Talking R&D: Evolving technical standards
pharmafile | October 5, 2010 | Feature | Manufacturing and Production, Research and Development |Â Â Talking R&D, eCTD, eCTD submissionsÂ
The European Union (EU) Module 1 specification works in parallel with the ICH eCTD Specification. It was first introduced in July 2001, with fifteen further drafts taking us to a final version 1.0 in July 2004.
Four more versions have since been released to incorporate regulatory updates and accommodate technical changes. These included:
-V1.1 the integrating of Product Information Management, known as PIM
-V1.2.1 supporting the Decentralised Procedure, the accession of Bulgaria and Romania and to align with the CTD (Common Technical Document)
-V1.3 incorporating paediatrics requirements and change requests.
In August 2009, the release note for the new EU Module 1 specification v1.4 (EU M1 v1.4) was issued by the EMA highlighting the modifications between the new version and v1.3. The main update for this new version was to support the New EU Variation Regulation, and in particular grouped variations and worksharing.
Changes to be implemented
The implementation guidance, issued at the same time as the specification, had a two phase approach to assist applicants; from 1 January 2010 the EU M1 v1.4 must be used for eCTD submissions for any European procedure that contains grouped variations or was subject to a worksharing agreement and as of 1st July 2010, the EU M1 v1.4 must be used for all eCTD submissions for all European procedures.
To comply with the new EU variation regulation, the EU envelope required updating and vendors were asked to update their publishing and validation tools to accommodate the changes. The EU envelope has a new attribute, ‘submission mode’, to be used for variation and line extension regulatory activities only. Within this attribute are three options:
• single – a single regulatory activity (e.g. Type II variation)
• grouping – a grouped activity (e.g. several variations grouped into a single submission, or a periodic report of Type IA variations applicable to one or more marketing authorisations)
• worksharing – an activity subject to a worksharing agreement (e.g. Type II variation applicable to more than one marketing authorisation).
The attribute ‘application number’ has been replaced with ‘tracking number’ to accommodate for grouping/worksharing. Depending on the procedure and agency, the tracking number could be the procedure number, EU licence, Mutual Recognition Procedure (MRP) or Decentralised Procedure (DCP) number or national procedure/tracking number.
The new EU M1 v1.4 also gave the chance to make other approved changes. The ‘submission type’ was updated to support the following procedures; ‘Plasma Master File’, ‘National Variations’ and ‘Paediatric Submission, Article 46’. The ATC code was deleted as it was agreed that this information resides best in the application form. In addition, the maximum path length was reset to hold 180 characters, as there were concerns that file path lengths between the start of the overall folder and the end of the file name were too long and could cause problems when processing the submission.
Understanding the changes
The new specification provides guidance on a number of other issues raised around areas such as additional data, product information, related sequence/tracking number, and the usage of the ‘common’ country field for the MRP and DCP have been extended for further clarity.
Examples are also available to provide visual guides on style sheets, including where to place the tracking table for the MRP and DCP and how to references files across sequences. To accompany the specification, an annex was created to provide examples of XML coding for new applications, supplemental inform-ation, MRP, DCP and national procedures.
More importantly, it illustrates requirements to create separate sequences for each product involved in a group/worksharing variation.
After the release of EU M1 v1.4, it was decided that more guidance was required and therefore the eCTD Q&A variation document was published in December 2009. This is a useful guide for all applicants who are about to embark on an eCTD variation, and the link to this can be found visiting the EMA website.
The few obstacles encountered so far have been with path lengths, tracking tables and Member States validating submissions.
Member States were expected to accept eCTD submissions built using EU M1 v1.4 from 1 January 2010, but a few agencies had not updated their viewing software and validation tools causing the submission to fail validation. For us, no further issues have been experienced since the mandatory date of 1 July 2010. However, it is worth checking with the agency that the EU M1 v1.4 has been implemented if your submission encounters problems.
By now, vendors should have updated the publishing and validation tool and tests should have been performed and installed on your ‘live’ system. As the EU M1 v.14 is now mandatory, familiarise yourself with this latest specification before your next submission, especially if the next sequence is a variation.
Kathryn Brouder is a publishing specialist at NDA Regulatory Science Ltd. Visit: www.ndareg.com
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