The MHRA has posted a blog cautioning the use of AI for regulatory responses (dated 29 June 2026). This reinforces the need for the ‘human in the loop’ and highlights that AI use is no longer a hypothetical concern but an element that can create errors that are now being actively encountered.
‘AI tools are being used to draft inspection responses supplied to the MHRA. The technology offers genuine benefits: helping articulate complex technical issues, improving consistency, speeding up routine drafting and enabling innovation. Used properly, AI can support better regulatory outcomes and improve patient safety.
However, we have also encountered responses containing references to MHRA guidance that doesn’t exist, citations of inappropriate regulatory frameworks and responses to serious deficiencies that appear designed to mislead rather than address underlying problems. For example, one inspection response received by the MHRA totalled over 90 pages and did not address the deficiencies identified. This resulted in a disproportionate use of Inspector time and expertise to review and respond.
In at least one case, an AI-generated response to a serious, patient safety impacting deficiency contained material inaccuracies, including non-existent references as well as inaccurate information that delayed the resolution of serious compliance failures, creating additional administrative burden and delays. The contents of this response required review from multidisciplinary teams, as well as a full analysis of previously issued MHRA guidance, resulting in the time needed to review and respond increasing from around 4 hours to over 20 hours. Aside from being a strain on resource, the use of AI being applied inappropriately has shifted from theoretical risk into actual, realised risk.’
To read the full post, see: https://mhrainspectorate.blog.gov.uk/2026/06/29/use-of-ai-for-gxp-inspection-responses-setting-standards-without-stifling-innovation/
RSSL delivers data integrity, GMP and inspection readiness training alongside consultancy support for CAPA management and regulatory response processes. Our subject matter experts can review your quality systems and ensure your teams maintain the human oversight regulators continue to expect.
As of 16 July 2026, EudraLex Volume 4, the EU GMP guidelines, only applies to human medicines. GMP for veterinary medicines is now defined in the Commission Implementing Regulations (EU) 2025/2091 that lays down GMP for veterinary medicinal products and Regulation (EU) 2025/2154 that lays down GMP for active substances used as starting materials in veterinary medicinal products.
The future for EudraLex Volume 4 Annexes 4 and 5 remains unclear as they still appear on the Volume 4 webpage.
RSSL provides GMP training and consultancy to support organisations updating quality systems and documentation in response to regulatory framework changes. Our consultants can help ensure your SOPs and references remain aligned with current requirements for both human and veterinary medicines.
The European Medicines Agency (EMA) has updated ‘Abbreviations used in EMA scientific committees & CMD documents and in relation to EMA’s regulatory activities’. This becomes the fifth revision.
The list can be accessed here: https://www.ema.europa.eu/en/documents/other/abbreviations-used-ema-scientific-committees-coordination-group-mutual-recognition-decentralised-procedures-cmd-documents-relation-emas-regulatory-activities_en.pdf
The ICH Guideline for Good Clinical Practice (GCP) establishes an international standard for the design, conduct, recording and reporting of clinical trials involving human participants. It outlines the responsibilities of sponsors, investigators and other stakeholders to protect the rights, safety and wellbeing of trial participants, while ensuring the integrity and credibility of clinical trial data.
Annex 1 came into force on 23 July 2025. Annex 2 will come into effect on 15 January 2027, having been adopted by the EMA committee on 25 June 2026.
The guideline provides a unified framework to facilitate the mutual acceptance of clinical trial results by regulatory authorities across ICH member regions, supporting global collaboration in drug development and ensuring consistent regulatory standards.
The document can be accessed here: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6r3-guideline-good-clinical-practice-step-5_en.pdf
RSSL delivers quality risk management and process validation consultancy that directly supports clinical development teams preparing for ICH E6 R3 implementation. Our services cover the risk-based and quality-by-design approaches now expected by regulators.
The July 2026 version (Rev. 118) of the EMA’s ‘Post-Authorisation Procedural Advice for Users of the Centralised Procedure’ adds updates in the form of revised a Q&A. The key updates focus on variation procedures, product information management, orphan medicines, paediatric requirements and submission processes.
The main revisions in the 2025-2026 update cycle:
1. Updated variation and submission requirements
Several sections relating to Type IA, IB and Type II variations were revised during 2025–2026 including:
2. Product Information and linguistic review changes
EMA has updated guidance on:
This is marked as being particularly relevant for companies managing frequent post-authorisation changes.
3. Paediatric compliance updates
The document contains revised guidance on:
4. Orphan medicine guidance strengthened
Several sections were revised in late 2025 and 2026 covering:
5. Increased emphasis on submission planning
EMA stresses:
This reflects EMA’s increasing focus on efficient lifecycle management and avoiding validation delays.
The guide reinforces the requirement that:
The document includes updated information on the end of the Irish-language derogation and the situations in which Irish translations may be required for Commission decisions and product information.
The document can be accessed here: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/european-medicines-agency-post-authorisation-procedural-advice-users-centralised-procedure_en.pdf
RSSL’s regulatory consultants support variation submission strategy, lifecycle management and compliance with evolving EMA procedural requirements. We can review your current processes and ensure alignment with the updated guidance before submission.
US Pharmacopeia (USP) chapter <81> is undergoing an update. The revised USP <81> ‘Antibiotics - Microbial Assays’ chapter represents a significant modernisation of the traditional antibiotic potency assay, moving from largely prescriptive procedures toward a more science (and statistics) based framework. The chapter introduces explicit requirements for assay design, verification and data analysis for both cylinder-plate and turbidimetric methods. It standardises the use of five-point standard curves, regression-based potency calculations and suitability criteria such as Relative Standard Deviation (%RSD) and coefficient of determination (R²) acceptance limits. It also formalises the expectation that three or more independent assays are required to establish a reliable potency estimate and introduces confidence interval calculations to demonstrate assay precision.
A major enhancement is the inclusion of detailed guidance on culture maintenance, organism storage, inoculum preparation, assay variability management and outlier handling. The chapter emphasises risk reduction through improved temperature control, rack randomisation for turbidimetric assays, plate-to-plate correction factors for cylinder-plate assays and predefined laboratory acceptance criteria. Explicit statistical examples are provided to support consistent implementation.
The revision also acknowledges advances in analytical technology, noting that some antibiotics may eventually transition from microbiological potency testing to validated physicochemical methods when supported by appropriate bridging studies. Overall, the updated chapter strengthens assay robustness, reproducibility, data integrity and regulatory defensibility while retaining microbiological assays as the compendial standard for antibiotics where biological activity remains the critical quality attribute.
USP <62> is undergoing revision. The 2026 revision of USP <62> ‘Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms’ primarily clarifies and strengthens existing requirements rather than introducing new microorganism tests. The chapter places greater emphasis on method suitability, requiring laboratories to demonstrate that specified microorganisms can be detected in the presence of the product and to reconfirm suitability whenever product characteristics or test performance change. It reinforces the use of seed-lot culture systems, limits culture passage history and provides expanded guidance for growth-promotion, inhibitory and indicative testing of culture media.
The chapter also provides clearer expectations for negative controls, media qualification, inoculum preparation and handling of products with antimicrobial properties. Testing procedures for specified microorganisms including Escherichia coli, Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus, Clostridia and Candida albicans have been standardised with defined enrichment, selective media, incubation conditions and interpretation criteria.
In addition, the chapter updates and consolidates the recommended formulations for diluents and culture media, aligning with a lifecycle approach to microbiological method control. Overall, the changes improve method robustness, standardisation and regulatory defensibility while supporting the use of validated alternative microbiological methods where equivalence can be demonstrated.
RSSL offers full microbiological examination services for nonsterile products including method suitability testing, specified organism detection and media qualification to current pharmacopoeial standards. Our team works to USP <62> and equivalent Ph. Eur. requirements.
The 2026 revision of USP <60> ‘Microbiological Examination of Nonsterile Products - Tests for Burkholderia cepacia Complex (BCC)’ reinforces method suitability, media qualification and recovery expectations for BCC detection in nonsterile products. The chapter strengthens requirements for demonstrating that the method can recover B. cepacia, B. cenocepacia and B. multivorans in the presence of the product, including those with antimicrobial properties. Suitability must be reassessed following changes to either the product or the test method.
The chapter also provides clearer requirements for growth-promotion, inhibitory and indicative testing of Burkholderia cepacia Selective Agar (BCSA), including the use of defined challenge organisms and inoculum levels. Standardised incubation conditions, enrichment procedures, colony morphology descriptions and confirmation requirements have been clarified to improve consistency and reliability of testing.
In addition, the chapter updates and consolidates recommended media and buffer formulations, supporting a more robust and standardised approach to BCC testing while maintaining flexibility for validated alternative methods and media.
The EMA has issued a concept paper which proposes a major revision of its guideline on the clinical evaluation of antifungal agents for the treatment and prophylaxis of Invasive Fungal Disease (IFD), reflecting significant developments in medical mycology and antifungal drug development since the current guideline was last revised in 2010.
Key proposed updates include guidance for antifungal agents targeting rare and emerging fungal pathogens such as Candida auris, Scedosporium spp. and Mucorales, where traditional randomised controlled trials may not be feasible. The revision will explore alternative study designs, minimum data packages and approaches to support regulatory approval in these settings.
The guideline will also incorporate updated EORTC/MSGERC consensus definitions for IFD, revised response criteria and recognised definitions of breakthrough fungal infections to improve consistency in clinical trial endpoints.
Additional sections will address salvage therapy for refractory disease, the development of inhaled antifungal agents and revised expectations for paediatric development, including extrapolation strategies and studies in neonates. The update will also align with the ICH E9(R1) estimand framework and modern statistical principles. Overall, the revision aims to provide a more flexible and scientifically current regulatory framework for innovative antifungal therapies.
The document can be accessed here: https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-revision-guideline-clinical-evaluation-antifungal-agents-treatment-prophylaxis-invasive-fungal-disease_en.pdf
* The estimand framework is a structured approach used in clinical trials to clearly define what treatment effect is being estimated to answer a specific research objective.
The 2026 revision to USP Chapter <77> ‘Mycoplasma Nucleic Acid Amplification Tests’ establishes a dedicated compendial framework for the validation and routine use of Nucleic Acid Amplification Techniques (NAATs), such as PCR, qPCR, and dPCR, for mycoplasma detection in biologics, cell therapies, gene therapies and other biotechnology-derived products. It supplements, rather than replaces, USP <63> Mycoplasma Tests.
Key changes are:
Clear focus on NAT-based methods
New primary validation requirements
Updated method suitability testing
Introduction of genome-copy based standards
Expanded guidance on controls
RSSL offers NAT-based detection methods for mycoplasma testing serving the biologics, cell and gene therapies and biotechnology-derived products sectors. We can support method validation and preparation of structured validation packages aligned with the revised USP <77> framework.
The European Pharmacopoeia Commission has issued a new revised general chapter on alternative microbiological methods, supporting advancement of the field by modernising quality standards. The revised chapter 5.1.6. ‘Alternative methods for control of microbiological quality’ is published in Issue 13.2 of the European Pharmacopoeia (Ph. Eur.)
The chapter includes updated descriptions of technologies and includes modern approaches, removing outdated quality control methods. This means the framework offers a clearer definition of the responsibilities of suppliers as well as microbiologists using the chapter.
The change aligns with an earlier publication from the Eur. Ph. In January, it published a new general chapter on quality of data 5.38. The framework aids stakeholders with digitalisation during pharmaceutical quality decision-making.
RSSL supports the development, validation and implementation of alternative and rapid microbiological methods. Our scientists can advise on method equivalence, risk-based validation strategies and regulatory justification aligned with the revised Ph. Eur. 5.1.6 framework.
ICH is drafting guidance on Patient Preference Studies (PPS). The guideline aims to assess the relative desirability or acceptability of actual or potential health interventions or their characteristics and outcomes. PPS can generate structured insights about the relative importance of characteristics, also referred to as attributes, that are considered by patients when making decisions about drugs. These attributes may include efficacy or safety outcomes or any other potentially relevant characteristics.
This harmonised guideline outlines general considerations about the use, design, conduct, analysis and submission of PPS aimed at informing drug development, regulatory submission and evaluation, drug approvals and maintenance of such approvals.
The guideline addresses PPS and the value that patients place on characteristics of drugs. It does not focus on patient reported outcome measures.
The document has completed its public comments stage. The comments can be accessed here: https://www.ema.europa.eu/en/documents/comments/overview-comments-received-ich-e22-guideline-general-considerations-patient-preference-studies-ema-chmp-ich-371537-2025_en.pdf
New U.S. Food and Drug Administration (FDA) technical guidance (July 2026) ‘Submitting Next-Generation Sequencing Data to the Division of Antivirals’ provides recommendations for sponsors submitting Next-Generation Sequencing (NGS) data to the FDA Division of Antiviral Products to support antiviral drug development and resistance assessments. The FDA emphasises that NGS is increasingly important for detecting antiviral resistance mutations and characterising viral populations. However, their complexity requires standardised documentation and transparent analytical methods.
Sponsors are expected to submit detailed information on NGS protocols, sample preparation methods, bioinformatics pipelines, raw sequencing data (FASTQ format), frequency tables of mutations and summary datasets suitable for independent FDA review. The guidance recommends early interaction with the FDA and submission of mock datasets to ensure compatibility with regulatory expectations.
The document also outlines expectations for sequencing quality, read coverage, handling of sequencing errors, reference mapping, variant calling, de novo assembly, barcode processing and reporting of amino acid substitutions associated with resistance. A strong emphasis is placed on transparency, reproducibility and the ability of FDA reviewers to independently verify resistance analyses. Ultimately, the guidance aims to improve consistency in antiviral resistance evaluation and support accurate product labelling and public health decision-making.
The FDA guidance can be accessed here: https://www.fda.gov/media/129126/download
FDA has issued a draft document titled ‘Master Protocols for Drug and Biological Product Development: Guidance for Industry’.
The document provides recommendations for the design, conduct, analysis and regulatory submission of clinical trials using a master protocol framework. Master protocols allow multiple therapies, diseases or patient subgroups to be studied within a single overarching trial structure and include umbrella, platform and basket trials.
The guidance focuses on ensuring that these complex trials generate reliable evidence of safety and effectiveness. Key topics include randomisation, control groups, blinding, adaptive designs, multiplicity control, safety monitoring, informed consent, trial oversight, data sharing and dissemination of results. FDA emphasises the need to maintain scientific validity while gaining operational efficiencies from shared infrastructure and common trial procedures.
The document also provides regulatory recommendations covering Investigational New Drug (IND) management, protocol amendments, sponsor responsibilities, communication with FDA and submission requirements. Overall, the guidance aims to support more efficient drug development while ensuring participant safety, data integrity and robust evidence generation suitable for regulatory decision-making.
The document can be accessed here: https://www.fda.gov/media/174976/download
The FDA has issued draft guidance titled ‘Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products’.
This document clarifies how sponsors can meet the statutory standard for demonstrating effectiveness in New Drug Applications (NDAs) and Biologics License Applications (BLAs). The guidance reflects advances in science, trial design and data generation, replacing earlier approaches that were often interpreted as requiring two positive pivotal trials.
The document explains that substantial evidence may be established through several approaches, including one adequate and well-controlled clinical trial supported by confirmatory evidence, multiple adequate and well-controlled studies, or scientifically justified extrapolation from existing evidence. It emphasises that the strength of evidence depends on trial design, conduct, statistical analysis, robustness of results and the overall development programme.
The guidance also discusses regulatory flexibility for serious diseases, unmet medical needs and challenging development settings, while maintaining the requirement for scientifically rigorous evidence. FDA stresses the importance of early interaction with the Agency to agree on development strategies and evidentiary expectations. Safety and benefit-risk considerations remain critical components of the eventual approval decision.
The document can be found here: https://www.fda.gov/media/133660/download
RSSL provides comprehensive biologics testing including product characterisation and impurity profiling, activity assays including cell based assays, GMP batch release testing, biosimilar analysis. Our multi-disciplinary team supports biopharmaceutical programmes from early development through to commercial release.
While this Regulatory Round-up gives you a broad snapshot of changes across the pharmaceutical landscape, our quarterly Key GMP Regulatory Updates webinar offers the chance to go deeper on what matters most for your quality systems.
In this focused two-hour session, our expert tutor will guide you through the latest changes to GMP law and guidance, covering UK GMP expectations, MHRA approaches, EU developments and key international updates, designed to support you in understanding the practical implications for your organisation and the actions you need to take to remain compliant.
Ideal for QPs, quality professionals and anyone responsible for maintaining GMP standards, it's the perfect complement to this newsletter for those who need to stay ahead of the detail.
