EMA: Chapter 4 - new Requirements for GMP Documentation?

Since 7 July 2025, three new draft guidance documents have been available on the EMA website, which can be commented on until 7 October 2025. The documents were drafted by the EMA GMP/GDP Inspectors Working Group (IWG) together with the PIC/S and are to be published as final versions from 2026. These include Chapter 4, Annex 11 and Annex 22.  Following you will find an initial assessment of Chapter 4.

Chapter 4

The draft of Chapter 4 (Documentation) of the EU GMP Guideline published on 7 July 2025 is to replace the 2011 version. It has been revised due to numerous new technologies. The working group has developed a very comprehensive document, which has grown from 9 to 17 pages and thus follows the trend we have been observing for years to achieve a higher level of detail. An initial comparison shows that around 50% of the document has been completely rewritten. The remainder has been heavily revised, i.e. Chapter 4 must be dealt with in depth, as it is intended to regulate all documentation requirements in the pharmaceutical environment, regardless of whether this is kept on paper, electronically or in hybrid form within the company.

As expected, the chapter defines a "life cycle approach" for the documentation, which is to be set up taking data governance into account. In addition, the assessment of potential risks in accordance with ICH Q9 is included throughout. In this context, the increasing outsourcing of GMP activities to service providers is also considered, including the archiving of documentation by these companies.

According to the draft of chapter 4, the pharmaceutical quality management system (PQS) is expected to regulate all of these activities, taking patient safety into account. There is also a reference to artificial intelligence (4.23 and see draft Annex 22), if this should play a role in batch release.

Chapter 4, which is very extensive, also contains the descriptions of the various master document types used in pharmaceutical production and control, which have been adopted from the previous version but are now much more detailed and expanded. In addition, the control of the numbered form sets of the test protocols (4.62., blank forms), which has not yet been implemented in practice in the quality control of numerous companies, has been included. The additional labour required for this is likely to lead to an increase in quality control costs without contributing to a measurable improvement in quality.

The retention periods for GMP documentation, which are not clearly defined in many companies, are clearly defined in sections 4.76. to 4.79., also with regard to clinical trial samples with reference to ATMPs.

The importance of the specially executed signature in the GMP area is discussed in detail. Hybrid systems should be avoided for electronic signatures. In the case of signatures that exist in parallel on paper and in electronic form (4.70.), it is necessary to define which signature is the relevant one for regulatory purposes. The permanence of the electronic signature over the entire lifetime of a document is also mentioned in this context.

The ALCOA++ principles of data integrity for static and dynamic data, which can be found in numerous guidelines, are of course also mentioned here. However, the definition of raw data, which has not yet been clearly described in the GMP sector, is only listed in the glossary and is likely to lead to discussions. There you will also find clear definitions for True Copy, Certified Copy and Verified Copy. The Official Copy is mentioned in the text, but not defined. A Controlled Copy, on the other hand, is no longer listed.

Conclusion

To summarise, the draft of the new Chapter 4 answers many questions with regard to modern technologies, outsourcing and data integrity, but also includes increased requirements for GMP documentation. Comments regarding this draft can be submitted until 7 October 2025 on the EMA website in the "Consultations" section. The new draft of Chapter 4 can also be found there.