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Questions and Answers for the Guidance for Industry: Preparation of Drug Submissions in the Electronic Common Technical Document (eCTD) Format
Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.
(PDF Version - 100 K)The Health Canada document, Questions and Answers for the Guidance to Industry: Preparation of Drug Submissions in the eCTD Format has been revised to reflect current practices.
Should you have any questions or comments regarding the content of this document, please contact the Submission and Information Policy division (SIPD) at: ereview@hc-sc.gc.ca.
Questions:
- Must a sponsor submit an electronic drug submission only in eCTD format? Revised
- Must a sponsor submit both paper and electronic submissions? Revised
- What plans does Health Canada have in progressing towards the acceptance of electronic only, eCTD-compliant submissions? Revised
- What kind of submission types will Health Canada accept as of September, 2010 in eCTD format? Revised
- Why is it not possible for Health Canada to move immediately to accept "hybrid submissions"? Question Withdrawn
- Must the submission in eCTD format be filed at the same time as the paper submission? Revised
- Once a drug sponsor files a submission in eCTD format for a particular drug, do subsequent related submissions need to be in the eCTD format? Revised
- Can a drug sponsor file a submission in eCTD format for a paper-based submission in CTD format that is in backlog and for which an update notice has been received?
- Will a submission be given review priority by virtue of it being in the eCTD format?
- What security procedures is Health Canada putting in place for the submitted compact disk (CDs) and digital versatile discs (DVDs)?
- What maximum and minimum scan resolution is acceptable for scanned images included in submissions in eCTD format?
- Will Health Canada accept modified FDA submissions that include Study Tagging Files (STFs)? Revised
- How does the Health Canada eCTD system handle lifecycle management? Revised
- What constitutes the legal record in terms of filed submissions? Revised
- Can there be multiple leafs per node?
- How are Clarifaxes handled for submissions in eCTD format? Revised
- What is the change request process for Health Canada's eCTD guidance document?
- Do hyperlinks in the eCTD format need to be shown as cross references in the paper-based submission of Module 1 and Module 2 in CTD format? Revised
- How and when, does one obtain the unique eCTD Identifier for the initial submission in eCTD format? Revised
- With the acceptance of submissions in eCTD format, are there any changes to the process for paper-based submissions in CTD format? Question Withdrawn
- Where does one include the Letter of Attestation in the submission in eCTD format?
- Will sponsors have access to Health Canada's eCTD viewing tool? Revised
- Where can drug sponsors place bioequivalence (BE) data sets in submissions in the eCTD format?
- Where does one send sample submissions in the eCTD format? Revised
- Will Health Canada provide a style sheet for Module 1?
- What kind of external hyperlinks does Health Canada accept (and not accept) in the eCTD format? New
- Should the paper and electronic portions of an eCTD be filed at the same time for Clarifaxes? New
- What other media formats are acceptable when submitting an eCTD submission? New
- What should the package include when submitting an eCTD sample? New
- What version of PDF files should be provided for submission in eCTD format? New
- If Sponsors are not ready to provide a submission in eCTD format is there an alternative? New
- Will the validation report be sent to the sponsor once the eCTD sequence has been validated by Health Canada? New
- Is the printed content of the md-5 checksum (Appendix II) still required by Health Canada? New
- How should the Yearly Biologic Product Reports (YBPR) be submitted in eCTD format? New
- How should information related to submission fees be provided when filing a submission in eCTD format? New
- What are the folder and structure requirements when including the Applicant's part of the Drug Master File (DMF) as part of a drug submission in eCTD format? New
Questions and Answers:
1. Must a sponsor submit an electronic drug submission only in eCTD format?
(Modified October 2010)
No. Health Canada strongly recommends electronic submission in eCTD format; However for a transitional period, sponsors may submit their paper submissions with electronic data (not in eCTD format) on compact discs (CDs) and digital versatile discs (DVDs) using the requirements in the following posted documents:
- Submission in CTD format - Notice Release of Health Canada's Revisions to "1.6 Electronic Review Documents" in Draft Guidance for Industry: Preparation of New Drug Submissions in CTD Format, posted February 25, 2008.
- Clinical Trial Applications - Notice: Release of Draft Electronic Specifications for Clinical Trial Applications and Amendments filed in accordance with Guidance for Clinical Trial Sponsors: Clinical Trial Applications, posted July 2, 2009.
- Class IV Medical Device License - Guidance for Industry: Preparation of a Premarket Review Document in Electronic Format for a Class IV Medical Device License Application, posted January 1st, 2010.
2. Must a sponsor submit both paper and electronic submissions?
(Modified October 2010)
This question is related to eCTD submissions in the co-submission filing format. As of January 2010, Health Canada no longer accepts eCTD submissions in the co-submission filing format.
3. What plans does Health Canada have in progressing towards the acceptance of electronic only, eCTD-compliant submissions?
(Modified October 2010)
Health Canada's transition plan is as follows:
- Acceptance of submissions in eCTD format on CDs and DVDs along with the full paper-based submissions in CTD format ("co-submission"), Health Canada accepted eCTD submissions in co-submission format from September 1st, 2004 until January 1st, 2010 when they were no longer accepted.
- Acceptance of submissions in eCTD format on CDs and DVDs along with partial paper-based submissions in CTD format ("hybrid submission"), effective since June, 2006
- Acceptance of submissions in eCTD format on CDs and DVDs without paper-based submission in CTD format ("electronic only"). Effective August 2010, selected submission types may be filed in electronic only filing format.
Note: Paper-based and electronically based submissions in CTD format will continue to be accepted for the foreseeable future.
4. What kind of submission types will Health Canada accept as of September, 2010 in eCTD format?
(Modified October 2010)
As of September 2010, Health Canada will accept the following submission types in eCTD format:
- New Drug Submissions (NDS);
- Abbreviated New Drug Submissions (ANDS);
- Supplement to a New Drug Submissions (SNDS);
- Supplement to an Abbreviated New Drug Submissions (SANDS);
- Notifiable Changes (NC)
- Periodic Safety Update Reports (PSUR) (pre-market, submitted to Therapeutic Products Directorate (TPD) and Biologics and Genetic Therapies Directorate (BGTD);
- Forms summarizing the Post Notice of Compliance (NOC): Notices of Change Level III changes (if related to a previously filed submission for a drug product in eCTD format.);
- Drug Notification Forms (DNF) (If related to a previously filed submission for a drug product in eCTD format.);
- PSURs submitted to the Marketed Health Products Directorate (MHPD);
- Risk Management Plans (RMP) submitted to the Marketed Health Products Directorate (MHPD);
- Yearly Biologic Product Reports (YBPR);
- Request for Priority Review Status: New drug Submissions (PRNDS); and Supplement to a New Drug Submission (PRSNDS).
Note: For more information, please refer to Notice - Increased Scope of Submissions being accepted in Electronic Common Technical Document (eCTD) Format and acceptance of electronic-only submissions, posted August 2010.
5. Why is it not possible for Health Canada to move immediately to accept "hybrid submissions"?
Question withdrawn
6. Must the submission in eCTD format be filed at the same time as the paper submission?
(Modified October 2010)
Yes. The paper-based CTD submission has to be filed at the same time as the eCTD version. This applies to Modules 1 and 2 for eCTD submissions in the hybrid filing format.
7. Once a drug sponsor files a submission in eCTD format for a particular drug, do subsequent related submissions need to be in the eCTD format?
(Modified October 2010)
Yes, as per section 2.3 of the Guidance for Industry: Preparation of Drug Submissions in eCTD Format once a sponsor files a submission in eCTD format, all additional information and subsequent submissions for the same drug product should be filed in eCTD format.
8. Can a drug sponsor file a submission in eCTD format for a paper-based submission in CTD format that is in backlog and for which an update notice has been received?
(Created October 2005)
Health Canada can accept such a submission in eCTD format on a case-by-case basis. The drug sponsor is encouraged to discuss this with the Office of Regulatory Affairs (ORA) for submissions to the Biologics and Genetic Therapies Directorate (BGTD) and the Regulatory Project Management Division (RPMD) for submissions to the Therapeutic Products Directorate (TPD).
9. Will a submission be given review priority by virtue of it being in the eCTD format?
(Created October 2005)
No.
10. What security procedures is Health Canada putting in place for the submitted compact disks (CDs) and digital versatile discs (DVDs)?
(Created October 2005)
Health Canada will be uploading the data found on CDs and DVDs to a secure server, on which all processing and review will be performed. The CDs and DVDs will be stored in a secure environment.
11. What maximum and minimum scan resolution is acceptable for scanned images included in submissions in eCTD format?
(Created October 2005)
Health Canada will adhere to the specifications outlined in the Electronic Common Technical Document Specification (Version 3.22), developed by the International Conference on Harmonisation (ICH) M2 Expert Working Group (EWG).
12. Will Health Canada accept modified United States Food and Drug Administration (FDA) submissions that include Study Tagging Files (STFs)?
(Modified October 2010)
The submission in eCTD format must include the Canadian Module 1 DTD and adhere to the International Conference on Harmonisation (ICH) specifications. Files organized with STFs will be accepted but are not required. However, if STFs are included, they must pass validation. If an FDA submission containing STFs is modified by removing the STFs, the Study files and the Case Report Form (CRF) files must be organized using node extensions. The CRF files must be moved to section 5.3.7.
13. How does Health Canada handle lifecycle management?
(Modified October 2010)
The answer to this question can be found in the eCTD Guidance Document. Please refer to section 4.3 of the Guidance for Industry: Preparation of Drug Submission in eCTD Format.
14. What constitutes the legal record in terms of filed submissions?
(Modified October 2010)
For submissions in the Hybrid filing format, the electronic submission in eCTD format is the legal record.
15. Can there be multiple leafs per node?
(Created October 2005)
Yes.
16. How are Clarifaxes handled for submissions in eCTD format?
(Created October 2005)
The paper response to a Clarifax must be sent directly to the Health Canada official who requested the information. The response in eCTD format should be sent to the Submission and Information Policy Division (SIPD). Responses to Clarifaxes must otherwise conform to procedures described in Section 5.2.6 of Health Canada's Guidance for Industry: Management of Drug Submissions.
17. What is the change request process for Health Canada's eCTD guidance document?
(Created October 2005)
Interested parties are welcome to forward comments at any time on Health Canada's Guidance for Industry: Preparation of Drug Submissions in the eCTD Format. It is expected that this guidance document will be further modified at intervals based on comments received, experience gained, and further ICH developments. Comments may be forwarded to ereview@hc-sc.gc.ca. Health Canada will review all requests and comments for inclusion in consultation with stakeholders.
18. Do hyperlinks in the eCTD format need to be shown as cross references in the paper-based submission of Module 1 and Module 2 in CTD format?
(Modified October 2010)
Health Canada prefers that the paper-based cross-references converted to electronic hyperlinks also be spelled out as cross-references in the electronic files, with explicit citation of module, and section, as appropriate.
19. How and when, does one obtain the unique eCTD Identifier for the initial submission in eCTD format?
(Modified October 2010)
Before a sponsor files a submission in eCTD format, they should obtain an eCTD Identifier by submitting a written request to SIPD, via email (ereview@hc-sc.gc.ca), prior to sending the submission in eCTD format.
20. With the acceptance of submissions in eCTD format, are there any changes to the process for paper-based submissions in CTD format?
Question Withdrawn
21. Where does one include the Letter of Attestation in the submission in eCTD format?
(Created October 2005)
The Letter of Attestation (as defined in Health Canada's Guidance for Industry: Preparation of Drug Submissions in the eCTD Format) should be placed in Section 1.2.3 of Module 1 (m1-2-3-letter-of-attestation leaf element).
22. Will sponsors have access to Health Canada's eCTD viewing tool?
(Modified October 2010)
Health Canada will not provide access to their eCTD viewing tool since Health Canada has selected a commercial, off-the-shelf solution.
23. Where can drug sponsors place bioequivalence (BE) data sets in submissions in the eCTD format?
(Created October 2005)
Since this information is a regional requirement and since there is no specific place holder defined in the DTD for Module 1, this information should be placed in Section 1.2.8, "Other Application Information" (m1-2-8-other-application-information leaf element).
24. Where does one send sample submissions in the eCTD format?
(Modified October 2010)
Sample submissions, as defined in Health Canada's Guidance for Industry: Preparation of Drug Submissions in the eCTD Format, should be sent to the same address as regular submissions:
Submission and Information Policy Division
Health Canada
Finance Building #2, Address Locator 0201A1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9
Fax: (613) 941-0825
25. Will Health Canada provide a style sheet for Module 1?
(Created October 2005)
No.
26. What kind of external hyperlinks does Health Canada accept (and not accept) in the eCTD format?
(Created Oct. 2010)
External hyperlinks currently result in a validation error that would normally cause a submission to fail validation. However, including some links to a web page "www.*****" (such as sponsors own websites) or e-mail addresses "*****@****" are acceptable. Any external links to information pertinent to the review process will result in a validation failure. Information pertinent to the review process should be included within the submission as a portable document format (PDF) or another appropriate file type.
27. Should the paper and electronic portions of an eCTD be filed at the same time for clarifaxes?
(Created October 2010)
Yes, the paper and electronic portions of an eCTD should be filed on the same day. The summary of the response may be faxed directly to the Health Canada official who requested the information. The full response to a clarifax in eCTD format should be submitted to SIPD the same day as the summary is faxed.
28. What other media formats are acceptable when submitting an eCTD submission?
(Created October 2010)
The media formats acceptable when submitting an eCTD submission are:
- Compact Disc-Recordable (CD-R);
- Digital Versatile Disc-Random Access Memory (DVD-RAM) Universal Disk Format (UDF) standard;
- Digital Versatile Disc-Recordable (DVD+R/-R) recorded in the Universal Disk Format (UDF) standard; and
- Health Canada now also accepts both single and dual layer Blu-ray discs.
29. What should the package include when submitting an eCTD sample?
(Created October 2010)
The package should include the paper cover letter and the disc (slim jewel case) containing the eCTD sample. Since the content of the eCTD sample is not reviewed, no paper-based CTD documents are required to be submitted.
30. What version of PDF files should be provided for submission in eCTD format?
(Created October 2010)
Health Canada accepts PDF files up to version 1.7.
31. If Sponsors are not ready to provide a submission in eCTD format is there an alternative?
(Created October 2010)
Yes, Health Canada recognizes that not every sponsor is in a position to transition to the eCTD format right away. In order for Health Canada to benefit from electronic submissions, as soon as possible and also to receive as little paper as possible, Health Canada is encouraging sponsors to provide large submissions (25 binders or more) in non-eCTD hybrid filing format. A non-eCTD hybrid submission is a full electronic submission as PDF files that is accompanied by a partial paper-based submission, where only module 1 and 2 are provided in paper.
Non-eCTD hybrid filing format is an interim provision to the transition to the eCTD format. More information can be obtained by sending an email request to ereview@hc-sc.gc.ca.
32. Will the validation report be sent to the sponsor once the eCTD sequence has been validated by Health Canada?
(Created October 2010)
Every sequence received by Health Canada is validated and the report is generated by the validator. However, the report will be emailed to the sponsor only if there is an email address included in the cover letter indicating to whom the validation report should be sent. Multiple email addresses are acceptable.
33. Is the printed content of the md-5 checksum (Appendix II) still required by Health Canada?
(Created October 2010)
No, the printed content of the checksum file (index-md-5.txt) is no longer required to be included as an Appendix II to the cover letter.
34. How should the Yearly Biologic Product Reports (YBPR) be submitted in eCTD format?
(Created October 2010)
When the Yearly Biologic Product Report (YBPR) is provided as a single summary type document, it should be filed as a leaf element under the m1-2-8-other-application-information subheading (section 1.2.8 of the CTD structure).
When the YBPR is provided as multiple summary documents, the "YBPR", the "Analysis of Adverse Drug Reaction" and the "Recalls", should be filed as leaf elements under the m1-2-8-other-application-information subheading and all other documents listed in section 5.1 of the Guidance for Sponsors: Lot Release Program for Schedule D (Biologic) Drug, should be filed as leaf elements under the appropriate subheadings in module 3.
In both of the cases indicated above, the CPID should be submitted as a separate document, filed as a leaf element under the m1-4-1-certified-product-information-document subheading.
35. How should information related to submission fees be provided when filing a submission in eCTD format?
(Created October 2010)
When filing a submission in eCTD format, any payment related information (such as: credit card numbers, credit card expiry dates, and bank account numbers) must be included in the "Submission Fee Application Form" in the paper format only. However, the "Submission Fee Application Form", excluding the payment related information, should also be provided in electronic format.
36. What are the folder and structure requirements when including the Applicant's Part of the Drug Master File (DMF) in a drug submission in eCTD format?
(Created October 2010)
The "Applicant's Part" of the DMF should be included in section m3-2-s of the eCTD for the drug submission. If there is more than one DMF used for the active substance(s), each DMF "Applicant's Part" should be provided in its own m-3-2-s section, clearly distinguished by appropriate eCTD metadata values, leaf titles and file names.
If the Sponsor has their own quality documents relating to the active substance, in addition to those provided by the DMF owner, then these should be placed in their own m3-2-s section. This section should be identified by suitable metadata values to distinguish it from the content provided by the DMF owner(s).
When the Sponsor incorporates the "Applicant's Part" of the DMF into the NDS, there is no need to rename the leaf titles and files that were in the original DMF. The figures below are an example of an NDS that refers to two different DMF Owners (Company Y Ltd and Company X Inc.) as well as content from the sponsor. These have been identified in the metadata and the naming of the folders.
Note: The "Applicant's Part" of the DMF referred to in this document is equivalent to the "Sponsor's Part" in the Draft Guidance Document - Drug Master Files (DMFs).
