New EU GMP Guide Chapter 4 on Documentation

The final Chapter 4 ("Documentation") of the EU Guideline to GMP has now been published and will come into operation on 30 June 2011. Chapter 4 has been mainly updated as a consequence of the new Annex 11 on Computerised Systems, which was published on the same day. However, other important changes were included. Here is a short summary:


The requirements apply to all forms of document media types like paper, electronic documentation, photographic media or hybrid types.

Quality Management System

The new Chapter 4 calls for a Quality Management System (QMS), where documents and media should be fully defined. As part of the QMS, an inventory of documents should be maintained. All documents establishing, controlling, monitoring and recording activities which directly or indirectly impact the quality of medicinal products should be included in the QMS.

Major types of documentation

1. Instructions (directions or requirements):

  • Specifications
  • Manufacturing Formulae, Processing, Packaging and Testing Instructions
  • Procedures
  • Protocols
  • Technical Agreements

It is pointed out, that documents containing instructions should be laid out in an orderly fashion, have unambiguous contents, be uniquely identifiable and easy to check and they should be approved, signed and dated by appropriate and authorised persons. The effective date should be defined. New are also expectations regarding the style and language of those kind of documents; these should fit with their intended use. Standard Operating Procedures (SOPs) and other working instructions for example should be written in an imperative mandatory style.

2. Records and reports:

  • Records
  • Certificates of Analysis
  • Reports

Plus the Site Master File

Retention periods

The requirements on retention periods are now given in more detail. It is still expected that batch documentation must be kept for one year after the expiry date. But also the date of the batch certification by the Qualified Person (QP) needs to be considered. The documentation needs to be kept five years after this act.

For investigational medicinal products (IMPs), the batch documentation must be kept for at least five years after the completion or formal discontinuation of the last clinical trial in which the batch was used. Other requirements which are described in additional legislation might specify even longer retention periods.

Critical documentation, including raw data (for example relating to validation or stability), which supports information in the Marketing Authorisation should be retained as long as the authorisation is valid.

Line Clearance

A formal line clearance has been introduced. Both processing instructions and packaging instructions should include documented checks to show "that the equipment and work station are clear of previous products, documents or materials not required for the planned process, and that equipment is clean and suitable for use".

Acknowledgements of new developments

As an acknowledgement to new initiatives and guidance regarding PAT or real time release, the new chapter will allow to limit batch records to reports on compliance summaries and exception/ out-of specification (OOS) data reports, if the process is validated and continuously monitored and controlled. Where robust electronic controls are in place, there may also be justification for including less information for example on reconciliation.

Activities of the Qualified Person

The role of the Qualified Person is also explained in more detail. All records should be available to the QP for review when requested. Appropriate records should routinely be provided to the QP for batch certification and a system should be in place to indicate special observations and changes to critical data. However there is no obligation implemented that the QP is obliged to review and approve (sign) all GMP-relevant documents.

More detailed SOP-list

The list of policies, procedures, protocols, reports and the associated records has been amended with the following examples:

  • Technology transfer
  • Change control
  • Investigations into deviations and non-conformances
  • Internal quality/GMP compliance audits
  • Summaries of records where appropriate (e.g. product quality review)
  • Supplier audits


It has been emphasised that logbooks are also expected for critical analytical testing equipment.

Please also see the new document. You can find a detailled electronic comparison of the new chapter 4 with the previous version in the ECA Members Area.

Wolfgang Schmitt
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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