Raising the Bar in GxP Compliance – Part 27: Preparing for Annex 22 on AI & Machine Learning in Pharma Manufacturing.
Welcome to the twenty-seventh instalment of Raising the Bar in GxP Compliance, Rephine’s expert-led blog series for QA and regulatory professionals. In this edition, we delve into the EMA’s draft Annex 22 — the first regulatory framework for the use of artificial intelligence and machine learning in GxP manufacturing. As AI becomes increasingly embedded in deviation detection, process optimisation, and automated decision-making, regulators are setting clear expectations for validation, governance, and human oversight. With public consultation open until October 2025, now is the time for manufacturers to map their AI use, strengthen governance strategies, and ensure their systems are inspection-ready. Discover how Rephine helps organisations align with Annex 22 while unlocking the benefits of AI innovation safely and compliantly.
AI is no longer a futuristic concept in pharma manufacturing — it’s here, and regulators are taking notice.
The EMA’s draft Annex 22 signals a shift toward structured, transparent, and risk-based control of artificial intelligence in GxP environments. From model validation to human oversight, companies must be ready to demonstrate not just technical capability, but regulatory maturity.
The introduction of Annex 22 – Artificial Intelligence in EMA’s 2025 draft guidance marks a historic step in regulating the use of AI and machine learning (ML) within the manufacturing of medicines and active substances. For the first time, the use of AI in GxP environments is framed within clear regulatory expectations.
Why EMA Annex 22 is a Game-Changer for AI in Pharma Manufacturing
As AI becomes more prevalent in automated decision-making, deviation detection, and process optimisation, its impact on product quality and patient safety can no longer be left to ad hoc governance. Annex 22 sets the tone for future oversight by requiring companies to:
- Define the intended use of AI models in the manufacturing process
- Establish documented performance metrics and acceptance criteria
- Validate the model with high-quality training data
- Ensure human oversight, particularly where decisions impact GxP outcomes
- Maintain control over model evolution and change management
Annex 22 Compliance Requirements for AI and Machine Learning in GxP
- Training and test data quality must be representative, curated, and documented
- AI model validation must align with its intended use, performance thresholds, and risk level
- Continuous performance monitoring and alerts for model drift or bias are required
- Change control procedures must cover updates, re-training, and versioning
- Human-in-the-loop approaches must be defined for review, override, or escalation
How Pharma Manufacturers Can Prepare for Annex 22 and AI Governance
- Map current or planned uses of AI in manufacturing and identify those in GxP scope
- Define governance and SOPs for model lifecycle, validation, and monitoring
- Ensure transparency and explainability of AI-based decisions
- Establish multidisciplinary review teams (QA, data science, operations)
Partnering with Rephine for Annex 22 AI Compliance and Inspection Readiness
Rephine works with pharma and biotech clients to:
✅ Review AI-based processes and assess GxP relevance
✅ Define intended use and documentation frameworks for AI models
✅ Design risk-based validation and monitoring strategies
✅ Support inspection readiness and alignment with Annex 22
📅 EMA consultation closes 7 October 2025. This article is part of Rephine’s strategic content series on 2025 EMA draft guideline revisions.
Dr. Eduard Cayón
CSO (Chief Scientific Officer)
About the Author:
Dr. Eduard Cayón is the Chief Scientific Officer (CSO) at Rephine, a global leader in GxP compliance and quality assurance.
We don’t just deliver audits or consultancy services — we partner with clients at every stage of their quality journey, offering end-to-end solutions that empower confidence and compliance.
With over 25 years of experience, Rephine has built an enviable reputation as the gold standard in the industry operating from four primary locations: Stevenage in the UK, Barcelona in Spain, India, and Shanghai in China.
Dr. Cayón, who holds a Ph.D. in Organic Chemistry, is a deeply experienced pharmaceutical industry consultant and auditor.
He is dedicated to supporting pharmaceutical, biotech, and medical device companies in meeting the highest standards of manufacturing and supply chain integrity.