Part C, Division 5 of the Food and Drug Regulations "Drugs for Clinical Trials Involving Human Subjects" (GUI-0100): Appendices

Appendix A: Glossary

Acronyms and abbreviations

Acronym: An identifier formed from the initial letter of each word in a phrase or compound term (for example, "CTA" represents "Clinical Trial Application").

Abbreviation: A shortened form of a word or phrase (for example, "AE" represents "Adverse Event").

ADR: Adverse Drug Reaction
AE: Adverse Event
ALCOAC: Attributable, Legible, Contemporaneous, Original, Accurate, and Complete
ANDS: Abbreviated New Drug Submission
API: Active Pharmaceutical Ingredient
BRDD: Biologic and Radiopharmaceutical Drugs Directorate
CGSB: Canadian General Standards Board
CoA: Certificate of Analysis
CRF: Case Report Form
CTA: Clinical Trial Application
CTA-A: Clinical Trial Application Amendment
CTSI: Clinical Trial Site Information
CV: Curriculum Vitae
DIN: Drug Identification Number
eCRF: Electronic Case Report Form
FAQ: Frequently Asked Questions
FDA: Food and Drug Administration
GCP: Good Clinical Practices
GMP: Good Manufacturing Practices
GUI: Guide/Guidance Document
HC-SC: Health Canada-Santé Canada
ICF: Informed Consent form
ICH: International Conference on Harmonization
I.E.: Id Est ("that is")
IEC: Independent Ethics Committee
IP: Investigational Product
IRB: Institutional Review Board
ITA: Investigational Testing Authorization
MHRA: Medicines and Healthcare products Regulatory Agency
NC: Non-Compliant
NDS: New Drug Submission
NHP: Natural Health Product
NOC: Notice of Compliance
NOL: No Objection Letter
NSN: Not Satisfactory Notice
PDD: Pharmaceutical Drugs Directorate
PIC/S: Pharmaceutical Inspection Co-Operation Scheme
QI: Qualified Investigator
QIU: Qualified Investigator Undertaking
REB: Research Ethics Board
SAE: Serious Adverse Event
SADR: Serious Adverse Drug Reaction
SNDS: Supplemental New Drug Submission
SOAD: Summary of Additional Drugs Form
SOP: Standard Operating Procedure
SP: Service Provider
SUADR: Serious Unexpected Adverse Drug Reaction
SUSAR: Suspected Unexpected Serious Adverse Reaction
TCPS: Tri-Council Policy Statement
Vs.: Versus
WHO: World Health Organization

Terms

These definitions explain how terms are used in this document. If there is a conflict with a definition in the Food and Drugs Act or associated regulations, the definition in the Act or regulations prevails. Definitions quoted from other documents are identified in brackets at the end of the definition.

Adverse drug reaction (ADR): means any noxious and unintended response to a drug that is caused by the administration of any dose of the drug.

This definition is consistent with, but further expanded on, in glossary of ICH E6, which reads:

"In the pre-approval clinical experience with a new investigational product or its new usages (particularly as the therapeutic dose(s) may not be established): unfavourable and unintended responses, such as a sign (for example, laboratory results), symptom or disease related to any dose of a medicinal product where a causal relationship between a medicinal product and an adverse event is a reasonable possibility. The level of certainty about the relatedness of the adverse drug reaction to an investigational product will vary. If the ADR is suspected to be medicinal product-related with a high level of certainty, it should be included in the reference safety information (RSI) and/or the Investigator's Brochure (IB)".

If the study includes marketed medicinal products, that is, Phase IV: "a response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of diseases or for modification of physiological function."

Adverse event (AE): means any adverse occurrence in the health of a clinical trial participant who is administered a drug, that may or may not be caused by the administration of the drug, and includes an adverse drug reaction. Further expanded on in glossary of ICH E6, the definition of "adverse event" reads: "Any unfavourable medical occurrence in a trial participant administered the investigational product. The adverse event does not necessarily have a causal relationship with the treatment."

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

This definition is consistent with the glossary of ICH E6.

Comparator (Product): An investigational or marketed product (active control), placebo or standard of care used as a reference in a clinical trial (ICH E6, glossary).

Drug: means a drug for human use. In the context of clinical trials, a drug would include a drug for human use that is to be tested in a clinical trial and includes pharmaceuticals, biologics, gene therapies, blood products, vaccines and radiopharmaceuticals (Guidance document for Clinical Trial Sponsors: Clinical trial applications).

Consistent with Section 2 of the Food and Drugs Act, a drug is defined as any substance or mixture of substances used in the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, and in restoring, correcting or modifying organic functions.

ICH E6 does not define the word "drug", but the glossary defines "investigational product" (IP) as:

"A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use. Investigational products should be considered synonymous with drugs, medicines, medicinal products, vaccines and biological products."

Good clinical practices (GCP): means generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of participants and other persons, and the good clinical practices referred to in section C.05.010.

Consistent with, but further expanded on in the glossary of ICH E6, which defines GCP as:

"A standard for the planning, initiating, performing, recording, oversight, evaluation, analysis and reporting of clinical trials that provides assurance that the data and reported results are reliable and that the rights, safety and well-being of trial participants are protected."

Import: means to import a drug into Canada for the purpose of sale in a clinical trial.

Importer: The sponsor or person designated by the sponsor who is responsible for the import of the drug into Canada for the purpose of sale in a clinical trial. Individual investigators at the clinical trial sites in Canada may serve as Canadian Importers (Guidance document for clinical trial sponsors: Clinical trial applications).

Investigator's brochure: means, in respect of a drug, a document containing the preclinical and clinical data on the drug that are described in paragraph C.05.005(e).

This is consistent with the definition of "investigator's brochure" in ICH E6, glossary.

Paragraph C.05.005(e) of the Regulations describes the content that must be included in an investigator's brochure that is submitted to Health Canada.

Appendix A of ICH E6 provides additional guidance on the content of an investigator's brochure.

Label: includes any legend, word or mark attached to, included in, belonging to or accompanying any food, drug, cosmetic, device or package.

Observation: A deficiency or deviation from Part C, Division 5 of the Regulations noted by an Inspector during the inspection of a clinical trial that is confirmed in writing in the Inspection Exit Notice. (More information in Risk classification guide for observations related to inspections of clinical trials of human drugs (GUI-0043)).

Package: includes anything in which any food, drug, cosmetic or device is wholly or partly contained, placed or packed.

Participant means a person who participates in a clinical trial.

Protocol: means a document that describes the objectives, design, methodology, statistical considerations and organization of a clinical trial.

The use of the term "protocol" is consistent with ICH E6, glossary.

In accordance with paragraph C.05.005(a) of the Regulations, the application by a sponsor to sell or import a drug for the purpose of conducting a clinical trial in Canada must submit a protocol as part of their application.

Appendix B of ICH E6 describes the information found in a protocol.

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

in the case of a clinical trial respecting a drug to be used for dental purposes only, a physician or dentist and a member in good standing of a professional medical or dental association; and
in any other case, a physician and a member in good standing of a professional medical association.

ICH E6 uses the word "Investigator" to describe the individual responsible for the conduct of a clinical trial at a site.

The use of the term "Principal Investigator" is commonly used to refer to an investigator that is leading a team of individuals conducting a trial at a site, and though would have the same meaning as qualified investigator (QI), "Principal Investigator" is not a legally defined term used in Canada.

Note that paragraph C.05.010(e) of the Regulations states that there be no more than one QI at each clinical trial site. However, there may be Sub-Investigators/Co-Investigators in the study under the supervision of a QI.

Research ethics board (REB): means a body that is not affiliated with the sponsor, and

the principal mandate of which is to approve the initiation of, and conduct periodic reviews of, biomedical research involving human subjects in order to ensure the protection of their rights, safety and well-being; and
that has at least five members, that has a majority of members who are Canadian citizens or permanent residents under the Immigration and Refugee Protection Act, that is composed of both men and women and that includes at least
1. two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
2. one member knowledgeable in ethics,
3. one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
4. one member whose primary experience and expertise are in a non- scientific discipline, and
5. one member who is from the community or is a representative of an organization interested in the areas of research to be approved and who is not affiliated with the sponsor or the site where the clinical trial is to be conducted.

ICH E6 uses the terms "institutional review board" (IRB) and "independent ethics committee" (IEC) interchangeably, the definition of which is consistent with that of an REB. In glossary of ICH E6, an IRB or an IEC is defined as:

"An independent body (a review board or committee, institutional, regional, national or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human participants involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favorable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial participants. The legal status, composition, function, operations and regulatory requirements pertaining to IRBs/IECs may differ among countries but should allow the IRB/IEC to act in agreement with GCP as described in this guideline."

Note: REBs in Canada are held to more stringent composition requirements than are described in this section for ICH E6.

Sell: includes offer for sale, expose for sale, have in possession for sale and distribute, whether or not the distribution is made for consideration. The definition is broad in scope, and includes dispensing of drugs to participants by physicians.

Serious adverse drug reaction (SADR): means an adverse drug reaction that requires in-patient hospitalization or prolongation of existing hospitalization, that causes congenital malformation, that results in persistent or significant disability or incapacity, that is life threatening or that results in death.

Serious unexpected adverse drug reaction (SUADR): means a serious adverse drug reaction (SADR) that is not identified in nature, severity or frequency in the risk information set out in the investigator's brochure or on the label of the drug.

The definitions for SADR and SUADR are consistent with those found in glossary of ICH E6.

The acronym SUSAR (Suspected unexpected serious adverse reaction) is often used to identify serious adverse reactions that require reporting to a regulatory authority.

These definitions are expanded on in ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (ICH E2A).

Service Provider: A person or organization (commercial, academic or other) providing a service used by either the sponsor or the investigator to fulfil trial-related activities.

Site or trial site means the location(s) where trial-related activities are actually conducted. The ICH E6 Glossary defines investigator site as "The location(s) where trial-related activities are conducted and/or coordinated under investigator's/institution's oversight."

Health Canada's interpretation is one site equals one trial by one QI at one location (address).

Sponsor: means an individual, corporate body, institution or organization that conducts a clinical trial. ICH E6 elaborates on this definition in glossary to include: "An individual, company, institution or organization that take responsibility for the initiation, management and arrangement of the financing of a clinical trial. A clinical trial may have one or several sponsors where permitted under regulatory requirements."

The sponsor is ultimately responsible for all regulatory requirements regarding the conduct of the trial in Canada. Where a third party, such as a service provider has been delegated by written contract to carry out some or all of the sponsor's responsibilities, they must also demonstrate adherence to the applicable regulatory requirements.

If a physician is identified on the clinical trial application (CTA) as the sponsor, they must assume the responsibilities of both the sponsor and the QI. This would include ensuring that all of the sponsor's obligations under section C.05.010 of Part C, Division 5 are met at all sites at which the trial is being conducted, as well as all other applicable sections of Part C, Division 5.

Note: Part C, Division 5 of the Regulations does not differentiate between a commercial and a non-commercial sponsor.

Standard operating procedure (SOP): Detailed, documented instructions to achieve uniformity of the performance of a specific activity (ICH E6, glossary).

Appendix B: References

Web addresses were accurate at the time of publication of this document.

Law and Regulations

Health Canada guidances and documents

Other guidances and policies

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2026-03-02

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