EU M1 Changes Require Action from Publishing Vendors

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Europe recently made some fairly significant changes to eCTD Module 1 Guidance. You can see and download the specification, release notes, examples, and overall package at: Look for an update from your publishing vendor as DTD and publishing tool changes are needed to support the new spec – and remember that EMEA has said that they require compliance by the end of 2008, so plan now for system updates and any validation impact they may have.

The following changes were determined by comparing the new EU Module 1 Specification Version 1.3 (May 2008) against the previous approved version 1.2.1 (October 2006).

Changes to Main Body

  • Acceptability of XML for cover letter, variation form and renewal form.
    Inability to accept digital signatures.
  • Instruction not to use placeholders for content sections that are absent, but to discuss in summary documents instead.
  • Confirmation that files in M1 can be referred to in index.xml and files in M2-M5 can be referred to in eu-regional.xml.
  • Additional guidance on the envelope, covering the “eu-envelope” values of “emea“, “common” and specific member state values. (See the section Envelope.)
  • Additional guidance on directory structure. The recommended directory structure for the use of country and language identifiers is described in Appendix 2. In general, Modules 1.0, 1.2, 1.3.2, 1.3.3, 1.3.4, 1.3.5, ‘Additional Data’ and ‘Responses’ have country subdirectories. Module 1.3.1 (Product Information) has both country and language subdirectories. (see the section Directory / File Structure.)
  • Additional guidance on node extensions (finally). Discusses use, placement and nesting. (See the section Node Extensions.)

Changes to Appendix 1: Envelope Element Description
Changes to agency element – has been changed from agency-name, mandatory, repeatable to an agency parent element and code, with the code mandatory and unique.

  • Addition of new submission types (metadata valid values).
  • Removal of the Country element under Related Sequence.
  • Updates to guidance and examples around Related Sequences.
  • Changes to Appendix 2: Directory / File Structure for Module 1
  • Note that the operation attribute for the eu.regional.xml should always be set to ‘new’.
  • Instructions on the placement of a “tracking table” (this is within the context of the Cover Letter). (See “MRP/DCP Tracking Table Description”, Version 0.1, May 2008.)
  • Additional/clarified guidance on naming of labels for one language or multiple languages.
  • Addition of element for 1.10 Information relating to Paediatrics.
  • Instruction that “Additional Data” should only be used for information required for National, MR and Decentralised Procedures and not being applicable for the Centralised Procedure.
  • Recommendation against the use of custom stylesheets.

Changes to Appendix 2.1: Destination Codes

  • New destination (country) code Common
  • Removed * stating that Bulgarian and Romanian languages should not be used before those countries join the EU.

What Does It Mean?

Some of these changes will be taken care of by your eCTD tool or in how it is used by your publishers. Others may require changes in your processes

  • If you have been using placeholder documents, you will need to update your process to discuss “missing” documents in summaries (this is not really new – the authorities have been stating this position in meetings and presentations for some time)
  • You may want to review your use of node extensions in organizing your clinical study documents
  • You will need to introduce the “tracking table” for MRP/DCP
  • Ensure that you are not using the “Additional Data” section for the Centralised procedure
  • Review your use of metadata since new values and changes have been introduced
  • Ensure that your procedures are in place for creating, reviewing and approving documents 1.10 Information relating to Paediatrics.

With the recent clarifications to the use of the Related Sequence in both US and EU, now is also a good time to make sure your team understands how to use this critical piece of metadata.

Author: GS

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