Food and Drug Regulations (C.R.C., c. 870)

Prohibition

C.05.003 Despite sections C.01.014, C.08.002, C.08.002.02 and C.08.003, no person shall sell or import a drug for the purposes of a clinical trial unless

• (a) the person is authorized under this Division;

• (b) the person complies with this Division and sections C.01.015, C.01.036, C.01.037 to C.01.040, C.01.040.2, C.01.064 to C.01.067, C.01.070, C.01.134 to C.01.136, and C.01.435; and

• (c) if the drug is to be imported, the person has a representative in Canada who is responsible for the sale of the drug.

General

C.05.004 Despite these Regulations, a sponsor may submit an application under this Division to sell or import a drug for the purposes of a clinical trial that contains a substance the sale of which is prohibited by these Regulations, if the sponsor establishes, on the basis of scientific information, that the inclusion of the substance in the drug may result in a therapeutic benefit for a human being.

Application for Authorization

C.05.005 An application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial under this Division shall be submitted to the Minister, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer and shall contain the following information and documents:

• (a) a copy of the protocol for the clinical trial;

• (b) a copy of the statement, as it will be set out in each informed consent form, that states the risks and anticipated benefits arising to the health of clinical trial subjects as a result of their participation in the clinical trial;

• (c) a clinical trial attestation, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, containing

  • (i) the title of the protocol and the clinical trial number,

  • (ii) the brand name, the chemical name or the code for the drug,

  • (iii) the therapeutic and pharmacological classifications of the drug,

  • (iv) the medicinal ingredients of the drug,

  • (v) the non-medicinal ingredients of the drug,

  • (vi) the dosage form of the drug,

  • (vii) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the sponsor,

  • (viii) if the drug is to be imported, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the sponsor’s representative in Canada who is responsible for the sale of the drug,

  • (ix) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the qualified investigator, if known at the time of submitting the application,

  • (x) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the research ethics board that approved the protocol referred to in paragraph (a) and approved an informed consent form containing the statement referred to in paragraph (b), if known at the time of submitting the application, and

  • (xi) a statement

    • (A) that the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and

    • (B) that all information contained in, or referenced by, the application is complete and accurate and is not false or misleading;

• (d) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any research ethics board that has previously refused to approve the protocol referred to in paragraph (a), its reasons for doing so and the date on which the refusal was given, if known at the time of submitting the application;

• (e) an investigator’s brochure that contains the following information, namely,

  • (i) the physical, chemical and pharmaceutical properties of the drug,

  • (ii) the pharmacological aspects of the drug, including its metabolites in all animal species tested,

  • (iii) the pharmacokinetics of the drug and the drug metabolism, including the biological transformation of the drug in all animal species tested,

  • (iv) any toxicological effects in any animal species tested under a single dose study, a repeated dose study or a special study in respect of the drug,

  • (v) any results of carcinogenicity studies in any animal species tested in respect of the drug,

  • (vi) any results of clinical pharmacokinetic studies of the drug,

  • (vii) any information regarding drug safety, pharmacodynamics, efficacy and dose responses of the drug that were obtained from previous clinical trials in humans, and

  • (viii) if the drug is a radiopharmaceutical as defined in section C.03.201, information regarding directions for preparing the radiopharmaceutical, the radiation dosimetry in respect of the prepared radiopharmaceutical and a statement of the storage requirements for the prepared radiopharmaceutical;

• (f) if the drug contains a human-sourced excipient, including any used in the placebo,

  • (i) information that indicates the human-sourced excipient has been assigned a drug identification number under subsection C.01.014.2(1) or, in the case of a new drug, issued a notice of compliance under subsection C.08.004(1), as the case may be, or

  • (ii) in any other case, sufficient information to support the identity, purity, potency, stability and safety of the human-sourced excipient;

• (g) if the drug has not been assigned a drug identification number under subsection C.01.014.2(1) or, in the case of a new drug, a notice of compliance has not been issued under section C.08.004 or C.08.004.01, the chemistry and manufacturing information in respect of the drug, including its site of manufacture; and

• (h) the proposed date for the commencement of the clinical trial at each clinical trial site, if known at the time of submitting the application.

Authorization

• C.05.006 (1) Subject to subsection (3), a sponsor may sell or import a drug, other than a drug described in subsection (2), for the purposes of a clinical trial if

  • (a) the sponsor has submitted to the Minister an application in accordance with section C.05.005;

  • (b) the Minister does not, within 30 days after the date of receipt of the application, send to the sponsor a notice in respect of the drug indicating that the sponsor may not sell or import the drug for any of the following reasons:

    • (i) that the information and documents in respect of the application

      • (A) were not provided in accordance with these Regulations, or

      • (B) are insufficient to enable the Minister to assess the safety and risks of the drug or the clinical trial, or

    • (ii) that based on an assessment of the application, an assessment of any information submitted under section C.05.009 or a review of any other information, the Minister has reasonable grounds to believe that

      • (A) the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or other person,

      • (B) the clinical trial is contrary to the best interests of a clinical trial subject, or

      • (C) the objectives of the clinical trial will not be achieved;

  • (c) for each clinical trial site, the sponsor has obtained the approval of the research ethics board in respect of the protocol referred to in paragraph C.05.005(a) and in respect of an informed consent form that contains the statement referred to in paragraph C.05.005(b); and

  • (d) before the sale or importation of the drug at a clinical trial site, the sponsor submits to the Minister the information referred to in subparagraphs C.05.005(c)(ix) and (x) and paragraphs C.05.005(d) and (h), if it was not submitted in respect of that clinical trial site at the time of submitting the application.

• (2) Subject to subsection (3), a sponsor may sell or import a drug for the purposes of a clinical trial in respect of

  • (a) a new drug that has been issued a notice of compliance under subsection C.08.004(1), if the clinical trial is in respect of a purpose or condition of use for which the notice of compliance was issued; or

  • (b) a drug, other than a new drug, that has been assigned a drug identification number under subsection C.01.014.2(1), if the clinical trial is in respect of a use or purpose for which the drug identification number was assigned.

• (3) A sponsor may not sell or import a drug for the purposes of a clinical trial

  • (a) during the period of any suspension made under section C.05.016 or C.05.017; or

  • (b) after a cancellation made under section C.05.016 or C.05.017.

Notification

C.05.007 If the sale or importation of a drug is authorized under this Division, the sponsor may make one or more of the following changes if the sponsor notifies the Minister in writing within 15 days after the date of the change:

• (a) a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug, other than a change for which an amendment is required by section C.05.008; and

• (b) a change to the protocol that does not alter the risk to the health of a clinical trial subject, other than a change for which an amendment is required by section C.05.008.

Amendment

• C.05.008 (1) Subject to subsections (4) and (5), when the sale or importation of a drug is authorized under this Division and the sponsor proposes to make an amendment referred to in subsection (2), the sponsor may sell or import the drug for the purposes of the clinical trial in accordance with the amended authorization, if the following conditions are met:

  • (a) the sponsor has submitted to the Minister an application for amendment in accordance with subsection (3);

  • (b) the Minister does not, within 30 days after the date of receipt of the application for amendment, send to the sponsor a notice in respect of the drug indicating that the sponsor may not sell or import the drug in accordance with the amendment for any of the following reasons, namely,

    • (i) that the information and documents in respect of the application for amendment

      • (A) were not provided in accordance with these Regulations, or

      • (B) are insufficient to enable the Minister to assess the safety and risks of the drug or the clinical trial, or

    • (ii) that based on an assessment of the application for amendment, an assessment of any information submitted under section C.05.009 or a review of any other information, the Minister has reasonable grounds to believe that

      • (A) the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or other person,

      • (B) the clinical trial is contrary to the best interests of a clinical trial subject, or

      • (C) the objectives of the clinical trial will not be achieved;

  • (c) before the sale or importation of the drug, the sponsor submits to the Minister

    • (i) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of the research ethics board that approved any amended protocol submitted under paragraph (3)(a) or approved any amended statement submitted under paragraph (3)(c), and

    • (ii) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any research ethics board that has previously refused to approve any amendment to the protocol, its reasons for doing so and the date on which the refusal was given;

  • (d) before the sale or importation of the drug, the sponsor maintains records concerning

    • (i) the information referred to in paragraph C.05.005(h), and

    • (ii) the information referred to in subparagraph C.05.005(c)(ix), if any of that information has changed since it was submitted;

  • (e) before the sale or importation of the drug in accordance with the amended authorization, the sponsor ceases to sell or import the drug in accordance with the existing authorization; and

  • (f) the sponsor conducts the clinical trial in accordance with the amended authorization.

• (2) For the purposes of subsection (1), amendments are

  • (a) amendments to the protocol that affect the selection, monitoring or dismissal of a clinical trial subject;

  • (b) amendments to the protocol that affect the evaluation of the clinical efficacy of the drug;

  • (c) amendments to the protocol that alter the risk to the health of a clinical trial subject;

  • (d) amendments to the protocol that affect the safety evaluation of the drug;

  • (e) amendments to the protocol that extend the duration of the clinical trial; and

  • (f) amendments to the chemistry and manufacturing information that may affect the safety or quality of the drug.

• (3) The application for amendment referred to in subsection (1) shall contain a reference to the application submitted under section C.05.005 and shall contain the following documents and information:

  • (a) if the application is in respect of an amendment referred to in any of paragraphs (2)(a) to (e), a copy of the amended protocol that indicates the amendment, a copy of the protocol submitted under paragraph C.05.005(a), and the rationale for the amendment;

  • (b) if the application is in respect of an amendment referred to in paragraph (2)(e), a copy of the amended investigator’s brochure or an addendum to the investigator’s brochure that indicates the new information, including supporting toxicological studies and clinical trial safety data;

  • (c) if the application is in respect of an amendment referred to in any of paragraphs (2)(a) to (f) and, as a result of that amendment, it is necessary to amend the statement referred to in paragraph C.05.005(b), a copy of the amended statement that indicates the amendment; and

  • (d) if the application is in respect of an amendment referred to in paragraph (2)(f), a copy of the amended chemistry and manufacturing information that indicates the amendment, and the rationale for that amendment.

• (4) If the sponsor is required to immediately make one or more of the amendments referred to in subsection (2) because the clinical trial or the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or other person, the sponsor may immediately make the amendment and shall provide the Minister with the information referred to in subsection (3) within 15 days after the date of the amendment.

• (5) A sponsor may not sell or import a drug for the purposes of a clinical trial

  • (a) during the period of any suspension made under section C.05.016 or C.05.017; or

  • (b) after a cancellation made under section C.05.016 or C.05.017.

Additional Information and Samples

C.05.009 If the information and documents submitted in respect of an application under section C.05.005 or an application for amendment under section C.05.008 are insufficient to enable the Minister to determine whether any of the reasons referred to in paragraph C.05.006(1)(b) or C.05.008(1)(b) exist, the Minister may require the sponsor to submit, within two days after receipt of the request, samples of the drug or additional information relevant to the drug or the clinical trial that are necessary to make the determination.

Sponsor’s Obligations

Good Clinical Practices

C.05.010 Every sponsor shall ensure that a clinical trial is conducted in accordance with good clinical practices and, without limiting the generality of the foregoing, shall ensure that

• (a) the clinical trial is scientifically sound and clearly described in a protocol;

• (b) the clinical trial is conducted, and the drug is used, in accordance with the protocol and this Division;

• (c) systems and procedures that assure the quality of every aspect of the clinical trial are implemented;

• (d) for each clinical trial site, the approval of a research ethics board is obtained before the clinical trial begins at the site;

• (e) at each clinical trial site, there is no more than one qualified investigator;

• (f) at each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the supervision of the qualified investigator;

• (g) each individual involved in the conduct of the clinical trial is qualified by education, training and experience to perform his or her respective tasks;

• (h) written informed consent, given in accordance with the applicable laws governing consent, is obtained from every person before that person participates in the clinical trial but only after that person has been informed of

  • (i) the risks and anticipated benefits to his or her health arising from participation in the clinical trial, and

  • (ii) all other aspects of the clinical trial that are necessary for that person to make the decision to participate in the clinical trial;

• (i) the requirements respecting information and records set out in section C.05.012 are met; and

• (j) the drug is manufactured, handled and stored in accordance with the applicable good manufacturing practices referred to in Divisions 2 to 4 except sections C.02.019, C.02.025 and C.02.026.