Revision of Chapter 4 - Documentation
The revised Chapter 4 incorporates changes which highlight the importance of documentation in GMP compliance and support the use of new technologies, hybrid solutions and new services in the management of documentation. Risk-management principles are now central and integrated within the data governance system to ensure the accuracy, integrity, availability and legibility of documents across all formats, whether paper, digital or hybrid.
All documentation, whether in text, image, video or audio form, must remain complete and readable throughout its lifecycle. The guideline also clarifies the requirements for the management of electronic records, signatures and data integrity while ensuring consistency with the concurrent revision of Annex 11.
To view the draft, see: https://health.ec.europa.eu/document/download/fa336a6e-753b-46fc-b53b-9178bacd8878_en?filename=mp_vol4_chap4_consultation_guideline_en.pdf
Revision to Annex 11 - computerised systems
The revised Annex 11 establishes enhanced requirements for the lifecycle management of computerised systems, mandating that Quality Risk Management principles be comprehensively applied during all steps. The updated provisions reinforce obligations concerning the definition and ongoing maintenance of system requirements and the oversight of suppliers and external service providers. Furthermore, the Annex strengthens controls related to the assurance of data integrity, audit trails, electronic signatures and system security.
To view the draft, see: https://health.ec.europa.eu/document/download/40231f18-e564-4043-94de-c031f813d38b_en?filename=mp_vol4_chap4_annex11_consultation_guideline_en.pdf
New Annex 22
The new annex on Artificial Intelligence (AI) establishes requirements for the use of AI and machine learning in the manufacturing of active substances and medicinal products. It sets up requirements for the selection, training and validation of AI models.
Emphasis is made on the definition of the intended use of the model, the establishment of performance metrics, the quality of model training data and the management and processing of test data. Annex 22 foresees a continuous oversight of AI systems, including change control, model performance monitoring and procedures for human review when necessary.
These three documents aim to provide a comprehensive and robust framework that supports the implementation of IT in pharma manufacturing, while safeguarding product quality and patient safety.
To view the draft, see: https://health.ec.europa.eu/document/download/5f38a92d-bb8e-4264-8898-ea076e926db6_en?filename=mp_vol4_chap4_annex22_consultation_guideline_en.pdf
The European Pharmacopoeia (Ph. Eur.) is updating its guidance on glass containers for pharmaceutical use (Chapter 3.2.1):
The draft can be accessed via Pharmeuropa (requires registration).
The European Pharmacopeia is updating its chapter for the quality control of vaccines. The chapter is: ‘5.2.14. Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines’.
The changes relate to safety tests:
‘The example on the substitution of animal tests for extraneous agent detection by novel molecular methods has been updated in order to: i) focus specifically on high-throughput sequencing; and ii) reflect current approaches for substitution, in line with ICH Q5A(R2) (Guideline on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin); a reference to the new general chapter 2.6.41. High-throughput sequencing for the detection of viral extraneous agents (to be published in Issue 12.2) has been introduced.
‘In addition, the term “one-to-one comparison” has been replaced by “head-to-head comparison” throughout the English version of the text to align with the terminology used in general chapter 5.27. Comparability of alternative analytical procedures. The equivalent term in the French version is unchanged.’
The draft can be accessed via Pharmeuropa (requires registration).
The European Pharmacopeia is updating its chapter on gene therapy – ‘5.34. Additional information on gene therapy medicinal products for human use’.
Plasmid vectors for human use are freeze-dried or liquid preparations of double-stranded circular forms of bacterial DNA that carry a gene of interest or a nucleotide sequence coding for antisense sequences or ribozymes and its expression cassette. They are amplified in bacteria extrachromosomally and are directly administered in humans to transfer genetic material into somatic cells in vivo.
Plasmid vectors for human use may be presented as naked DNA or be formulated with synthetic delivery systems such as lipids (lipoplexes), polymers (polyplexes) and/or peptide ligands that facilitate transfer across the cell membrane and delivery to the cell, or that target delivery via specific receptors.
This general chapter is being revised to add a section (section 6) on mRNA-based Gene Therapy Medicinal Products (GTMPs) for human use. While most quality aspects are common to both mRNA-based GTMPs and mRNA vaccines, there are unique considerations specific to GTMPs. Therefore, this new section:
The draft can be accessed via Pharmeuropa (requires registration).
The U.S. Food and Drug Administration (FDA) has issued a final guidance for industry entitled ‘Post-Warning Letter Meetings Under GDUFA’.
This guidance provides information on the implementation of the post-warning letter meeting process for certain drug manufacturing facilities, a programme enhancement agreed upon by the FDA and industry as part of the negotiations relating to the reauthorisation of the Generic Drug User Fee Amendments (GDUFA), as described in ‘GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027’ (GDUFA III commitment letter).
This guidance describes the process detailed in the GDUFA III commitment letter for how an eligible facility may request a post-warning letter meeting with FDA regarding the facility’s ongoing remediation efforts to address Current Good Manufacturing Practice (CGMP) deficiencies described in a warning letter, how to prepare and submit a complete meeting package and how FDA intends to conduct the post-warning letter meeting.
To access, see: https://www.fda.gov/media/171785/download
The FDA has finalised a guidance document on the use of digital technology to conduct remote assessments. This is titled ‘Conducting Remote Regulatory Assessments - Questions & Answers’.
A remote regulatory assessment is an examination of an FDA-regulated establishment and/or its records, conducted entirely remotely, to evaluate compliance with applicable FDA requirements. These assessments assist in protecting human and animal health, informing regulatory decisions and verifying certain information submitted.
A Remote Regulatory Assessment (RRA) is an examination of an FDA-regulated establishment and/or its records, conducted entirely off-site.
RRAs are not inspections under §704(a)(1) - no Form 482 is issued and a Form 483 will only appear later if FDA confirms observations during a separate on-site inspection.
Examples include:
The document indicates that RRAs will never run simultaneously with an on-site inspection but can precede or follow one.
See: https://www.fda.gov/media/160173/download
The FDA has released draft guidance document on drug stability testing that was first published earlier this year by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). In April 2025, the ICH issued a consolidated draft titled ‘Stability Testing of Drug Substances and Drug Products (Q1)’.
On 25th June 2025, the FDA issued the guidance for U.S. comment.
The guideline outlines the stability data expectations for drug substances and drug products. The guideline is also applicable to marketed drug products, including those associated with registration and lifecycle/post-approval changes and, when applicable, master files.
The document is the ICH-endorsed consolidation of the entire legacy Q1A-F series and Q5C - meaning one global standard now governs stability for synthetic APIs, biologics, vaccines, gene and cell therapies, conjugates, ATMPs, drug-device combinations and co-packaged diluents
.
When it becomes final, the guidance will cover every U.S. stability submission, from IND-enabling batches through lifecycle changes.
Comments on the draft close on August 25, 2025.
See: https://www.fda.gov/media/187161/download
The FDA has issued a final guidance question and answer document titled ‘Antibacterial Therapies for Patients with an Unmet Medical Need for the Treatment of Serious Bacterial Diseases - Questions and Answers’.
Antibacterial drug resistance continues to be a public health concern. It has led to an increasing number of patients with serious bacterial diseases, such as hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, complicated intra-abdominal infections and complicated urinary tract infections, which may not respond to currently available antibacterial drugs. Hence, new approaches are required.
The document assists in the clinical development of new antibacterial drugs to treat serious bacterial diseases in patients with unmet medical needs, including patients with a serious bacterial disease for which effective antibacterial drugs are limited or lacking.
For new antibacterial drugs that treat serious bacterial diseases with a potential to address an unmet medical need, a more flexible development programme may be acceptable to facilitate development.
For details, see: https://www.fda.gov/media/158589/download
The US Pharmacopeia (USP) is revising chapter 〈111〉 ‘Design and Analysis of Biological Assays’. This is based on the version of the chapter official as of August 1, 2020.
In developing 〈1034〉‘Analysis of Biological Assays’, the Bioassay Subcommittee decided that one of the three options for combining results from independent assays included in 〈111〉 should be dropped from 〈1034〉.
The removed option was the one involving a preliminary chi-square test. The purpose of this revision is to align 〈111〉 with 〈1034〉 by removing that one option. The other two options and the other sections of this chapter have not been revised.
The chapter can be accessed via the USP website (requires registration).
The USP is revising its chapter for protein determination - 〈507〉 ‘Protein Determination Procedures’.
This proposal is based on the version of the chapter official as of August 1, 2016. It is proposed to add a new method, Method IC. Ultraviolet Light Absorbance Under Variable Path Length under Method I.
The chapter can be accessed via the USP website (requires registration).
A new USP chapter is being proposed on resuspendability / redispersibility as a drug product performance attribute. This is typically assessed during drug product design and development and is evaluated to characterise the product performance during the shelf-life and develop appropriate Instructions for Use (IFU). This chapter provides recommendations for the assessment of resuspendability and redispersibility of suspensions and powders, granules and pellets that result in a suspension when reconstituted according to the instructions for use.
The proposed new chapter 〈1003〉 ‘Resuspendability and Redispersibility’, will provide recommendations on the assessment and evaluation of resuspendability and redispersibility for all types of suspensions.
The chapter can be accessed via the USP website (requires registration).
The USP has a new draft chapter, issued for comment titled <1029> ‘Good Documentation Guidelines and Data Integrity’.
The text contains definitions and principles of ALCOA - Attributable, Legible, Contemporaneous, Original and Accurate. This includes ALCOA+, ALCOA++ and guidance on life cycle models.
The focus is with producing GMP-compliant instructions and records. Whether another guideline is needed on this subject remains to be seen, however readers can assess the Chapter.
Formats for data collection and recording include, but are not limited to:
The chapter can be accessed via the USP website (requires registration).
The USP is proposing a new general chapter for stability studies. 〈1049.1〉 ‘Design of Stability Studies for Biotechnological and Biological Product Development and Life Cycle Management’.
This proposed new general chapter, a companion to 〈1049〉 ‘Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products’, provides details regarding the overall stability strategy and life cycle management of biotechnological and biological products, as well as the design of stability studies through all stages of the product life cycle.
This general chapter focuses on the complexity of formal stability studies designed to support the expiration period and storage conditions, as well as other studies that build knowledge of the product stability necessary for product characterisation, transportation, handling and patient and physician use.
The chapter can be accessed via the USP website (requires registration).
The USP plans to revise 〈1072〉 ‘Disinfectants and Antiseptics’. This proposal is based on the version of the chapter official prior to 2013. The previously published proposal in PF 46(5) has been cancelled, as it has been more than two years since it was presented for public comments.
The following revisions are being proposed:
1. Remove the ‘Definitions’ section. Definitions and glossary terms related to the microbiology chapters can be found in 〈1117.1〉 ‘Microbiological Chapters - Glossary’
2. Add a new section detailing methods for decontaminating large spaces, including vapor phase hydrogen peroxide and chlorine dioxide gas
3. Remove the following sections:
4. Expand considerations for selecting disinfectants, including bioburden, spectrum of activity and compatibility with surfaces
5. Provide clarification to ‘Disinfectant Challenge Testing’, including the recommended acceptance criteria
6. Update guidance for the use of disinfectants in a cleaning and sanitisation programme, including ‘In Situ Qualification of Disinfectant Effectiveness and Personnel Safety’.
The chapter can be accessed via the USP website (requires registration).
The European Pharmacopeia revision to chapter ‘2.4.44 Total Organic Carbon in Water for Pharmaceutical Use’ has been accepted by the European Commission (this featured in a 2024 Regulatory Update).
This chapter is set to come into force from 1st January 2026.
The FDA has provided draft recommendations for replacing colour additives in approved or marketed drug products. If a colour additive is used in a drug product, it must conform to the FDA’s colour additive regulations.
If FDA deems the colour additive unsafe and repeals the colour additive regulation, it must be removed or replaced. Colour additives can also be replaced for other reasons (e.g., as a business decision).
The FDA draft guidance is titled ‘Replacing Color Additives in Approved or Marketed Drug Products’ and it is accessible here: https://www.fda.gov/media/186692/download
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