EU Clinical Trials Regulation
From 31 January 2025, all clinical trials in the European Union (EU), including ongoing trials that were approved under the previous legal framework (the Clinical Trials Directive) - are governed by the Clinical Trials Regulation (CTR).
This marks the end of a three-year transition period, during which more than 5,000 clinical trials were transitioned to the CTR through submission to the Clinical Trials Information System (CTIS), the single-entry point for sponsors and regulators for the submission and assessment of applications for clinical trials in the EU.
To view the regulation: https://eur-lex.europa.eu/legalcontent/EN/TXT/?uri=celex%3A32014R0536
ICH updates GCP guidelines
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has issued document E6(R3). This is a rewrite of the previous version of the guideline on Good Clinical Practice (GCP), which sets international standards for clinical trials involving human participants.
The update aims to apply GCP principles to the increasingly diverse trial types and data sources supporting regulatory and healthcare related decision-making on medicines. It is also designed to provide flexibility, where appropriate, to facilitate the use of technological innovations in clinical trials.
To view, see: https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
Introductory training for E6(R3) has been made available on the ICH website: https://ich.org/news/ich-e6r3-introductory-training-presentation-now-available-ich-website
Fungal resistance
The European Medicines Agency (EMA) has issued a warning about the extensive use of azole fungicides, particularly in some agricultural and horticultural practices. The use of these chemicals can increase the risk of Aspergillus fungi developing resistance to essential antifungal treatments.
This finding is highlighted in a report by the five EU health and environment agencies, with support from the European Commission’s Joint Research Centre (JRC). The Agencies collaborated under a One Health approach to address this growing threat.
A summary of the report can be found here: https://www.ema.europa.eu/en/news/one-health-eu-agencies-unite-tackle-azole-fungicide-resistance-aspergillus-fungi
Data transparency
The EMA and the HMA (Heads of Medicines Agencies) have published a comprehensive overhaul of their guidance on the identification of Commercially Confidential Information (CCI) and personal data in Marketing Authorisation Applications (MAA) for human medicines.
The update reaffirms the commitment of regulatory authorities across the European Economic Area (EEA) to extensive transparency when disclosing information, both in response to access-to-document requests and in the proactive publication of data once a medicine is authorised.
The guidance can be found here: https://www.ema.europa.eu/en/documents/other/heads-medicines-agencies-european-medicines-agency-guidance-document-identification-commercially-confidential-information-personal-data-within-structure-marketing-authorisation-application_en.pdf
Requests for expedited review of new drug application
The U.S. FDA’s Office of Pharmaceutical Quality (OPQ) has published a revised Manual of Policies and Procedures (MAPP) entitled ‘Requests for Expedited Review of New Drug Application and Biologics License Application Prior Approval Supplements Submitted for Chemistry, Manufacturing, and Controls Changes’.
To access: https://www.fda.gov/media/72405/download?source=email&utm_source=substack&utm_medium=email
Balances
The Ph. Eur. is updating chapter ‘2.1.7. Balances for analytical purposes’. The scope of this chapter is limited to balances used for analytical purposes and does not cover balances used for manufacturing or other purposes. Any weighings performed to establish compliance with a monograph of the European Pharmacopoeia must be carried out according to the principles outlined in this chapter.
The chapter is out for public comment it can be viewed via Pharmeuropa (requires registration).
New USP chapter
The United States Pharmacopeia (USP) is creating a new chapter ‘〈1120〉 Ensuring Microbiological Quality of Articles of Botanical Origin’.
This new chapter is being proposed by the Joint Subcommittee on Microbiological Issues in Dietary Supplements and Food Ingredients and will provide information on practices to prevent (and methods to treat) the microbiological contamination of articles of botanical origin. The information is not limited by the regulatory framework - microbiological quality is relevant to articles of botanical origin, whether such materials are components of conventional food products, dietary supplement products or over-the-counter drug products.
The chapter is out for public comment it can be viewed via Pharmacopeial Forum (requires registration).
Vaccines for vetinary use
The EMA has issued a document ‘Guideline on quality aspects of mRNA vaccines for veterinary use’. This is in the form of a concept paper, which addresses the need to establish a guideline on the quality aspects of mRNA vaccines. This is in relation to recent advances with mRNA vaccines.
The paper is open for public comment: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-concept-paper-development-guideline-quality-aspects-mrna-vaccines-veterinary-use_en.pdf
Automated processing
The US FDA has issued a draft guidance document titled ‘Considerations for Complying With 21 CFR 211.110: Guidance for Industry’.
To ensure batch uniformity and drug product integrity, the current Good Manufacturing Practice regulations require that manufacturing processes are designed and controlled to ensure that in-process materials consistently and reliably meet predetermined quality requirements. This guidance explains the requirements for drug product manufacturing in § 211.110.
This document also describes considerations for the use of advanced manufacturing (e.g. 3D printing, continuous manufacturing) and the use of process models as a part of commercial manufacturing control strategies. The FDA supports the adoption of advanced manufacturing as a foundation for improving the overall quality and availability of drug products for patients.
To review, see: https://www.fda.gov/media/184825/download
Sterilisation of health care products
The following ISO standards are under revision:
- ISO/CD 11138-6.2 Sterilization of health care products — Biological indicators — Part 6: Biological indicators for hydrogen peroxide sterilization processes
- ISO/CD 19253.2 Sterilization of health care products — Moist heat — Requirements for sterilizers used for the terminal sterilization of aqueous liquid in sealed containers
The following ISO standards are at the final draft stage, pending national body ratification:
- ISO/FDIS 11137-1 Sterilization of health care products — Radiation — Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices 2025-02-11 (Revision of ISO 11137-1:2006)
- ISO/FDIS 15883-7 Washer-disinfectors — Part 7: Requirements and tests for washer disinfectors employing chemical disinfection for non-critical thermolabile medical devices and health care equipment 2025-02-11 (Revision of ISO 15883-7:2016)
The following ISO standard has been issued:
- ISO 15883-2:2024 Washer-disinfectors — Part 2: Requirements and tests for washer-disinfectors employing thermal disinfection for critical and semi-critical medical devices
Quality Assurance
The following ISO standard has been issued:
- ISO 10009:2024 Quality management — Guidance for quality tools and their application
Risk management
The following ISO standard has been issued:
- ISO 31073:2022 Risk management Risk management — Vocabulary
Food
The following ISO standards have been drafted and are open for public comment through national standards bodies:
- ISO 16140- 3:2021/DAmd 1 Microbiology of the food chain — Method validation — Part 3: Protocol for the verification of reference methods and validated alternative methods in a single laboratory — Amendment 1: Validated identification methods of microorganisms — Technical protocol for verification
- ISO 16140- 4:2020/DAmd 2 Microbiology of the food chain — Method validation — Part 4: Protocol for method validation in a single laboratory — Amendment 2: Protocol for single-laboratory validation of identification methods of microorganism
