Release of Health Canada's Revisions to"1.6 Electronic Review Documents" in Draft Guidance for Industry: Preparation of New Drug Submissions in the CTD Format.

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Contact: eReview

Notice

February 25, 2008

Our file number: 08-105099-944

Health Canada is pleased to announce a revision to the Draft Guidance for Industry: Preparation for New Drug Submissions in the CTD Format. This revision is specific to "1.6 Electronic Review Documents" in Subsection 4.1, "Module 1: Administrative Information and Prescribing Information," and will assist sponsors to prepare electronic media as part of submissions in the common technical document (CTD) format.

This notice defines the electronic file requirements and provides guidance on the structure, content, and format of electronic information to be included with submissions in the CTD format. The scope covers the following submission types: New Drug Submission (NDS), Abbreviated New Drug Submission (ANDS), Supplemental New Drug Submission (SNDS), Supplemental Abbreviated New Drug Submission (SANDS), Notifiable Change (NC), Drug Identification Number Application (DINA), application for DIN - Biological Product (DINB), Application for a DIN - Disinfectant Product (DIND), and application for a DIN - Category IV Product (DINF).

The recommendation for submitting Module 1, "Administrative Information and Prescribing Information," and Module 2, "Common Technical Document Summaries," of a paper submission in electronic format is part of Health Canada's transition to the acceptance of stand-alone submissions in electronic common technical document (eCTD) format in compliance with the International Conference on Harmonization (ICH) eCTD specification. This notice reflects Health Canada process enhancements. The implementation of this revision to the guidance document is ongoing. Further refinements to this notice will continue to be necessary as a result of experience gained during implementation; subsequent iterations will be released.

This notice should be read in conjunction with the Draft Guidance for Industry: Preparation of New Drug Submissions in the CTD Format published on June 2003 and the Draft Guidance for Industry: Preparation of Drug Submissions in eCTD Format published in January 2006. Sponsors should also consult the other Health Canada guidance documents and notices on the Health Canada web site.

1. The CTD and eCTD Formats

Health Canada is developing a phased migration plan from the current paper-based and proprietary standards to the ICH eCTD specification. The CTD format is an interim format that remains paper-based. Although providing various parts of submissions in CTD format electronically is encouraged, this provision is not meant to replace submission in eCTD format. It is meant only to facilitate transition to it.

Any updates to the CTD requirements or to this notice will only be introduced following advance consultation and notification, and will not be applied retroactively to submissions pending review. For submissions currently in preparation, sponsors may continue to follow the Health Canada guidance documents, in effect, prior to the date of release of this notice. Effective April 1, 2008, all subsequent submissions should be compiled using the most recent revisions to the guidance documents.

2. Electronic Data Structure and Content

2.1 Files in Word Processed and ASCII Format

Table 1 lists the components of Modules 1 and 2, that should be submitted as electronic files and the formats in which they should be submitted.

Table 1: Components to be Submitted as Electronic Files

Electronic Files	When To File	Format
Product Monograph (PM)	File annotated and non-annotated versions of PM at time of submission	word processedFootnote 1
Quality Overall Summary (QOS)	File at time of submission
Certified Product Information Document (CPID)	BGTD/TPD: NDSs/ANDSs File upon request during review process BGTD: SNDSs/NCs File annotated and non-annotated versions at time of submission TPD: SNDSs/SANDSs/NCs File at time of submission
Comprehensive Summary: Bioequivalance (CS:BE)	File at time of submission
Summary of responses in a question and answer format to Screening Deficiency Notices (SDNs), Clarifaxes, Notices of Noncompliance (NONs), and Notices of Deficiency (NODs)	BGTD: File upon request TPD: File with response
Bioequivalance (BE) data sets (*inf and *dat)	File at time of submission See Health Canada's Draft Guidance for Industry: Preparation of Comparative Bioavailability Information for Drug Submissions in the CTD Format, Appendix B, "Computer Format for the Submission of Data for Comparative Bioavailability Studies"	ASCII format

Notes:

• When all Case Report Forms (CRFs) are available in portable document format (PDF), applicants are not required to provide the paper copy of the CRFs. (See "5.3.7 Case Report Forms and Individual Patient Listings," Subsection 4.5, "Module 5: Clinical Study Reports," of Draft Guidance for Industry: Preparation of New Drug Submissions in the CTD Format.)
• All files provided should include the extension of the software used, in their name. (i.e. MSWord: xxx.doc; WordPerfect: xxx.wpd; Portable Document Format: xxx.pdf; etc.).
• Sponsors should continue to submit responses to solicited data in both electronic and paper formats.

2.2 Files in Portable Document Format

In addition to the electronic files listed in Table 1, Health Canada encourages sponsors to submit the remaining documents in Module 1 and Module 2 electronically as PDF files. Sponsors are also encouraged to submit Notifiable Changes (NCs) electronically, as PDF files as well.

The provision of sections of the CTD formatted submission 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 it will be immediately accessible to all Health Canada staff involved with the submission review. This eliminates the burden and delay of sharing compact disks (CDs). Accessing the documents using the viewing tool will also contribute to good record management by ensuring authenticity, integrity, availability, traceability, and non-repudiation of the data.

If Module 1 and 2 are provided electronically, only one copy of each Module's binder is required for paper-based submissions.

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 also important that documents be properly bookmarked.

2.3 Letter of Attestation

A Letter of Attestation, on applicants own letterhead should be provided, which confirms that the electronic documents are identical to the paper format. This letter should be filed under subsection 1.2.3 Submission Certification Form.

2.4 File Structure

The contents of the electronic media should be organized in folders. Those folders should be named according to the information provided in the first two columns of the table in Appendix C, "Correlation of CTD versus 1991 Canadian Formats," Draft Guidance for Industry: Preparation of New Drug Submissions in the CTD Format. No abbreviations should be used. No additional sub-folders should be created other then the ones indicated in Appendix C.

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

Figure 1: CD/DVD Contents Folder Structure

• If an applicant chooses to include a cover letter, it should be filed under Subsection 1.0, "Cover Letter - Request and Response to."
• The copy of the original request and the summary response in a question and answer format to SDNs, Clarifaxes, NONs and NODs should also be filed under Subsection 1.0, "Cover Letter - Request and Response."
• Bioequivalence data should be filed under Subsection1.2.8, "Other Application Information."
• Files submitted electronically should not be zipped.

3. Media for Submitting Electronic Data in the CTD Format

The only formats accepted at this time are CD-R conforming to the Joliet specification, and DVD-RAM and DVD+R/-R recorded in the Universal Disk Format (UDF) standard. These are the formats that are currently supported. Contact Health Canada for other formats that may be acceptable at the time of filing.

Sponsors should fit all documents in as few CDs or digital video disks (DVDs) as possible. Duplicate copies of the CDs/DVDs are not required. The discs should be submitted in individual slim jewel cases. Only the discs should be labeled.

The labels on the discs should contain the following information:

• Sponsor name and brand name;
• Control number, if known;
• "Protected B";^{Footnote 2}
• Virus free certification, the software used for the virus check and the date of the virus definition file or files;
• Month and year of the submission; and
• Disc number and total number discs (i.e., Disc 1 of 5).

Note: Cases do not need to be labeled since Health Canada will be placing their own 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.

4. Further Information

Should you have any questions regarding the content of this notice, please contact:

Submission and Information Policy Division (SIPD)
Finance Building
101 Tunney's Pasture Driveway
A.L. #0201A1
Ottawa, ON K1A 0K9
eReview@hc-sc.gc.ca