Natural Health Products Regulations (SOR/2003-196)

PART 4Clinical Trials Involving Human Subjects

Interpretation

63 The following definitions apply in this Part.

adverse event

adverse event means any adverse occurrence in the health of a clinical trial subject who is administered a natural health product, that may or may not be caused by the administration of the natural health product, and includes an adverse reaction, a serious adverse reaction and a serious unexpected adverse reaction. (incident thérapeutique)

clinical trial

clinical trial means an investigation in respect of a natural health product that involves human subjects and that is intended to discover or verify its clinical, pharmacological or pharmacodynamic effects, to identify any adverse events that are related to its use, to study its absorption, distribution, metabolism and excretion, or to ascertain its safety or efficacy. (essai clinique)

good clinical practices

good clinical practices means generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of clinical trial subjects and other persons, and the good clinical practices referred to in section 74. (bonnes pratiques cliniques)

import

import means to import a natural health product into Canada for the purpose of sale in a clinical trial. (importer)

investigator’s brochure

investigator’s brochure means a document containing the preclinical and clinical information in respect of the natural health product that is described in paragraph 66(e). (brochure du chercheur)

protocol

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

qualified investigator

qualified investigator means the person responsible to the sponsor for the conduct of the clinical trial at a clinical trial site, who is entitled to provide health care under the laws of the province where the clinical trial site is located and who is

• (a) in the case of a clinical trial respecting a natural health product to be used for dental purposes only, a physician or dentist and a member in good standing of a professional medical or dental association; and

• (b) in any other case, a physician and a member in good standing of a professional medical association. (chercheur qualifié)

research ethics board

research ethics board means a body that is not affiliated with the sponsor, and

• (a) the principal mandate of which is to approve the initiation of, and conduct periodic reviews of, biomedical research involving human subjects in order to ensure the protection of their rights, safety and well-being; and

• (b) that has at least five members, that has a majority of members who are Canadian citizens or permanent residents under the Immigration Act, that is composed of both men and women and that includes at least

  • (i) 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, if the clinical trial is in respect of a natural health product to be used for dental purposes only, is from a medical or dental discipline,

  • (ii) one member knowledgeable in complementary or alternative health care,

  • (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 from the community or is a representative of an organization interested in the areas of research to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted. (comité d’éthique de la recherche)

sponsor

sponsor means an individual, corporate body, institution or organization that conducts a clinical trial. (promoteur)

Application

• 64 (1) Subject to subsection (2), this Part applies to the sale or importation of natural health products to be used for the purposes of clinical trials involving human subjects.

• (2) Except for paragraph 65(1)(a), subsection 65(2), section 68, paragraphs 74(a) to (i), subsections 75(1) and 76(1) and (2), paragraphs 76(3)(a) to (d) and (f) to (h), subsection 76(4) and sections 77 and 80 to 83, this Part does not apply to the sale or importation of a natural health product for the purposes of a clinical trial authorized under section 68.

Prohibition

• 65 (1) Despite section 4 and subject to subsection (2), no person shall sell or import a natural health product for the purposes of a clinical trial unless

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

  • (b) the person complies with this Part and section C.01.064 of the Food and Drug Regulations; and

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

• (2) No person shall sell a natural health product for the purposes of a clinical trial

  • (a) during the period of any suspension of the authorization under section 80 or 81; or

  • (b) after cancellation of the authorization under paragraph 82(b).

Application for Authorization

66 An application by a sponsor for authorization to sell or import a natural health product for the purposes of a clinical trial shall be submitted to the Minister 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, containing

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

  • (ii) the brand name or the code for the natural health product,

  • (iii) for each medicinal ingredient of the natural health product

    • (A) the proper name and common name of the ingredient, and

    • (B) the quantity of the ingredient per dosage unit of the natural health product,

  • (iv) a qualitative list of the non-medicinal ingredients of the natural health product,

  • (v) the dosage form of the natural health product,

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

  • (vii) if the natural health product 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 natural health product,

  • (viii) the address of each clinical trial site,

  • (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,

  • (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),

  • (xi) for each clinical trial site, 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, and

  • (xii) 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) an attestation, signed and dated by the research ethics board for each clinical trial site, that it has reviewed and approved the protocol referred to in paragraph (a) and an informed consent form containing the statement referred to in paragraph (b) and that the board carries out its functions in a manner consistent with good clinical practices;

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

  • (i) the physical, chemical and, if any, the pharmaceutical properties of the natural health product,

  • (ii) the chemistry and manufacturing information of each synthetically manufactured medicinal ingredient of the natural health product,

  • (iii) the pharmacological properties of the natural health product, if any, including its metabolites in all animal species tested,

  • (iv) the pharmacokinetics of the natural health product and the natural health product metabolism, if any, including the biological transformation of the natural health product in all animal species tested,

  • (v) the toxicological effects, if any, in any animal species tested under a single dose study, a repeated dose study or a special study in respect of the natural health product,

  • (vi) the results of carcinogenicity studies in any animal species tested in respect of the natural health product, if any,

  • (vii) the results of clinical pharmacokinetic studies of the natural health product, if any,

  • (viii) the information regarding natural health product safety, pharmacodynamics, efficacy and dose responses of the natural health product that were obtained from previous clinical trials in humans, if any,

  • (ix) the known contra-indications for and the precautions to be taken in respect of the natural health product, and

  • (x) the recommended treatment in the event of an overdose of the natural health product, if any; and

• (f) the proposed date for the commencement of the clinical trial at each clinical trial site.

Authorization

• 67 (1) The Minister shall authorize a sponsor to sell or import a natural health product for the purposes of a clinical trial if

  • (a) the sponsor submits an application to the Minister that is in accordance with section 66;

  • (b) the sponsor provides the Minister with all additional information or samples requested under section 73; and

  • (c) the Minister has reasonable grounds to believe, based on an assessment of the application, an assessment of any samples or information provided under section 73 or a review of any other information that

    • (i) the use of the natural health product for the purposes of the clinical trial will not endanger the health of a clinical trial subject or other person,

    • (ii) the clinical trial is not contrary to the best interests of the clinical trial subjects, and

    • (iii) the objectives of the clinical trial will be achieved.

• (2) The Minister shall authorize the sponsor to sell or import a natural health product for the purposes of a clinical trial by sending the sponsor a notice of the authorization.

68 A sponsor is authorized to sell or import a natural health product for the purposes of a clinical trial if the clinical trial is in respect of a recommended use or purpose for which that natural health product is issued a product licence.

Commencement Notice

69 The sponsor shall notify the Minister of the date of the sale or importation of a natural health product for the purposes of a clinical trial at a clinical trial site at least 15 days before the date of that sale or importation.

Notification

70 If the sale or importation of a natural health product for the purposes of a clinical trial is authorized under this Part, the sponsor may make one or more of the following changes if the sponsor provides the Minister with notification of the change within 15 days after the day on which the change is made:

• (a) a change to the information referred to in subparagraph 66(e)(ii) that does not affect the quality or safety of the natural health product; 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 71.

Amendment

• 71 (1) Subject to subsection (2), if the sale or importation of a natural health product for the purposes of a clinical trial is authorized under this Part, the sponsor shall not make any of the following amendments unless the authorization is amended accordingly:

  • (a) an amendment to the protocol that affects the selection, monitoring or dismissal of a clinical trial subject;

  • (b) an amendment to the protocol that affects the evaluation of the clinical efficacy of the natural health product;

  • (c) an amendment to the protocol that alters the risk to the health of a clinical trial subject;

  • (d) an amendment to the protocol that affects the safety evaluation of the natural health product;

  • (e) an amendment to the protocol that extends the duration of the clinical trial; and

  • (f) an amendment to the information referred to in subparagraph 66(e)(ii) that may affect the safety or quality of that natural health product.

• (2) If the sponsor is required to immediately make one or more of the amendments referred to in subsection (1) because the clinical trial or the use of the natural health product 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 day on which the amendment is made.

• (3) An application by the sponsor to amend the authorization for the sale or importation of a natural health product under this Part shall be submitted to the Minister and, in addition to a reference to the application submitted under section 66, shall contain the following information and documents:

  • (a) if as a result of the amendment it is necessary to amend the statement referred to in paragraph 66(b),

    • (i) a copy of the amended statement that indicates the new information, and

    • (ii) 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 amended statement;

  • (b) if the application is in respect of an amendment referred to in any of paragraphs (1)(a) to (e),

    • (i) a copy of the amended protocol that indicates the amendment,

    • (ii) a copy of the protocol submitted under paragraph 66(a),

    • (iii) the rationale for the amendment,

    • (iv) 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 amended protocol, and

    • (v) 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;

  • (c) if the application is in respect of an amendment referred to in paragraph (1)(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, if any; and

  • (d) if the application is in respect of an amendment referred to in paragraph (1)(f), a copy of the amended chemistry and manufacturing information that indicates the amendment, and the rationale for that amendment.

• (4) The Minister shall amend the authorization to sell or import a natural health product for the purposes of a clinical trial if

  • (a) the sponsor submits an application for amendment to the Minister that is in accordance with subsection (3);

  • (b) the sponsor provides the Minister with all additional information or samples requested under section 73; and

  • (c) the Minister has reasonable grounds to believe, based on an assessment of the application for amendment, an assessment of any samples or information submitted under section 73 or a review of any other information that

    • (i) the use of the natural health product for the purposes of the clinical trial will not endanger the health of a clinical trial subject or other person,

    • (ii) the clinical trial is not contrary to the best interests of the clinical trial subjects, and

    • (iii) the objectives of the clinical trial will be achieved.

• (5) The Minister shall amend the authorization to sell or import a natural health product for the purposes of a clinical trial by sending the sponsor a notice of the amendment.