Notice : Pilot project for the Implementation of the Development Safety Update Report Regulatory Review at Health Canada

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December 20, 2012

Our file number: 12-122199-139

Pilot project for the Implementation of the Development Safety Update Report Regulatory Review at Health Canada

In June 2012 Health Canada adopted the International Conference on Harmonisation (ICH) guidance E2F: Development Safety Update Report (DSUR). By way of this Notice, stakeholders are being advised that Health Canada is initiating a Pilot project to assess how DSURs can be integrated into the drug review processes within the Health Product and Food Branch (HPFB).

1. Objectives of the DSUR pilot project

The objective of the pilot project is to determine how best to integrate the review of these documents into the review of Clinical Trial Applications (CTA), New Drug Submissions (NDS), Supplemental New Drug Submissions (SNDS) and into the safety surveillance of drugs in development. Also, the pilot will capture performance metrics for the resources required to support their review in HPFB.

2. DSURs for the pilot project

During the pilot phase, a limited number of drugs DSURs from each area of HPFB will be requested from sponsors and reviewed by Health Canada.

Unless specifically requested, DSURs should only be submitted to Health Canada when significant new safety information or any important changes to the safety profile of the drug need to be conveyed. In these cases, the DSURs should be accompanied by a rationale/justification in the cover letter.

3. Product lines affected by the pilot phase:

The DSUR pilot project will apply to submissions received from clinical trial sponsors and will cover the following product lines:

• pharmaceuticals;
• biologics and biotechnology products, including blood products; vaccines.

Please refer to the Appendices below for the following instructions:

• Appendix I. Instructions for Submitting Requested Development Safety Update Reports (DSUR) in Electronic Format;
• Appendix II. Check list to be completed with the submission.

Appendix I

1. Instructions for Submitting Requested Development Safety Update Reports (DSUR) in Electronic Format

As part of Health Canada's ongoing commitment for improved submission (regulatory activity) management, all DSUR regulatory activities will be processed and tracked within Health Canada using the Drug Submissions Tracking System (DSTS), which is managed by the Office of Submission and Intellectual Property (OSIP) of the Therapeutic Products Directorate (TPD). DSURs should be submitted as a stand-alone regulatory activity, separate from any other information. They should not be submitted with a Clinical Trial Application (CTA), New Drug Submissions (NDS), Supplement to a New Drug Submission (SNDS) or any other regulatory activity, unless specifically requested by Health Canada.

1.1 General Requirements

When requested, DSURs must be submitted to Health Canada electronically on Compact Disc / Digital Versatile Disc (CD/DVD); No paper copy of the DSUR should be submitted. 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 regulatory activity. This will contribute to good record management and ensure authenticity, integrity, availability, traceability, and non-repudiation of the data.

All DSURs must be submitted with an electronic and a paper cover letter which clearly explains the intent of the package and should address any special requests (such as whether the DSUR is being submitted upon request from Health Canada, or if it is being provided voluntarily).

Health Canada encourages sponsors to submit the DSUR documents as portable document format (PDF) (1.4 to 1.7) files. 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 (regulatory activity) 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.

1.1.1 Folder Structure and Folder Content

The content of the electronic media should be organized in folders. Files submitted electronically should not be zipped or password protected.

• With the exception of the file extension, 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.
• ICH requires that the file names be limited to a maximum of 64 characters, including the file extension. See the ICH Electronic Common Technical Document Specification (Version 3.2), "Name," pages 2-5.

1.1.2 Media for Submitting Electronic Data

The media formats acceptable when submitting any electronic regulatory activity 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;
• Universal Serial Bus Version 2.0 [Universal Serial Bus (USB) 2.0] drive.

These are the formats that are currently supported. Contact OSIP for other formats that may be acceptable at the time of filing. See below for full contact information.

Media should not be password protected.

Sponsors should provide all documents on a single disc/drive. Duplicate copies are not required.

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

• Sponsor name and brand name;
• Electronic Common Technical Document (eCTD) Identifier (if applicable);
• Sequence number (if applicable) ;
• "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.

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

As per guidance documents posted on the Health Canada website, there are currently two acceptable formats in which sponsors can file DSUR regulatory activities.

• Electronically in eCTD format
• Electronically in non-eCTD format

1.2 eCTD Format Requirements

Health Canada requests that all DSURs be submitted in eCTD format, if they are related to a previously filed regulatory activity for a dossier in eCTD format. The DSUR Check List (Appendix II) and DSUR should be filed as two separate leaf elements under the m-1-3-8-4-other-pharmacovigilance-information heading. The naming convention used for the leaf is up to the sponsor's discretion; however, meaningful names should be applied.  Please refer to Draft Guidance Document: Preparation of Drug Regulatory Activities in Electronic Common Technical Document (eCTD) for further information concerning regulatory activities in eCTD format.

1.3 Non-eCTD Format Requirements

If DSURs are not submitted in eCTD format, sponsors must submit them in electronic non-eCTD format. The DSUR Check List and DSUR should be filed as two separate files in the subfolder "1.3.8.4 Other Pharmacovigilance Information" using the structure template recommended in "Appendix D: Common Technical Document (CTD) Format" of the guidance document Preparation of Drug Regulatory Activities in the Common Technical Document (CTD) Format.

1.4 Contact Information

As of December 20, 2012 sponsors are required to submit DSURs and related information directly to OSIP using the following address:

Office of Submissions and Intellectual Property (OSIP)
Therapeutic Products Directorate
Health Canada
Postal Locator 0201A1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9

For inquiries related to electronic format, please contact Health Canada using the following e-mail address:

E-mail: ereview@hc-sc.gc.ca

If you have any questions or comments about the above messaging, please do not hesitate to contact TPD or BGTD for clarification.

Office of Clinical Trials
Therapeutic Products Directorate
Health Canada
Holland Cross, Tower B,
5th floor, 1600 Scott Street
Address Locator 3105A
Ottawa, Ontario
K1A 0K9

E-mail: DSUR@hc-sc.gc.ca
Telephone: 613-948-8895
Facsimile: 613-954-4474

Office of Regulatory Affairs
Biologics and Genetic Therapies Directorate
Health Canada
200 Tunney's Pasture Driveway
Address Locator 0700A
Ottawa, Ontario
K1A 0K9

E-mail: bgtd_ora@hc-sc.gc.ca
Telephone: 613-957-1722
Facsimile: 613-946-9520

Appendix II

Check list for Submitting Requested Development Safety Update Reports (DSUR) in Electronic Format