[December 07, 2002] In October 2002 a Version 3.0 Electronic Common Technical Document Specification (ICH eCTD Specification V 3.0) was issued in the form of a PDF document and an accompanying ICH eCTD XML DTD. See the reference section below.
[August 02, 2002] The ICH Multi-disciplinary Group 2 (M2) Expert Working Group (EWG) is developing an XML-based specification governing electronic submission of pharmaceutical regulatory information. A version 1.0 XML DTD was frozen in February 2002, along with the publication of a version 2.0 Electronic Common Technical Document (eCTD) specification. The Step 2 eCTD specification was signed by representatives of the EWG's three regulatory bodies (European Commission, Japanese Ministry of Health, Labor and Welfare, and US Food and Drug Administration), together with leading industry groups (European Federation of Pharmaceutical Industries and Associations, Pharmaceutical Research and Manufacturers of America, Japan Pharmaceutical Manufacturers Association). The Step 2 consultation period in the EU ended on 30-July-2002; another meeting is scheduled for September 2002.
The ICH [International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use] Multi-disciplinary Group 2 (M2) Expert Working Group (EWG) "was established in 1994 in Brussels to determine electronic standards and provide solutions to facilitate international electronic communication in three ICH regions: Europe, Japan, and USA (and Canada as observer). The Expert Working Group (EWG) was established to facilitate international electronic communication by evaluating and recommending, open and non-proprietary -- to the extent possible -- Electronic Standards for the Transfer of Regulatory Information (ESTRI) that will meet the requirements of the pharmaceutical companies and regulatory authorities... The EWG recommends global technical standards that are supported by multiple vendors, affordable and mature, at low risk of obsolescence, and capable of providing the following functionality: (1) Structured messaging; (2) File transfer to complement structured messaging; (3) Directory services to manage and access data; (4) Documents to handle heterogeneous data formats, like simple text, multi-lingual text, tables, graphics, pictures, and complex/compound documents; (5) Formatted data for transferring information between heterogeneous databases (Electronic Data Interchange); (6) Security to ensure, if and when required, confidentiality, integrity, authentication, and non-repudiation..." [from the Background document]
From the ICH eCTD Version 2.0 Specification Introduction: "The ICH M4 Expert Working Group (EWG) has defined the Common Technical Document (CTD). The ICH M2 EWG has defined, in the current document, the specification for the Electronic Common Technical Document (eCTD). The eCTD is defined as an interface for industry to Agency transfer of regulatory information while at the same time taking into consideration the facilitation of the creation, review, lifecycle management and archival of the electronic submission. The eCTD specification lists the criteria that will make an electronic submission technically valid. The focus of the specification is to provide the ability to transfer the registration application electronically from industry to a regulatory authority. Industry to industry and Agency to Agency transfer is not addressed... The specification for the eCTD is based upon content defined within the CTD issued by the ICH M4 EWG. The CTD describes the organization of modules, sections and documents. The structure and level of detail specified in the CTD has been used as the basis for defining the eCTD structure and content but where appropriate, additional details have been developed within the eCTD specification. The philosophy of the eCTD is to utilize open standards. Open standards, including proprietary standards, which through their widespread usage can be considered de facto standards, are deemed to be appropriate in general..."
The XML DTD:
"The XML eCTD DTD (Document Type Definition) defines the overall structure of the submission. The purpose of the XML backbone is two-fold: (1) to manage meta-data for the entire submission and each document within the submission and (2) to constitute a comprehensive table of contents and provide corresponding navigation aids. Meta-data on submission level includes information about submitting and receiving organization, manufacturer, publisher, ID and kind of the submission, and related data items. Examples for meta-data on document level are versioning information, language, descriptive information such as document names, checksums, etc. Details are defined in appendix 6.
The XML instance of any submission should be created and validated according to the XML eCTD DTD as defined in appendix 8.
The XML eCTD DTD describes the hierarchical structure according to the CTD as defined by the ICH M4 expert working group. It includes multiple hierarchical levels depending on the specific module as defined in the CTD. The actual submission can include more hierarchical levels below those defined in the CTD. The XML eCTD instance covers the entire submission including all hierarchical levels and includes references to each individual file.
The submission should include a style sheet that supports presentation of the XML instance, navigation according to the table of contents and provides access to all documents within the submission. A standard style sheet is defined and provided by the ICH M2 EWG. Presentation and navigation via other style sheets on the receiving side should be possible.
The XML eCTD DTD includes a reference for each document to the physical file within the folder structure. The XML eCTD DTD includes attributes for descriptive names of folders and documents. [from the version 2.0 spec]
Bibliographic information for the Version 2.0 specification: Electronic Common Technical Document Specification." From the ICH M2 Expert Working Group. Reference: ICH eCTD Specification V 2.0. February 12, 2002. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 'This specification has been developed by the ICH M2 Expert Working Group in accordance with the ICH Process as pertains to the M2 EWG.' 160 pages. "The three regulatory authorities represented in the ICH M2 Expert Working Group are responsible for initiating changes to the eCTD Specification, based on industry or regulatory input. A change can be proposed by any of the regulatory authorities... The approach to the management of the specification for the eCTD is to divide the documentation into a series of independent but related appendices. This will facilitate the maintenance of the specification, as it will not require that all documentation be updated even for a small change to one part of the specification. Each appendix can be updated independently as and when required, thus being able to more readily support the currency of the specification as a whole.
Module 1 of an eCTD submission is regional in nature. See the summary description from the EU Module 1: "In line with the general principles of the eCTD, it is intended that XML will become the submission format for application forms and product information as they contain structured data. As the XML documents become available for practical implementation, they will be introduced into Module 1 and the current file formats will be replaced after a transition period... The EU Module 1 architecture is similar to that of modules 2 to 5 of the eCTD, comprising a directory structure and a backbone. The backbone must be a valid XML document according tot the XML EU Index Document Type Definition (DTD). The XML EU Index instance contains meta-data for the leaves, including pointers to the files in the directory structure. In addition, the XML EU Index DTD defines meta-data at the submission level in the form of an envelope. The root element is 'eubackbone' and contains two elements: 'envelope' and 'm1-eu'. A full description of the EU Index DTD can be found in annex A to this guideline..."
From the README of the EU Module 1 Template: "The draft EU Module 1 Template follows the EU Module 1 Specification, as required in Appendix 5 (Regional specific information: Module 1) of the ICH eCTD Specification V 2.0 February 12, 2002. It also contains the Application Form (old Part 1 A) DTD and example according to Electronic Application Form Specification. The EU regional DTDs are in the directory util/dtd. The EU DTDs have the prefix eu-. They are modularized; i.e., the DTDs are in several files as opposed to one file. The DTDs have the extension dtd and the modules (fragments) the extension mod. For example, eu-envelope.mod is included in eu-index.dtd and eu-application.dtd, a place holder file for Application Form. Comments on the EU Module 1 Template should be forwarded to M.T. Carrasco Benitez..."
