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Clinical Trial Applications - Comparative Bioavailability Studies

The CTA is composed of three parts (modules):

  • Module 1 - contains administrative and clinical information about the proposed trial
  • Module 2 - contains Quality (Chemistry and Manufacturing) information about the drug product(s) to be used in the proposed trial
  • Module 3 - contains additional supporting Quality information

The modules are organized and numbered consistently in an internationally adopted format  - the Common Technical Document (CTD). Adhering to the CTD format facilitates evaluation by Health Canada and ensures consistency of documents in subsequent stages of the drug authorization process. Additional information about the  CTD format is available on the web site of the International Conference on Harmonisation (ICH).

The following guidance documents may be useful in the preparation of the application:

How to Organize Your Application

Health Canada encourages the submission of applications in Common Technical Document (CTD) format. This format, as applied to a CTA, is shown below.

Each Module should be submitted in a separate binder.

Module 1: Administrative / Clinical Information

[1.2.1] Drug Submission Application Form (HC/SC 3011)

A completed Drug Submission Application Form (including Appendix 3), must be signed by the Senior Medical or Scientific Officer in Canada AND the Senior Executive Officer. Appendix 1 ("Authorization for a third party to import...") and Appendix 2 ("Authorization for a third party to sign/file..") should be submitted only if applicable.

[1.2.2] Information on Prior-related Applications (if applicable)

This is a list of the sponsor's ongoing clinical trials in Canada, previously authorized by Health Canada.

[1.2.3] Product monograph / Prescribing Information

A copy of the Product Monograph/Prescribing Information for the reference product must be submitted.

The Product Monograph / Prescribing Information must be submitted in both hard copy and electronic format. Note that electronic copies must be submitted on CD-ROM or diskette, in either editable PDF, MS Word, or WordPerfect format.

[1.2.4] Protocol Synopsis (PCERT)

A protocol synopsis in the format of the Pre-clinical and Clinical Evaluation Report Template (PCERT) must be submitted. A submission rationale and a brief summary are included in the PCERT.

The PCERT must be submitted in both hard copy and electronic format. Note that electronic copies must be submitted on CD-ROM or diskette, in either editable PDF, MS Word, or WordPerfect format.

[1.2.5] Study Protocol(s)

A copy of the final study protocol must be submitted. The information in the protocol should follow the Health Canada / ICH Guidance Document E6: Good Clinical Practice: Consolidated Guideline.

The study protocol must be submitted in both hard copy and electronic format. Note that electronic copies must be submitted on CD-ROM or diskette, in either editable PDF, MS Word, or WordPerfect format.

[1.2.6] Informed Consent Document(s)

A copy of the Informed Consent document(s) to be used in conjunction with the clinical trial must be submitted. The Informed Consent document(s) must include a statement regarding the risks and anticipated benefits to the clinical trial subjects as a result of their participation in the clinical trial(s).

The Informed Consent document(s) should be prepared in accordance with the Health Canada / ICH Guidance Document E6: Good Clinical Practice: Consolidated Guideline.

[1.2.7] Clinical Trial Site Information (CTSI)

A completed Clinical Trial Site Information Form (CTSI Form) for each proposed clinical trial site, if known at the time of the application, is to be submitted. Please do not provide forms until all fields are completed. Dates for sections 35 and 47 of the CTSI Form must be provided. In addition, the sponsor may also utilize their cover page to provide additional and relevant information related to specific sections of the form when submitting it to the relevant Directorate, if applicable.

For clinical trial site information which becomes available after the time of application, a completed CTSI Form must be provided to the appropriate Directorate before the trial is initiated at that site.

In the event that an amendment must be implemented prior to the approval due to safety reasons, the commencement date of the amendment should reflect the date the amendment was implemented at the site. To avoid any confusion during the data entry, a supplemental document should also be attached to the CTSI form justifying the situation. Please refer to the section C.05.008 (4) of the Food and Drug Regulations for additional information." The word 'safety' can also be inserted in brackets next to the date [eg: January 15th, 2008 (safety)].

If any changes are made to the CTSI Form (e.g., change of qualified investigator) a revised form should be submitted. Receipt of the CTSI Form will not be subject to an acknowledgment letter.

[1.2.8] Canadian Research Ethics Board(s) Refusals (if applicable)

If known at the time of submitting the application, the following information must be provided: the name, address and telephone number and, if applicable, the fax number and electronic mail address of any Research Ethics Board (REB) in Canada that has previously refused to approve the clinical trial protocol, its reasons for doing so, and the date on which the refusal was given.

[1.2.9] Foreign Refusals (if applicable)

Information regarding refusals by regulatory authorities outside Canada must be included.

[1.2.10] Letters of Access (if applicable)

If applicable, letters authorizing Health Canada to access related files (e.g., Drug Master Files) must be submitted.

The CTA sponsor should ensure that the supporting Drug Master File (including submission of the letter of access and payment of related fees) has been submitted to and accepted by Health Canada prior to filing a CTA.

[1.2.11] Other Information (if applicable)

Any additional information that may be relevant to the application should be submitted, if applicable.

[1.3] Electronic Review Documents

Module 1 electronic files should be placed under this section. The following documents must be submitted in electronic format:

  • Product Monograph / Prescribing Information
  • PCERT
  • Study Protocol(s)

Electronic documents must be identical to the hard copies provided in the CTA.

Electronic review documents must be submitted on CD-ROM or diskette, in either editable PDF, MS Word, or WordPerfect format.

Module 2: Common Technical Document Summaries - Quality (Chemistry and Manufacturing) Information

This section does not apply if the test product to be used in the clinical trial has received a Notice of Compliance (NOC) and/or a Drug Identification Number (DIN).

For a CTA, this module reflects Quality (Chemistry and Manufacturing) information only. The Common Technical Document Summaries Module should include:

[2.1] Common Technical Document Table of Contents

A listing of the contents of Modules 2 and 3.

[2.2] CTD Introduction

Not applicable to CTAs. This section has been reserved for use during the preparation of drug submissions at later stages of development (e.g., New Drug Submissions) and maintained to ensure consistent numbering of subsequent sections (e.g., Section 2.3).

[2.3] Quality Overall Summary (QOS)

This document must be submitted in both hard copy and electronic format. Note that electronic copies must be submitted on CD-ROM or diskette, in either MS Word or WordPerfect format (PDF format of the QOS is not acceptable). Module 2 electronic files should be placed at the beginning of Module 2.

If the reference lot used in the clinical trial is for a Reference Drug Product that is marketed in Canada, US, EU, Australia or Switzerland, sponsors should complete the QOS-CE (CTA - BA). Otherwise, the QOS-CE (CTA - Phase I) should be completed.

For detailed instructions on completing the Quality Overall Summary - Chemical Entities templates, see Guidance for Sponsors of Clinical Trial Applications, Quality (Chemistry and Manufacturing)

Module 3: Quality (additional supporting Quality information)

The Quality Module should include:

[3.1] Table of Contents of Module 3

A listing of the contents of Module 3 (Quality).

[3.2] Body of Data

Where there is additional supporting Quality information to that provided in Module 2.3, this information should be provided separately in the appropriate Module 3 section and cross-referenced under Module 2.3. The extent of available supporting information may vary depending upon the stage of drug development (e.g., Phase I-III studies). Sponsors should also refer to the applicable Health Canada Quality guidances for additional information.

Filing a CTA - Comparative Bioavailability Studies

The CTA should be sent directly to the appropriate Directorate. The outer label should be clearly state "Clinical Trial Application".

Note: Where a sponsor wishes to make changes to the CTA under review, the sponsor should withdraw the active CTA and submit a new CTA.

Records Related to Clinical Trials

Records of clinical trials should be maintained by the sponsor for 25 years, as required in Part C, Division 5 of the Food and Drug Regulations. (C.05.012 - Sponsor's Obligations - Records ).

A Qualified Investigator Undertaking and a Research Ethics Board Attestation must be completed for each clinical trial site.

Records must be made available to Health Canada within 2 days if there is a concern regarding the use of a clinical trial drug and/or a risk to the health of the clinical trial subject. In any other case, records must be provided within 7 days of request. ( C.05.013 - Sponsors' Obligations - Submission of Information and Samples).

Post-Authorization Changes

For proposed Clinical and/or Quality (Chemistry and Manufacturing) changes to a previously authorized application, see Clinical Trial Application - Amendments (CTA-As) or Notifications for requirements.

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