Electronic Specifications for Clinical Trial Applications and Amendments filed in accordance with Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications

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May 29, 2013

Notice

Our file number: 13-108466-338

Release of Electronic Specifications for Clinical Trial Applications and Amendments filed in accordance with Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications

This Notice serves as a revision to the Release of Draft Electronic Specifications for Clinical Trial Applications and Amendments filed in accordance with Guidance for Clinical Trial Sponsors: Clinical Trial Applications, published on July 2, 2009.

On June 25, 2003 Health Canada published the Guidance for Clinical Trial Sponsors: Clinical Trial Applications which extended the modular format of the Common Technical Document (CTD) to Clinical Trial Applications (CTA) and Clinical Trial Application - Amendments (CTA-A). This guidance document was updated on November 7, 2011, and incorporated a revised CTD structure, in accordance with Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format (June 22, 2012). The revisions in this Notice are to align the electronic components in CTAs & CTA-As with the revised CTD structure.

This Notice provides guidance to assist sponsors in preparing the electronic components of the application. It also provides the guidance on the structure, content, format and media of electronic information.

All the electronic components of CTAs and CTA-As should be filed using the specifications outlined in this Notice. Sponsors may use the information in this Notice immediately.

Scope and Application

The information in this Notice applies to both CTAs and CTA-As, for which the application is being submitted in an electronic format in accordance with the Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications (2013-05-29).

The submission of electronic documents as part of a paper-based application is part of Health Canada's transition to the acceptance of stand-alone submissions in International Conference on Harmonization (ICH) eCTD specifications. Health Canada continues to work on the ICH eCTD and will provide further guidance as progress is made for a fully electronic environment.

This Notice should be read in conjunction with the Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications (2013-05-29) and Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format (June 22, 2012). Sponsors should also consult the other relevant Health Canada guidance documents and notices on the Health Canada website.

1. Electronic Data Structure and Content

1.1 Files in Word Processed Format

The component of Module 1, Section 1.4.1: PSEAT-CTA, and Module 2, Section 2.3: Quality Overall Summary (QOS) should be submitted as electronic files in a word processed format at the time of submission of a CTA or CTA-A (if applicable).

Sponsors should submit the original files in Microsoft Word 2010 or earlier, or WordPerfect Version 10 format. Templates compatible with these word-processing formats can be found on the Health Canada Web site.

1.2 Files in Portable Document Format (PDF)

In addition to the electronic files mentioned in section 1.1, Health Canada encourages sponsors to submit the remaining applicable documents in Module 1, Module 2, and Module 3 electronically as PDF files.

The provision of all sections of the submission in CTD format electronically has many benefits for both Health Canada and sponsors, and will ease the transition toward eCTD submissions. Electronic documents will be uploaded onto the Health Canada viewing tool, where they will be immediately accessible to Health Canada staff involved with the review of the submission. This will also contribute to good record management by ensuring authenticity, integrity, availability, traceability, and non-repudiation of the data.

PDF versions of documents should be generated from electronic source documents and not from scanned material, except where access to the source electronic file is unavailable or where a signature is required. It is important that PDF files be properly bookmarked. The following are recommended as good bookmarking practices:

• Documents of ten pages or more should be bookmarked;
• Bookmarks are equivalent to and should be organized like a document table of contents, and should not include the submission level;
• Sections, subsections, tables, figures, and appendices should all be bookmarked;
• Too many levels of bookmarks are inefficient; in most instances, four levels of bookmarks should be sufficient:
  • 1 Heading
    • 1.1 Subheading
      • 1.1.1 Sub-subheading
        • 1.1.1.1 Sub-sub-subheading

Health Canada recognizes that bookmarks are generated automatically from document headings, but nevertheless recommends they be kept concise.

1.3 Naming of Files

All names of all files submitted should incorporate the file extension of the software that was used to create the file (for example: MSWord: xxx.docx; Wordperfect: xxx.wpd; Portable Document Format: xxx.pdf; etc.).

1.4 Letter of Attestation for full electronic copy received with paper-based applications

A Letter of Attestation should be provided on the applicant's letterhead, attesting that the electronic documents are identical to the content in the paper-based submission. The Letter of Attestation should be filed under subsection 1.2.3 Certification and Attestation Forms of the paper-based submission in CTD format. The Letter of Attestation should be signed by the senior regulatory affairs officer or the official delegate.

1.5 Structure of Folders and their Naming Convention

The contents of the electronic media should be organized in folders. Those folders should be named according to the information provided in the following guidance documents:

• Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications (2013-05-29) for Module 1, Module 2, and Module 3 and
• Guidance Document: Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format (June 22, 2012)

No additional sub-folders should be created other than the ones indicated in the above guidance.

Figure 1 shows an example of the folder structure in which sponsors are recommended to submit their data.

• Empty folders should not be included in the structure (that is, if a Letter of Access is not applicable for an application, then folder 1.2.6 should not be created in the structure).
• Files submitted electronically should not be zipped or password protected.
• With the exception of the file extension (see section 1.3), the file naming convention within each folder is left to the sponsor. However, Health Canada suggests that the file names be kept as brief and meaningful as possible.
• Commonly used and meaningful abbreviations, such as IB for Investigator's Brochure, or QOS for Quality Overall Summary, may be used to shorten file names.
• ICH requires that the file names should be limited to a maximum of 64 characters, including the file extension. See the ICH Electronic Common Technical Document Specification (Version 3.2), "Name," pp. 2-5.

2. Media for Submitting Electronic Data in the CTD Format

The media formats acceptable when submitting CTAs and CTA-As are:

• Compact Disc-Recordable (CD-R) conforming to the Joliet specification;
• Digital Versatile Disc-Random Access Memory (DVD-RAM) Universal Disc Format (UDF) standard;
• Digital Versatile Disc-Recordable (DVD+R/-R) recorded in the Universal Disc Format (UDF) standard;

These are the formats that are currently supported. Contact the Office of Clinical Trials (OCT) within the Therapeutic Products Directorate (TPD) or the Office of Regulatory Affairs (ORA) within the Biologics and Genetic Therapies Directorate (BGTD) for other formats that may be acceptable at the time of submission.

Sponsors should provide all documents on a single disc/drive. Duplicate copies are not required. The discs should be submitted in individual slim jewel cases.

Media should not be password protected.

All media should be labeled. The labels on the disc/drive should contain the following information:

• Sponsor name and brand name;
• Control number, if known;
• "Protected B";^{Footnote 1}
• Virus free certification, the software used for the virus check and the date of the virus definition file or files; and
• Month and year of filing

Note: Jewel cases do not need to be labeled since Health Canada will be placing a label on the front cover.

Subsequent to burning the CD or DVD sponsors should ensure that all files can be opened and that no files are corrupt.

3. Further Information

Any questions regarding the content of this Notice should be sent via email to the appropriate organization listed below. In order for your correspondence to be routed appropriately please quote "Electronic CTAs" in your subject line.

Clinical Trial Applications
Office of Clinical Trials (OCT)
Therapeutic Products Directorate
Health Canada
5th Floor, Holland Cross, Tower B
1600 Scott Street, Address Locator 3105A
Ottawa, Ontario, Canada
K1A 0K9
E-mail: OCT_BEC_Enquiries@hc-sc.gc.ca

Office of Regulatory Affairs
Biologics and Genetic Therapies Directorate (BGTD)
Health Canada
200 Tunney's Pasture Driveway, Address Locator 0700A
Ottawa, Ontario, Canada
K1A 0K9
E-mail: BGTD_ORA@hc-sc.gc.ca