Raising the Bar in GxP Compliance – Part 22: From Paper to Hybrid – Adapting to the New GMP Chapter 4.
Welcome to the twenty-second instalment of Raising the Bar in GxP Compliance, Rephine’s expert-led blog series for QA and regulatory professionals. In this edition, we explore the transformative revisions to EU GMP Chapter 4 on documentation. No longer confined to paper or static digital formats, documentation now encompasses hybrid systems—including audio, video, and image-based records. To stay compliant, organisations must rethink their documentation strategies through the lens of data integrity, QRM, and digital readiness. Discover how Rephine helps clients modernise their documentation practices while staying ahead of evolving regulatory expectations.
As pharmaceutical operations embrace digital transformation, documentation can no longer be confined to paper or static files.
The new GMP Chapter 4 sets a bold precedent—demanding that hybrid records be managed with the same rigour, integrity, and risk-awareness as traditional formats.
From Paper to Hybrid: Complying with the New EU GMP Chapter 4 on Documentation
The revision of EU GMP Chapter 4 – Documentation marks a significant shift in how documentation is managed, validated, and maintained across the pharmaceutical industry. With the inclusion of hybrid formats, emphasis on data governance, and deeper integration of Quality Risk Management (QRM) principles, this update demands a strategic response from regulated organisations.
Why the New Chapter 4 Matters and What Pharmaceutical Companies Must Now Ensure
The revised Chapter 4 recognises that documentation is no longer limited to paper or static digital files. The scope now includes images, audio, video, and hybrid formats. Companies are expected to ensure:
- Accuracy, integrity, legibility, and availability of all documents throughout their lifecycle
- Consistent application of QRM principles across all formats
- Robust systems to manage electronic records, signatures, and audit trails
These changes align with ongoing digitalisation and the upcoming revisions of Annex 11 and the new Annex 22.
Key Changes Introduced in the Revised GMP Chapter 4
- Expanded definition of documentation formats: Including text, audio, video, and image-based records.
- Lifecycle governance: Records must remain complete, readable, and retrievable for their entire retention period.
- Risk-based documentation control: QRM must be embedded in how documents are created, reviewed, stored, and archived.
- Alignment with data integrity principles: ALCOA+ still applies – now to more formats and technologies.
- Electronic signatures and records: Stronger expectations for authentication, authorisation, and access control.
What This Means for GxP Documentation and Quality Systems
Pharma and biotech companies will need to:
- Review and update SOPs to reflect hybrid and digital documentation practices
- Implement or validate Document Management Systems (DMS) capable of handling diverse file types securely
- Ensure data integrity and traceability across digital repositories
- Train staff in recognising and managing hybrid documentation risks
Supporting Compliance with Hybrid Documentation – How Rephine Can Help
At Rephine, we support clients in achieving compliance with the new Chapter 4 through:
✅ Gap assessments of current documentation practices.
✅ Digital documentation strategy and QRM integration.
✅ Support with validation of document management systems.
✅ Consulting on the implementation of data integrity controls for hybrid formats.
✅ Training and awareness programmes for quality and operational staff.
Prepare Now – Public Consultation Closes 7 October 2025
📅 The public consultation is open until 7 October 2025. Rephine is actively reviewing and preparing its contribution.
This article is part of Rephine’s dedicated content series on the EMA’s 2025 GMP updates — designed to help clients navigate these changes confidently.
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.