EU GMP Guidelines: Upcoming Updates by the European Commission

The manufacture of medicinal products is subject to strict regulations to ensure the quality and efficacy of the products. In addition to general requirements under the German Medicinal Products Act, particularly the requirement for a manufacturing authorisation, quality assurance in the manufacture of medicinal products is governed by the Good Manufacturing Practice Guidelines (“GMP Guidelines”) of the European Commission. 

The GMP Guidelines, which have been in place for many years, are currently being revised by the European Commission to align them with international best practices and technological developments in the industry. The revision is intended to provide users of the GMP Guidelines with clear requirements for dealing with new technological procedures in pharmaceutical manufacturing in order to create legal certainty and ensure the quality and availability of medicinal products.

Stakeholders can comment on the proposed changes in two consultations. The adjustments particularly concern the pharmaceutical quality system and the use of artificial intelligence. 

Update of Chapter 1 of the GMP Guidelines: Update of the requirements for Pharmaceutical Quality System

Part of the revision of the GMP Guidelines concerns the pharmaceutical quality system to be maintained by manufacturers of medicinal products, governed by Chapter 1 of the GMP Guidelines, which has been in operation since 31 January 2013. The revision is intended to reflect the updated ICH Guidelines on Quality Risk Management ICH Q9(R1) and aims to reduce variability in quality outcomes. 

The proposed changes focus on the following aspects:

• Embedding risk-based decision-making and emphasising scientific justification and proportionality in risk assessment.
• Emphasising the proactive identification of manufacturing risks to avoid shortages and mitigate vulnerabilities in the supply chain.
• Clarifying the requirements for the review of product quality, in particular with regard to product groupings and situations in which only a limited number of batches were manufactured during the review period. 

Comments on the preliminary draft may be issued until 3 December 2025.

Update of Chapter 4 of the GMP Guidelines: Update of the requirements on Documentation, Computerised Systems and the use of Artificial Intelligence

In a parallel process, the European Commission is working on amendments to Chapter 4 (Documentation), Annex 11 (Computerised Systems), as well as the introduction of a new Annex 22 on Artificial Intelligence (“AI”). 

The updating of these parts of the GMP Guidelines reflects the progress of digital technologies, in particular the increasing implementation of AI systems in the context of pharmaceutical manufacturing. The changes aim to support innovation in pharmaceutical manufacturing and harmonise legal requirements. 

Update of Chapter 4 of the GMP Guidelines – Documentation

The preliminary draft of the new Chapter 4 of the GMP Guidelines emphasises the importance of documentation for compliance with GMP requirements and supports the use of new technologies, hybrid solutions and new services for document management. Risk management principles are integrated into the data management system to ensure the accuracy, integrity, availability and readability of documents in all formats. The documentation must remain complete and legible throughout its entire life cycle, regardless of its format. 

The requirements for the management of electronic records, signatures and data integrity are also clarified. 

Update of Annex 11 of the GMP Guidelines – Computerised Systems

The preliminary draft of Annex 11 of the GMP Guidelines tightens the requirements for the management of computerised systems and prescribes the comprehensive application of the principles of quality risk management in all phases. 

In particular, stricter provisions are envisaged for the following areas:

• Definition and ongoing maintenance of system requirements.
• Monitoring of suppliers and external service providers.
• Controls relating to ensuring data integrity, audit trails, electronic signatures and system security. 

New Annex 22 of the GMP Guidelines – Artificial Intelligence

A new Annex 22 of the GMP Guidelines is intended to regulate the use of AI in the manufacture of active substances and medicinal products, particularly insofar as it concerns the selection, training and validation of AI models. 

The new Annex 22 is intended to cover, in particular, the following quality aspects of AI systems:

Definition and documentation of the intended use of the AI model used. 

• Establishment of test metrics and acceptance criteria to monitor the performance of the AI model.
• Appropriate selection of model training data.
• Monitoring of AI systems. 

The upcoming changes to the GMP Guidelines are a necessary step to regulate the rapid technological change in pharmaceutical manufacturing from a quality perspective. How users will receive the proposed changes to the GMP Guidelines remains to be seen. Changes to the drafts discussed may therefore occur and are also to be expected in the course of the consultation process. Nevertheless, users of the GMP Guidelines should already familiarise themselves intensively with the planned changes in order to prepare their processes for the transition at an early stage.