Guidance - Use of Positron-emitting Radiopharmaceuticals in Basic Clinical Research

Foreword

Guidance documents are meant to provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. Guidance documents also provide assistance to staff on how Health Canada mandates and objectives should be implemented in a manner that is fair, consistent, and effective.

Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. Alternate approaches should be discussed in advance with the relevant programme area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As a corollary to the above, it is equally important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, in order to allow the Department to adequately assess the safety, efficacy, or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read in conjunction with the accompanying notice and the relevant sections of other applicable Guidance documents.

Table of Contents

Forms

1. Introduction

1.1 Purpose/Overview

The purpose of this guidance document is to provide information to sponsors who use positron-emitting radiopharmaceuticals (PERs) in basic clinical research studies and to assist them in satisfying applicable federal regulatory requirements as set out in Sections C.03.301 to C.03.319 of the Food and Drug Regulations (the Regulations).

In order to conduct a study, a sponsor must submit a completed Application for Authorization and Research Ethics Board Attestation to Health Canada for review. After examining the application and if it complies with the regulatory requirements, Health Canada will issue the authorization allowing the use of the PER in the basic clinical research study.

The applications for the authorization for the use of PERs in basic clinical research studies are referred to as Basic Research Applications: PERs (BRAP).

1.2 Scope and application

The Regulations and this Guidance document apply to PERs used in basic clinical research studies that involve human subjects as described in sections C.03.304 and C.03.305 of the Regulations or as an investigative tool as a part of a clinical trial conducted with another drug. Basic clinical research studies are aimed at advancing scientific knowledge and are not intended to fulfill any immediate diagnostic or therapeutic purposes.

A basic clinical research study using PERs with a predefined safety profile in humans is exempted from the clinical trial application (CTA) requirements in Part C, Division 5, of the Regulations and from the New Drug requirements in Part C, Division 8, of the Regulations. This exemption does not apply to PERs that have not previously been used in humans or a PER manufactured from a Schedule D bulk process intermediate (i.e., a biologic PER). For first-use-in-human studies and all biologic PERs, a CTA must be submitted as per Part C, Division 5, of the Regulations. Additionally, the approval for the use of a PER in a basic clinical research study is not sufficient to support approval for the use of a PER in a clinical trial.

This Guidance document supersedes the previous Health Canada’s guidance policy Use of Positron Emitting Radiopharmaceuticals (PERs) in Basic Research [POL-0053] and guidance document Factors Considered in the Assessment of Risks Involved in the Use of Certain Positron Emitting Radiopharmaceuticals in Basic Research Involving Humans (February 24, 2006).

1.3 Policy objectives

The policy objective is to provide researchers with a streamlined application process for gaining approval to conduct basic clinical research studies using PERs, while keeping sufficient checks and balances in place with respect to the safety and quality for the drugs in use and the health and safety of the study subjects.

1.4 Policy statements

Sections C.03.301 to C.03.319 of the Regulations provide appropriate regulatory oversight and a simplified application process for basic clinical research studies using PERs that meet the specified inclusion criteria.

Sponsors must conduct basic clinical research studies according to good clinical practices (GCP) that are designed to protect the rights, safety and well-being of clinical trial subjects and other persons. It is the responsibility of the sponsor to ensure that the use of PERs in basic clinical research meet the requirements set out within the Regulations.

Research Ethics Boards (REBs) have an important role in the oversight of the conduct of basic clinical research studies. Sponsors are required by section C.03.307(2)(q) of the Regulations to obtain REB approval for each study site prior to filing for authorization at that site.

The Regulations facilitate the expedited access to PERs for the intent of performing basic research, while allowing Health Canada to conduct an appropriate risk assessment of the PER used in research studies.

Regulatory decision-making regarding PERs used in human research are based on the same scientific and regulatory principles on which the Food and Drug Regulations are based.

1.5 Background

Prior to 2013, researchers performing basic research in positron emission tomography (PET) with PERs in humans were subject to Part C, Division 5 of the Food and Drug Regulations (Drugs for Clinical Trials Involving Human Subjects), and were required to submit clinical trial applications.

Health Canada recognizes that the use of PERs in basic research in humans typically posed minimal health risks, provided certain criteria were met. Therefore, Health Canada, in collaboration with members of the research community, developed a more appropriate regulatory oversight for the use of PERs in basic research that reduced and simplified regulatory requirements while mitigating the risks to humans by ensuring that the PERs used were safe and of high quality. On February 24, 2006, the Guidance Document: Factors considered in the Assessment of Risks involved in the Use of Positron Emitting Radiopharmaceuticals in Basic Research involving Humans was implemented.  This document accompanied a guidance policy Use of Positron Emitting Radiopharmaceuticals in Basic Research [POL-0053].  These documents remained in effect until the regulatory amendment regarding the use of positron emitting radiopharmaceuticals in basic research came into force on January 4, 2013.

1.6 Glossary

1.6.1 Acronyms

ADR
Adverse Drug Reaction
BGTD
Biologics and Genetic Therapies Directorate
BRAP
Basic Research Applications: PERs
CIOMS
Council for International Organizations of Medical Sciences
CTA
clinical trial application
GCP
Good Clinical Practices
MBq
Megabecquerel
mCi
millicurie
mSv
millisievert
PER
positron-emitting radiopharmaceutical
REB
research ethics board
rem
Roentgen equivalent in man

1.6.2 Definitions

Adverse reaction              
An undesirable and unintended response in a study subject or other person to a study drug that is caused by the administration of any dose of the study drug.

Effective dose
The sum of doses to all organs, each adjusted to account for the sensitivity of the organ to radiation. Effective dose is also known as whole-body dose. Expressed in millisieverts (mSv).

Good Clinical Practices  
Generally accepted clinical practices that are designed to protect the rights, safety and well-being of study subjects and other persons.

Import 
In respect of a study drug, to import it into Canada for sale for the purpose of a study.

Other person    
An individual who comes into physical contact with a study subject.

Protocol              
A document that describes the objectives, design, methodology, statistical considerations and organization of a study.

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

Research Ethics Board   
A decision-making body that is not affiliated with the sponsor, whose principal mandate is to approve the initiation of and to periodically review biomedical research that involves human subjects in order to protect their rights, safety and well-being.

Sell        
To offer for sale, to expose for sale, to have in possession for sale or to distribute, whether or not the distribution is made for consideration (Section 2 of the Food and Drugs Act).

Serious adverse reaction               
An adverse reaction that results in any of the following consequences for the study subject or other person:

  1. their in-patient hospitalization or its prolongation;
  2. a congenital malformation;
  3. persistent or significant disability or incapacity;
  4. a life-threatening condition; or
  5. death.

Serious unexpected adverse reaction
A serious adverse reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the study drug.

Sponsor
An individual, institution or organization who is responsible for the conduct of a study.

Study
A basic clinical research study in respect of a positron-emitting radiopharmaceutical that has been previously shown to be safe in human subjects that meets the following inclusion and exclusion criteria.
The purpose of the study is to obtain data on any of the following:

The study is not primarily intended to do any of the following:

A study must also meet the requirements as listed in section C.03.305 of the Regulations.

Study drug
Means a specific positron-emitting radiopharmaceutical product that is used in a study. A study drug must have been previously tested in humans and must not be manufactured from a bulk process intermediate that is of biological origin.

Study site
The location where all or part of a study is conducted.

2. Guidance for implementation

The next part of this document provides:

2.1 Roles and Responsibilities

2.1.1 Section C.03.301 Sponsor

“A sponsor means a person who is responsible for the conduct of a study.”

The sponsor is an individual, institution or organization that is responsible for conducting the basic clinical research study. The sponsor’s responsibilities include, but are not limited to: submitting an application for authorization for the study drug; ensuring that the study is conducted according to Good Clinical Practices; fulfilling the requirements with respect to labelling and records management; providing additional information as requested by Health Canada; reporting serious and unexpected adverse reactions; sending written notification to the qualified investigator when a study is discontinued and providing reasons for discontinuance; and also notifying Health Canada and REB regarding the discontinuance of the study if the reason for the discontinuance is related to the health or safety of the study subjects or other persons.

The sponsor is responsible for the sale and use of the study drug and ensuring compliance with all applicable laws.

2.1.2 Section C.03.306 Research Ethics Board

“A research ethics board has all of the following characteristics:

  1. its principal mandate is to approve the initiation of and to periodically review biomedical research that involves human subjects in order to protect their rights, safety and well-being;
  2. it has at least five members, a majority of whom are Canadian citizens or permanent residents under the Immigration and Refugee Protection Act, is composed of both men and women and includes at least the following:
    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,
    2. one member knowledgeable in ethics,
    3. one member knowledgeable in Canadian laws relevant to the 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 with the study site; and
  3. it has no affiliations with the sponsor that could compromise its ability to fulfil its principal mandate, or that could be perceived to do so.”

An REB attestation that the study, protocol and informed consent forms have been reviewed and approved must be provided for each study site.

The sponsor is required to seek REB approval prior to filing an application with Health Canada.

The responsibility of research ethics boards with respect to basic clinical research studies using PERs will remain the same as their responsibilities to oversee clinical trials under the clinical trial regulations. However, the sponsor is required to obtain REB approval of the basic clinical research study prior to the sponsor’s submission of an application to Health Canada.

2.1.3 Paragraph C.03.315 (3)(f) Qualified Investigator

The qualified investigator is a physician and member in good standing of a professional medical association in Canada to whom a sponsor gives the responsibility for the proper conduct of the study at a given study site in accordance with the Food and Drug Regulations and good clinical practices (GCPs). Additionally, the qualified investigator is responsible for immediately informing the study subjects if the study is discontinued prematurely, including the reason(s) for the discontinuance and information about any potential risk to the health of the study subjects or other persons.

2.2 Section C.03.303 Limits on the Distribution of the Study Drugs

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

  1. the study drug is for use only in a study;
  2. the study drug has been previously tested in human subjects and its safety in humans has been demonstrated;
  3. if the study drug is to be imported, the manufacturer of the drug has a representative in Canada who is responsible for its sale;
  4. the sponsor is authorized under section C.03.309 to sell or import the study drug; and
  5. the sponsor complies with sections C.03.310 to C.03.316.”

No drug can be sold in Canada unless Health Canada has issued an authorization for that sale through one of the regulatory mechanisms outlined in the Regulations.

The prohibitions to sale in section C.05.003 (for clinical trial drugs) and sections C.08.002 and C.08.003 (for new drugs) do not apply to PERs used in a basic clinical research study.

2.3 Study Criteria

2.3.1 Subsection C.03.305 (1) Study Requirements

“A study shall meet all of the following requirements:

  1. before the study drug is used in the study, there is sufficient data from testing it in animals and humans to demonstrate its safety in humans;
  2. the amount of active ingredients or combination of active ingredients in the study drug has been shown not to cause any clinically detectable pharmacodynamic effect in humans;
  3. the total radiation dose incurred annually by a study subject, including from multiple administrations of the study drug, from significant contaminants or from impurities and from the use of other procedures for the purposes of the study, shall not be more than 50 mSv;
  4. any concomitant drug used in the study has been assigned a drug identification number under subsection C.01.014.2(1) or, in the case of a concomitant drug that is a new drug, has been issued a notice of compliance under section C.08.004;
  5. study subjects shall be at least 18 years old and have legal capacity at the time of the study.
  6. female subjects shall:
    1. be confirmed at the outset of the study, on the basis of a pregnancy test, as not being pregnant or state in writing that they are not pregnant, and
    2. be advised that if they are lactating, they are to suspend lactation for 24 hours after the administration of the study drug; and
  7. The study shall not involve more than 30 study subjects.”

In regards to subsection (a) of these regulations, the data on the testing of the study drug in animals and humans to demonstrate the drug’s safety in humans can be obtained through original research or from the body of scientific literature. An appropriately evaluated, Phase I safety study conducted in a country that adopts International Council of Harmonisation (ICH) guidelines is considered as sufficient data.  Alternatively, subject to regulatory discretion, a thorough analysis of historical data available from human exposure obtained outside a Phase I safety study is considered sufficient.

2.3.2 Subsection C.03.305 (2) Exemptions

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

This exemption to paragraph C.03.305 (1)(g) is only applicable to minor increases in study population. Any study proposal with a significant increase in study population would not be applicable for a BRAP, and a CTA must be submitted as per Part C, Division 5, of the Regulations.

2.4 Overview of the Application, Regulatory Review, and Notification Process

Prior to commencing a basic clinical research study, the sponsor is required to submit an Application for Authorization of Positron-emitting Radiopharmaceuticals (PERs) for Use in a Basic Clinical Research Study (Application for Authorization) as well as a Research Ethics Board Attestation (REB Attestation) or a Research Ethics Board approval letter that includes the Research Ethics Board certification statement to the Biologics and Genetic Therapies Directorate (BGTD). These submissions are referred to as Basic Research Applications: PERs (BRAP). Applications should be sent to the address in section 4.2 below.

Within 15 business days of receiving the completed Application for Authorization form, and if the application is complete and all the requirements have been met, BGTD will issue an authorization to sell the PER for the purposes of the study as described in the application.

If the application is complete but the requirements have not been met, BGTD will issue a Not-Satisfactory-Notice to indicate the sponsor has not received authorization for the sale of the study drug. If the sponsor still wants to pursue the clinical trial, a Clinical Trial Application may be filed for a formal review and authorization prior to initiating the study.

If clarification on information provided in the application is required, BGTD will issue a Clarifax to request additional information. The sponsor is required to provide the requested information within 2 business days of receipt of the Clarifax. BGTD will then review the additional information and inform the sponsor whether the requirements have been met.

The sponsor must send a written notification to Health Canada of the day on which the sale or importation of the study drug is intended to start. The start date may be included in the BRAP, or submitted as a notification at least 15 business days ahead of the date of the first sale, as outlined in section C.03.310 of the Regulations.

Any change to the application must be communicated to Health Canada by submitting a revised Application for Authorization and REB Attestation. These changes may include, but are not limited to, a change of an ongoing site, the addition of a new site, the change/addition of a study start date, a change in the qualified investigator, and/or a change to the REB. If one of the attested criteria in the Application for Authorization changes to a “no”, then the sponsor is advised to file a Clinical Trial Application for a formal review in order to obtain authorization to conduct the study.

It is the sponsor’s responsibility to maintain records of any amendments to the study protocols and informed consent forms.  Sponsors are not required to submit these amendments to Health Canada. 

2.4.1 Subsection C.03.307 (1) Criteria for Application

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

  1. the use of the study drug will not endanger the health of any study subject or other person;
  2. the study is not contrary to the best interests of the study subjects; and
  3. the objectives of the study can reasonably be achieved.”

The study drug must have previously been tested in human subjects and must have evidence that demonstrates its safety in humans. If the PER and the source of its manufacturing have been previously reviewed and authorized by BGTD in a CTA, the control number of any previous CTA should be identified in the Application for Authorization, Part 1 (D).

2.4.2 Subsection C.03.307 (2) Information Required

“The application shall contain all of the following information:

  1. the title of the study and the protocol code or identification;
  2. the purposes and a concise description of the study;
  3. the number of study subjects;
  4. the brand name, if any, of the study drug;
  5. the chemical or generic name of the active ingredients in the study drug;
  6. a qualitative list of the non-active ingredients of the study drug;
  7. the maximum mass of the study drug to be administered to each study subject;
  8. the radioactive dose range of the study drug, expressed in MBq or mCi;
  9. the effective dose or effective dose equivalent of the study drug, expressed in mSv/MBq or rem/mCi;
  10. the sponsor’s name and civic address, its postal address if different, and its telephone number, fax number and email address;
  11. the manufacturer’s name and civic address, its postal address if different, and its telephone number, fax number and email address;
  12. in the case of an application for importation, the name and civic address, the postal address if different, and the telephone number, fax number and email address of the manufacturer’s representative in Canada who is responsible for the sale of the study drug;
  13. the name and civic address for each study site;
  14. for each study site, the name, civic address, telephone number, fax number and email address of the qualified investigator;
  15. the proposed starting date for the study at each study site, if known;
  16. for each study site, the name, civic address, telephone number, fax number and email address of the research ethics board;
  17. a statement, dated and signed by the research ethics board for each study site, that certifies that it has reviewed and approved the study, the protocol and the statement of the risks and anticipated benefits arising to the health of study subjects as a result of participating in the study that is set out in the informed consent form;
  18. a list of any previous applications for an authorization to sell or import a drug for a study related to the current study; and
  19. a statement, dated and signed by the sponsor’s senior medical or scientific officer in Canada and senior executive officer, that certifies the following:
    1. the study will be conducted in accordance with these Regulations; and
    2. all of the information contained or referred to in the application is complete and accurate and is not false or misleading.”

In regards to subsection (i) of these regulations, the effective dose or effective dose equivalent of the study drug should be determined from human dosimetry studies or a combination of data from human safety studies and animal dosimetry studies with appropriate rationale.

Health Canada developed the Application for Authorization and REB Attestation forms for sponsors to use in filing an application, and facilitating the review of the information required. Sponsors should complete these forms and file them along with a covering letter that is dated and signed by a sponsor representative. Applications should be sent to the address in section 4.2 below.

2.5 Good Clinical Practices and Good Manufacturing Practices

2.5.1 Paragraph C.03.311 (a-h) Good Clinical Practices

“A sponsor shall ensure that each study is conducted in accordance with Good Clinical Practices and that

  1. the study is scientifically sound and clearly described in its protocol;
  2. the study is conducted, and the study drug is used, in accordance with the protocol and with these Regulations;
  3. systems and procedures are implemented that assure the quality of every aspect of the study;
  4. at each study site, there is only one qualified investigator;
  5. at each study site, medical care and medical decisions, in respect of the study, are under the supervision of the qualified investigator;
  6. each individual who is involved in the conduct of the study is qualified by their education, training and experience to perform their respective tasks;
  7. before a study subject participates in the study, a copy of their signed consent form is included in the records for the study;
  8. the requirements respecting information and records set out in section C.03.315 are met”

For further information on clinical trials, including links to various forms, please consult the Health Canada website

2.5.2  Paragraph C.03.311 (i) Good Manufacturing Practices

“The study drug is manufactured, handled and stored in accordance with Division 2, other than sections C.02.019, C.02.025 and C.02.026.”

As stated within subsection C.03.311, good clinical practices, which include Good Manufacturing Practices (GMP), must be followed. This Guidance document should be read in conjunction with the Annex 13 to the Current Edition of the Good Manufacturing Practices Guidelines: Drugs Used in Clinical Trials (Guide-0036) as well as the Annex to the Good Manufacturing Practices Guidelines Good Manufacturing Practices (GMP) for Positron Emitting Radiopharmaceuticals (PERs) (GUI-0071). The principles and approaches in these guides should be followed for PERs used in a basic research study.

2.6 Section C.03.312 Labelling Requirements

“Despite any other provisions of these Regulations respecting labelling, the sponsor shall ensure that the study drug

  1. bears an inner label that sets out both of the following:
    1. The unique batch number for the study drug, and
    2. The radiation warning symbol set out in Schedule 3 to the Radiation Protection Regulations and the words “RAYONNEMENT – DANGER – RADIATION”; and
  2. is accompanied by a package insert that sets out all of the following information:
    1. a statement that indicates that the study drug is to be used only under the supervision of a qualified investigator;
    2. the chemical or generic name of the active ingredients in the study drug;
    3. the name and civic address of the manufacturer;
    4. the name and civic address of the sponsor;
    5. the code or other identification of the protocol;
    6. the warnings and precautions in respect of the use of the study drug; and
    7. the possible adverse reactions that are associated with the use of the study drug.”

In regards to subparagraph (b)(v) of these regulations, the code or other identification of each protocol should be given if the study drug is used in more than one protocol.

2.7 Section C.03.313 Request for Additional Information

  1. “On the Minister’s written request, a sponsor shall submit, within the period specified in the request, information to establish the safety of the study drug if the Minister has reason to believe any of the following:
    1. the use of the study drug may endanger the health of the study subject or other person;
    2. the study may be contrary to the best interests of the study subjects;
    3. a qualified investigator is not respecting the requirements within subsection C.03.315(3)(f); or
    4. information about the study drug or study that was submitted previously is false or misleading.
  2. The Minister may, by notice in writing, require the sponsor to provide the Minister with any information or records referred to in subsection C.03.315(3) to assess the safety of the study drug or the health of the study subjects or other persons, by the date specified in the notice.”

2.8 Section C.03.314 Adverse Reaction Reporting

  1. “During the course of a study, the sponsor shall notify the Minister of any serious adverse reaction or serious unexpected adverse reaction that occurs inside or outside Canada, within the following period:
    1. if the adverse reaction is fatal or life-threatening, within seven days after becoming aware of it; or
    2. if the adverse reaction is not fatal or life-threatening, within 15 days after becoming aware of it.
  2. The sponsor shall, within eight days after having notified the Minister under subsection (1), file with the Minister a complete report in respect of the adverse reaction, including an assessment of the importance and implication of the findings.
  3. Sections C.01.016 to C.01.020 do not apply to study drugs.”

Each adverse drug reaction (ADR) which is subject to expedited reporting to Health Canada should be reported individually in accordance with the data element(s) specified in the Health Canada Guidance for Industry: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting ICH Topic E2A.

When submitting an ADR report to Health Canada, a complete ADR Expedited Reporting Summary Form (Form 01-03) and the CIOMS Form should be attached and mailed or faxed to the address in section 3 below. 

Once the sponsor has notified Health Canada as described above, the sponsor must submit to Health Canada a complete report in respect of the information, within 8 days, including an assessment of the importance and implications of the findings made.

There are situations in addition to the above that may necessitate rapid communication to Health Canada, and appropriate scientific and medical judgement should be applied to each situation.  Refer to the Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications  for examples of these types of situations. Any questions concerning the Regulations or this Guidance can be sent to the address in section 3 below.

2.9 Section C.03.315 Records Related to Basic Clinical Research Studies

  1. “The sponsor shall record, handle and store all information in respect of a study in a way that allows it to be reported completely and accurately and to be interpreted and verified.
  2. The sponsor shall maintain complete and accurate records to establish that the study is conducted in accordance with these Regulations.
  3. The sponsor shall maintain all of the following records in respect of the use of the study drug in each study:
    1. records respecting all adverse reactions that occur inside or outside Canada, including the indications for use and the dosage form of the study drug at the time of the adverse reaction;
    2. written procedures for subject monitoring and for the documentation and reporting of adverse reactions;
    3. articles from scientific journals or other publications that were used in support of the safety profile of the study drug in respect of humans;
    4. records in respect of each study subject, including respecting their enrolment, a copy of their signed consent form and sufficient information to enable them to be identified and contacted in the event that the sale of the study drug may endanger their health or that of another person;
    5. records respecting the shipment, receipt, sale, return and destruction or other disposition of the study drug;
    6. for each study site, an undertaking, dated and signed by the qualified investigator before the start of the study, that they will
      1. conduct the study in accordance with good clinical practices, and
      2. on discontinuance of the study by the sponsor, for any reason related to health or safety, immediately inform both the study subjects and the research ethics board of the discontinuance, provide them with the reasons for the discontinuance and advise them in writing of any potential risks to the health of study subjects or other persons;
  4. for each study site, a copy of the informed consent form; and
  5. for each study site, a copy of the certifying statement described in paragraph C.03.307(2)(q), of the protocol for the study and of the statement of the risks and anticipated benefits arising to the health of study subjects as a result of participating in the study that is set out in the informed consent form.
  6. The sponsor shall maintain all records for five years after the day on which the study ends.”

The information management system shall allow for the complete and accurate recording of the results of the study so that these results may be interpreted and verified at a later date. The sponsor’s records should provide evidence that the study was conducted according to GCP.

2.10 Section C.03.316 Discontinuance of a Study

  1. “If a sponsor discontinues a study in its entirety or at a study site, the sponsor must notify all qualified investigators of the discontinuance as soon as possible in writing. The sponsor must disclose reasons for the discontinuance and whether the study presented any risks to the health of study subjects or other persons.
  2. If the discontinuance is for reasons that would affect the health or safety of study subjects or other persons, the sponsor must notify Health Canada in writing within 15 days after the discontinuance. The notice must include the reasons for the discontinuance and state whether it will have an impact on any proposed or ongoing studies in respect of the study drug in Canada by the sponsor.”

2.11 Sections C.03.317, C.03.318 and C.03.319 Suspension, Reinstatement and Cancellation

There are provisions in the Regulations for the suspension or cancellation of the authorization for the sale of the study drug if it is believed that the health and safety of study subjects is at risk; if the sponsor has provided false, misleading or incomplete information; or if the sponsor has failed to meet the requirements for the reporting of adverse reactions.

A suspended authorization may be reinstated if the sponsor can demonstrate the reasons for the suspension are not valid.

Further details of these provisions can be found in the Regulations in the above noted sections.

3. Contact Information

3.1 Office of Regulatory Affairs

Inquiries and information requests regarding this Guidance document and serious adverse reaction reports should be submitted directly to:

Office of Regulatory Affairs

4. Basic Research Application: PERs (BRAP)

4.1 BRAP Submission Content and Format:

The Common Technical Document (CTD) format is the expected format for all drug regulatory activities. Refer to the Health Canada Guidance Document: Preparation of Regulatory Activities in the "Non-eCTD Electronic-Only" Format for more information on how to format drug regulatory activities in the non-eCTD electronic-only format. The following provides an overview of the Module 1 submission content for a BRAP in the non-eCTD electronic-only format:

1.0 Correspondence

1.2 Administrative Information

Note: The documents above must be signed (or digitally signed) by the appropriate representative

The attached zipped folder structure (in the HTML version of this document) can be used by adding documents in their respected folders. (Zip file - 9 K).

Empty folders should be deleted before filing to Health Canada.

4.2 Filing a BRAP

All BRAP submissions should be emailed to: hc.bgtd.bra-daerf.pbtg.sc@canada.ca

Refer to the Health Canada Guidance Document: Preparation of Regulatory Activities in the "Non-eCTD Electronic-Only" Format (Transmission of Electronic Data section) for information on how to submit electronic documents via email.

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