What is EudraLex Volume 4, and how are the EU GMP guidelines organised?

1Where Volume 4 sits in EU law.

EudraLex is the Commission’s publication “The rules governing medicinal products in the European Union”. The legislation itself is in Volume 1 for human medicines and Volume 5 for veterinary medicines; the other volumes hold guidelines. Volume 4 is the GMP guidelines.¹

The binding principles are in law. Article 47 of Directive 2001/83/EC empowers the Commission to set the principles of GMP and to publish detailed guidelines in line with them.² For medicines for human use those principles are now in Commission Directive (EU) 2017/1572, which replaced Directive 2003/94/EC; investigational medicines have their own Delegated Regulation (EU) 2017/1569.³ Directive 2017/1572 says manufacturers and competent authorities “shall take into account” the detailed guidelines when interpreting the principles.⁴ The guide is used to assess applications for manufacturing authorisations and as a basis for inspections, and it recognises that other methods can achieve the same principles of quality management.⁵

Veterinary medicines now have their own GMP rules. The Commission notes that Volume 4 applies to them only until 15 July 2026; Implementing Regulation (EU) 2025/2091 has set veterinary GMP since 16 July 2026.¹³

2How the guide is organised.

The chapters of Part I, with the dates each came into operation, are these.³

3The annexes people look up most.

The Commission’s Volume 4 page lists each annex with its status.³ These are the ones most often looked up.

The other current annexes cover radiopharmaceuticals (3), medicinal gases (6), herbal products (7), sampling of starting and packaging materials (8), liquids, creams and ointments (9), pressurised metered dose inhalers (10), ionising radiation (12) and products derived from human blood or plasma (14).³ Gaps in the numbering are not current annexes. Annex 18, for example, was replaced in the October 2005 restructuring that created Part II.⁵

4What is changing.

From 7 July to 7 October 2025 the Commission consulted on a revised Chapter 4 on documentation, a revised Annex 11 and a new Annex 22 on artificial intelligence. The EMA GMP/GDP Inspectors Working Group drafted all three in cooperation with PIC/S. The revised Annex 11 applies quality risk management throughout a system’s lifecycle and strengthens controls on data integrity, audit trails, electronic signatures and security. Annex 22 sets requirements for selecting, training and validating AI models used in manufacturing.⁷ They are drafts: the Volume 4 page still lists Chapter 4 and Annex 11 at their January 2011 versions.³

5Who publishes what.

The European Commission publishes the guidelines. EMA coordinates GMP inspections for centrally authorised medicines and harmonisation across the EU, and its GMP/GDP Inspectors Working Group interprets the guidelines in published questions and answers. National competent authorities inspect the sites on their territory.⁸ The PIC/S GMP Guide is developed in parallel with the EU guide, and PIC/S describes the two as “practically identical”.⁹

Two other GMP guides sit alongside Volume 4. WHO publishes its own GMP main principles, in Annex 2 of Technical Report Series 986 (2014), as the standard for the WHO Certification Scheme and a basis for inspections; it calls them “general guides” that may be adapted.¹⁰ In the UK, the MHRA lists its Orange Guide, Rules and Guidance for Pharmaceutical Manufacturers and Distributors (2022), alongside Volume 4 as GMP guidance.¹¹

6How it runs in Seal.

Seal’s quality management covers deviations, CAPA, change control, documents, training, audits, suppliers, complaints and risk, with workflows configured for the product and jurisdiction. A corrective action can be released as a controlled change to the workflow itself, with its own verification.

Each record keeps its audit history and electronic signatures, with controls to support EU GMP Annex 11 and 21 CFR Part 11. Regulatory and validation explains how requirements, configuration, verification and change control travel with every change, and how Neil fits the draft Annex 22: Neil is not used in GMP execution, and helps set up configuration that your team verifies and releases under change control.