain — sponsor

(2) The sponsor must ensure that records are maintained that include all of the following information in respect of the drug that is the subject of the selective approach:

• (a) information respecting any serious unexpected adverse drug reaction in respect of the drug that occurs inside or outside Canada, including the drug’s indication for use and the dosage form of the drug at the time of the reaction; and
• (b) information respecting any other adverse event in respect of the drug, as provided for by the selective approach, that occurs inside or outside Canada, including the drug’s indication for use and the dosage form of the drug at the time of the adverse event.

Exception — exempt sponsor

64 (1) Paragraph 61(2)(c) does not apply to the sponsor of a clinical trial — and subsection 62(2) does not apply, in respect of information referred to in paragraph 61(2)(c), to a service provider who conducts the clinical trial — if the sponsor is exempt, in respect of the clinical trial, under subsection 6(1) from section 3.1 of the Act.

Records to maintain — sponsor

(2) The sponsor must ensure that records are maintained that include information on any serious adverse drug reaction or serious unexpected adverse drug reaction in respect of a drug used in the clinical trial that occurs inside or outside Canada, including the drug’s indication for use and the dosage form of the drug at the time of the adverse drug reaction.

Exception — authorized drug

65 Paragraph 61(2)(e) does not apply to

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of the Food and Drug Regulations; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled.

Retention period after end of clinical trial

66 (1) A sponsor must retain the records referred to in sections 61 and 62 and subsections 63(2) and 64(2) for a period of at least 15 years.

Beginning of period

(2) The period referred to in subsection (1) begins on

• (a) if the sponsor is the former holder of an authorization in respect of the clinical trial, the day on which the authorization is revoked in whole; and
• (b) if the sponsor is, under subsection 6(1), exempt from section 3.1 of the Act, the earliest of
  • (i) the day on which the clinical trial is completed in whole,
  • (ii) the day on which the clinical trial is discontinued in whole by the sponsor, and
  • (iii) the day on which a direction to cease the conduct of the clinical trial in whole, imposed by the Minister under section 38 or 39, becomes permanent under section 42.

Labelling

Prohibition on conduct — without required label

67 (1) Subject to section 68, it is prohibited to conduct a clinical trial in respect of a drug unless the drug is labelled in accordance with subsections (2) to (8).

Required information

(2) The label of the drug must set out all of the following information in both English and French:

• (a) a statement to the effect that the drug is for use only in a clinical trial by an investigator;
• (b) the brand name, code or chemical name of the drug or a number or identifying mark assigned to the drug for the purposes of the clinical trial;
• (c) the expiration date of the drug, if any;
• (d) the recommended storage conditions for the drug;
• (e) the lot or batch number of the drug;
• (f) the sponsor’s name and information that enables a person in Canada to contact the sponsor; and
• (g) the protocol code.

Lot number preceded by designation

(3) The lot number of the drug must be preceded on the label by one of the following designations:

• (a) “Lot number”;
• (b) “Lot No.”;
• (c) “Lot”; or
• (d) “(L)”.

Pressurized containers

(4) If the drug is contained in a container described in subsection A.01.061(1) or A.01.062(1) of the Food and Drug Regulations, the label must meet the applicable requirements of sections A.01.061 to A.01.063 of those Regulations.

Required symbol and words

(5) In the case of a radiopharmaceutical, the label must display the symbol and the words referred to in subparagraph C.03.202(1)(b)(vi) of the Food and Drug Regulations.

Manner of display

(6) The information and symbols required under subsections (2) to (5) must be displayed on the label in a legible and prominent manner.

Manner of expression

(7) The information required under subsection (2) must be expressed in plain language.

Format

(8) The format of the label, including the manner in which any text or graphics are displayed on it, must not impede comprehension of the information required to be displayed under subsections (2) to (5).

Non-application — prohibition

68 Section 67 does not apply to any of the following drugs if it is labelled in accordance with the Food and Drug Regulations:

• (a) a new drug in respect of which a notice of compliance is issued under section C.08.004 or C.08.004.01 of those Regulations; or
• (b) a drug, other than a new drug, for which a drug identification number has been assigned under subsection C.01.014.2(1) of those Regulations but not cancelled.

Transitional Provisions

Interpretation

Definitions

69 (1) The following definitions apply in this section and in sections 70 to 81:

former Clinical Trials for Medical Devices Relating to COVID-19 Regulations

means the Clinical Trials for Medical Devices Relating to COVID-19 Regulations as they read immediately before the day on which these Regulations come into force. (ancien Règlement sur les essais cliniques d’instruments médicaux en lien avec la COVID-19)

former Food and Drug Regulations

means the Food and Drug Regulations as they read immediately before the day on which these Regulations come into force. (ancien Règlement sur les aliments et drogues)

Interpretation

(2) Despite subsection 1(2), unless the context otherwise requires, words and expressions used in sections 70 to 81 have the same meaning as in the former Food and Drug Regulations and the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations, as applicable.

Applications for Authorization

Deeming — applications for authorization

70 The following applications are deemed to be an application for an authorization submitted under these Regulations:

• (a) an application that is submitted under section C.05.005 of the former Food and Drug Regulations before the day on which these Regulations come into force and in respect of which the following conditions are met immediately before that day:
  • (i) the sponsor has not withdrawn the application,
  • (ii) the 30-day period referred to in paragraph C.05.006(1)(b) of the former Food and Drug Regulations has not ended,
  • (iii) the Minister has not sent a notice to the sponsor indicating that the Minister has no objection, under paragraph C.05.006(1)(b) of the former Food and Drug Regulations, to the sale or importation of a drug for the purposes of the clinical trial, and
  • (iv) the Minister has not sent a notice to the sponsor under paragraph C.05.006(1)(b) of the former Food and Drug Regulations indicating that the sponsor may not sell or import the drug; and
• (b) an application for a COVID-19 drug authorization that is submitted under section 20 of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force and in respect of which no decision is made before that day.

Applications in queue

71 (1) If an application referred to in paragraph 70(a) is submitted at least seven days before the day on which these Regulations come into force and the Minister determines the application to be complete,

• (a) subsection 14(1) does not apply to the application; and
• (b) the Minister must, on the day on which these Regulations come into force, issue to the sponsor
  • (i) a written notice that indicates the day on which the application was submitted, and
  • (ii) a contingent authorization in respect of the clinical trial.

Interpretation

(2) In the case of an application referred to in subsection (1),

• (a) the references to “paragraph 14(1)(b)” in the definition authorization in subsection 1(1) and in subsections 15(1), 15(2) and 16(1) are to be read as references to “subparagraph 71(1)(b)(ii)”; and
• (b) the references to “section 14” in subsections 15(1) and 16(1) are to be read as references to “subsection 71(1)”.

Deeming — applications to amend authorization

72 The following applications are deemed to be an application to amend an authorization submitted under these Regulations:

• (a) an application that is submitted under section C.05.008 of the former Food and Drug Regulations before the day on which these Regulations come into force and in respect of which the following conditions are met immediately before that day:
  • (i) the sponsor has not withdrawn the application,
  • (ii) the 30-day period referred to in paragraph C.05.008(1)(b) of the former Food and Drug Regulations has not ended,
  • (iii) the Minister has not sent a notice to the sponsor indicating that the Minister has no objection, under paragraph C.05.008(1)(b) of the former Food and Drug Regulations, to the sale or importation of a drug for the purposes of the clinical trial in accordance with the amendment, and
  • (iv) the Minister has not sent a notice to the sponsor under paragraph C.05.008(1)(b) of the former Food and Drug Regulations indicating that the sponsor may not sell or import the drug in accordance with the amendment; and
• (b) an application to amend a COVID-19 drug authorization that is submitted under subsection 24(2) of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force and in respect of which no decision has been made before that day.

Authorizations

Deeming — Budget Implementation Act, 2019, No. 1

73 (1) Subject to subsections (2) to (4), a sponsor is deemed to be the holder of an authorization issued under these Regulations in respect of a clinical trial if the following conditions are met immediately before the day on which these Regulations come into force:

• (a) the sponsor is deemed to hold an authorization to conduct the clinical trial under section 180 of the Budget Implementation Act, 2019, No. 1;
• (b) the authorization referred to in paragraph (a) has not been revoked in whole under subsection 41(3) of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations;
• (c) the sponsor is authorized under subsection C.05.006(1) of the former Food and Drug Regulations to sell or import a drug for the purposes of the clinical trial; and
• (d) the clinical trial has not been completed or discontinued in its entirety.

Amendment

(2) If the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is amended under section C.05.008 of the former Food and Drug Regulations before the day on which these Regulations come into force, the authorization that the sponsor is deemed to hold under subsection (1) is deemed to be amended to the same extent if either of the following conditions is met immediately before that day:

• (a) the sponsor is authorized under subsection C.05.008(1) of the former Food and Drug Regulations to sell or import the drug for the purposes of the clinical trial in accordance with the amended authorization referred to in that subsection, or
• (b) in the case where the 30-day period referred to in paragraph C.05.008(1)(b) of the former Food and Drug Regulations has not ended in regard to an application for amendment submitted by the sponsor under subsection C.05.008(3) of those Regulations in respect of the clinical trial, the sponsor has received from the Minister a notice indicating that the Minister has no objection, under paragraph C.05.008(1)(b) of those Regulations, to the sale or importation of the drug for the purposes of the clinical trial in accordance with the amendment.

Suspension

(3) If, immediately before the day on which these Regulations come into force, the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is suspended in its entirety or at a clinical trial site, the authorization that the sponsor is deemed to hold under subsection (1) is

• (a) in the case of a suspension under subsection C.05.016(1) of the former Food and Drug Regulations, deemed to be suspended to the same extent under subsection 26(1) of these Regulations; and
• (b) in the case of a suspension under subsection C.05.017(1) of the former Food and Drug Regulations, deemed to be suspended to the same extent under subsection 27(1) of these Regulations.

Revocation in part

(4) If the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is cancelled at a clinical trial site under Division 5 of Part C of the former Food and Drug Regulations before the day on which these Regulations come into force, the authorization that the sponsor is deemed to hold under subsection (1) is deemed to be revoked to the same extent under these Regulations.

Deeming — certain drugs

74 (1) Subject to subsections (3) to (5), a sponsor is deemed to be the holder of an authorization issued under these Regulations in respect of a clinical trial if the following conditions are met immediately before the day on which these Regulations come into force:

• (a) the sponsor is not deemed to hold an authorization to conduct the clinical trial under section 180 of the Budget Implementation Act, 2019, No. 1;
• (b) the sponsor
  • (i) is authorized under subsection C.05.006(1) of the former Food and Drug Regulations to sell or import a drug for the purposes of the clinical trial, or
  • (ii) has received a notice indicating that the Minister has no objection, under paragraph C.05.006(1)(b) of the former Food and Drug Regulations, to the sale or importation of a drug for the purposes of the clinical trial, in the case where the 30-day period referred to in paragraph C.05.006(1)(b) of those Regulations has not ended in regard to an application for authorization submitted by the sponsor under section C.05.005 of those Regulations in respect of the clinical trial; and
• (c) the clinical trial has not been completed or discontinued in its entirety.

Application of rules

(2) Subsections (3) to (5) apply to the case referred to in subparagraph (1)(b)(i).

Amendment

(3) If the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is amended under section C.05.008 of the former Food and Drug Regulations before the day on which these Regulations come into force, the authorization that the sponsor is deemed to hold under subsection (1) is deemed to be amended to the same extent if either of the following conditions is met immediately before the day on which these Regulations come into force:

• (a) the sponsor is authorized under subsection C.05.008(1) of the former Food and Drug Regulations to sell or import the drug for the purposes of the clinical trial in accordance with the amended authorization referred to in that subsection, or
• (b) in the case where the 30-day period referred to in paragraph C.05.008(1)(b) of the former Food and Drug Regulations has not ended in regard to an application for amendment submitted by the sponsor under subsection C.05.008(3) of those Regulations in respect of the clinical trial, the sponsor has received from the Minister a notice indicating that the Minister has no objection, under paragraph C.05.008(1)(b) of those Regulations, to the sale or importation of the drug for the purposes of the clinical trial in accordance with the amendment.

Suspension

(4) If, immediately before the day on which these Regulations come into force, the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is suspended in its entirety or at a clinical trial site, the authorization that the sponsor is deemed to hold under subsection (1) is

• (a) in the case of a suspension under subsection C.05.016(1) of the former Food and Drug Regulations, deemed to be suspended to the same extent under subsection 26(1) of these Regulations; and
• (b) in the case of a suspension under subsection C.05.017(1) of the former Food and Drug Regulations, is deemed to be suspended to the same extent under subsection 27(1) of these Regulations.

Revocation in part

(5) If the sponsor’s authorization to sell or import a drug for the purposes of the clinical trial is cancelled at a clinical trial site under Division 5 of Part C of the former Food and Drug Regulations before the day on which these Regulations come into force, the authorization that the sponsor is deemed to hold under subsection (1) is deemed to be revoked to the same extent under these Regulations.

Deeming — COVID-19 drugs

75 (1) Subject to subsections (2) to (5), a COVID-19 drug authorization that is issued under the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force is deemed to be an authorization issued under these Regulations if the following conditions are met immediately before the day on which these Regulations come into force:

• (a) the COVID-19 drug authorization has not been revoked in whole under the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations; and
• (b) the clinical trial has not been completed or discontinued in whole.

Terms and conditions

(2) Any terms and conditions imposed on the COVID-19 drug authorization by the Minister under the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force are deemed to have been imposed by the Minister on that authorization under these Regulations.

Amendment

(3) If the COVID-19 drug authorization is amended under the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force, it is deemed to be an authorization amended to the same extent under these Regulations.

Suspension

(4) If, immediately before the day on which these Regulations come into force, the COVID-19 drug authorization is suspended in whole or in part under subsection 29(1) of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations, it is deemed to be suspended to the same extent under subsection 26(1) of these Regulations.

Revocation in part

(5) If the COVID-19 drug authorization is revoked in part under the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations before the day on which these Regulations come into force, it is deemed to be an authorization revoked to the same extent under these Regulations.

Revocation of authorization — Budget Implementation Act, 2019, No. 1

76 An authorization to conduct a clinical trial in respect of a drug that is held by a sponsor is revoked if the following conditions are met immediately before the day on which these Regulations come into force:

• (a) the sponsor is deemed to hold the authorization under section 180 of the Budget Implementation Act, 2019, No. 1; and
• (b) the authorization has not been revoked in whole under subsection 41(3) of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations.

Other Matters

Service providers — notification by sponsor

77 (1) A sponsor who is deemed to be the holder of an authorization in respect of a clinical trial under any of sections 73 to 75 must notify the Minister in writing of the name and contact information of each service provider who began to conduct the clinical trial before the day on which these Regulations come into force.

Time limit

(2) The sponsor must notify the Minister in writing before the day that, in the sixth month after the month in which these Regulations come into force, has the same calendar number as the day on which they come into force or, if that sixth month has no day with that number, the last day of that sixth month.

Clarification

(3) For greater certainty, section 51 does not apply to the sponsor in respect of service providers referred to in subsection (1).

Deeming — requests

78 A request by the Minister described in column 1 of the table to this section is deemed to have been made by the Minister under the provision of these Regulations set out in column 2 if the request is made before the day on which these Regulations come into force and is in respect of a clinical trial that, immediately before the day on which these Regulations come into force, has not been completed or discontinued in whole.

TABLE

Item	Column 1 Description of Request	Column 2 Provision of these Regulations Under Which the Request is Deemed to Have Been Made
1	Request made under section C.05.009 of the former Food and Drug Regulations in respect of an application for authorization referred to in paragraph 70(a) of these Regulations	13
2	Request made under section C.05.009 of the former Food and Drug Regulations in respect of an application for amendment referred to in paragraph 72(a) of these Regulations	21
3	Request made under section C.05.013 of the former Food and Drug Regulations to a sponsor who is deemed, under section 73 or 74 of these Regulations, to hold an authorization issued under these Regulations	35
4	Request made under section C.05.013 of the former Food and Drug Regulations to a sponsor who is exempt, in respect of a clinical trial, from section 3.1 of the Act under subsection 6(1) of these Regulations	44
5	Request made under section 30 of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations in respect of an application for an authorization referred to in paragraph 70(b) of these Regulations	13
6	Request made under section 30 of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations in respect of an application for amendment referred to in paragraph 72(b) of these Regulations	21
7	Request made under section 30 of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations — to a sponsor who is deemed, under section 75 of these Regulations, to hold an authorization issued under these Regulations — to enable the Minister to determine whether to suspend a COVID-19 drug authorization	35
8	Request made under section 30 of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations — to a sponsor who is exempt, in respect of a clinical trial, from section 3.1 of the Act under subsection 6(1) of these Regulations — to enable the Minister to determine whether to suspend a COVID-19 drug authorization	44

Deeming — direction to cease

79 If, immediately before the day on which these Regulations come into force, a sponsor’s authorization to sell or import a drug for the purposes of a clinical trial under subsection C.05.006(2) of the former Food and Drug Regulations is suspended in its entirety or at a clinical trial site, the sponsor is

• (a) in the case of a suspension under subsection C.05.016(1) of the former Food and Drug Regulations, deemed to be subject to a direction imposed by the Minister under subsection 38(1) of these Regulations to cease the conduct of the clinical trial to the same extent; or
• (b) in the case of a suspension under subsection C.05.017(1) of the former Food and Drug Regulations, deemed to be subject to a direction imposed under subsection 39(1) of these Regulations to cease the conduct of the clinical trial to the same extent.

Deeming — permanent direction to cease

80 If, before the day on which these Regulations come into force, a sponsor’s authorization to sell or import a drug for the purposes of a clinical trial under subsection C.05.006(2) of the former Food and Drug Regulations, is cancelled, the sponsor is

• (a) in the case of a cancellation of the authorization at a clinical trial site under paragraph C.05.016(4)(b) or C.05.017(3)(b) of the former Food and Drug Regulations, deemed to be subject to a permanent direction to cease the conduct of the clinical trial — referred to in section 42 — to the same extent; or
• (b) in the case of a cancellation of the authorization in its entirety under paragraph C.05.016(4)(b) or C.05.017(3)(b) of the former Food and Drug Regulations, deemed to be subject to a permanent direction to cease the conduct of the clinical trial — referred to in section 42 — in whole.

Records — continuation of obligation

81 (1) If, immediately before the day on which these Regulations come into force, subsection C.05.012(4) of the former Food and Drug Regulations or subsection 35(3) of the former Clinical Trials for Medical Devices Relating to COVID-19 Regulations applies to a sponsor in respect of records, that subsection continues to apply to the sponsor in respect of those records.

Clarification

(2) For greater certainty, section 66 does not apply to any records referred to in subsection (1).

Coming into Force

First anniversary of publication

82 These Regulations come into force on the first anniversary of the day on which they are published in the Canada Gazette, Part II.

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