EU GMP Annex 11 and Chapter 4 Revision: What the 2025 Draft Changes

Every QA head we talk to has heard that "Annex 11 is being rewritten". Fewer have read the draft, and some assume it is already law. It is not. This article sets out what was published, where it stands today, what the draft text actually says, and what a laboratory or QA unit can sensibly do before anything is final. Everything described below as changing is draft text, not in force.

What was published, and where it stands on 11 November 2026

On 7 July 2025 the European Commission and PIC/S opened a joint stakeholder consultation on three documents: a revised Chapter 4 (Documentation), a revised Annex 11 (Computerised Systems) and a new Annex 22 (Artificial Intelligence). The drafts were prepared by the EMA GMDP Inspectors Working Group in cooperation with PIC/S. The consultation ran until 7 October 2025, 23:59 CEST (European Commission consultation page; PIC/S announcement).

As of today, this is what we could confirm on the primary pages:

• The Commission's consultation page says the response period has ended. It publishes no summary of responses and no final text, only links to the three drafts.
• The EudraLex Volume 4 page still lists Chapter 4 and Annex 11 as the January 2011 versions, and has no entry for Annex 22 (EudraLex Volume 4).
• The PIC/S publications page lists all three documents in its drafts section, dated 7 July 2025 (PIC/S publications, drafts).

Our conclusion: still draft. We did not find an adoption date on these pages, and we are not going to guess one. Check the EudraLex page before you rely on anything in this article, because that is where a final text would appear first.

Annex 11: what the draft changes

The 2011 Annex 11 is short. The draft is a different animal, built around the same ideas but with far more operational detail. Its sections are: Scope, Principles, Pharmaceutical Quality System, Risk Management, Personnel and Training, System Requirements, Supplier and Service Management, Alarms, Qualification and Validation, Handling of Data, Identity and Access Management, Audit Trails, Electronic Signatures, Periodic Review, Security, Backup and Archiving (draft Annex 11).

Scope and principles

The draft applies to "all types of computerised systems used in the manufacturing of medicinal products and active substances". Its principles state lifecycle validation, quality risk management, the possibility of alternative practices proven to give the same or higher control, data integrity framed by ALCOA+, and that the regulated user remains fully responsible for outsourced activities. It also keeps the old no-risk-increase rule when a system replaces a manual operation.

Pharmaceutical quality system

Section 3 is new. It says the quality system should cover all computerised systems and the people involved, with deviations investigated and CAPA effectiveness verified, controlled change including configuration, hardware and platform, internal audits, management review of performance indicators and senior management oversight of the state of control.

Cloud and service providers

The draft says requirements apply whether a system is developed in-house, bought off the shelf, or "provided as-a-service" (6.1). Where a vendor supplies the requirement specification for a SaaS product, the regulated user must review and approve it and take ownership of the document covering the implemented version (6.3). Section 7 adds that relying on a vendor's qualification does not change the user's responsibility (7.1), that an audit or thorough assessment should follow risk (7.2), and that the user must oversee service providers against SLAs and KPIs (7.3). Contracts (7.5) should cover support during regulatory inspections, an exit strategy by which the user retains control of its data, and the user's chance to test new versions before release.

System requirements and validation

The draft wants documented, maintained requirements that reflect the implemented system (2.5, 6.4), a controlled configuration specification (6.6), and traceability from requirements through design to test cases. Section 9 points back to Annex 15 principles and says test cases that cannot be traced to a requirement "do not meet the requirements" of qualification and validation (9.5). It also names where to focus testing: access privileges, release of products and results, calculations, audit trails, error handling, alarms, boundary and negative tests, interfaces and restore from backup (9.6). A new alarm section (8) adds alarm limits, acknowledgement by authorised users with a reason, an alarm log that users cannot edit, and periodic review of alarm logs.

Audit-trail review expectations

This is the largest shift for laboratories. Today's clause 9 says audit trails should be "regularly reviewed". The draft spells out what that means:

• The audit trail logs all manual user interactions and records who, what (old and new value), when, and the reason, with the reason prompted automatically (12.1, 12.2).
• It is enabled and locked at all times, and nobody can edit it. If settings or system time can be changed, that change is itself logged and limited to an administrator not involved in GMP activities (12.3).
• Review follows a documented procedure for the system or type of system, stating who reviews what and when (12.5).
• Review is done by people not directly involved in the activity (12.6), is targeted and risk-based, with "a key element" being to verify the reason for a change (12.7), and takes place before batch release unless a later check can be justified (12.8).
• Reviews with direct impact on release must be available to the QP at release (12.10), and a complete searchable electronic copy must be obtainable; "flat and locked files are not acceptable" (12.9).

Identity, access and electronic signatures

Identity and Access Management is a new section: unique personal accounts, with shared accounts permitted only if read-only (11.1); timely granting and revocation (11.2); authentication that rules out a token or card another person could use (11.3); multifactor authentication for remote access to critical systems (11.6); lockout after failed attempts (11.7); inactivity logout (11.8); an access log (11.9); segregation of duties and least privilege (11.10); and documented recurrent access reviews (11.11).

For signatures, the draft requires full re-authentication when signing (13.3), a visible meaning such as reviewer or approver (13.5), a manifestation showing full name, username, role, meaning and date and time (13.6), and a permanent link to the record such that a later change either is blocked or makes the record appear unsigned (13.8). A wet-ink signature on an electronic record (a hybrid solution) must make any later change to the record invalidate the signature, for example with a checksum printed on the signature page (13.9).

Data handling, periodic review, security, backup, archiving

Section 10 says critical data should move between systems through validated interfaces rather than manual transcription where possible, and that migration needs a validated process. Periodic review (14) lists what to examine: changes since last review including undocumented ones, audit trail and access reviews, incidents, vendor contracts, backup and restore adequacy, and archival, with a final review when a system leaves service. Security (15) is now concrete: patching, supported platforms, controlled USB use, segmentation, firewall review, penetration testing for internet-facing critical systems, and a disaster recovery plan with a Recovery Time Objective. Backup (16) requires physical and logical separation and documented restore tests, and archiving (17) requires protection from change after process completion, integrity checks on moves, and retrieval in a searchable format.

One thing to note: the draft has no standalone sections called incident management, batch release or business continuity, which the current text does. The subject matter is spread across deviations and CAPA (3.1), disaster recovery (15.7) and QP availability of audit trail reviews (12.10).

Chapter 4: what the draft changes

The draft Chapter 4 is much longer, numbering paragraphs 4.1 to 4.85 (draft Chapter 4). The new material is mostly about data.

Data governance

A new section requires a data governance system, integral to the quality system, whatever the medium, covering the whole data lifecycle from creation through processing, verification, decision making, retention and controlled destruction (4.10 to 4.12). It is risk-based on data criticality and data risk (4.13), addresses data ownership (4.15), and includes periodic review of service providers' data management policies (4.18). Risk management gets its own section, and 4.22 says electronic data generation must be in the qualification and validation scope under Annex 11.

Hybrid records and documentation lifecycle

Hybrid systems get a section (4.82 to 4.85): they must be clearly defined, each element validated and controlled, the interface between manual and computerised parts controlled, and there must be procedures for reviewing, approving and archiving the electronic and paper data together. The draft goes further on signatures: "if records exist electronically such records should be signed electronically. The use of a hybrid system should be avoided" (4.70). A signature policy is required (4.67). The draft also adds a table of ALCOA++ attributes (4.63) and controls for paper raw data such as issuing bound notebooks and numbered forms (4.62). Records on hosted services remain the regulated user's responsibility to understand, approve and justify against an SLA (4.76), and disposal of records needs a documented process (4.79).

Automatic means and AI in documentation

Paragraphs 4.24 and 4.25 say accountability for records produced or processed with artificial intelligence or other automatic means rests with the regulated user, and that such support belongs in the quality system whether on premise or hosted.

Annex 22: AI in critical GMP use

The draft is narrow on purpose (draft Annex 22). It applies to machine learning models used in critical applications with direct impact on patient safety, product quality or data integrity. It covers static models and deterministic outputs only. The draft says dynamic models that keep learning during use, and models with probabilistic outputs, "should not be used in critical GMP applications", and the same applies to generative AI and large language models. Where generative AI or LLMs are used in non-critical GMP work, the draft expects a qualified human in the loop.

For models that are in scope, the draft asks for a described intended use approved by a process subject matter expert; test metrics and acceptance criteria defined before testing, at least as high as the process being replaced (4.3); representative, adequately sized and verified test data; independence between test data and anyone who trained the model (section 6); a test plan; recorded feature attribution for explainability (8.1); confidence scores, and consideration of an "undecided" outcome (9); and, in operation, change control, configuration control, performance monitoring and input drift monitoring (section 10).

What labs and QA should do now

Do not wait for a final text to fix things the current Annex 11 already expects. Work in this order:

1. Run a gap assessment of your top critical systems against the draft, and label every result "against 2025 draft". Prioritise audit trail review, access review and supplier contracts, because they are the largest increases.
2. Write or tighten the audit trail review procedure: reviewer independence, risk-based scope, timing relative to batch release.
3. Reconcile user accounts against leavers and role changes, remove shared logins, and schedule documented access reviews.
4. Check SaaS and hosted-service contracts for inspection support, exit strategy and version testing rights.
5. List your hybrid records. For each, decide which signature is the regulated one and what proves the paper and electronic parts belong together.
6. Define raw data for every electronic system in writing.
7. Inventory anything using machine learning, and mark the critical ones.

What does not change

The principle that validated systems stay in a validated state, risk-based decisions with documented rationale, the regulated user's accountability for outsourced work, and QP certification as the release all carry over. The draft Chapter 4 repeats the current batch documentation retention rule: one year after expiry or at least five years after QP certification, whichever is longer (4.77), and keeps the note that where a validated process is continuously monitored and controlled, automatically generated reports may be limited to compliance summaries and exception or out-of-specification reports (note to 4.36). Until the Commission publishes final texts, the 2011 versions are what EudraLex lists.

Where software helps

We sell CORPEX software that sits inside these requirements: CORPEX LIMS for the laboratory, Corpex-eQMS for quality records and Corpex-EBR for batch records, each a separate product. We do not claim conformance to a draft. We can say that the eQMS writes every GMP change to an append-only, hash-chained audit trail with user, time, old and new value and reason, that CORPEX LIMS keeps a hash-chained audit trail, and that electronic signatures in Corpex-EBR send the signer through the identity provider to re-authenticate. Review, procedures and validation remain yours.

Frequently Asked Questions

Is the revised Annex 11 in force?

No. The revised Annex 11, revised Chapter 4 and new Annex 22 were published as drafts on 7 July 2025 and the consultation closed on 7 October 2025. As of 11 November 2026, the EudraLex Volume 4 page still lists the January 2011 Annex 11 and Chapter 4 and has no Annex 22.

What is Annex 22?

Annex 22 is a draft new EU GMP annex on artificial intelligence. It covers static, deterministic machine learning models used in critical GMP applications, and says dynamic, probabilistic, generative AI and large language models should not be used in critical GMP applications.

Does the draft change audit trail review?

Yes. The draft asks for a documented review procedure, review by people not involved in the activity, risk-based scope, review before batch release unless a later check is justified, and availability of relevant reviews to the QP at release.

Does the draft cover cloud systems?

Yes. It applies to systems provided as a service, requires the user to approve the requirement specification, oversee providers through SLAs and KPIs, and agree contract terms including inspection support and an exit strategy for data.

Sources

• PIC/S and EMA, draft revised Annex 11: Computerised Systems (7 July 2025)
• Draft revised Chapter 4: Documentation (7 July 2025)
• Draft new Annex 22: Artificial Intelligence (7 July 2025)
• European Commission, stakeholder consultation page
• PIC/S, joint stakeholders consultation
• European Commission, EudraLex Volume 4
• PIC/S publications, drafts