Q&A related to the Electronic CTD Specification Introduction This question and answer document is a summary of questions reviewed by the eCTD Implementation Working Group (IWG) on the eCTD Specification. The questions answered here relate to common questions that relate to the eCTD in all three ICH regions. Many of the questions received on the Step 2 specification were addressed in Step 4 and do not appear in the list. Questions concerning the timeframe for implementation of region-specific application types, module 1 implementation, lifecycle management and those questions that relate to items in the specification that direct the reader to each region are answered in guidance documents published for each region. Questions related to the table of contents for the Common Technical Document (CTD) should be directed to the CTD question and answer section of the ICH Website. Some of the questions posed so far address change requests to the eCTD Specification. The change request section of this document addresses all those items received by the eCTD IWG and indicates their status. This document will be updated as the specification undergoes change control or as new questions are submitted to the eCTD IWG. eCTD Questions and Answers Date of Approval Questions Answers 1 Feb 2002 Margins A4 vs. Letter Paper In the 'Electronic Common Technical Document Specification', page 12-2 section 'Page Size and Margins' it is stated "The print area for pages should fit on a sheet of A4 or Letter paper". Does this mean that it will be acceptable to submit an eCTD to the FDA with documents having A4 page margins? Thereby not allowing printing on Letter paper without loss of information or alternatively 'Fit to page' printing (shrink) option. The US FDA still requires 8.5 x 11 inch paper and the other regions require A4 paper. The intent of the section it is sited is that the sponsor should use a template that allows the text to be printed on either paper size. While this does result in some unused space in both formats, it does allow each region to use the paper size that is standard in that region. 2 Feb 2003 A paper CTD may contain more than one copy of the same document. In the eCTD, do you have to include more than one copy of a file? Separate entries in the XML backbone for each reference of the file can accommodate this need. The file should be included once in an appropriate place in the folder structure. Avoid duplicating the file. eCTD Questions and Answers Date of Approval Questions Answers 3 Feb 2003 How should cross-references be presented in the eCTD? CTD cross-references can be supported in the eCTD through the use of hyperlinks. 4 Feb 2003 Is it possible to change the values previously assigned to XML node attributes (e.g., the case where no value or the wrong value is placed in indication and later it is decided that a value/different value is necessary)? Currently no. This question generated change requests 00200 and 00210. 5 Feb 2003 It is very difficult to work out how to construct a valid index.xml file for the Control of Excipients section of Module 3 (3.2.P.4) without having to duplicate entries in the backbone and without deviating from the intended CTD structure. CTD expects that for each excipient a separate section 3.2.P.4.1 through 3.2.P.4.4 can be provided and that 3.2.P.4.5 and 3.2.P.4.6 are separate files. The eCTD cannot deliver a structure in which entries for 3.2.P.4.5 and 3.2.P.4.6 are not repeated either in the folder structure or as entries in the backbone. This question was generated by change request 00100. One way to construct a backbone is as follows: Repeat the element m3-2-p-4-control-of-excipients for each excipient and assign the excipient attribute (e.g., magnesium stearate, and purified water) for each repeat. Under each of these include the leaf elements covering documents for 3.2.P.4.1, 3.2.P.4.2, 3.2.P.4.3 & 3.2.P.4.4. It is not necessary to include the leaf elements for 3.2.P.4.5 & 3.2.P.4.6 here. Then create another repeat of the element m3-2-p-4-control-of-excipients and assign the excipient attribute value 'animal-human-novel'. Include the leaf elements for 3.2.P.4.5 & 3.2.P.4.6 here. The directory/file structure may this look something like this : eCTD Questions and Answers Date of Approval Questions Answers whilst the structure of the index.xml file would be like the image on the next page: eCTD Questions and Answers Date of Approval Questions Answers eCTD Questions and Answers Date of Approval Questions Answers 6 Feb 2003 Certain TOC tags are not required by the DTD. It is unclear if these need to be completed 1) always if possible 2) only if this element is repeated or 3) only if a regional authority requests it. Please clarify. To be consistent with CTD general Q&A, always include these attributes as appropriate: substance manufacturer product-name excipient indication dosageform 7 Feb 2003 Appendix 4 provides specific folder names for some sections and states other sections can typically be submitted, as individual files. What is the definition of 'typically' and what should be done when they are not typical? There are now clear definitions of what is recommended for the granularity of documents provided in the ICH guidance on 'Organisation of the Common Technical Document for the Registration of Pharmaceuticals for Human Use'. This describes what is considered to be the appropriate granularity for each section of the CTD and hence eCTD. Where there is no definition provided in the organisation document, applicants are free to construct the dossier as they see fit so long as it adheres to the conventions for folder and file naming described in the eCTD specification. 8 Feb 2003 Is there any control in the eCTD Specification over terminology to be used for indications? No. 9 Feb 2003 How will the reviewer view and use the "append" operation attribute? It would also be useful to have clarifications on how review tools within agencies will handle these attributes. The eCTD Specification is concerned with the transport of electronic CTDs from applicant to regulator. Consult regulatory authorities in each region on the electronic review tools each use to view this format. eCTD Questions and Answers Date of Approval Questions Answers 10 Feb 2003 Will questions from Health Authorities be provided electronically using the specification? The eCTD Specification provides a transport mechanism for one-way traffic from applicant to agency. This question generated change request 00220. 11 Feb 2003 It is recommended to have the name of the root folder to be the application number or registration number of the drug. Unfortunately, in some European countries companies don't get the application number prior to the submission. In the case of an MRP each country will give a different number creating an issue for naming the root folder. In some countries, the application number is given per pack size and/or strength, and the unique application number will be difficult to identify. A unique identifier such as for the FDA submission is therefore quite difficult to achieve in Europe. Contact the regulatory authority for guidance. 12 Feb 2003 For the ID attribute, is it allowable to utilize an internal applicant identifier or would it need to be more understandable in order to support reasonable human identification (e.g. in reviewer to applicant correspondence about an issue). The ID attribute is intended to be a unique reference within the submission that can be used to reference the item from another item within the XML document. XML requires the ID to begin with an alphabetic character. If an internal ID generator uses only numbers, appending a number to a leading alphabetic character that then could be used as the ID can create the ID. 13 Feb 2003 The eCTD Specification allows for one novel excipient in 3.2.A.3. What happens if there is more than one? to be changed to a repeating element This question is identified in change request 00050. Consult the regulatory authority for a solution until the change request is resolved.