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

• C.04.656 (1) Notwithstanding section C.04.554, a person who holds an establishment licence may sell Insulin Injection made from zinc-insulin crystals contained in vials of approximately 20 cubic centimetre capacity each of which vials

  • (a) contains an excess volume sufficient to permit withdrawal of 20 cubic centimetres, and

  • (b) provides 500 International Units of insulin per cubic centimetre,

  if

  • (c) notwithstanding section C.04.651, both the inner and outer labels are printed in black ink on white stock and overprinted in narrow brown and white diagonal stripes, of which there shall be at least five but not more than 20 to each inch;

  • (d) both the inner and the outer labels carry the statement “Warning — High Potency — Not for Ordinary Use”; and

  • (e) each package contains a descriptive circular that conforms to the requirements of section C.04.655 and, in addition, includes,

    • (i) at the beginning of the circular the statement:

      “Warning — This insulin preparation contains 500 International Units of insulin in each cubic centimetre. Extreme caution must be observed in the measurement of doses because inadvertent overdose may result in irreversible shock. Serious consequences may result if it is used other than under constant medical supervision. Unless specifically prescribed it should never be used by patients to replace use of any other insulin preparations.”,

    • (ii) a statement that Insulin made from Zinc-Insulin crystals 500 International Units per cubic centimetre should not be administered intravenously, and

    • (iii) a statement giving information for the safe and effective use by physicians of the drug in insulin shock therapy and in the treatment of diabetic patients with high insulin resistance (daily requirement more than 200 International Units of insulin).

• (2) [Repealed, SOR/95-203, s. 10]

Anterior Pituitary Extracts

C.04.675 Anterior pituitary extract shall include all natural products, prepared from the anterior lobe of the pituitary gland of animals, having physiological properties associated with the hormones of the anterior pituitary gland and their proper names shall be

• (a) Adrenocorticotrophic Hormone, Corticotrophin,

• (b) Thyrotrophic Hormone, Thyrotrophin,

• (c) Growth Hormone Pituitary, Somatotrophin,

• (d) Lactogenic Hormone, Prolactin,

• (e) Gonadotrophic Hormone, Gonadotrophin, followed by qualifying words to indicate the gonadotrophic activity associated with the extract,

and if unpurified anterior pituitary extract

• (f) Pituitary Extract Anterior Lobe followed by qualifying words to indicate the physiological properties associated with it.

C.04.676 Reference standards for anterior pituitary extract shall be

• (a) the International Standard,

• (b) where no International Standard exists, the Canadian Reference Standard shall be that established and kept by the Minister from whom portions for comparative testing may be had upon application, and

• (c) where neither an International Standard nor a Canadian Reference Standard exists, a provisional reference standard that shall be a suitable quantity of the product submitted by the distributor referred to in paragraph C.01A.003(b) to the Minister for checking the uniformity of the product.

C.04.677 Both the inner and outer labels of an anterior pituitary extract shall carry a statement of the potency in terms of the reference standard for anterior pituitary extract provided in section C.04.676 as determined by an acceptable method, except that where no reference standard for an anterior pituitary extract exists, the distributor referred to in paragraph C.01A.003(b) shall include, with every package of the anterior pituitary extract, an acceptable statement of the unit of potency and the method of assay used.

C.04.678 No person who holds an establishment licence shall sell corticotrophic hormones for subcutaneous or intramuscular use unless the preparation has been assayed by an acceptable method involving subcutaneous injection and, where the preparation is recommended for intravenous use, the label carries specific dosage instructions for that use.

C.04.679 No person shall sell as such adrenocorticotrophic hormone, thyrotrophic hormone, growth hormone pituitary, lactogenic hormone, or gonadotrophic hormone that is not acceptable free from any anterior pituitary extract other than the one for which it is named.

C.04.680 The outer label of a mixture of two or more of adrenocorticotrophic hormone, thyrotrophic hormone, growth hormone pituitary, lactogenic hormone and gonadotrophic hormone, or a mixture of any of those with pituitary extract anterior lobe, shall carry a declaration of the proper name and the amount of each component of the mixture.

C.04.681 The outer label of an anterior pituitary extract or mixture of anterior pituitary extracts shall carry a statement

• (a) showing the species of animal from which the glands used in the preparation of the anterior pituitary extract were obtained,

• (b) that it shall be stored at refrigerator temperature, and

• (c) that, except in the case of gonadotrophic hormones, it is to be used only on the advice or on the prescription of a physician.

C.04.682 Both the inner and outer labels of adrenocorticotrophic hormone shall carry a statement indicating the route of administration, in addition to meeting the requirements of paragraphs C.04.681(a) and (b).

C.04.683 The expiration date for an anterior pituitary extract or mixture of anterior pituitary extracts shall be not more than two years after the date of passing a potency test.

DIVISION 5Drugs for Clinical Trials Involving Human Subjects

Interpretation

C.05.001 The definitions in this section apply in this Division.

adverse drug reaction

adverse drug reaction means any noxious and unintended response to a drug that is caused by the administration of any dose of the drug. (réaction indésirable à une drogue)

adverse event

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

clinical trial

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

drug

drug means a drug for human use that is to be tested in a clinical trial. (drogue)

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 C.05.010. (bonnes pratiques cliniques)

import

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

investigator’s brochure

investigator’s brochure means, in respect of a drug, a document containing the preclinical and clinical data on the drug that are described in paragraph C.05.005(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 that clinical trial site is located, and who is

• (a) in the case of a clinical trial respecting a drug 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 and Refugee Protection 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 drug to be used for dental purposes only, is from a medical or dental discipline,

  • (ii) one member knowledgeable in ethics,

  • (iii) one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,

  • (iv) one member whose primary experience and expertise are in a non-scientific discipline, and

  • (v) 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)

serious adverse drug reaction

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

serious unexpected adverse drug reaction

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 investigator’s brochure or on the label of the drug. (réaction indésirable grave et imprévue à une drogue)

sponsor

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

Application

• C.05.002 (1) Subject to subsection (2), this Division applies to the sale or importation of drugs to be used for the purposes of clinical trials involving human subjects.

• (2) Except for paragraph C.05.003(a), subsections C.05.006(2) and (3), paragraphs C.05.010(a) to (i), section C.05.011, subsections C.05.012(1) and (2), paragraphs C.05.012(3)(a) to (d) and (f) to (h), subsection C.05.012(4) and sections C.05.013, C.05.016 and C.05.017, this Division does not apply to the sale or importation of a drug for the purposes of a clinical trial authorized under subsection C.05.006(2).

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.01.131, C.01.133 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.