Stakeholders’ Consultation on GMP Annex 11, Chapter 4, and New Annex 22

In March 2025, the European Medicines Agency (EMA) published a three-year work plan (2025–2027) for the Good Manufacturing and Distribution Practice (GMDP) Inspectors Working Group (IWG), focusing on the Network Strategy and Regulatory Science Strategy (RSS) goals. The work plan emphasized the importance of supply chain integrity and resilience, product quality, and the potential impact of new manufacturing technologies on the supply chain(1). The overall objectives of the plan included:

• Analyze the possible implications of new manufacturing technologies to regulate the new supply chains needed
• Enhance inspector capacity building at the European Union and international levels
• Enhance traceability, oversight, and security in the human/veterinary medicine supply chain
• Encourage supply chain resilience and review long-term risks resulting from dependency on a limited number of manufacturers and sites

• Reinforce the responsibility for product quality by harmonising and reinforcing guidance (1).

On 7 July 2025, the GMDP-Inspectors Working Group, in cooperation with the Pharmaceutical Inspection Co-operation Scheme (PIC/S), launched a public consultation regarding the revision of the EU’s good manufacturing practice (GMP) guidelines, EudraLex, Annex 11 and Chapter 4, along with the introduction of a dedicated Annex 22 on artificial intelligence (AI) (2). The revision of Chapter 4 and Annex 11 will expand the scope of documentation requirements and raise the bar on digital system validation and oversight. Whilst the addition of Annex 22 sets clear boundaries for the safe and acceptable use of AI and machine learning (ML) in a regulated GMP environment, it will help to ensure regulatory harmonization in the manufacturing of medicines (3).

Revision of Chapter 4

The revised Chapter 4 includes changes that emphasize the importance of documentation in GMP compliance and support the adoption of new technologies, hybrid solutions, and services for managing documentation (4). Risk-management principles are now central and integrated into the data governance system to ensure the accuracy, integrity, availability, and readability of documents in all formats. All documentation, whether in text, image, video, or audio form, must remain complete and legible throughout its lifecycle. The guideline also clarifies the requirements for managing electronic records, signatures, and data integrity, and aligns with the recent revision of Annex 11.

Revision of Annex 11

The revised Annex 11 establishes improved requirements for managing the entire lifecycle of computerized systems, requiring that quality risk management (QRM) principles be thoroughly applied at all stages to ensure product quality, patient safety, and data integrity. The updated provisions strengthen obligations related to defining and continuously maintaining system requirements, as well as overseeing suppliers and external service providers (5). Additionally, the Annex enhances controls for ensuring data integrity, audit trails, electronic signatures, system security, as well as backup and archiving.

New Annex 22

The new annex on AI sets requirements for using AI/ML in manufacturing active substances and medicinal products (6). It details how to select, train, and validate AI models and places emphasis on defining the intended use of the model, establishing performance metrics, ensuring the quality of training data, and managing test data. Annex 22 requires ongoing oversight of AI systems, including change control, performance monitoring, and procedures for human review when needed. The document does not apply to generative AI and large language models, and these models should not be used in critical GMP applications.

Impact of GMP revisions on pharma

By 2026, the updates to Chapter 4 and Annex 11, along with the introduction of Annex 22, will bring about a significant transformation in European GMP regulations for the pharmaceutical industry. These revisions could enforce tighter controls and redefine standards, setting the stage for a new era in GMP compliance.

In response to these changes, pharmaceutical companies will need to review their documentation processes and platforms and reevaluate and validate their legacy systems (such as quality control, laboratory information management systems, or commercial off-the-shelf applications) to ensure compliance with the updated traceability and audit trail requirements. Overall, organizations will need to plan for system lifecycle governance and supplier management. If activities are outsourced, they must ensure regulatory accountability remains in-house. Additionally, companies deploying AI technologies in a GMP environment will need to develop robust internal capabilities to ensure data science governance and validate AI models (3).

The pharmaceutical industry must act swiftly to align with the evolving regulatory expectations. The stakeholder consultation closes on October 7, 2025, so there is still time to submit opinions on the three documents that will shape the future of GMP in Europe (7–9).

References

1. EMA. The 3-Year Work Plan for the Inspectors Working Group 2025-2027. EC.europa.eu. 27 Mar 2025.
2. EC. Stakeholders’ Consultation on EudraLex Volume 4 - Good Manufacturing Practice Guidelines: Chapter 4, Annex 11 and New Annex 22. EC.europa.eu. 7 July 2025.
3. Johanning, E. and Damgaard, P. Preparing for EMA's 20226 Good Manufacturing Practice (GMP) Revisions: Chapter 4, Annex 11 & Annex 22.Epista Life Science. July 2025.
4. EC. Chapter 4: Documentation. EC.europa.eu. 7 July 2025.
5. EC. Annex 11: Computerized Systems. EC.europa.eu. 7 July 2025.
6. EC. Annex 22: Artificial Intelligence.EC.europa.eu. 7 July 2025.
7. EC. Revision of Chapter 4. EC.europa.eu.
8. EC. Revision of Annex 11. EC.europa.eu.
9. EC. New Annex 22. EC.europa.eu.

About the author

Cheryl Barton is founder and director of PharmaVision, Pharmavision.co.uk.