0A4F4F9BD490A749D5437F821CF06DF1
Regulations Amending the Food and Drug Regulations (1024 – Clinical Trials)
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| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
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p.000001: Regulations Amending the Food and Drug Regulations (1024 – Clinical Trials)
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p.000001: and
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p.000001: Extract from Regulatory Impact Analysis Statement
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p.000001: The reproduction is not represented as an official version of the materials reproduced, nor as having been made, in
p.000001: affiliation with or with the endorsement of Health Canada.
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p.000001: Canada Gazette Part II, Vol. 135, No. 13, 20 June 2001 Health Canada
p.000001:
p.000001:
p.000001: For the official version, go to: http://www.hc‐sc.gc.ca/dhp‐mps/compli‐conform/clini‐pract‐prat/reg/1024‐eng.php
p.000001:
p.000001: Health Canada
p.000001: Guidance for Industry Regulations Amending the Food & Drug
p.000001: Regulations
p.000001:
p.000001:
p.000001: Table of Contents
p.000001:
p.000001: REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS
p.000001: Amendments 1-3 :
p.000001: 1
p.000001: Amendment 4 : Division 5 Drugs for Clinical Trials Involving Human Subjects 1
p.000001: C.05.001 Interpretation
p.000001: 1
p.000001: C.05.002 Application
p.000003: 3
p.000003: C.05.003 Prohibition
p.000003: 3
p.000003: C.05.004 General
p.000004: 4
p.000004: C.05.005 Application for Authorization 4
p.000004: C.05.006 Authorization
p.000006: 6
p.000006: C.05.007 Notification
p.000008: 8
p.000008: C.05.008 Amendment
p.000008: 8
p.000008: C.05.009 Additional Information and Samples 10
p.000008: C.05.010 Sponsor's Obligations 11
p.000008: C.05.011 Labeling
p.000012: 12
p.000012: C.05.012 Records
p.000012: 12
p.000012: C.05.013 Submission of Information and Samples 13
p.000012: C.05.014 Serious Unexpected Adverse Drug Reaction Reporting 14
p.000012: C.05.015 Discontinuance of a Clinical Trial 14
p.000012: C.05.016 Suspension and Cancellation 15
p.000012: Amendments 5-7
p.000017: 17
p.000017: Amendments 8-10
p.000018: 18
p.000018: Amendments 11 - 12
p.000019: 19
p.002001: 2001
p.002001: i
p.002001:
p.002001: Health Canada
p.002001: Guidance for Industry Regulations Amending the Food & Drug
p.002001: Regulations
p.002001: REGULATORY IMPACT ANALYSIS STATEMENT
p.002001: Description
p.000020: 20
p.000020: Current Canadian Situation
p.000020: 20
p.000020: New Regulatory Framework
p.000022: 22
p.000022: Good Clinical Practices (GCP)
p.000023: 23
p.000023: Labeling
p.000024: 24
p.000024: Adverse Drug Reaction Reporting
p.000024: 24
p.000024: Records
p.000024: 24
p.000024: 30-Day Default System
p.000025: 25
p.000025: Amendments
p.000026: 26
p.000026: Notification
p.000026: 26
p.000026: Inspection System
p.000027: 27
p.000027: Coming Into Force
p.000027: 27
p.000027: Expectations
p.000027: 27
p.000027: Cost Recovery
p.000028: 28
p.000028: International Perspective
p.000028: 28
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p.002001: 2001
p.002001: ii
p.002001:
p.002001: Health Canada
p.002001: Guidance for Industry Regulations Amending the Food & Drug
p.002001: Regulations
p.002001:
p.002001:
p.002001: AMENDMENTS
p.002001:
p.002001: 1. Paragraph C.01A.002(1)(c)1 of the Food and Drug Regulations2 is replaced by the following:
p.002001:
p.002001: (c) any activity with respect to a drug that is used only for the purposes of clinical testing in accordance with
p.002001: subsection C.05.006(1) or section C.08.005; and
p.002001:
p.002001: 2. Subsection C.03.202(2) of the Regulations is repealed.
p.002001:
p.002001: 3. Section C.03.208 of the Regulations is amended by adding the word "and" at the end of paragraph (n), by striking out
p.002001: the word "and" at the end of paragraph (o) and by repealing paragraph (p).
p.002001:
p.002001: 4. Part C of the Regulations is amended by adding the following after Division 4:
p.002001:
p.002001:
p.002001: Division 5
p.002001:
p.002001: Drugs for Clinical Trials Involving Human Subjects
p.002001:
p.002001: Interpretation
p.002001:
p.002001: C.05.001. The definitions in this section apply in this Division.
p.002001:
p.002001: "adverse drug reaction" means any noxious and unintended response to a drug that is caused by the administration of any
p.002001: dose of the drug. (réaction indésirable à une drogue)
p.002001:
p.002001: "adverse event" means any adverse occurrence in the health of a clinical trial subject who is administered a drug, that
p.002001: may or may not be caused by the administration of the drug, and includes an adverse drug reaction. (incident
p.002001: thérapeutique)
p.002001:
p.002001: "clinical trial" means an investigation in respect of a drug for use in humans that involves human subjects and that is
p.002001: intended to discover or verify the clinical, pharmacological or pharmacodynamic effects of the drug, identify any
p.002001: adverse events in respect of the drug, study the absorption, distribution, metabolism and excretion of the drug, or
p.002001: ascertain the safety or efficacy of the drug. (essai clinique)
p.002001:
p.002001: "drug" means a drug for human use that is to be tested in a clinical trial. (drogue)
p.002001:
p.002001: "good clinical practices" means generally accepted clinical practices that are designed to ensure the protection of the
p.002001: rights, safety and well-being of clinical trial subjects and other persons, and the good clinical practices referred to
p.002001: in section C.05.010. (bonnes pratiques cliniques)
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.000001: 1
p.000001:
p.000001: Health Canada
p.000001: Guidance for Industry Regulations Amending the Food & Drug
p.000001: Regulations
p.000001:
p.000001:
p.000001: "import" means to import a drug into Canada for the purpose of sale in a clinical trial.
p.000001: (importer)
p.000001:
p.000001: "investigator's brochure" means, in respect of a drug, a document containing the preclinical and clinical data on the
p.000001: drug that are described in paragraph C.05.005(e). (brochure du chercheur)
p.000001:
p.000001: "protocol" means a document that describes the objectives, design, methodology, statistical considerations and
p.000001: organization of a clinical trial. (protocole)
p.000001:
p.000001: "qualified investigator" means the person responsible to the sponsor for the conduct of the clinical trial at a
p.000001: clinical trial site, who is entitled to provide health care under the laws of the province where that clinical trial
p.000001: site is located, and who is
p.000001:
p.000001: (a) in the case of a clinical trial respecting a drug to be used for dental purposes only, a physician or dentist and a
p.000001: member in good standing of a professional medical or dental association; and
p.000001:
p.000001: (b) in any other case, a physician and a member in good standing of a professional medical association. (chercheur
p.000001: qualifié)
p.000001:
p.000001: "research ethics board" means a body that is not affiliated with the sponsor, and
p.000001:
p.000001: (a) the principal mandate of which is to approve the initiation of, and conduct periodic reviews of, biomedical
p.000001: research involving human subjects in order to ensure the protection of their rights, safety and well-being; and
p.000001:
p.000001: (b) that has at least five members, that has a majority of members who are Canadian citizens or permanent residents
p.000001: under the Immigration Act, that is composed of both men and women and that includes at least
p.000001:
p.000001: (i) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the
p.000001: methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is
p.000001: in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
p.000001:
p.000001: (ii) one member knowledgeable in ethics,
p.000001:
p.000001: (iii) one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
p.000001:
p.000001: (iv) one member whose primary experience and expertise are in a nonscientific discipline, and
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p.000001:
p.000001:
p.002001: 2001
p.000002: 2
p.000002:
p.000002: Health Canada
p.000002: Guidance for Industry Regulations Amending the Food & Drug
p.000002: Regulations
p.000002:
p.000002:
p.000002: (v) one member who is from the community or is a representative of an organization interested in the areas of research
p.000002: to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted.
p.000002: (comité d'éthique de la recherche)
p.000002:
p.000002: "serious adverse drug reaction" means an adverse drug reaction that requires in-patient hospitalization or prolongation
p.000002: of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability
p.000002: or incapacity, that is life threatening or that results in death. (réaction indésirable grave à une drogue)
p.000002:
p.000002: "serious unexpected adverse drug reaction" means a serious adverse drug reaction that is not identified in nature,
p.000002: severity or frequency in the risk information set out in the investigator's brochure or on the label of the drug.
p.000002: (réaction indésirable grave et imprévue à une drogue)
p.000002:
p.000002: "sponsor" means an individual, corporate body, institution or organization that conducts a clinical trial. (promoteur)
p.000002:
p.000002:
p.000002: Application
p.000002:
p.000002: C.05.002.(1) Subject to subsection (2), this Division applies to the sale or importation of drugs to be used for the
p.000002: purposes of clinical trials involving human subjects.
p.000002:
p.000002: (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,
p.000002: 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
p.000002: 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
p.000002: a clinical trial authorized under subsection C.05.006(2).
p.000002:
p.000002:
p.000002: Prohibition
p.000002:
p.000002: C.05.003. Despite sections C.01.014, C.08.002 and C.08.003, no person shall sell or import a drug for the purposes of a
p.000002: clinical trial unless
p.000002:
p.000002: (a) the person is authorized under this Division;
p.000002:
p.000002: (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
p.000002: to C.01.067, C.01.070, C.01.131, C.01.133 to C.01.136, and C.01.435; and
p.000002:
p.000002: (c) if the drug is to be imported, the person has a representative in Canada who is responsible for the sale of the
p.000002: drug.
p.000002:
p.000002:
p.000002:
p.002001: 2001
p.000003: 3
p.000003:
p.000003: Health Canada
p.000003: Guidance for Industry Regulations Amending the Food & Drug
p.000003: Regulations
p.000003:
p.000003:
p.000003:
p.000003: General
p.000003:
p.000003: C.05.004. Despite these Regulations, a sponsor may submit an application under this Division to sell or import a drug
p.000003: for the purposes of a clinical trial that contains a substance the sale of which is prohibited by these Regulations, if
p.000003: the sponsor establishes, on the basis of scientific information, that the inclusion of the substance in the drug may
p.000003: result in a therapeutic benefit for a human being.
p.000003:
p.000003:
p.000003: Application for Authorization
p.000003:
p.000003: C.05.005. An application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial
p.000003: under this Division shall be submitted to the Minister, signed and dated by the sponsor's senior medical or scientific
p.000003: officer in Canada and senior executive officer and shall contain the following information and documents:
p.000003:
p.000003: (a) a copy of the protocol for the clinical trial;
p.000003:
p.000003: (b) a copy of the statement, as it will be set out in each informed consent form, that states the risks and anticipated
p.000003: benefits arising to the health of clinical trial subjects as a result of their participation in the clinical trial;
p.000003:
p.000003: (c) a clinical trial attestation, signed and dated by the sponsor's senior medical or scientific officer in Canada and
p.000003: senior executive officer, containing
p.000003:
p.000003: (i) the title of the protocol and the clinical trial number,
p.000003:
p.000003: (ii) the brand name, the chemical name or the code for the drug,
p.000003:
p.000003: (iii) the therapeutic and pharmacological classifications of the drug,
p.000003:
p.000003: (iv) the medicinal ingredients of the drug,
p.000003:
p.000003: (v) the non-medicinal ingredients of the drug,
p.000003:
p.000003: (vi) the dosage form of the drug,
p.000003:
p.000003: (vii) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of
p.000003: the sponsor,
p.000003:
p.000003: (viii) if the drug is to be imported, the name, address and telephone number and, if applicable, the facsimile number
p.000003: and electronic mail address of the sponsor's representative in Canada who is responsible for the sale of the drug,
p.000003:
p.000003:
p.000003:
p.002001: 2001
p.000004: 4
p.000004:
p.000004: Health Canada
p.000004: Guidance for Industry Regulations Amending the Food & Drug
p.000004: Regulations
p.000004:
p.000004:
p.000004: (ix) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and
p.000004: electronic mail address of the qualified investigator, if known at the time of submitting the application,
p.000004:
p.000004: (x) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and
p.000004: electronic mail address of the research ethics board that approved the protocol referred to in paragraph (a) and
p.000004: approved an informed consent form containing the statement referred to in paragraph (b), if known at the time of
p.000004: submitting the application, and
p.000004:
p.000004: (xi) a statement
p.000004:
p.000004: (A) that the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and
p.000004:
p.000004: (B) that all information contained in, or referenced by, the application is complete and accurate and is not false or
p.000004: misleading;
p.000004:
p.000004: (d) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any
p.000004: research ethics board that has previously refused to approve the protocol referred to in paragraph (a), its reasons for
p.000004: doing so and the date on which the refusal was given, if known at the time of submitting the application;
p.000004:
p.000004: (e) an investigator's brochure that contains the following information, namely,
p.000004:
p.000004: (i) the physical, chemical and pharmaceutical properties of the drug,
p.000004:
p.000004: (ii) the pharmacological aspects of the drug, including its metabolites in all animal species tested,
p.000004:
p.000004: (iii) the pharmacokinetics of the drug and the drug metabolism, including the biological transformation of the drug in
p.000004: all animal species tested,
p.000004:
p.000004: (iv) any toxicological effects in any animal species tested under a single dose study, a repeated dose study or a
p.000004: special study in respect of the drug,
p.000004:
p.000004: (v) any results of carcinogenicity studies in any animal species tested in respect of the drug,
p.000004:
p.000004: (vi) any results of clinical pharmacokinetic studies of the drug,
p.000004:
p.000004: (vii) any information regarding drug safety, pharmacodynamics, efficacy and dose responses of the drug that were
p.000004: obtained from previous clinical trials in humans, and
p.000004:
p.000004:
p.000004:
p.002001: 2001
p.000005: 5
p.000005:
p.000005: Health Canada
p.000005: Guidance for Industry Regulations Amending the Food & Drug
p.000005: Regulations
p.000005:
p.000005:
p.000005: (viii) if the drug is a radiopharmaceutical as defined in section C.03.201, information regarding directions for
p.000005: preparing the radiopharmaceutical, the radiation dosimetry in respect of the prepared radiopharmaceutical and a
p.000005: statement of the storage requirements for the prepared radiopharmaceutical;
p.000005:
p.000005: (f) if the drug contains a human-sourced excipient, including any used in the placebo,
p.000005:
p.000005: (i) information that indicates the human-sourced excipient has been assigned a drug identification number under
p.000005: 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
p.000005: the case may be, or
p.000005:
p.000005: (ii) in any other case, sufficient information to support the identity, purity, potency, stability and safety of the
p.000005: human-sourced excipient;
p.000005:
p.000005: (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
p.000005: new drug, a notice of compliance has not been issued under subsection C.08.004(1), the chemistry and manufacturing
p.000005: information in respect of the drug, including its site of manufacture; and
p.000005:
p.000005: (h) the proposed date for the commencement of the clinical trial at each clinical trial site, if known at the time of
p.000005: submitting the application.
p.000005:
p.000005:
p.000005: Authorization
p.000005:
p.000005: C.05.006. (1) Subject to subsection (3), a sponsor may sell or import a drug, other than a drug described in subsection
p.000005: (2), for the purposes of a clinical trial if
p.000005:
p.000005: (a) the sponsor has submitted to the Minister an application in accordance with section C.05.005;
p.000005:
p.000005: (b) the Minister does not, within 30 days after the date of receipt of the application, send to the sponsor a notice in
p.000005: respect of the drug indicating that the sponsor may not sell or import the drug for any of the following reasons:
p.000005:
p.000005: (i) that the information and documents in respect of the application
p.000005:
p.000005: (A) were not provided in accordance with these Regulations, or
p.000005:
p.000005: (B) are insufficient to enable the Minister to assess the safety and risks of the drug or the clinical trial, or
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.002001: 2001
p.000006: 6
p.000006:
p.000006: Health Canada
p.000006: Guidance for Industry Regulations Amending the Food & Drug
p.000006: Regulations
p.000006:
p.000006:
p.000006: (ii) that based on an assessment of the application, an assessment of any information submitted under section C.05.009
p.000006: or a review of any other information, the Minister has reasonable grounds to believe that
p.000006:
p.000006: (A) the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or
p.000006: other person,
p.000006:
p.000006: (B) the clinical trial is contrary to the best interests of a clinical trial subject, or
p.000006:
p.000006: (C) the objectives of the clinical trial will not be achieved;
p.000006:
p.000006: (c) for each clinical trial site, the sponsor has obtained the approval of the research ethics board in respect of the
p.000006: protocol referred to in paragraph C.05.005(a) and in respect of an informed consent form that contains the statement
p.000006: referred to in paragraph C.05.005(b); and
p.000006:
p.000006: (d) before the sale or importation of the drug at a clinical trial site, the sponsor submits to the Minister the
p.000006: information referred to in subparagraphs C.05.005(c)(ix) and (x) and paragraphs C.05.005(d) and (h), if it was not
p.000006: submitted in respect of that clinical trial site at the time of submitting the application.
p.000006:
p.000006: (2) Subject to subsection (3), a sponsor may sell or import a drug for the purposes of a clinical trial in respect of
p.000006:
p.000006: (a) a new drug that has been issued a notice of compliance under subsection C.08.004(1), if the clinical trial is in
p.000006: respect of a purpose or condition of use for which the notice of compliance was issued; or
p.000006:
p.000006: (b) a drug, other than a new drug, that has been assigned a drug identification number under subsection C.01.014.2(1),
p.000006: if the clinical trial is in respect of a use or purpose for which the drug identification number was assigned.
p.000006:
p.000006: (3) A sponsor may not sell or import a drug for the purposes of a clinical trial
p.000006:
p.000006: (a) during the period of any suspension made under section C.05.016 or C.05.017; or
p.000006:
p.000006: (b) after a cancellation made under section C.05.016 or C.05.017.
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.002001: 2001
p.000007: 7
p.000007:
p.000007: Health Canada
p.000007: Guidance for Industry Regulations Amending the Food & Drug
p.000007: Regulations
p.000007:
p.000007:
p.000007:
p.000007: Notification
p.000007:
p.000007: C.05.007.If the sale or importation of a drug is authorized under this Division, the sponsor may make one or more of
p.000007: the following changes if the sponsor notifies the Minister in writing within 15 days after the date of the change:
p.000007:
p.000007: (a) a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug,
p.000007: other than a change for which an amendment is required by section C.05.008; and
p.000007:
p.000007: (b) a change to the protocol that does not alter the risk to the health of a clinical trial subject, other than a
p.000007: change for which an amendment is required by section C.05.008.
p.000007:
p.000007:
p.000007:
p.000007: Amendment
p.000007:
p.000007: C.05.008. (1) Subject to subsections (4) and (5), when the sale or importation of a drug is authorized under this
p.000007: Division and the sponsor proposes to make an amendment referred to in subsection (2), the sponsor may sell or import
p.000007: the drug for the purposes of the clinical trial in accordance with the amended authorization, if the following
p.000007: conditions are met:
p.000007:
p.000007: (a) the sponsor has submitted to the Minister an application for amendment in accordance with subsection (3);
p.000007:
p.000007: (b) the Minister does not, within 30 days after the date of receipt of the application for amendment, send to the
p.000007: sponsor a notice in respect of the drug indicating that the sponsor may not sell or import the drug in accordance with
p.000007: the amendment for any of the following reasons, namely,
p.000007:
p.000007: (i) that the information and documents in respect of the application for amendment
p.000007:
p.000007: (A) were not provided in accordance with these Regulations, or
p.000007:
p.000007: (B) are insufficient to enable the Minister to assess the safety and risks of the drug or the clinical trial, or
p.000007:
p.000007: (ii) that based on an assessment of the application for amendment, an assessment of any information submitted under
p.000007: section C.05.009 or a review of any other information, the Minister has reasonable grounds to believe that
p.000007:
p.000007: (A) the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or
p.000007: other person,
p.000007:
p.000007:
p.002001: 2001
p.000008: 8
p.000008:
p.000008: Health Canada
p.000008: Guidance for Industry Regulations Amending the Food & Drug
p.000008: Regulations
p.000008:
p.000008:
p.000008: (B) the clinical trial is contrary to the best interests of a clinical trial subject, or
p.000008:
p.000008: (C) the objectives of the clinical trial will not be achieved;
p.000008:
p.000008: (c) before the sale or importation of the drug, the sponsor submits to the Minister
p.000008:
p.000008: (i) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and
p.000008: electronic mail address of the research ethics board that approved any amended protocol submitted under paragraph
p.000008: (3)(a) or approved any amended statement submitted under paragraph (3)(c), and
p.000008:
p.000008: (ii) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any
p.000008: research ethics board that has previously refused to approve any amendment to the protocol, its reasons for doing so
p.000008: and the date on which the refusal was given;
p.000008:
p.000008: (d) before the sale or importation of the drug, the sponsor maintains records concerning
p.000008:
p.000008: (i) the information referred to in paragraph C.05.005(h), and
p.000008:
p.000008: (ii) the information referred to in subparagraph C.05.005(c)(ix), if any of that information has changed since it was
p.000008: submitted;
p.000008:
p.000008: (e) before the sale or importation of the drug in accordance with the amended authorization, the sponsor ceases to sell
p.000008: or import the drug in accordance with the existing authorization; and
p.000008:
p.000008: (f) the sponsor conducts the clinical trial in accordance with the amended authorization.
p.000008:
p.000008: (2) For the purposes of subsection (1), amendments are
p.000008:
p.000008: (a) amendments to the protocol that affect the selection, monitoring or dismissal of a clinical trial subject;
p.000008:
p.000008: (b) amendments to the protocol that affect the evaluation of the clinical efficacy of the drug;
p.000008:
p.000008: (c) amendments to the protocol that alter the risk to the health of a clinical trial subject;
p.000008:
p.000008: (d) amendments to the protocol that affect the safety evaluation of the drug;
p.000008:
p.000008: (e) amendments to the protocol that extend the duration of the clinical trial; and
p.000008:
p.000008:
p.000008:
p.000008:
p.002001: 2001
p.000009: 9
p.000009:
p.000009: Health Canada
p.000009: Guidance for Industry Regulations Amending the Food & Drug
p.000009: Regulations
p.000009:
p.000009:
p.000009: (f) amendments to the chemistry and manufacturing information that may affect the safety or quality of the drug.
p.000009:
p.000009: (3) The application for amendment referred to in subsection (1) shall contain a reference to the application submitted
p.000009: under section C.05.005 and shall contain the following documents and information:
p.000009:
p.000009: (a) if the application is in respect of an amendment referred to in any of paragraphs (2)(a) to (e), a copy of the
p.000009: amended protocol that indicates the amendment, a copy of the protocol submitted under paragraph C.05.005(a), and the
p.000009: rationale for the amendment;
p.000009:
p.000009: (b) if the application is in respect of an amendment referred to in paragraph (2)(e), a copy of the amended
p.000009: investigator's brochure or an addendum to the investigator's brochure that indicates the new information, including
p.000009: supporting toxicological studies and clinical trial safety data;
p.000009:
p.000009: (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
p.000009: that amendment, it is necessary to amend the statement referred to in paragraph C.05.005(b), a copy of the amended
p.000009: statement that indicates the new information; and
p.000009:
p.000009: (d) if the application is in respect of an amendment referred to in paragraph (2)(f), a copy of the amended chemistry
p.000009: and manufacturing information that indicates the amendment, and the rationale for that amendment.
p.000009:
p.000009: (4) If the sponsor is required to immediately make one or more of the amendments referred to in subsection (2) because
p.000009: the clinical trial or the use of the drug for the purposes of the clinical trial endangers the health of a clinical
p.000009: trial subject or other person, the sponsor may immediately make the amendment and shall provide the Minister with the
p.000009: information referred to in subsection (3) within 15 days after the date of the amendment.
p.000009:
p.000009: (5) A sponsor may not sell or import a drug for the purposes of a clinical trial
p.000009:
p.000009: (a) during the period of any suspension made under section C.05.016 or C.05.017; or
p.000009:
p.000009: (b) after a cancellation made under section C.05.016 or C.05.017.
p.000009:
p.000009:
p.000009: Additional Information and Samples
p.000009:
p.000009: C.05.009. If the information and documents submitted in respect of an application under section
p.000009: C.05.005 or an application for amendment under section C.05.008 are insufficient to enable the Minister to determine
p.000009: 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
p.000009: the sponsor to submit, within two days after receipt of the request, samples of the drug or additional information
p.000009: relevant to the drug or the
p.000009:
p.000009:
p.002001: 2001
p.000010: 10
p.000010:
p.000010: Health Canada
p.000010: Guidance for Industry Regulations Amending the Food & Drug
p.000010: Regulations
p.000010:
p.000010:
p.000010: clinical trial that are necessary to make the determination.
p.000010:
p.000010:
p.000010:
p.000010: Sponsor's Obligations Good Clinical Practices
p.000010: C.05.010. Every sponsor shall ensure that a clinical trial is conducted in accordance with good clinical practices and,
p.000010: without limiting the generality of the foregoing, shall ensure that
p.000010:
p.000010: (a) the clinical trial is scientifically sound and clearly described in a protocol;
p.000010:
p.000010: (b) the clinical trial is conducted, and the drug is used, in accordance with the protocol and this Division;
p.000010:
p.000010: (c) systems and procedures that assure the quality of every aspect of the clinical trial are implemented;
p.000010:
p.000010: (d) for each clinical trial site, the approval of a research ethics board is obtained before the clinical trial begins
p.000010: at the site;
p.000010:
p.000010: (e) at each clinical trial site, there is no more than one qualified investigator;
p.000010:
p.000010: (f) at each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the
p.000010: supervision of the qualified investigator;
p.000010:
p.000010: (g) each individual involved in the conduct of the clinical trial is qualified by education, training and experience to
p.000010: perform his or her respective tasks;
p.000010:
p.000010: (h) written informed consent, given in accordance with the applicable laws governing consent, is obtained from every
p.000010: person before that person participates in the clinical trial but only after that person has been informed of
p.000010:
p.000010: (i) the risks and anticipated benefits to his or her health arising from participation in the clinical trial, and
p.000010:
p.000010: (ii) all other aspects of the clinical trial that are necessary for that person to make the decision to participate in
p.000010: the clinical trial;
p.000010:
p.000010: (i) the requirements respecting information and records set out in section C.05.012 are met; and
p.000010:
p.000010: (j) the drug is manufactured, handled and stored in accordance with the applicable good manufacturing practices
p.000010: referred to in Divisions 2 to 4 except sections C.02.019,
p.000010:
p.000010:
p.002001: 2001
p.000011: 11
p.000011:
p.000011: Health Canada
p.000011: Guidance for Industry Regulations Amending the Food & Drug
p.000011: Regulations
p.000011:
p.000011:
p.000011: C.02.025 and C.02.026.
p.000011:
p.000011:
p.000011: Labeling
p.000011:
p.000011: C.05.011. Despite any other provision of these Regulations respecting labeling, the sponsor shall ensure that the drug
p.000011: bears a label that sets out the following information in both official languages:
p.000011:
p.000011: (a) a statement indicating that the drug is an investigational drug to be used only by a qualified investigator;
p.000011:
p.000011: (b) the name, number or identifying mark of the drug;
p.000011:
p.000011: (c) the expiration date of the drug;
p.000011:
p.000011: (d) the recommended storage conditions for the drug;
p.000011:
p.000011: (e) the lot number of the drug;
p.000011:
p.000011: (f) the name and address of the sponsor;
p.000011:
p.000011: (g) the protocol code or identification; and
p.000011:
p.000011: (h) if the drug is a radiopharmaceutical as defined in section C.03.201, the information required by subparagraph
p.000011: C.03.202(1)(b)(vi).
p.000011:
p.000011: Records
p.000011:
p.000011: C.05.012.(1) The sponsor shall record, handle and store all information in respect of a clinical trial in a way that
p.000011: allows its complete and accurate reporting as well as its interpretation and verification.
p.000011:
p.000011: (2) The sponsor shall maintain complete and accurate records to establish that the clinical trial is conducted in
p.000011: accordance with good clinical practices and these Regulations.
p.000011:
p.000011: (3) The sponsor shall maintain complete and accurate records in respect of the use of a drug in a clinical trial,
p.000011: including
p.000011:
p.000011: (a) a copy of all versions of the investigator's brochure for the drug;
p.000011:
p.000011: (b) records respecting each change made to the investigator's brochure, including the rationale for each change and
p.000011: documentation that supports each change;
p.000011:
p.000011:
p.000011:
p.000011:
p.002001: 2001
p.000012: 12
p.000012:
p.000012: Health Canada
p.000012: Guidance for Industry Regulations Amending the Food & Drug
p.000012: Regulations
p.000012:
p.000012:
p.000012: (c) records respecting all adverse events in respect of the drug that have occurred inside or outside Canada, including
p.000012: information that specifies the indication for use and the dosage form of the drug at the time of the adverse event;
p.000012:
p.000012: (d) records respecting the enrollment of clinical trial subjects, including information sufficient to enable all
p.000012: clinical trial subjects to be identified and contacted in the event that the sale of the drug may endanger the health
p.000012: of the clinical trial subjects or other persons;
p.000012:
p.000012: (e) records respecting the shipment, receipt, disposition, return and destruction of the drug;
p.000012:
p.000012: (f) for each clinical trial site, an undertaking from the qualified investigator that is signed and dated by the
p.000012: qualified investigator prior to the commencement of his or her responsibilities in respect of the clinical trial, that
p.000012: states that
p.000012:
p.000012: (i) the qualified investigator will conduct the clinical trial in accordance with good clinical practices, and
p.000012:
p.000012: (ii) the qualified investigator will immediately, on discontinuance of the clinical trial by the sponsor, in its
p.000012: entirety or at a clinical trial site, inform both the clinical trial subjects and the research ethics board of the
p.000012: discontinuance, provide them with the reasons for the discontinuance and advise them in writing of any potential risks
p.000012: to the health of clinical trial subjects or other persons;
p.000012:
p.000012: (g) for each clinical trial site, a copy of the protocol, informed consent form and any amendment to the protocol or
p.000012: informed consent form that have been approved by the research ethics board for that clinical trial site; and
p.000012:
p.000012: (h) for each clinical trial site, an attestation, signed and dated by the research ethics board for that clinical trial
p.000012: site, stating that it has reviewed and approved the protocol and informed consent form and that the board carries out
p.000012: its functions in a manner consistent with good clinical practices.
p.000012:
p.000012: (4) The sponsor shall maintain all records referred to in this Division for a period of 25 years.
p.000012:
p.000012:
p.000012:
p.000012: Submission of Information and Samples
p.000012:
p.000012: C.05.013. (1) The Minister shall require a sponsor to submit, within two days after receipt of the request, information
p.000012: concerning the drug or the clinical trial, or samples of the drug, if the Minister has reasonable grounds to believe
p.000012: that
p.000012:
p.000012:
p.000012:
p.000012:
p.002001: 2001
p.000013: 13
p.000013:
p.000013: Health Canada
p.000013: Guidance for Industry Regulations Amending the Food & Drug
p.000013: Regulations
p.000013:
p.000013:
p.000013: (a) the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or
p.000013: other person;
p.000013:
p.000013: (b) the clinical trial is contrary to the best interests of a clinical trial subject;
p.000013:
p.000013: (c) the objectives of the clinical trial will not be achieved;
p.000013:
p.000013: (d) a qualified investigator is not respecting the undertaking referred to in paragraph C.05.012(3)(f); or
p.000013:
p.000013: (e) information submitted in respect of the drug or the clinical trial is false or misleading.
p.000013:
p.000013: (2) The Minister may require the sponsor to submit, within seven days after receipt of the request, any information or
p.000013: records kept under section C.05.012, or samples of the drug, in order to assess the safety of the drug or the health of
p.000013: clinical trial subjects or other persons.
p.000013:
p.000013:
p.000013:
p.000013: Serious Unexpected Adverse Drug Reaction Reporting
p.000013:
p.000013: C.05.014. (1) During the course of a clinical trial, the sponsor shall inform the Minister of any serious unexpected
p.000013: adverse drug reaction in respect of the drug that has occurred inside or outside Canada as follows:
p.000013:
p.000013: (a) if it is neither fatal nor life threatening, within 15 days after becoming aware of the information; and
p.000013:
p.000013: (b) if it is fatal or life threatening, within seven days after becoming aware of the information.
p.000013:
p.000013: (2) The sponsor shall, within eight days after having informed the Minister under paragraph (1)(b), submit to the
p.000013: Minister a complete report in respect of that information that includes an assessment of the importance and implication
p.000013: of any findings made.
p.000013:
p.000013: (3) Sections C.01.016 and C.01.017 do not apply to drugs used for the purposes of a clinical trial.
p.000013:
p.000013:
p.000013:
p.000013: Discontinuance of a Clinical Trial
p.000013:
p.000013: C.05.015. (1) If a clinical trial is discontinued by the sponsor in its entirety or at a clinical trial site, the
p.000013: sponsor shall
p.000013:
p.000013: (a) inform the Minister no later than 15 days after the date of the discontinuance;
p.000013:
p.000013:
p.000013:
p.002001: 2001
p.000014: 14
p.000014:
p.000014: Health Canada
p.000014: Guidance for Industry Regulations Amending the Food & Drug
p.000014: Regulations
p.000014:
p.000014:
p.000014: (b) provide the Minister with the reason for the discontinuance and its impact on the proposed or ongoing clinical
p.000014: trials in respect of the drug conducted in Canada by the sponsor;
p.000014:
p.000014: (c) as soon as possible, inform all qualified investigators of the discontinuance and of the reasons for the
p.000014: discontinuance, and advise them in writing of any potential risks to the health of clinical trial subjects or other
p.000014: persons; and
p.000014:
p.000014: (d) in respect of each discontinued clinical trial site, stop the sale or importation of the drug as of the date of the
p.000014: discontinuance and take all reasonable measures to ensure the recovery of all unused quantities of the drug that have
p.000014: been sold.
p.000014:
p.000014: (2) If the sponsor has discontinued the clinical trial in its entirety or at a clinical trial site, the sponsor may
p.000014: resume selling or importing the drug for the purposes of a clinical trial in its entirety or at a clinical trial site
p.000014: if, in respect of each clinical trial site where the sale or importation is to be resumed, the sponsor submits to the
p.000014: Minister the information referred to in subparagraphs C.05.005(c)(ix) and (x) and paragraphs C.05.005(d) and (h).
p.000014:
p.000014:
p.000014:
p.000014: Suspension and Cancellation
p.000014:
p.000014: C.05.016. (1) Subject to subsection (2), the Minister shall suspend the authorization to sell or import a drug for the
p.000014: purposes of a clinical trial, in its entirety or at a clinical trial site, if the Minister has reasonable grounds to
p.000014: believe that
p.000014:
p.000014: (a) the sponsor has contravened these Regulations or any provisions of the Act relating to the drug;
p.000014:
p.000014: (b) any information submitted in respect of the drug or clinical trial is false or misleading;
p.000014:
p.000014: (c) the sponsor has failed to comply with good clinical practices; or
p.000014:
p.000014: (d) the sponsor has failed to provide
p.000014:
p.000014: (i) information or samples of the drug as required under section C.05.009 or C.05.013, or
p.000014:
p.000014: (ii) information or a report under section C.05.014.
p.000014:
p.000014: (2) Subject to section C.05.017, the Minister shall not suspend an authorization referred to in subsection (1) unless
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.002001: 2001
p.000015: 15
p.000015:
p.000015: Health Canada
p.000015: Guidance for Industry Regulations Amending the Food & Drug
p.000015: Regulations
p.000015:
p.000015:
p.000015: (a) the Minister has sent to the sponsor a written notice of the intention to suspend the authorization that indicates
p.000015: whether the authorization is to be suspended in its entirety or at a clinical trial site and the reason for the
p.000015: intended suspension;
p.000015:
p.000015: (b) the sponsor has not, within 30 days after receipt of the notice referred to in paragraph (a), provided the Minister
p.000015: with information or documents that demonstrate that the authorization should not be suspended on the grounds that
p.000015:
p.000015: (i) the situation giving rise to the intended suspension did not exist, or
p.000015:
p.000015: (ii) the situation giving rise to the intended suspension has been corrected; and
p.000015:
p.000015: (c) the Minister has provided the sponsor with the opportunity to be heard in paragraph (b).
p.000015:
p.000015: (3) The Minister shall suspend the authorization by sending to the sponsor a written notice of suspension of the
p.000015: authorization that indicates the effective date of the suspension, whether the authorization is suspended in its
p.000015: entirety or at a clinical trial site and the reason for the suspension.
p.000015:
p.000015: (4) If the Minister has suspended an authorization, the Minister shall
p.000015:
p.000015: (a) reinstate the authorization in its entirety or at a clinical trial site, as the case may be, if within 30 days
p.000015: after the effective date of the suspension the sponsor provides the Minister with information or documents that
p.000015: demonstrate that the situation giving rise to the suspension has been corrected; or
p.000015:
p.000015: (b) cancel the authorization in its entirety or at a clinical trial site, as the case may be, if within 30 days after
p.000015: the effective date of the suspension the sponsor has not provided the Minister with the information or documents
p.000015: referred to in paragraph (a).
p.000015:
p.000015: C.05.017. (1) The Minister shall suspend an authorization to sell or import a drug for the purposes of a clinical
p.000015: trial, in its entirety or at a clinical trial site, before giving the sponsor an opportunity to be heard if the
p.000015: Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a clinical
p.000015: trial subject or other person.
p.000015:
p.000015: (2) The Minister shall suspend the authorization by sending to the sponsor a written notice of suspension of the
p.000015: authorization that indicates the effective date of the suspension, whether the authorization is suspended in its
p.000015: entirety or at a clinical trial site and the reason for the suspension.
p.000015:
p.000015: (3) If the Minister has suspended an authorization, the Minister shall
p.000015:
p.000015: (a) reinstate the authorization in its entirety or at a clinical trial site, as the case may be, if within 60 days
p.000015: after the effective date of the suspension the sponsor provides the Minister
p.000015:
p.000015:
p.002001: 2001
p.000016: 16
p.000016:
p.000016: Health Canada
p.000016: Guidance for Industry Regulations Amending the Food & Drug
p.000016: Regulations
p.000016:
p.000016:
p.000016: with information or documents that demonstrate that the situation giving rise to the suspension did not exist or that
p.000016: it has been corrected; or
p.000016:
p.000016: (b) cancel the authorization in its entirety or at a clinical trial site, as the case may be, if within 60 days after
p.000016: the effective date of the suspension the sponsor has not provided the Minister with the information or documents
p.000016: referred to in paragraph (a).
p.000016:
p.000016:
p.000016:
p.000016: 5. Section C.08.003.13 of the Regulations is replaced by the following:
p.000016:
p.000016: C.08.003.1. The Minister may examine any information or material filed with the Minister by any person pursuant to
p.000016: Division 5 or section C.08.002, C.08.002.1, C.08.003, C.08.005 or
p.000016: C.08.005.1 to establish the safety and effectiveness of the new drug for which the submission or supplement has been
p.000016: filed.
p.000016:
p.000016:
p.000016: 6. (1) The portion of subsection C.08.005(1)4 of the Regulations before paragraph (a) is replaced by the following:
p.000016:
p.000016: C.08.005. (1) Subject to subsection (1.1) and notwithstanding sections C.08.002 and C.08.003, a manufacturer of a new
p.000016: drug may sell it to a qualified investigator to be used solely for the purpose of clinical testing to obtain evidence
p.000016: with respect to the safety, dosage and effectiveness of that new drug, when the following conditions are met:
p.000016:
p.000016: (2) Section C.08.005 of the Regulations is amended by adding the following after subsection (1):
p.000016:
p.000016: (1.1) This section applies only in respect of a new drug for veterinary use.
p.000016:
p.000016:
p.000016:
p.000016: 7. (1) The portion of subsection C.08.005.1(1)33 of the Regulations before paragraph (a) is replaced by the following:
p.000016:
p.000016: C.08.005.1. (1) Every manufacturer who files a new drug submission, an abbreviated new drug submission, a supplement to
p.000016: a new drug submission, a supplement to an abbreviated new drug submission or a submission for the clinical testing of a
p.000016: new drug for veterinary use shall, in addition to any information and material that is required under section C.08.002,
p.000016: C.08.003 and C.08.005, include in the submission or supplement
p.000016:
p.000016: (2) Subsection C.08.005.1(6)3 of the Regulations is replaced by the following:
p.000016:
p.000016: (6) Every manufacturer who has filed a new drug submission, an abbreviated new drug submission, a supplement to a new
p.000016: drug submission, a supplement to an abbreviated new drug
p.000016:
p.000016:
p.002001: 2001
p.000017: 17
p.000017:
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p.000017: Regulations
p.000017:
p.000017:
p.000017: submission or a submission for the clinical testing of a new drug for veterinary use, and has any relating clinical
p.000017: case reports or raw data that were not included therein, shall keep those reports or data and shall, within 30 days
p.000017: after receiving a written request from the Minister, submit them to the Minister.
p.000017:
p.000017:
p.000017:
p.000017: 8. Subsection C.08.006(1)3 of the Regulations is replaced by the following:
p.000017:
p.000017: C.08.006. (1) For the purposes of this section, evidence or new information obtained by the Minister includes any
p.000017: information or material filed by any person pursuant to Division 5 or section C.08.002, C.08.002.1, C.08.003, C.08.005
p.000017: or C.08.005.1.
p.000017:
p.000017:
p.000017:
p.000017: 9. Paragraph C.08.009(1)(a) of the Regulations is replaced by the following:
p.000017:
p.000017: (a) to notify the manufacturer of a new drug for veterinary use that the sale of that drug to qualified investigators
p.000017: is prohibited, or
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.002001: 2001
p.000018: 18
p.000018:
p.000018: Health Canada
p.000018: Guidance for Industry Regulations Amending the Food & Drug
p.000018: Regulations
p.000018:
p.000018: 10. Paragraph C.08.017(b)5 of the Regulations is replaced by the following:
p.000018:
p.000018: (b) report immediately to the Director all serious adverse drug reactions associated with the use of the new drug;
p.000018:
p.000018:
p.000018:
p.000018: TRANSITIONAL
p.000018:
p.000018: 11. An application concerning the sale of a drug for human use for the purposes of a clinical trial that is received
p.000018: under Division 8 of the Food and Drug Regulations before September 1, 2001 is subject to those Regulations and any
p.000018: procedures established under those Regulations as they read at the time the application was received.
p.000018:
p.000018:
p.000018:
p.000018: COMING INTO FORCE
p.000018:
p.000018: 12. These Regulations come into force on September 1, 2001.
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.002001: 2001
p.000019: 19
p.000019:
p.000019: Health Canada
p.000019: Guidance for Industry Regulations Amending the Food & Drug
p.000019: Regulations
p.000019:
p.000019:
p.000019: REGULATORY IMPACT ANALYSIS STATEMENT
p.000019:
p.000019: (This statement is not part of the regulation)
p.000019:
p.000019: Description
p.000019:
p.000019: This amendment introduces regulatory requirements for the sale and importation of drugs for use in human clinical
p.000019: trials. The new requirements are located in Division 5 of the Food and Drug Regulations and apply to clinical trials in
p.000019: humans using both new and old drugs.
p.000019:
p.000019: Consequential amendments are required to Division 8 of the Regulations to maintain the status quo for clinical trials
p.000019: in animals using new veterinary drugs. Although the Veterinary Drugs Program of the Health Products and Food Branch
p.000019: (the unit in Health Canada responsible for the regulation of veterinary drugs) has indicated that a broader framework
p.000019: is desirable for veterinary drugs, this will be dealt with at a later date.
p.000019:
p.000019: This framework incorporates the following features:
p.000019:
p.000019: • a 30-day default review period for applications to sell a drug for the conduct of human drug clinical trials in
p.000019: Canada in Phases I to III of development;
p.000019:
p.000019: • clear and transparent requirements for application, information, amendments, notification, labeling, record
p.000019: keeping and adverse drug reaction reporting;
p.000019:
p.000019: • introduction of an inspection system against internationally accepted good clinical practice principles and good
p.000019: manufacturing practices; and,
p.000019:
p.000019: • clear authority to refuse an application, suspend or cancel the sale of drugs for use in clinical trials in Canada
p.000019: where they do not meet the updated regulatory requirements.
p.000019:
p.000019: The use of a marketed drug by a physician or dentist for individual patient treatment is not considered to be a
p.000019: clinical trial. The application requirements under this amendment do not apply to clinical trials on marketed drugs
p.000019: where the investigation is conducted within the parameters of the approved Notice of Compliance (NOC) or Drug
p.000019: Identification Number (DIN) application.
p.000019: These trials are often referred to as Phase IV clinical trials. Sponsors must conduct all clinical trials, including
p.000019: Phase IV trials in accordance with the generally accepted principles of good clinical practice.
p.000019:
p.000019:
p.000019: Current Canadian Situation
p.000019:
p.000019: In Canada, the responsibility for developing drugs relies on an effective partnership among many stakeholders including
p.000019: industry, the research granting councils, the medical community, the ethics community and the federal government.
p.000019: Within this partnership, the Therapeutic Products
p.000019:
p.000019:
p.000019:
p.002001: 2001
p.000020: 20
p.000020:
p.000020: Health Canada
p.000020: Guidance for Industry Regulations Amending the Food & Drug
p.000020: Regulations
p.000020:
p.000020:
p.000020: Directorate [TPD] and the Biologics and Genetic Therapies Directorate [BGTD] of Health Canada provide a critical
p.000020: service by ensuring that clinical trials are properly designed and undertaken and that subjects are not exposed to
p.000020: undue risk.
p.000020:
p.000020: It is also Health Canada's responsibility to ensure that its decisions are made in a timely fashion thereby not
p.000020: discouraging the research and development of human drugs in Canada.
p.000020:
p.000020: The Food and Drug Regulations currently include several provisions which define the requirements for the sale of drugs
p.000020: for use in clinical trials in humans. These investigations are generally divided into four phases depending on the
p.000020: stage of drug development:
p.000020:
p.000020: Phase I: Initial safety studies on a new drug, including the first administration of the drug into humans, usually
p.000020: conducted in healthy volunteers. These trials may be conducted in patients when administration of the drug to healthy
p.000020: volunteers is not ethical.
p.000020:
p.000020: Phase I trials are designed mainly to determine the pharmacological actions of the drug and the side effects associated
p.000020: with increasing doses. Pharmacokinetic as well as drug-drug interaction studies are usually considered as Phase I
p.000020: trials regardless of when they are conducted during drug development as these are generally conducted in healthy
p.000020: volunteers. Phase I trials also include trials in which new drugs are used as research tools to explore biological
p.000020: phenomena or disease processes.
p.000020:
p.000020: Phase II: Clinical trials to evaluate the efficacy of the drug in patients with medical conditions to be treated,
p.000020: diagnosed or prevented and to determine the side effects and risks associated with the drug. If a new indication for a
p.000020: marketed drug is to be investigated, then those clinical trials may generally be considered Phase II trials.
p.000020:
p.000020: Phase III: Controlled or uncontrolled trials conducted after preliminary evidence suggesting efficacy of the drug has
p.000020: been demonstrated. These are intended to gather the additional information about efficacy and safety that is needed for
p.000020: further risk/benefit assessment of the drug. In this phase, clinical trials are also conducted in special patient
p.000020: populations (e.g., renal failure patients), or under special conditions dictated by the nature of the drug and disease.
p.000020:
p.000020: Phase IV: All studies performed after the drug has been approved by the regulator for the market, and related to the
p.000020: approved indication. These studies are often important for optimizing the drug's use. They may be of any type but must
p.000020: have valid scientific objectives. Commonly conducted studies include safety studies and studies designed to support use
p.000020: under the approved indication such as mortality and morbidity studies, or epidemiological studies.
p.000020:
p.000020: The current regulatory requirements respecting drugs to be used for the purposes of clinical trials were originally
p.000020: developed in the early 1960s and have remained essentially unchanged. Those Regulations defined specific
p.000020: Investigational New Drug Submission (IND) application requirements which must be complied with before a new drug could
p.000020: be distributed for trial purposes. In 1987, the Regulations were amended to introduce a 60 day default period. Since
p.000020: that time TPD, BGTD and the Veterinary Drugs Program, in the case of a veterinary drug, notify the
p.000020:
p.000020:
p.002001: 2001
p.000021: 21
p.000021:
p.000021: Health Canada
p.000021: Guidance for Industry Regulations Amending the Food & Drug
p.000021: Regulations
p.000021:
p.000021:
p.000021: sponsor within 60 days if its submission is found to be deficient or else the sponsor may proceed. The 60 day default
p.000021: was introduced in 1987 in an attempt to remedy industry's uncertainty in the planning process and to encourage research
p.000021: opportunities in Canada. A move to shorten the review time provided a positive benefit to all Canadians as it permitted
p.000021: faster access to new innovative therapies through the conduct of a clinical trial.
p.000021:
p.000021: The Directorates currently review the safety, efficacy and quality data submitted by the sponsor and approve the
p.000021: distribution of the drug to the investigator. The Directorates may authorize the sale of the drug if the protocol is
p.000021: scientifically sound and the drug would not pose unacceptable risks to the trial subjects under the proposed conditions
p.000021: of use. The sponsor of the trial is required to maintain accurate records, report adverse drug reactions, and ensure
p.000021: that the investigator adheres to the approved protocol. Trials in humans should be conducted according to generally
p.000021: accepted principles of good clinical practice. These standards provide assurance that the data and reported results are
p.000021: credible and accurate, and that the rights, integrity, and privacy of clinical trial subjects are protected.
p.000021:
p.000021: The Directorates encourage sponsors to obtain the approval of a Research Ethics Board (REB) prior to conducting trials
p.000021: in Canada. A REB is an independent body, including both men and women, which is responsible for approving the
p.000021: initiation, and conduct of periodic reviews of biomedical research involving human subjects. The principal mandate of
p.000021: the REB is to ensure the protection of the rights, safety and well-being of subjects in the clinical trial. This
p.000021: structure helps to ensure that conflict of interest situations are avoided and that the health and safety of the trial
p.000021: subjects remain the paramount concern. The role of a Canadian REB includes the provision of recommendations concerning
p.000021: a trial's ethical acceptability and conduct. At the present time, there is no accreditation system in Canada for REBs.
p.000021: This situation is being reviewed by Health Canada in conjunction with the Canadian Institutes of Health Research
p.000021: (CIHR), the National Council on Ethics in Human Research (NCEHR) and other stakeholders in the Canadian clinical
p.000021: research community. Some Canadian REBs have limited resources and experience with the review of drug clinical trials.
p.000021:
p.000021: The Minister of Health can stop the sale of a drug to an investigator if the Minister believes it is in the public
p.000021: interest to do so. This provision in subsection C.08.005(3) of the Food and Drug Regulations, has not been used
p.000021: extensively nor has a routine inspection scheme been implemented.
p.000021:
p.000021:
p.000021: New Regulatory Framework
p.000021:
p.000021:
p.000021: These Regulations have been developed to recognize the generally accepted principles of good clinical practice and
p.000021: internationally competitive submission review time lines. They reflect extensive consultation with stakeholders. A
p.000021: brief summary of the elements contained in the Regulations follows.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.002001: 2001
p.000022: 22
p.000022:
p.000022: Health Canada
p.000022: Guidance for Industry Regulations Amending the Food & Drug
p.000022: Regulations
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: Good Clinical Practices (GCP)
p.000022:
p.000022:
p.000022: Sponsors of clinical trials conducted in Canada must be able to demonstrate that the trials are conducted according to
p.000022: generally accepted principles of good clinical practice. These principles include:
p.000022:
p.000022: • clinical trials must be conducted in accordance with good clinical practices and the applicable regulatory
p.000022: requirement(s).
p.000022:
p.000022: • before a trial is initiated, foreseeable risks and inconveniences must be weighed against the anticipated benefit
p.000022: for the individual trial subject and society. A trial should be initiated and continued only if the anticipated
p.000022: benefits justify the risks.
p.000022:
p.000022: • the rights, safety, and well-being of the trial subjects are the most important considerations and must prevail
p.000022: over interests of science and society.
p.000022:
p.000022: • the available non-clinical and clinical information on an investigational drug must be adequate to support the
p.000022: proposed clinical trial.
p.000022:
p.000022: • clinical trials must be scientifically sound, and described in a clear, detailed protocol.
p.000022:
p.000022: • a trial must be conducted in compliance with a protocol that has received REB approval prior to initiation.
p.000022:
p.000022: • the medical care given to, and medical decisions made on behalf of, subjects must always be the responsibility of
p.000022: a qualified physician or, when appropriate, of a qualified dentist.
p.000022: • each individual involved in conducting a trial should be qualified by education, training, and experience to
p.000022: perform his or her respective task(s).
p.000022:
p.000022: • freely given informed consent must be obtained from every subject prior to clinical trial participation.
p.000022:
p.000022: • all clinical trial information must be recorded, handled, and stored in a way that enables its accurate reporting,
p.000022: interpretation and verification.
p.000022:
p.000022: • the confidentiality of records that could identify subjects must be protected, respecting the privacy and
p.000022: confidentiality rules in accordance with the applicable regulatory requirement(s).
p.000022:
p.000022: • investigational drugs must be fabricated, handled, and stored in accordance with applicable good manufacturing
p.000022: practices (GMP). They must be used in accordance with
p.000022:
p.000022:
p.000022:
p.000022:
p.002001: 2001
p.000023: 23
p.000023:
p.000023: Health Canada
p.000023: Guidance for Industry Regulations Amending the Food & Drug
p.000023: Regulations
p.000023:
p.000023:
p.000023: the approved protocol.
p.000023:
p.000023: • systems with procedures that assure the quality of every aspect of the trial must be implemented.
p.000023:
p.000023:
p.000023: Labeling
p.000023:
p.000023: Drugs used in clinical trials must be labeled in accordance with specified labeling requirements. These requirements
p.000023: include the following:
p.000023:
p.000023: • a statement, to ensure that the drug is identified as an investigational drug to be used only by a qualified
p.000023: investigator;
p.000023:
p.000023: • the name, number, or identifying mark of the drug;
p.000023:
p.000023: • the expiration date;
p.000023:
p.000023: • the recommended storage conditions;
p.000023:
p.000023: • the lot number of the drug;
p.000023:
p.000023: • the name and address of the sponsor; and
p.000023:
p.000023: • the protocol code or identification number.
p.000023:
p.000023: In addition to the above, radiopharmaceuticals must display the radiation symbol required by the Atomic Energy Control
p.000023: Regulations and a statement "Caution--Radioactive Material" « Attention-- produit radioactif ».
p.000023:
p.000023:
p.000023: Adverse Drug Reaction Reporting
p.000023:
p.000023: The sponsor must report to the TPD or BGTD on an expedited basis any serious unexpected adverse drug reactions based on
p.000023: the reporting schedule contained within the attached Regulations. These requirements are consistent with international
p.000023: standards. The Regulations also provide the Minister with the authority to request additional information from the
p.000023: sponsor if there is concern respecting the safety of the clinical trial drug and to take action if required.
p.000023:
p.000023:
p.000023: Records
p.000023:
p.000023: The sponsor must keep all records related to the conduct of a clinical trial in a format that facilitates verification
p.000023: for the purpose of an inspection. The records must be maintained for a
p.000023:
p.000023:
p.002001: 2001
p.000024: 24
p.000024:
p.000024: Health Canada
p.000024: Guidance for Industry Regulations Amending the Food & Drug
p.000024: Regulations
p.000024:
p.000024:
p.000024: period of 25 years. The sponsor must submit requested records within 48 hours if safety concerns arise. Additionally,
p.000024: the Minister can request the submission of information within seven days to facilitate an inspection of a site. This
p.000024: will enable Health Canada to investigate health and safety concerns and to respond in a timely fashion.
p.000024:
p.000024:
p.000024: 30-Day Default System
p.000024:
p.000024:
p.000024: Sponsors wishing to conduct clinical trials in Phases I to III of development must apply under the 30-day default
p.000024: system. The Directorates will establish shorter administrative targets of seven days for the review of bioequivalence
p.000024: trials and Phase I trials in adult healthy volunteers under the 30-day default system. Applications to conduct Phase I
p.000024: clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines or reproductive and
p.000024: genetic technologies will not be included in the seven day target system.
p.000024:
p.000024: Quarterly and annual performance reports will provide a mechanism to publicly report on the Directorates' performance
p.000024: under the seven day target system. These performance statistics will provide the baseline data for an initial
p.000024: evaluation of this initiative, one year following implementation. This will be followed by a comprehensive review of
p.000024: the Regulations in three to five years.
p.000024:
p.000024: Applications must contain the information described in the Regulations, including:
p.000024:
p.000024: • a clinical trial attestation,
p.000024:
p.000024: • a protocol,
p.000024:
p.000024: • statements to be contained in each informed consent form, that set out the risks posed to the health of clinical
p.000024: trial subjects as a result of their participation in the clinical trial,
p.000024:
p.000024: • an investigator's brochure,
p.000024:
p.000024: • applicable information on human-sourced excipients,
p.000024:
p.000024: • chemistry and manufacturing information must also be submitted for clinical trials involving drug products which
p.000024: have not received a DIN or NOC.
p.000024:
p.000024: Applications will be accepted for review without prior REB approval of the informed consent form and protocol. The
p.000024: sponsor must keep copies of undertakings signed by each qualified investigator that the trial will be conducted
p.000024: according to generally accepted principles of good clinical practice. The sponsor must also keep records of
p.000024: attestations signed by the REB that the Board carries out its functions in a manner consistent with these same
p.000024: practices. Prior to the commencement of the clinical trial, the identification of all investigators and REBs is
p.000024: required for each clinical trial site.
p.000024:
p.000024:
p.000024:
p.002001: 2001
p.000025: 25
p.000025:
p.000025: Health Canada
p.000025: Guidance for Industry Regulations Amending the Food & Drug
p.000025: Regulations
p.000025:
p.000025:
p.000025: The sponsor can proceed with the clinical trial if the Directorates have not objected to the sale or importation of the
p.000025: drug within 30 days after the date of receipt of the clinical trial application and REB approval for the conduct of the
p.000025: trial at the site has been obtained.
p.000025:
p.000025: The sponsor must submit additional information or samples if the information and documents submitted are insufficient
p.000025: to assess the quality and safety of the drug to be used in the clinical trial. The sponsor must provide the information
p.000025: requested within two calendar days. The application will be rejected if the information is not provided within two
p.000025: days. The current Management of Drug Submissions Policy will be modified to incorporate this concept.
p.000025:
p.000025:
p.000025: Amendments
p.000025:
p.000025:
p.000025: Sponsors must submit an application for an amendment prior to introducing the following changes. Applications for an
p.000025: amendment are subject to a 30-day default system. Applications must be filed for:
p.000025:
p.000025: • changes to the protocol that affect patient selection and monitoring, clinical efficacy and safety requirements,
p.000025: and patient discontinuation;
p.000025:
p.000025: • changes to the protocol that result in the extension of the duration of the clinical trial; and
p.000025:
p.000025: • changes to the chemistry and manufacturing information that may affect drug safety and quality. (For example:
p.000025: o specifications for the drug where the limits of the test are relaxed or deleted;
p.000025: o where a new impurity or degradation product has been identified; and,
p.000025: o the addition of new raw materials, solvents, reagents, catalysts or any other material used in the fabrication of the
p.000025: drug substance.)
p.000025:
p.000025: The sponsor can make the changes described above without prior authorization to limit an unacceptable risk which has
p.000025: been identified. In that case, the sponsor must provide the required information respecting that change within 15
p.000025: calendar days.
p.000025:
p.000025:
p.000025: Notification
p.000025:
p.000025:
p.000025: Sponsors must notify Health Canada of the following changes, within 15 calendar days of the date of the change:
p.000025:
p.000025: • changes to the chemistry and manufacturing information that do not affect the quality or safety of the drug.
p.000025: (For example: changes to the specifications for the drug substance where the limits of the test are tightened or
p.000025: additional tests are added)
p.000025:
p.000025: • changes to the protocol that do not affect the safety of the trial subjects.
p.000025:
p.000025:
p.002001: 2001
p.000026: 26
p.000026:
p.000026: Health Canada
p.000026: Guidance for Industry Regulations Amending the Food & Drug
p.000026: Regulations
p.000026:
p.000026:
p.000026: Inspection System
p.000026:
p.000026: Health Canada will inspect clinical trial sites and trial sponsors to ensure that the generally accepted principles of
p.000026: good clinical practice are met. The objectives of the inspection will be to ensure that participants in clinical trials
p.000026: are not subjected to undue risks, to validate the quality of the data generated or to investigate complaints.
p.000026:
p.000026: The Minister will use the information collected as a result of these inspections to ensure compliance with the
p.000026: regulatory framework and will take enforcement action, when deemed necessary.
p.000026:
p.000026:
p.000026: Coming Into Force
p.000026:
p.000026: These Regulations will become effective on September 1, 2001. Health Canada is proceeding with staffing actions and
p.000026: implementing new administrative and process measures to provide the required level of increased service.
p.000026:
p.000026: Submissions received prior to the coming into force of the new framework will be subject to the current 60 day default
p.000026: and the regulatory requirements in place prior to the effective date of these new Regulations.
p.000026:
p.000026:
p.000026: Expectations
p.000026:
p.000026: This framework has been designed to meet the following objectives:
p.000026:
p.000026: • shorten the time required for clinical trial application review, without endangering the health and safety of
p.000026: Canadians;
p.000026:
p.000026: • improve safety mechanisms for clinical trial subjects, such as compliance with generally accepted principles of
p.000026: good clinical practice;
p.000026:
p.000026: • address the Auditor General's recommendation that the regulator be more involved in the monitoring and follow-up
p.000026: of conduct of clinical trials;
p.000026:
p.000026: • ensure that Canada has a clinical trial framework which is flexible but contains sufficient safeguards to ensure
p.000026: that the review of clinical trial applications is not unduly delayed as recommended by the Standing Committee on Health
p.000026: in its report "Organs and Tissue Donation and Transplantation: A Canadian Approach" dated April 22, 1999;
p.000026:
p.000026: • introduce additional operational efficiencies;
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.002001: 2001
p.000027: 27
p.000027:
p.000027: Health Canada
p.000027: Guidance for Industry Regulations Amending the Food & Drug
p.000027: Regulations
p.000027:
p.000027:
p.000027: • remove obstacles to additional research and development in Canada, where they do not endanger the health and
p.000027: safety of Canadians;
p.000027:
p.000027: • evaluate the proposed changes and their impact on research and development in Canada and the health and safety of
p.000027: trial subjects;
p.000027:
p.000027: • ensure that Canadians have improved access to innovative therapies and advice from Canadian physicians with
p.000027: research expertise in these new therapies.
p.000027:
p.000027: The Directorates will monitor the impact of these changes on the conduct of clinical trials and on the development of
p.000027: drugs in Canada. Health Canada will conduct a policy review to evaluate the impact of these Regulations commencing
p.000027: September 1, 2002.
p.000027:
p.000027:
p.000027: Cost Recovery
p.000027:
p.000027:
p.000027: Cost recovery initiatives do not apply to the evaluation of clinical trial applications as such is considered a "public
p.000027: good". Funding to implement this regulatory change has been secured through Appropriations. Therefore, Canadian
p.000027: taxpayers provide all the funding to support this review.
p.000027:
p.000027:
p.000027: International Perspective
p.000027:
p.000027:
p.000027: In the United States of America (USA), all clinical trial applications are subject to a 30-day default review period.
p.000027: In cases where the U.S. Food and Drug Administration (FDA) has safety concerns regarding an application, a clinical
p.000027: hold may be issued. The sponsor must delay the proposed clinical trial or suspend an ongoing investigation until the
p.000027: issues surrounding the hold are resolved.
p.000027:
p.000027: In the United Kingdom (UK), Phase I clinical trials in healthy volunteers are currently exempt from regulatory review
p.000027: European Union member states recently signed a new Directive on clinical trials which mandates a 60 day default review
p.000027: period for the review of clinical trial applications. Implementation of this Directive will harmonize review practices
p.000027: across member jurisdictions. For example, Phase I clinical trials in healthy volunteers in the UK will become subject
p.000027: to an assessment under this new system.
p.000027:
p.000027: The USA, Japan, the EU and Canada are coordinating their efforts to use a uniform guideline for good clinical
p.000027: practices. This guideline was developed by the International Conference on Harmonization. In addition the European
p.000027: Parliament is in the process of developing a guideline for the performance of inspection function based on the current
p.000027: version of the Declaration of Helsinki and the Convention du Conseil de l'Europe pour la protection des droits de
p.000027: l'Homme et de la dignité humaine à l'égard des applications de la biologie et de la médecine. Those guidelines are
p.000027: expected to be adopted by each individual country of the European Community.
p.000027:
p.000027:
p.000027:
p.002001: 2001
p.000028: 28
p.000028:
p.000028: Health Canada
p.000028: Guidance for Industry Regulations Amending the Food & Drug
p.000028: Regulations
p.000028:
p.000028:
p.000028: The current trends in clinical trial review indicate that:
p.000028:
p.000028: • there is approximately a 20% annual increase in the number of trials worldwide;
p.000028:
p.000028: • reports from the United States indicate that over 60 % of all clinical trials are performed overseas with the
p.000028: majority conducted in the United Kingdom;
p.000028:
p.000028: • Canada ranks 3rd behind the EU and the USA as the location where clinical trials are routinely conducted;
p.000028:
p.000028: • there are global pressures to harmonize requirements, and expedite trial reviews;
p.000028:
p.000028: • the use of electronic data has become more widely accepted;
p.000028:
p.000028: • there are increased ethical concerns about human safety in clinical research;
p.000028:
p.000028: • there is a need to conduct clinical trials in specific patient populations; and
p.000028:
p.000028: • clarifications are required to better define the roles and responsibilities of the various players in the review
p.000028: of clinical trials
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
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p.000028:
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p.000028:
p.002001: 2001
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p.000002: a clinical trial authorized under subsection C.05.006(2).
p.000002:
p.000002:
p.000002: Prohibition
p.000002:
p.000002: C.05.003. Despite sections C.01.014, C.08.002 and C.08.003, no person shall sell or import a drug for the purposes of a
p.000002: clinical trial unless
p.000002:
p.000002: (a) the person is authorized under this Division;
p.000002:
p.000002: (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
p.000002: to C.01.067, C.01.070, C.01.131, C.01.133 to C.01.136, and C.01.435; and
p.000002:
p.000002: (c) if the drug is to be imported, the person has a representative in Canada who is responsible for the sale of the
p.000002: drug.
p.000002:
p.000002:
p.000002:
p.002001: 2001
p.000003: 3
p.000003:
p.000003: Health Canada
p.000003: Guidance for Industry Regulations Amending the Food & Drug
p.000003: Regulations
p.000003:
p.000003:
p.000003:
p.000003: General
p.000003:
p.000003: C.05.004. Despite these Regulations, a sponsor may submit an application under this Division to sell or import a drug
p.000003: for the purposes of a clinical trial that contains a substance the sale of which is prohibited by these Regulations, if
p.000003: the sponsor establishes, on the basis of scientific information, that the inclusion of the substance in the drug may
p.000003: result in a therapeutic benefit for a human being.
p.000003:
p.000003:
p.000003: Application for Authorization
p.000003:
p.000003: C.05.005. An application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial
p.000003: under this Division shall be submitted to the Minister, signed and dated by the sponsor's senior medical or scientific
p.000003: officer in Canada and senior executive officer and shall contain the following information and documents:
p.000003:
p.000003: (a) a copy of the protocol for the clinical trial;
p.000003:
p.000003: (b) a copy of the statement, as it will be set out in each informed consent form, that states the risks and anticipated
p.000003: benefits arising to the health of clinical trial subjects as a result of their participation in the clinical trial;
p.000003:
p.000003: (c) a clinical trial attestation, signed and dated by the sponsor's senior medical or scientific officer in Canada and
p.000003: senior executive officer, containing
p.000003:
p.000003: (i) the title of the protocol and the clinical trial number,
p.000003:
p.000003: (ii) the brand name, the chemical name or the code for the drug,
p.000003:
...
p.000025: requested within two calendar days. The application will be rejected if the information is not provided within two
p.000025: days. The current Management of Drug Submissions Policy will be modified to incorporate this concept.
p.000025:
p.000025:
p.000025: Amendments
p.000025:
p.000025:
p.000025: Sponsors must submit an application for an amendment prior to introducing the following changes. Applications for an
p.000025: amendment are subject to a 30-day default system. Applications must be filed for:
p.000025:
p.000025: • changes to the protocol that affect patient selection and monitoring, clinical efficacy and safety requirements,
p.000025: and patient discontinuation;
p.000025:
p.000025: • changes to the protocol that result in the extension of the duration of the clinical trial; and
p.000025:
p.000025: • changes to the chemistry and manufacturing information that may affect drug safety and quality. (For example:
p.000025: o specifications for the drug where the limits of the test are relaxed or deleted;
p.000025: o where a new impurity or degradation product has been identified; and,
p.000025: o the addition of new raw materials, solvents, reagents, catalysts or any other material used in the fabrication of the
p.000025: drug substance.)
p.000025:
p.000025: The sponsor can make the changes described above without prior authorization to limit an unacceptable risk which has
p.000025: been identified. In that case, the sponsor must provide the required information respecting that change within 15
p.000025: calendar days.
p.000025:
p.000025:
p.000025: Notification
p.000025:
p.000025:
p.000025: Sponsors must notify Health Canada of the following changes, within 15 calendar days of the date of the change:
p.000025:
p.000025: • changes to the chemistry and manufacturing information that do not affect the quality or safety of the drug.
p.000025: (For example: changes to the specifications for the drug substance where the limits of the test are tightened or
p.000025: additional tests are added)
p.000025:
p.000025: • changes to the protocol that do not affect the safety of the trial subjects.
p.000025:
p.000025:
p.002001: 2001
p.000026: 26
p.000026:
p.000026: Health Canada
p.000026: Guidance for Industry Regulations Amending the Food & Drug
p.000026: Regulations
p.000026:
p.000026:
p.000026: Inspection System
p.000026:
p.000026: Health Canada will inspect clinical trial sites and trial sponsors to ensure that the generally accepted principles of
p.000026: good clinical practice are met. The objectives of the inspection will be to ensure that participants in clinical trials
p.000026: are not subjected to undue risks, to validate the quality of the data generated or to investigate complaints.
p.000026:
p.000026: The Minister will use the information collected as a result of these inspections to ensure compliance with the
p.000026: regulatory framework and will take enforcement action, when deemed necessary.
p.000026:
p.000026:
p.000026: Coming Into Force
p.000026:
p.000026: These Regulations will become effective on September 1, 2001. Health Canada is proceeding with staffing actions and
p.000026: implementing new administrative and process measures to provide the required level of increased service.
p.000026:
p.000026: Submissions received prior to the coming into force of the new framework will be subject to the current 60 day default
p.000026: and the regulatory requirements in place prior to the effective date of these new Regulations.
p.000026:
p.000026:
p.000026: Expectations
p.000026:
p.000026: This framework has been designed to meet the following objectives:
p.000026:
...
Health / Healthy People
Searching for indicator healthy volunteers:
(return to top)
p.000019: industry, the research granting councils, the medical community, the ethics community and the federal government.
p.000019: Within this partnership, the Therapeutic Products
p.000019:
p.000019:
p.000019:
p.002001: 2001
p.000020: 20
p.000020:
p.000020: Health Canada
p.000020: Guidance for Industry Regulations Amending the Food & Drug
p.000020: Regulations
p.000020:
p.000020:
p.000020: Directorate [TPD] and the Biologics and Genetic Therapies Directorate [BGTD] of Health Canada provide a critical
p.000020: service by ensuring that clinical trials are properly designed and undertaken and that subjects are not exposed to
p.000020: undue risk.
p.000020:
p.000020: It is also Health Canada's responsibility to ensure that its decisions are made in a timely fashion thereby not
p.000020: discouraging the research and development of human drugs in Canada.
p.000020:
p.000020: The Food and Drug Regulations currently include several provisions which define the requirements for the sale of drugs
p.000020: for use in clinical trials in humans. These investigations are generally divided into four phases depending on the
p.000020: stage of drug development:
p.000020:
p.000020: Phase I: Initial safety studies on a new drug, including the first administration of the drug into humans, usually
p.000020: conducted in healthy volunteers. These trials may be conducted in patients when administration of the drug to healthy
p.000020: volunteers is not ethical.
p.000020:
p.000020: Phase I trials are designed mainly to determine the pharmacological actions of the drug and the side effects associated
p.000020: with increasing doses. Pharmacokinetic as well as drug-drug interaction studies are usually considered as Phase I
p.000020: trials regardless of when they are conducted during drug development as these are generally conducted in healthy
p.000020: volunteers. Phase I trials also include trials in which new drugs are used as research tools to explore biological
p.000020: phenomena or disease processes.
p.000020:
p.000020: Phase II: Clinical trials to evaluate the efficacy of the drug in patients with medical conditions to be treated,
p.000020: diagnosed or prevented and to determine the side effects and risks associated with the drug. If a new indication for a
p.000020: marketed drug is to be investigated, then those clinical trials may generally be considered Phase II trials.
p.000020:
p.000020: Phase III: Controlled or uncontrolled trials conducted after preliminary evidence suggesting efficacy of the drug has
p.000020: been demonstrated. These are intended to gather the additional information about efficacy and safety that is needed for
...
p.000023: the reporting schedule contained within the attached Regulations. These requirements are consistent with international
p.000023: standards. The Regulations also provide the Minister with the authority to request additional information from the
p.000023: sponsor if there is concern respecting the safety of the clinical trial drug and to take action if required.
p.000023:
p.000023:
p.000023: Records
p.000023:
p.000023: The sponsor must keep all records related to the conduct of a clinical trial in a format that facilitates verification
p.000023: for the purpose of an inspection. The records must be maintained for a
p.000023:
p.000023:
p.002001: 2001
p.000024: 24
p.000024:
p.000024: Health Canada
p.000024: Guidance for Industry Regulations Amending the Food & Drug
p.000024: Regulations
p.000024:
p.000024:
p.000024: period of 25 years. The sponsor must submit requested records within 48 hours if safety concerns arise. Additionally,
p.000024: the Minister can request the submission of information within seven days to facilitate an inspection of a site. This
p.000024: will enable Health Canada to investigate health and safety concerns and to respond in a timely fashion.
p.000024:
p.000024:
p.000024: 30-Day Default System
p.000024:
p.000024:
p.000024: Sponsors wishing to conduct clinical trials in Phases I to III of development must apply under the 30-day default
p.000024: system. The Directorates will establish shorter administrative targets of seven days for the review of bioequivalence
p.000024: trials and Phase I trials in adult healthy volunteers under the 30-day default system. Applications to conduct Phase I
p.000024: clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines or reproductive and
p.000024: genetic technologies will not be included in the seven day target system.
p.000024:
p.000024: Quarterly and annual performance reports will provide a mechanism to publicly report on the Directorates' performance
p.000024: under the seven day target system. These performance statistics will provide the baseline data for an initial
p.000024: evaluation of this initiative, one year following implementation. This will be followed by a comprehensive review of
p.000024: the Regulations in three to five years.
p.000024:
p.000024: Applications must contain the information described in the Regulations, including:
p.000024:
p.000024: • a clinical trial attestation,
p.000024:
p.000024: • a protocol,
p.000024:
p.000024: • statements to be contained in each informed consent form, that set out the risks posed to the health of clinical
p.000024: trial subjects as a result of their participation in the clinical trial,
p.000024:
p.000024: • an investigator's brochure,
p.000024:
p.000024: • applicable information on human-sourced excipients,
p.000024:
p.000024: • chemistry and manufacturing information must also be submitted for clinical trials involving drug products which
p.000024: have not received a DIN or NOC.
p.000024:
p.000024: Applications will be accepted for review without prior REB approval of the informed consent form and protocol. The
p.000024: sponsor must keep copies of undertakings signed by each qualified investigator that the trial will be conducted
...
p.000027: safety of Canadians;
p.000027:
p.000027: • evaluate the proposed changes and their impact on research and development in Canada and the health and safety of
p.000027: trial subjects;
p.000027:
p.000027: • ensure that Canadians have improved access to innovative therapies and advice from Canadian physicians with
p.000027: research expertise in these new therapies.
p.000027:
p.000027: The Directorates will monitor the impact of these changes on the conduct of clinical trials and on the development of
p.000027: drugs in Canada. Health Canada will conduct a policy review to evaluate the impact of these Regulations commencing
p.000027: September 1, 2002.
p.000027:
p.000027:
p.000027: Cost Recovery
p.000027:
p.000027:
p.000027: Cost recovery initiatives do not apply to the evaluation of clinical trial applications as such is considered a "public
p.000027: good". Funding to implement this regulatory change has been secured through Appropriations. Therefore, Canadian
p.000027: taxpayers provide all the funding to support this review.
p.000027:
p.000027:
p.000027: International Perspective
p.000027:
p.000027:
p.000027: In the United States of America (USA), all clinical trial applications are subject to a 30-day default review period.
p.000027: In cases where the U.S. Food and Drug Administration (FDA) has safety concerns regarding an application, a clinical
p.000027: hold may be issued. The sponsor must delay the proposed clinical trial or suspend an ongoing investigation until the
p.000027: issues surrounding the hold are resolved.
p.000027:
p.000027: In the United Kingdom (UK), Phase I clinical trials in healthy volunteers are currently exempt from regulatory review
p.000027: European Union member states recently signed a new Directive on clinical trials which mandates a 60 day default review
p.000027: period for the review of clinical trial applications. Implementation of this Directive will harmonize review practices
p.000027: across member jurisdictions. For example, Phase I clinical trials in healthy volunteers in the UK will become subject
p.000027: to an assessment under this new system.
p.000027:
p.000027: The USA, Japan, the EU and Canada are coordinating their efforts to use a uniform guideline for good clinical
p.000027: practices. This guideline was developed by the International Conference on Harmonization. In addition the European
p.000027: Parliament is in the process of developing a guideline for the performance of inspection function based on the current
p.000027: version of the Declaration of Helsinki and the Convention du Conseil de l'Europe pour la protection des droits de
p.000027: l'Homme et de la dignité humaine à l'égard des applications de la biologie et de la médecine. Those guidelines are
p.000027: expected to be adopted by each individual country of the European Community.
p.000027:
p.000027:
p.000027:
p.002001: 2001
p.000028: 28
p.000028:
p.000028: Health Canada
p.000028: Guidance for Industry Regulations Amending the Food & Drug
p.000028: Regulations
p.000028:
p.000028:
p.000028: The current trends in clinical trial review indicate that:
p.000028:
p.000028: • there is approximately a 20% annual increase in the number of trials worldwide;
p.000028:
p.000028: • reports from the United States indicate that over 60 % of all clinical trials are performed overseas with the
p.000028: majority conducted in the United Kingdom;
p.000028:
p.000028: • Canada ranks 3rd behind the EU and the USA as the location where clinical trials are routinely conducted;
p.000028:
p.000028: • there are global pressures to harmonize requirements, and expedite trial reviews;
p.000028:
p.000028: • the use of electronic data has become more widely accepted;
p.000028:
...
Health / Mentally Disabled
Searching for indicator disability:
(return to top)
p.000001:
p.000001: (i) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the
p.000001: methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is
p.000001: in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
p.000001:
p.000001: (ii) one member knowledgeable in ethics,
p.000001:
p.000001: (iii) one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
p.000001:
p.000001: (iv) one member whose primary experience and expertise are in a nonscientific discipline, and
p.000001:
p.000001:
p.000001:
p.002001: 2001
p.000002: 2
p.000002:
p.000002: Health Canada
p.000002: Guidance for Industry Regulations Amending the Food & Drug
p.000002: Regulations
p.000002:
p.000002:
p.000002: (v) one member who is from the community or is a representative of an organization interested in the areas of research
p.000002: to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted.
p.000002: (comité d'éthique de la recherche)
p.000002:
p.000002: "serious adverse drug reaction" means an adverse drug reaction that requires in-patient hospitalization or prolongation
p.000002: of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability
p.000002: or incapacity, that is life threatening or that results in death. (réaction indésirable grave à une drogue)
p.000002:
p.000002: "serious unexpected adverse drug reaction" means a serious adverse drug reaction that is not identified in nature,
p.000002: severity or frequency in the risk information set out in the investigator's brochure or on the label of the drug.
p.000002: (réaction indésirable grave et imprévue à une drogue)
p.000002:
p.000002: "sponsor" means an individual, corporate body, institution or organization that conducts a clinical trial. (promoteur)
p.000002:
p.000002:
p.000002: Application
p.000002:
p.000002: C.05.002.(1) Subject to subsection (2), this Division applies to the sale or importation of drugs to be used for the
p.000002: purposes of clinical trials involving human subjects.
p.000002:
p.000002: (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,
p.000002: 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
p.000002: 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
p.000002: a clinical trial authorized under subsection C.05.006(2).
p.000002:
p.000002:
p.000002: Prohibition
p.000002:
p.000002: C.05.003. Despite sections C.01.014, C.08.002 and C.08.003, no person shall sell or import a drug for the purposes of a
p.000002: clinical trial unless
p.000002:
...
Social / Access to Social Goods
Searching for indicator access:
(return to top)
p.000020: have valid scientific objectives. Commonly conducted studies include safety studies and studies designed to support use
p.000020: under the approved indication such as mortality and morbidity studies, or epidemiological studies.
p.000020:
p.000020: The current regulatory requirements respecting drugs to be used for the purposes of clinical trials were originally
p.000020: developed in the early 1960s and have remained essentially unchanged. Those Regulations defined specific
p.000020: Investigational New Drug Submission (IND) application requirements which must be complied with before a new drug could
p.000020: be distributed for trial purposes. In 1987, the Regulations were amended to introduce a 60 day default period. Since
p.000020: that time TPD, BGTD and the Veterinary Drugs Program, in the case of a veterinary drug, notify the
p.000020:
p.000020:
p.002001: 2001
p.000021: 21
p.000021:
p.000021: Health Canada
p.000021: Guidance for Industry Regulations Amending the Food & Drug
p.000021: Regulations
p.000021:
p.000021:
p.000021: sponsor within 60 days if its submission is found to be deficient or else the sponsor may proceed. The 60 day default
p.000021: was introduced in 1987 in an attempt to remedy industry's uncertainty in the planning process and to encourage research
p.000021: opportunities in Canada. A move to shorten the review time provided a positive benefit to all Canadians as it permitted
p.000021: faster access to new innovative therapies through the conduct of a clinical trial.
p.000021:
p.000021: The Directorates currently review the safety, efficacy and quality data submitted by the sponsor and approve the
p.000021: distribution of the drug to the investigator. The Directorates may authorize the sale of the drug if the protocol is
p.000021: scientifically sound and the drug would not pose unacceptable risks to the trial subjects under the proposed conditions
p.000021: of use. The sponsor of the trial is required to maintain accurate records, report adverse drug reactions, and ensure
p.000021: that the investigator adheres to the approved protocol. Trials in humans should be conducted according to generally
p.000021: accepted principles of good clinical practice. These standards provide assurance that the data and reported results are
p.000021: credible and accurate, and that the rights, integrity, and privacy of clinical trial subjects are protected.
p.000021:
p.000021: The Directorates encourage sponsors to obtain the approval of a Research Ethics Board (REB) prior to conducting trials
p.000021: in Canada. A REB is an independent body, including both men and women, which is responsible for approving the
p.000021: initiation, and conduct of periodic reviews of biomedical research involving human subjects. The principal mandate of
p.000021: the REB is to ensure the protection of the rights, safety and well-being of subjects in the clinical trial. This
...
p.000026:
p.000026:
p.000026: Expectations
p.000026:
p.000026: This framework has been designed to meet the following objectives:
p.000026:
p.000026: • shorten the time required for clinical trial application review, without endangering the health and safety of
p.000026: Canadians;
p.000026:
p.000026: • improve safety mechanisms for clinical trial subjects, such as compliance with generally accepted principles of
p.000026: good clinical practice;
p.000026:
p.000026: • address the Auditor General's recommendation that the regulator be more involved in the monitoring and follow-up
p.000026: of conduct of clinical trials;
p.000026:
p.000026: • ensure that Canada has a clinical trial framework which is flexible but contains sufficient safeguards to ensure
p.000026: that the review of clinical trial applications is not unduly delayed as recommended by the Standing Committee on Health
p.000026: in its report "Organs and Tissue Donation and Transplantation: A Canadian Approach" dated April 22, 1999;
p.000026:
p.000026: • introduce additional operational efficiencies;
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.002001: 2001
p.000027: 27
p.000027:
p.000027: Health Canada
p.000027: Guidance for Industry Regulations Amending the Food & Drug
p.000027: Regulations
p.000027:
p.000027:
p.000027: • remove obstacles to additional research and development in Canada, where they do not endanger the health and
p.000027: safety of Canadians;
p.000027:
p.000027: • evaluate the proposed changes and their impact on research and development in Canada and the health and safety of
p.000027: trial subjects;
p.000027:
p.000027: • ensure that Canadians have improved access to innovative therapies and advice from Canadian physicians with
p.000027: research expertise in these new therapies.
p.000027:
p.000027: The Directorates will monitor the impact of these changes on the conduct of clinical trials and on the development of
p.000027: drugs in Canada. Health Canada will conduct a policy review to evaluate the impact of these Regulations commencing
p.000027: September 1, 2002.
p.000027:
p.000027:
p.000027: Cost Recovery
p.000027:
p.000027:
p.000027: Cost recovery initiatives do not apply to the evaluation of clinical trial applications as such is considered a "public
p.000027: good". Funding to implement this regulatory change has been secured through Appropriations. Therefore, Canadian
p.000027: taxpayers provide all the funding to support this review.
p.000027:
p.000027:
p.000027: International Perspective
p.000027:
p.000027:
p.000027: In the United States of America (USA), all clinical trial applications are subject to a 30-day default review period.
p.000027: In cases where the U.S. Food and Drug Administration (FDA) has safety concerns regarding an application, a clinical
p.000027: hold may be issued. The sponsor must delay the proposed clinical trial or suspend an ongoing investigation until the
p.000027: issues surrounding the hold are resolved.
p.000027:
p.000027: In the United Kingdom (UK), Phase I clinical trials in healthy volunteers are currently exempt from regulatory review
p.000027: European Union member states recently signed a new Directive on clinical trials which mandates a 60 day default review
p.000027: period for the review of clinical trial applications. Implementation of this Directive will harmonize review practices
...
Social / Marital Status
Searching for indicator single:
(return to top)
p.000004: approved an informed consent form containing the statement referred to in paragraph (b), if known at the time of
p.000004: submitting the application, and
p.000004:
p.000004: (xi) a statement
p.000004:
p.000004: (A) that the clinical trial will be conducted in accordance with good clinical practices and these Regulations, and
p.000004:
p.000004: (B) that all information contained in, or referenced by, the application is complete and accurate and is not false or
p.000004: misleading;
p.000004:
p.000004: (d) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of any
p.000004: research ethics board that has previously refused to approve the protocol referred to in paragraph (a), its reasons for
p.000004: doing so and the date on which the refusal was given, if known at the time of submitting the application;
p.000004:
p.000004: (e) an investigator's brochure that contains the following information, namely,
p.000004:
p.000004: (i) the physical, chemical and pharmaceutical properties of the drug,
p.000004:
p.000004: (ii) the pharmacological aspects of the drug, including its metabolites in all animal species tested,
p.000004:
p.000004: (iii) the pharmacokinetics of the drug and the drug metabolism, including the biological transformation of the drug in
p.000004: all animal species tested,
p.000004:
p.000004: (iv) any toxicological effects in any animal species tested under a single dose study, a repeated dose study or a
p.000004: special study in respect of the drug,
p.000004:
p.000004: (v) any results of carcinogenicity studies in any animal species tested in respect of the drug,
p.000004:
p.000004: (vi) any results of clinical pharmacokinetic studies of the drug,
p.000004:
p.000004: (vii) any information regarding drug safety, pharmacodynamics, efficacy and dose responses of the drug that were
p.000004: obtained from previous clinical trials in humans, and
p.000004:
p.000004:
p.000004:
p.002001: 2001
p.000005: 5
p.000005:
p.000005: Health Canada
p.000005: Guidance for Industry Regulations Amending the Food & Drug
p.000005: Regulations
p.000005:
p.000005:
p.000005: (viii) if the drug is a radiopharmaceutical as defined in section C.03.201, information regarding directions for
p.000005: preparing the radiopharmaceutical, the radiation dosimetry in respect of the prepared radiopharmaceutical and a
p.000005: statement of the storage requirements for the prepared radiopharmaceutical;
p.000005:
p.000005: (f) if the drug contains a human-sourced excipient, including any used in the placebo,
p.000005:
p.000005: (i) information that indicates the human-sourced excipient has been assigned a drug identification number under
...
Social / Police Officer
Searching for indicator officer:
(return to top)
p.000002: to C.01.067, C.01.070, C.01.131, C.01.133 to C.01.136, and C.01.435; and
p.000002:
p.000002: (c) if the drug is to be imported, the person has a representative in Canada who is responsible for the sale of the
p.000002: drug.
p.000002:
p.000002:
p.000002:
p.002001: 2001
p.000003: 3
p.000003:
p.000003: Health Canada
p.000003: Guidance for Industry Regulations Amending the Food & Drug
p.000003: Regulations
p.000003:
p.000003:
p.000003:
p.000003: General
p.000003:
p.000003: C.05.004. Despite these Regulations, a sponsor may submit an application under this Division to sell or import a drug
p.000003: for the purposes of a clinical trial that contains a substance the sale of which is prohibited by these Regulations, if
p.000003: the sponsor establishes, on the basis of scientific information, that the inclusion of the substance in the drug may
p.000003: result in a therapeutic benefit for a human being.
p.000003:
p.000003:
p.000003: Application for Authorization
p.000003:
p.000003: C.05.005. An application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial
p.000003: under this Division shall be submitted to the Minister, signed and dated by the sponsor's senior medical or scientific
p.000003: officer in Canada and senior executive officer and shall contain the following information and documents:
p.000003:
p.000003: (a) a copy of the protocol for the clinical trial;
p.000003:
p.000003: (b) a copy of the statement, as it will be set out in each informed consent form, that states the risks and anticipated
p.000003: benefits arising to the health of clinical trial subjects as a result of their participation in the clinical trial;
p.000003:
p.000003: (c) a clinical trial attestation, signed and dated by the sponsor's senior medical or scientific officer in Canada and
p.000003: senior executive officer, containing
p.000003:
p.000003: (i) the title of the protocol and the clinical trial number,
p.000003:
p.000003: (ii) the brand name, the chemical name or the code for the drug,
p.000003:
p.000003: (iii) the therapeutic and pharmacological classifications of the drug,
p.000003:
p.000003: (iv) the medicinal ingredients of the drug,
p.000003:
p.000003: (v) the non-medicinal ingredients of the drug,
p.000003:
p.000003: (vi) the dosage form of the drug,
p.000003:
p.000003: (vii) the name, address and telephone number and, if applicable, the facsimile number and electronic mail address of
p.000003: the sponsor,
p.000003:
p.000003: (viii) if the drug is to be imported, the name, address and telephone number and, if applicable, the facsimile number
p.000003: and electronic mail address of the sponsor's representative in Canada who is responsible for the sale of the drug,
p.000003:
p.000003:
p.000003:
p.002001: 2001
p.000004: 4
p.000004:
p.000004: Health Canada
p.000004: Guidance for Industry Regulations Amending the Food & Drug
p.000004: Regulations
p.000004:
p.000004:
p.000004: (ix) for each clinical trial site, the name, address and telephone number and, if applicable, the facsimile number and
p.000004: electronic mail address of the qualified investigator, if known at the time of submitting the application,
p.000004:
...
Social / Trade Union Membership
Searching for indicator union:
(return to top)
p.000027:
p.000027: • evaluate the proposed changes and their impact on research and development in Canada and the health and safety of
p.000027: trial subjects;
p.000027:
p.000027: • ensure that Canadians have improved access to innovative therapies and advice from Canadian physicians with
p.000027: research expertise in these new therapies.
p.000027:
p.000027: The Directorates will monitor the impact of these changes on the conduct of clinical trials and on the development of
p.000027: drugs in Canada. Health Canada will conduct a policy review to evaluate the impact of these Regulations commencing
p.000027: September 1, 2002.
p.000027:
p.000027:
p.000027: Cost Recovery
p.000027:
p.000027:
p.000027: Cost recovery initiatives do not apply to the evaluation of clinical trial applications as such is considered a "public
p.000027: good". Funding to implement this regulatory change has been secured through Appropriations. Therefore, Canadian
p.000027: taxpayers provide all the funding to support this review.
p.000027:
p.000027:
p.000027: International Perspective
p.000027:
p.000027:
p.000027: In the United States of America (USA), all clinical trial applications are subject to a 30-day default review period.
p.000027: In cases where the U.S. Food and Drug Administration (FDA) has safety concerns regarding an application, a clinical
p.000027: hold may be issued. The sponsor must delay the proposed clinical trial or suspend an ongoing investigation until the
p.000027: issues surrounding the hold are resolved.
p.000027:
p.000027: In the United Kingdom (UK), Phase I clinical trials in healthy volunteers are currently exempt from regulatory review
p.000027: European Union member states recently signed a new Directive on clinical trials which mandates a 60 day default review
p.000027: period for the review of clinical trial applications. Implementation of this Directive will harmonize review practices
p.000027: across member jurisdictions. For example, Phase I clinical trials in healthy volunteers in the UK will become subject
p.000027: to an assessment under this new system.
p.000027:
p.000027: The USA, Japan, the EU and Canada are coordinating their efforts to use a uniform guideline for good clinical
p.000027: practices. This guideline was developed by the International Conference on Harmonization. In addition the European
p.000027: Parliament is in the process of developing a guideline for the performance of inspection function based on the current
p.000027: version of the Declaration of Helsinki and the Convention du Conseil de l'Europe pour la protection des droits de
p.000027: l'Homme et de la dignité humaine à l'égard des applications de la biologie et de la médecine. Those guidelines are
p.000027: expected to be adopted by each individual country of the European Community.
p.000027:
p.000027:
p.000027:
p.002001: 2001
p.000028: 28
p.000028:
p.000028: Health Canada
p.000028: Guidance for Industry Regulations Amending the Food & Drug
p.000028: Regulations
p.000028:
p.000028:
p.000028: The current trends in clinical trial review indicate that:
p.000028:
p.000028: • there is approximately a 20% annual increase in the number of trials worldwide;
p.000028:
p.000028: • reports from the United States indicate that over 60 % of all clinical trials are performed overseas with the
...
Social / Women
Searching for indicator women:
(return to top)
p.000001: drug that are described in paragraph C.05.005(e). (brochure du chercheur)
p.000001:
p.000001: "protocol" means a document that describes the objectives, design, methodology, statistical considerations and
p.000001: organization of a clinical trial. (protocole)
p.000001:
p.000001: "qualified investigator" means the person responsible to the sponsor for the conduct of the clinical trial at a
p.000001: clinical trial site, who is entitled to provide health care under the laws of the province where that clinical trial
p.000001: site is located, and who is
p.000001:
p.000001: (a) in the case of a clinical trial respecting a drug to be used for dental purposes only, a physician or dentist and a
p.000001: member in good standing of a professional medical or dental association; and
p.000001:
p.000001: (b) in any other case, a physician and a member in good standing of a professional medical association. (chercheur
p.000001: qualifié)
p.000001:
p.000001: "research ethics board" means a body that is not affiliated with the sponsor, and
p.000001:
p.000001: (a) the principal mandate of which is to approve the initiation of, and conduct periodic reviews of, biomedical
p.000001: research involving human subjects in order to ensure the protection of their rights, safety and well-being; and
p.000001:
p.000001: (b) that has at least five members, that has a majority of members who are Canadian citizens or permanent residents
p.000001: under the Immigration Act, that is composed of both men and women and that includes at least
p.000001:
p.000001: (i) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the
p.000001: methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is
p.000001: in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
p.000001:
p.000001: (ii) one member knowledgeable in ethics,
p.000001:
p.000001: (iii) one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
p.000001:
p.000001: (iv) one member whose primary experience and expertise are in a nonscientific discipline, and
p.000001:
p.000001:
p.000001:
p.002001: 2001
p.000002: 2
p.000002:
p.000002: Health Canada
p.000002: Guidance for Industry Regulations Amending the Food & Drug
p.000002: Regulations
p.000002:
p.000002:
p.000002: (v) one member who is from the community or is a representative of an organization interested in the areas of research
p.000002: to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted.
p.000002: (comité d'éthique de la recherche)
p.000002:
p.000002: "serious adverse drug reaction" means an adverse drug reaction that requires in-patient hospitalization or prolongation
p.000002: of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability
...
p.000021: was introduced in 1987 in an attempt to remedy industry's uncertainty in the planning process and to encourage research
p.000021: opportunities in Canada. A move to shorten the review time provided a positive benefit to all Canadians as it permitted
p.000021: faster access to new innovative therapies through the conduct of a clinical trial.
p.000021:
p.000021: The Directorates currently review the safety, efficacy and quality data submitted by the sponsor and approve the
p.000021: distribution of the drug to the investigator. The Directorates may authorize the sale of the drug if the protocol is
p.000021: scientifically sound and the drug would not pose unacceptable risks to the trial subjects under the proposed conditions
p.000021: of use. The sponsor of the trial is required to maintain accurate records, report adverse drug reactions, and ensure
p.000021: that the investigator adheres to the approved protocol. Trials in humans should be conducted according to generally
p.000021: accepted principles of good clinical practice. These standards provide assurance that the data and reported results are
p.000021: credible and accurate, and that the rights, integrity, and privacy of clinical trial subjects are protected.
p.000021:
p.000021: The Directorates encourage sponsors to obtain the approval of a Research Ethics Board (REB) prior to conducting trials
p.000021: in Canada. A REB is an independent body, including both men and women, which is responsible for approving the
p.000021: initiation, and conduct of periodic reviews of biomedical research involving human subjects. The principal mandate of
p.000021: the REB is to ensure the protection of the rights, safety and well-being of subjects in the clinical trial. This
p.000021: structure helps to ensure that conflict of interest situations are avoided and that the health and safety of the trial
p.000021: subjects remain the paramount concern. The role of a Canadian REB includes the provision of recommendations concerning
p.000021: a trial's ethical acceptability and conduct. At the present time, there is no accreditation system in Canada for REBs.
p.000021: This situation is being reviewed by Health Canada in conjunction with the Canadian Institutes of Health Research
p.000021: (CIHR), the National Council on Ethics in Human Research (NCEHR) and other stakeholders in the Canadian clinical
p.000021: research community. Some Canadian REBs have limited resources and experience with the review of drug clinical trials.
p.000021:
p.000021: The Minister of Health can stop the sale of a drug to an investigator if the Minister believes it is in the public
p.000021: interest to do so. This provision in subsection C.08.005(3) of the Food and Drug Regulations, has not been used
p.000021: extensively nor has a routine inspection scheme been implemented.
p.000021:
p.000021:
p.000021: New Regulatory Framework
p.000021:
p.000021:
p.000021: These Regulations have been developed to recognize the generally accepted principles of good clinical practice and
...
Social / education
Searching for indicator education:
(return to top)
p.000009: relevant to the drug or the
p.000009:
p.000009:
p.002001: 2001
p.000010: 10
p.000010:
p.000010: Health Canada
p.000010: Guidance for Industry Regulations Amending the Food & Drug
p.000010: Regulations
p.000010:
p.000010:
p.000010: clinical trial that are necessary to make the determination.
p.000010:
p.000010:
p.000010:
p.000010: Sponsor's Obligations Good Clinical Practices
p.000010: C.05.010. Every sponsor shall ensure that a clinical trial is conducted in accordance with good clinical practices and,
p.000010: without limiting the generality of the foregoing, shall ensure that
p.000010:
p.000010: (a) the clinical trial is scientifically sound and clearly described in a protocol;
p.000010:
p.000010: (b) the clinical trial is conducted, and the drug is used, in accordance with the protocol and this Division;
p.000010:
p.000010: (c) systems and procedures that assure the quality of every aspect of the clinical trial are implemented;
p.000010:
p.000010: (d) for each clinical trial site, the approval of a research ethics board is obtained before the clinical trial begins
p.000010: at the site;
p.000010:
p.000010: (e) at each clinical trial site, there is no more than one qualified investigator;
p.000010:
p.000010: (f) at each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the
p.000010: supervision of the qualified investigator;
p.000010:
p.000010: (g) each individual involved in the conduct of the clinical trial is qualified by education, training and experience to
p.000010: perform his or her respective tasks;
p.000010:
p.000010: (h) written informed consent, given in accordance with the applicable laws governing consent, is obtained from every
p.000010: person before that person participates in the clinical trial but only after that person has been informed of
p.000010:
p.000010: (i) the risks and anticipated benefits to his or her health arising from participation in the clinical trial, and
p.000010:
p.000010: (ii) all other aspects of the clinical trial that are necessary for that person to make the decision to participate in
p.000010: the clinical trial;
p.000010:
p.000010: (i) the requirements respecting information and records set out in section C.05.012 are met; and
p.000010:
p.000010: (j) the drug is manufactured, handled and stored in accordance with the applicable good manufacturing practices
p.000010: referred to in Divisions 2 to 4 except sections C.02.019,
p.000010:
p.000010:
p.002001: 2001
p.000011: 11
p.000011:
p.000011: Health Canada
p.000011: Guidance for Industry Regulations Amending the Food & Drug
p.000011: Regulations
p.000011:
p.000011:
p.000011: C.02.025 and C.02.026.
p.000011:
p.000011:
p.000011: Labeling
p.000011:
p.000011: C.05.011. Despite any other provision of these Regulations respecting labeling, the sponsor shall ensure that the drug
p.000011: bears a label that sets out the following information in both official languages:
p.000011:
...
p.000022: Regulations
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: Good Clinical Practices (GCP)
p.000022:
p.000022:
p.000022: Sponsors of clinical trials conducted in Canada must be able to demonstrate that the trials are conducted according to
p.000022: generally accepted principles of good clinical practice. These principles include:
p.000022:
p.000022: • clinical trials must be conducted in accordance with good clinical practices and the applicable regulatory
p.000022: requirement(s).
p.000022:
p.000022: • before a trial is initiated, foreseeable risks and inconveniences must be weighed against the anticipated benefit
p.000022: for the individual trial subject and society. A trial should be initiated and continued only if the anticipated
p.000022: benefits justify the risks.
p.000022:
p.000022: • the rights, safety, and well-being of the trial subjects are the most important considerations and must prevail
p.000022: over interests of science and society.
p.000022:
p.000022: • the available non-clinical and clinical information on an investigational drug must be adequate to support the
p.000022: proposed clinical trial.
p.000022:
p.000022: • clinical trials must be scientifically sound, and described in a clear, detailed protocol.
p.000022:
p.000022: • a trial must be conducted in compliance with a protocol that has received REB approval prior to initiation.
p.000022:
p.000022: • the medical care given to, and medical decisions made on behalf of, subjects must always be the responsibility of
p.000022: a qualified physician or, when appropriate, of a qualified dentist.
p.000022: • each individual involved in conducting a trial should be qualified by education, training, and experience to
p.000022: perform his or her respective task(s).
p.000022:
p.000022: • freely given informed consent must be obtained from every subject prior to clinical trial participation.
p.000022:
p.000022: • all clinical trial information must be recorded, handled, and stored in a way that enables its accurate reporting,
p.000022: interpretation and verification.
p.000022:
p.000022: • the confidentiality of records that could identify subjects must be protected, respecting the privacy and
p.000022: confidentiality rules in accordance with the applicable regulatory requirement(s).
p.000022:
p.000022: • investigational drugs must be fabricated, handled, and stored in accordance with applicable good manufacturing
p.000022: practices (GMP). They must be used in accordance with
p.000022:
p.000022:
p.000022:
p.000022:
p.002001: 2001
p.000023: 23
p.000023:
p.000023: Health Canada
p.000023: Guidance for Industry Regulations Amending the Food & Drug
p.000023: Regulations
p.000023:
p.000023:
p.000023: the approved protocol.
p.000023:
p.000023: • systems with procedures that assure the quality of every aspect of the trial must be implemented.
p.000023:
p.000023:
p.000023: Labeling
p.000023:
p.000023: Drugs used in clinical trials must be labeled in accordance with specified labeling requirements. These requirements
p.000023: include the following:
p.000023:
p.000023: • a statement, to ensure that the drug is identified as an investigational drug to be used only by a qualified
p.000023: investigator;
p.000023:
...
General/Other / Incapacitated
Searching for indicator incapacity:
(return to top)
p.000001:
p.000001: (i) two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the
p.000001: methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is
p.000001: in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
p.000001:
p.000001: (ii) one member knowledgeable in ethics,
p.000001:
p.000001: (iii) one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
p.000001:
p.000001: (iv) one member whose primary experience and expertise are in a nonscientific discipline, and
p.000001:
p.000001:
p.000001:
p.002001: 2001
p.000002: 2
p.000002:
p.000002: Health Canada
p.000002: Guidance for Industry Regulations Amending the Food & Drug
p.000002: Regulations
p.000002:
p.000002:
p.000002: (v) one member who is from the community or is a representative of an organization interested in the areas of research
p.000002: to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted.
p.000002: (comité d'éthique de la recherche)
p.000002:
p.000002: "serious adverse drug reaction" means an adverse drug reaction that requires in-patient hospitalization or prolongation
p.000002: of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability
p.000002: or incapacity, that is life threatening or that results in death. (réaction indésirable grave à une drogue)
p.000002:
p.000002: "serious unexpected adverse drug reaction" means a serious adverse drug reaction that is not identified in nature,
p.000002: severity or frequency in the risk information set out in the investigator's brochure or on the label of the drug.
p.000002: (réaction indésirable grave et imprévue à une drogue)
p.000002:
p.000002: "sponsor" means an individual, corporate body, institution or organization that conducts a clinical trial. (promoteur)
p.000002:
p.000002:
p.000002: Application
p.000002:
p.000002: C.05.002.(1) Subject to subsection (2), this Division applies to the sale or importation of drugs to be used for the
p.000002: purposes of clinical trials involving human subjects.
p.000002:
p.000002: (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,
p.000002: 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
p.000002: 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
p.000002: a clinical trial authorized under subsection C.05.006(2).
p.000002:
p.000002:
p.000002: Prohibition
p.000002:
p.000002: C.05.003. Despite sections C.01.014, C.08.002 and C.08.003, no person shall sell or import a drug for the purposes of a
p.000002: clinical trial unless
p.000002:
p.000002: (a) the person is authorized under this Division;
p.000002:
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.000019: Regulations
p.000019:
p.000019:
p.000019: REGULATORY IMPACT ANALYSIS STATEMENT
p.000019:
p.000019: (This statement is not part of the regulation)
p.000019:
p.000019: Description
p.000019:
p.000019: This amendment introduces regulatory requirements for the sale and importation of drugs for use in human clinical
p.000019: trials. The new requirements are located in Division 5 of the Food and Drug Regulations and apply to clinical trials in
p.000019: humans using both new and old drugs.
p.000019:
p.000019: Consequential amendments are required to Division 8 of the Regulations to maintain the status quo for clinical trials
p.000019: in animals using new veterinary drugs. Although the Veterinary Drugs Program of the Health Products and Food Branch
p.000019: (the unit in Health Canada responsible for the regulation of veterinary drugs) has indicated that a broader framework
p.000019: is desirable for veterinary drugs, this will be dealt with at a later date.
p.000019:
p.000019: This framework incorporates the following features:
p.000019:
p.000019: • a 30-day default review period for applications to sell a drug for the conduct of human drug clinical trials in
p.000019: Canada in Phases I to III of development;
p.000019:
p.000019: • clear and transparent requirements for application, information, amendments, notification, labeling, record
p.000019: keeping and adverse drug reaction reporting;
p.000019:
p.000019: • introduction of an inspection system against internationally accepted good clinical practice principles and good
p.000019: manufacturing practices; and,
p.000019:
p.000019: • clear authority to refuse an application, suspend or cancel the sale of drugs for use in clinical trials in Canada
p.000019: where they do not meet the updated regulatory requirements.
p.000019:
p.000019: The use of a marketed drug by a physician or dentist for individual patient treatment is not considered to be a
p.000019: clinical trial. The application requirements under this amendment do not apply to clinical trials on marketed drugs
p.000019: where the investigation is conducted within the parameters of the approved Notice of Compliance (NOC) or Drug
p.000019: Identification Number (DIN) application.
p.000019: These trials are often referred to as Phase IV clinical trials. Sponsors must conduct all clinical trials, including
p.000019: Phase IV trials in accordance with the generally accepted principles of good clinical practice.
p.000019:
p.000019:
p.000019: Current Canadian Situation
p.000019:
p.000019: In Canada, the responsibility for developing drugs relies on an effective partnership among many stakeholders including
p.000019: industry, the research granting councils, the medical community, the ethics community and the federal government.
p.000019: Within this partnership, the Therapeutic Products
p.000019:
p.000019:
p.000019:
p.002001: 2001
p.000020: 20
p.000020:
p.000020: Health Canada
p.000020: Guidance for Industry Regulations Amending the Food & Drug
p.000020: Regulations
p.000020:
p.000020:
p.000020: Directorate [TPD] and the Biologics and Genetic Therapies Directorate [BGTD] of Health Canada provide a critical
...
p.000023:
p.000023: • systems with procedures that assure the quality of every aspect of the trial must be implemented.
p.000023:
p.000023:
p.000023: Labeling
p.000023:
p.000023: Drugs used in clinical trials must be labeled in accordance with specified labeling requirements. These requirements
p.000023: include the following:
p.000023:
p.000023: • a statement, to ensure that the drug is identified as an investigational drug to be used only by a qualified
p.000023: investigator;
p.000023:
p.000023: • the name, number, or identifying mark of the drug;
p.000023:
p.000023: • the expiration date;
p.000023:
p.000023: • the recommended storage conditions;
p.000023:
p.000023: • the lot number of the drug;
p.000023:
p.000023: • the name and address of the sponsor; and
p.000023:
p.000023: • the protocol code or identification number.
p.000023:
p.000023: In addition to the above, radiopharmaceuticals must display the radiation symbol required by the Atomic Energy Control
p.000023: Regulations and a statement "Caution--Radioactive Material" « Attention-- produit radioactif ».
p.000023:
p.000023:
p.000023: Adverse Drug Reaction Reporting
p.000023:
p.000023: The sponsor must report to the TPD or BGTD on an expedited basis any serious unexpected adverse drug reactions based on
p.000023: the reporting schedule contained within the attached Regulations. These requirements are consistent with international
p.000023: standards. The Regulations also provide the Minister with the authority to request additional information from the
p.000023: sponsor if there is concern respecting the safety of the clinical trial drug and to take action if required.
p.000023:
p.000023:
p.000023: Records
p.000023:
p.000023: The sponsor must keep all records related to the conduct of a clinical trial in a format that facilitates verification
p.000023: for the purpose of an inspection. The records must be maintained for a
p.000023:
p.000023:
p.002001: 2001
p.000024: 24
p.000024:
p.000024: Health Canada
p.000024: Guidance for Industry Regulations Amending the Food & Drug
p.000024: Regulations
p.000024:
p.000024:
p.000024: period of 25 years. The sponsor must submit requested records within 48 hours if safety concerns arise. Additionally,
p.000024: the Minister can request the submission of information within seven days to facilitate an inspection of a site. This
p.000024: will enable Health Canada to investigate health and safety concerns and to respond in a timely fashion.
p.000024:
p.000024:
p.000024: 30-Day Default System
p.000024:
p.000024:
p.000024: Sponsors wishing to conduct clinical trials in Phases I to III of development must apply under the 30-day default
p.000024: system. The Directorates will establish shorter administrative targets of seven days for the review of bioequivalence
p.000024: trials and Phase I trials in adult healthy volunteers under the 30-day default system. Applications to conduct Phase I
p.000024: clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines or reproductive and
p.000024: genetic technologies will not be included in the seven day target system.
p.000024:
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.000004: all animal species tested,
p.000004:
p.000004: (iv) any toxicological effects in any animal species tested under a single dose study, a repeated dose study or a
p.000004: special study in respect of the drug,
p.000004:
p.000004: (v) any results of carcinogenicity studies in any animal species tested in respect of the drug,
p.000004:
p.000004: (vi) any results of clinical pharmacokinetic studies of the drug,
p.000004:
p.000004: (vii) any information regarding drug safety, pharmacodynamics, efficacy and dose responses of the drug that were
p.000004: obtained from previous clinical trials in humans, and
p.000004:
p.000004:
p.000004:
p.002001: 2001
p.000005: 5
p.000005:
p.000005: Health Canada
p.000005: Guidance for Industry Regulations Amending the Food & Drug
p.000005: Regulations
p.000005:
p.000005:
p.000005: (viii) if the drug is a radiopharmaceutical as defined in section C.03.201, information regarding directions for
p.000005: preparing the radiopharmaceutical, the radiation dosimetry in respect of the prepared radiopharmaceutical and a
p.000005: statement of the storage requirements for the prepared radiopharmaceutical;
p.000005:
p.000005: (f) if the drug contains a human-sourced excipient, including any used in the placebo,
p.000005:
p.000005: (i) information that indicates the human-sourced excipient has been assigned a drug identification number under
p.000005: 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
p.000005: the case may be, or
p.000005:
p.000005: (ii) in any other case, sufficient information to support the identity, purity, potency, stability and safety of the
p.000005: human-sourced excipient;
p.000005:
p.000005: (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
p.000005: new drug, a notice of compliance has not been issued under subsection C.08.004(1), the chemistry and manufacturing
p.000005: information in respect of the drug, including its site of manufacture; and
p.000005:
p.000005: (h) the proposed date for the commencement of the clinical trial at each clinical trial site, if known at the time of
p.000005: submitting the application.
p.000005:
p.000005:
p.000005: Authorization
p.000005:
p.000005: C.05.006. (1) Subject to subsection (3), a sponsor may sell or import a drug, other than a drug described in subsection
p.000005: (2), for the purposes of a clinical trial if
p.000005:
p.000005: (a) the sponsor has submitted to the Minister an application in accordance with section C.05.005;
p.000005:
...
Orphaned Trigger Words
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| authority | Relationship to Authority |
| disability | Mentally Disabled |
| drug | Drug Usage |
| education | education |
| healthy volunteers | Healthy People |
| incapacity | Incapacitated |
| officer | Police Officer |
| placebo | participants in a control group |
| single | Marital Status |
| substance | Drug Usage |
| union | Trade Union Membership |
| women | Women |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| drug | ['substance'] |
| substance | ['drug'] |
Trigger Words
consent
developing
ethics
protection
risk
Applicable Type / Vulnerability / Indicator Overlay for this Input