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

C.03.209 A package insert shall be included in every kit and shall show

• (a) the proper name and the brand name, if any, of the kit and a description of its use;

• (b) a list of the contents of the kit;

• (c) the name and address of the distributor referred to in paragraph C.01A.003(b) of the kit;

• (d) identification of the radionuclides that can be used to prepare the radiopharmaceutical;

• (e) directions for preparing the radiopharmaceutical and a statement of the storage requirements for the prepared radiopharmaceutical;

• (f) a statement of the duration of the useful life of the prepared radiopharmaceutical;

• (g) a description of the biological actions of the prepared radiopharmaceutical;

• (h) indications and contraindications in respect of the prepared radiopharmaceutical;

• (i) warnings and precautions in respect of the components and the prepared radiopharmaceutical;

• (j) the adverse reactions, if any, associated with the prepared radiopharmaceutical;

• (k) where applicable, the pharmacology and toxicology of the prepared radiopharmaceutical or a statement that such information is available on request;

• (l) the radiation dosimetry in respect of the prepared radiopharmaceutical;

• (m) a statement of the recommended use for the prepared radiopharmaceutical and the recommended radioactivity to be administered for that use;

• (n) a statement of the route of administration of the prepared radiopharmaceutical; and

• (o) a recommendation that the radiochemical purity and radioactivity content of the prepared radiopharmaceutical be checked prior to administration.

Positron-emitting Radiopharmaceuticals

Interpretation

C.03.301 The following definitions apply in this section and in sections C.03.302 to C.03.319.

adverse reaction

adverse reaction means an undesirable and unintended response in a study subject or other person to a study drug that is caused by the administration of any dose of the study drug. (réaction indésirable)

good clinical practices

good clinical practices means generally accepted clinical practices that are designed to protect the rights, safety and well-being of study subjects and other persons. (bonnes pratiques cliniques)

import

import means, in respect of a study drug, to import it into Canada for sale for the purpose of a study. (importer)

other person

other person means an individual who comes into physical contact with a study subject. (autre personne)

protocol

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

qualified investigator

qualified investigator means the physician and member in good standing of a professional medical association in Canada to whom a sponsor gives the responsibility for the proper conduct of the study at a given study site, who is entitled to practise their profession under the laws of the province where the study site is located. (chercheur qualifié)

research ethics board

research ethics board means a body described in section C.03.306. (comité d’éthique de la recherche)

serious adverse reaction

serious adverse reaction means an adverse reaction that results in any of the following consequences for the study subject or other person:

• (a) their in-patient hospitalization or its prolongation;

• (b) a congenital malformation;

• (c) persistent or significant disability or incapacity;

• (d) a life-threatening condition; or

• (e) death. (réaction indésirable grave)

serious unexpected adverse reaction

serious unexpected adverse reaction means a serious adverse reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the study drug. (réaction indésirable grave et imprévue)

sponsor

sponsor means a person who is responsible for the conduct of a study. (promoteur)

study

study means a basic clinical research study that involves human subjects and that is described in sections C.03.304 and C.03.305. (étude)

study drug

study drug means a positron-emitting radiopharmaceutical that is used in a study. (drogue destinée à l’étude)

study site

study site means the location where all or part of a study is conducted. (lieu d’étude)

Application

• C.03.302 (1) Sections C.03.303 to C.03.319 apply to the sale and importation of study drugs.

• (2) Sections C.03.001 to C.03.209 and Divisions 5 and 8 do not apply to study drugs.

• (3) Sections C.03.303 to C.03.319 do not apply to a study drug manufactured from a bulk process intermediate that is of biological origin.

Prohibition

C.03.303 No person shall sell or import a study drug unless all of the following requirements are met:

• (a) the study drug is for use only in a study;

• (b) the study drug has been previously tested in human subjects and its safety in humans has been demonstrated;

• (c) if the study drug is to be imported, the manufacturer of the drug has a representative in Canada who is responsible for its sale;

• (d) the sponsor is authorized under section C.03.309 to sell or import the study drug; and

• (e) the sponsor complies with sections C.03.310 to C.03.316.

Purpose of Study

• C.03.304 (1) The purpose of a study is to obtain data on any of the following:

  • (a) the pharmacokinetics or metabolism of the study drug;

  • (b) normal human biochemistry or physiology; or

  • (c) changes caused to human biochemistry or physiology by aging, disease or medical interventions.

• (2) A study is not primarily intended to do any of the following:

  • (a) discover, identify or verify the pharmacodynamic effects of the study drug;

  • (b) identify adverse reactions;

  • (c) fulfil an immediate therapeutic or diagnostic purpose; or

  • (d) ascertain the safety or efficacy of the study drug.

Requirements

• C.03.305 (1) A study shall meet all of the following requirements:

  • (a) before the study drug is used in the study, there is sufficient data from testing it in animals and humans to demonstrate its safety in humans;

  • (b) the amount of active ingredients or combination of active ingredients in the study drug has been shown not to cause any clinically detectable pharmacodynamic effect in humans;

  • (c) the total radiation dose incurred annually by a study subject, including from multiple administrations of the study drug, from significant contaminants or from impurities and from the use of other procedures for the purposes of the study, will be not more than 50 mSv;

  • (d) any concomitant drug used in the study has been assigned a drug identification number under subsection C.01.014.2(1) or, in the case of a concomitant drug that is a new drug, has been issued a notice of compliance under section C.08.004;

  • (e) study subjects shall be at least 18 years old and have legal capacity at the time of the study;

  • (f) female study subjects shall

    • (i) be confirmed at the outset of the study, on the basis of a pregnancy test, as not being pregnant or state in writing that they are not pregnant, and

    • (ii) be advised that if they are lactating, they are to suspend lactation for 24 hours after the administration of the study drug; and

  • (g) the study shall not involve more than 30 study subjects.

• (2) Despite paragraph (1)(g), a study may involve more than 30 study subjects if the sponsor provides the Minister with a scientific rationale for the increase and the Minister approves it.

Research Ethics Board

C.03.306 A research ethics board has all of the following characteristics:

• (a) its principal mandate is to approve the initiation of and to periodically review biomedical research that involves human subjects in order to protect their rights, safety and well-being;

• (b) it has at least five members, a majority of whom are Canadian citizens or permanent residents under the Immigration and Refugee Protection Act, is composed of both men and women and includes at least the following:

  • (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,

  • (ii) one member knowledgeable in ethics,

  • (iii) one member knowledgeable in Canadian laws relevant to the 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 with the study site; and

• (c) it has no affiliations with the sponsor that could compromise its ability to fulfil its principal mandate, or that could be perceived to do so.

Application for Authorization

• C.03.307 (1) The sponsor shall submit to the Minister an application for authorization to sell or import a study drug that contains the information set out in subsection (2) as well as sufficient information to demonstrate that all of the following criteria are met:

  • (a) the use of the study drug will not endanger the health of any study subject or other person;

  • (b) the study is not contrary to the best interests of the study subjects; and

  • (c) the objectives of the study can reasonably be achieved.

• (2) The application shall contain all of the following information:

  • (a) the title of the study and the protocol code or identification;

  • (b) the purposes and a concise description of the study;

  • (c) the number of study subjects;

  • (d) the brand name, if any, of the study drug;

  • (e) the chemical or generic name of the active ingredients in the study drug;

  • (f) a qualitative list of the non-active ingredients of the study drug;

  • (g) the maximum mass of the study drug to be administered to each study subject;

  • (h) the radioactive dose range of the study drug, expressed in MBq or mCi;

  • (i) the effective dose or effective dose equivalent of the study drug, expressed in mSv/MBq or rem/mCi;

  • (j) the sponsor’s name and civic address, its postal address if different, and its telephone number, fax number and email address;

  • (k) the manufacturer’s name and civic address, its postal address if different, and its telephone number, fax number and email address;

  • (l) in the case of an application for importation, the name and civic address, the postal address if different, and the telephone number, fax number and email address of the manufacturer’s representative in Canada who is responsible for the sale of the study drug;

  • (m) the name and civic address of each study site;

  • (n) for each study site, the name, civic address, telephone number, fax number and email address of the qualified investigator;

  • (o) the proposed starting date for the study at each study site, if known;

  • (p) for each study site, the name, civic address, telephone number, fax number and email address of the research ethics board;

  • (q) a statement, dated and signed by the research ethics board for each study site, that certifies that it has reviewed and approved the study, the protocol and the statement of the risks and anticipated benefits arising to the health of study subjects as a result of participating in the study that is set out in the informed consent form;

  • (r) a list of any previous applications for an authorization to sell or import a drug for a study related to the current study; and

  • (s) a statement, dated and signed by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, that certifies both of the following:

    • (i) the study will be conducted in accordance with these Regulations, and

    • (ii) all of the information contained or referred to in the application is complete and accurate and is not false or misleading.

Additional Information

C.03.308 If the information submitted under section C.03.307 is insufficient to enable the Minister to determine whether the sale or importation of the study drug should be authorized, the Minister may, by notice in writing, request the sponsor to provide any additional information that is necessary to make the determination and that is relevant to the study drug, the study or the protocol, by the date specified in the notice.

Authorization

C.03.309 After examining the application and any additional information, the Minister shall authorize the sponsor to sell or import the study drug if she or he determines that the application complies with the requirements of section C.03.307, and shall send a notice of that decision to the sponsor that specifies the study sites in respect of which the sale or importation are authorized.

Notice

C.03.310 The sponsor shall notify the Minister in writing of the day on which the sale or importation of the study drug is intended to start in respect of each study site, not later than 15 days before that day.

Good Clinical Practices

C.03.311 A sponsor shall ensure that each study is conducted in accordance with good clinical practices and that

• (a) the study is scientifically sound and clearly described in its protocol;

• (b) the study is conducted, and the study drug is used, in accordance with the protocol and with these Regulations;

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

• (d) at each study site, there is only one qualified investigator;

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

• (f) each individual who is involved in the conduct of the study is qualified by their education, training and experience to perform their respective tasks;

• (g) before a study subject participates in the study, a copy of their signed consent form is included in the records for the study;

• (h) the requirements respecting information and records set out in section C.03.315 are met; and

• (i) the study drug is manufactured, handled and stored in accordance with Division 2, other than sections C.02.019, C.02.025 and C.02.026.