ILC Tag

The European Medicines Agency (EMA) has published an update concerns the section on “Reduced testing of incoming Starting Materials”.

The question is: “What information should be included in marketing authorisation dossiers regarding the actual testing performed by the finished product manufacturer, on receipt of any incoming starting materials (e.g. active substances, excipients, packaging materials, etc) and before use in production of the medicinal product?”

The answer from the EMA clarifies that the analyses to be performed on receipt are governed by GMP; therefore, the specifications for incoming starting materials registered in the marketing authorization application should not include any reference to reduced testing.

References:

• For human medicinal products: EU GMP part I, chapter 5 (5.27 to 5.39)
• For veterinary medicinal products: Commission Implementing Regulation (EU) 2025/2091, Article 28

SOURCE:

https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-guidelines/quality-medicines-questions-answers-introduction/quality-medicines-questions-answers-part-2#reduced-testing-of-incoming-starting-materials-6973

On June 15, 2026, the Brazilian health authority ANVISA published Regulatory Instruction No. 451, which updates the criteria for the recognition of equivalent foreign regulatory authorities (AREEs) and reorganizes the administrative procedures for obtaining the certification of good manufacturing practices (CBPF). The changes introduced aim to ensure increased transparency and to facilitate and accelerate regulatory processes.

Among the main changes introduced, the most significant is the formal recognition of the decentralized regulatory authorities of countries with decentralized regulatory models, such as Germany, Spain, Switzerland, and Japan. The amendment introduced by IN 451/2026 allows ANVISA to make use of the inspection reports drawn up by the competent regional bodies, as they are recognized as having the same level of reliability as those issued by the corresponding central regulatory authority.

Another significant change concerns the reorganization of the AREEs classification system, which now provides for the standardization of procedures for the designation and exclusion of authorities recognized by ANVISA.

Overall, the optimization of the document analysis flow should be more streamlined and transparent, enhancing the traceability of information and making the procedure more in line with the operational reality of the certification processes.

SOURCE:

Anvisa atualiza Instrução Normativa e orienta sobre novo fluxo para CBPF

On June 9, 2026, the United Kingdom launched an initiative to test how artificial intelligence (AI) can help make medicines safer for patients through a regulatory “sandbox.” The program will explore how AI can improve the assessment of accuracy and safety, better predict risks, and detect effects that existing approaches might miss.

The sandbox will allow for the testing of AI tools to predict how medicines behave in the body, including absorption, metabolism, and potential toxicity. The program will also explore how to optimize the use of clinical data to better understand how medicines work in different populations, including those often underrepresented in studies, such as children, older people, and minorities.

This is part of a broader effort to modernize medicines development by addressing the known limitations of traditional development models to improve how medicines safety and efficacy are assessed.

In the first phase, up to five AI-driven approaches will be tested. The MHRA will begin collaborating with partners from industry and academia starting in the summer of 2026 to define how the sandbox will operate.

This initiative positions the United Kingdom at the forefront of regulatory innovation integrated with AI, enabling faster validation of emerging methodologies and defining future regulatory expectations regarding the use of AI.

SOURCE:

https://www.gov.uk/government/news

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has published the updated version of the “Guideline on requirements for revision and renewal of certificates of suitability to the European Pharmacopoeia monographs” (PA/PH/CEP (04) 02).

Regulatory background

The guideline has been substantially revised with the aim of ensuring compliance with the requirements of current EU legislation specified in the following context by holders of a Certificate of Suitability (CEP):

• Regulation (EU) No. 1234/2008 of November 24, 2008, concerning the examination of variations to the terms of marketing authorizations for medicinal products for human use and veterinary medicinal products, and the documentation to be submitted pursuant to those procedures;
• Regulation (EU) No. 2024/1701 of March 11, 2024 amending Regulation (EC) No. 1234/2008 as regards the examination of variations to the terms of marketing authorizations for medicinal products for human use.
• Implementing Regulation (EU) 2021/17 of January 8, 2021 establishing a list of variations which, pursuant to Regulation (EU) 2019/6 (veterinary medicinal products), do not require an assessment.

In addition to formal legal alignment, the guideline addresses various points that are relevant from a pragmatic point of view:

• Distinction between “revision” and “new CEP application“: the guideline clarifies in which situations it is not possible to modify an existing CEP and a separate CEP application is instead required.
• Changes in the context of CEP 2.0: the guideline provides guidance on how to classify and manage changes in relation to the implementation of CEP 2.0.
• Risk assessment: the guideline describes when and how a risk assessment should be initiated, updated or adapted in the context of the changes to be implemented.

Transition period and date of full application

Following publication, a two-month transition period is planned. During this period, the application of the new requirements is expressly encouraged but not yet mandatory. The revised guideline will come into full force on July 1, 2026.

SOURCES:

The revised guideline can be found on the EDQM website under “Certification Policy Documents & Guidelines” in the section “Operational documents”.

The European Pharmacopoeia has published significant revisions to its standards for pharmaceutical water in Ph. Eur. Issue  12.3, affecting WATER FOR INJECTIONS (0169), WATER, PURIFIED (0008), and TOTAL ORGANIC CARBON IN WATER FOR PHARMACEUTICAL USE (2.2.44). These changes represent a major step toward international harmonization, particularly with the USP, by adopting state-of-the-art testing methodologies.

Transition to TOC Testing for Sterilised Water (SWFI)

The most notable regulatory shift is the complete replacement of the traditional test for oxidisable substances with the Total Organic Carbon (TOC) test for Sterilised Water for Injections (SWFI). This is facilitated by the addition of Method B to General Chapter 2.2.44, which is specifically designed for SWFI. Notably, Method B introduces container-dependent TOC limits, defining three different acceptance criteria based on the size of the container.

Refinements for Bulk Water (WFI and Purified)

For both Water for Injections and Purified Water in bulk, the revisions focus on clarification and alignment without introducing entirely new content requirements:

• Methodological Consistency: for the TOC test in bulk water, the monographs now explicitly refer to Method A of Chapter 2.2.44.
• Numerical Precision: the TOC limit value has been updated from 0.5 mg/L to 50 mg/L to align with the concentration of the standards used in the general chapter.
• Conductivity Calibration: a metrological clarification has been added to the conductivity test. The accuracy of the measurement and the permissible deviation during system calibration must now be based on the expected conductivity value of the reference solution rather than the measured value.

Reagents and Implementation

To simplify laboratory processes and enable the use of USP reference standards, the reagents sucrose R and 1,4-benzoquinone R are being replaced by Chemical Reference Substances (CRSs).

These revised monographs are scheduled to officially come into force on 1 July 2026

SOURCES:

European Pharmacopoeia (Ph. Eur.) Issue 12.3

The European Medicines Agency (EMA) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) have proposed a targeted revision of Annex 15 of the Good Manufacturing Practice guidelines. The concept paper proposes the transition of Annex 15 from its current status as optional supplementary guidance for active substance (AS) manufacturers to a mandatory requirement. This new scope will encompass manufacturers of both chemical and biological active substances.

The proposal stems from lessons learnt from the presence of N-nitrosamine impurities in sartan medicines, which was made public in June 2020. Investigations into these cases revealed that the contamination was often due to gaps in knowledge of processes and products, as well as GMP deficiencies among active pharmaceutical ingredient manufacturers. By making Annex 15 mandatory, regulatory authorities aim to ensure better contamination control and a more robust investigation of quality issues.

The revision intends to align validation practices with quality standards and includes several critical updates:

• Quality Risk Management (QRM): validation and qualification activities will be updated to align with the revised ICH Q9 (R1) guideline, emphasizing the use of QRM throughout the product lifecycle, including the design of monitoring systems.
• Enhanced Documentation: AS manufacturers will be expected to adopt the concepts of the “Validation Master File” and “Qualification and Validation policy” to improve how activities are defined and documented.
• Process Oversight: the new guidelines will focus on sound process development, stricter change control as part of knowledge management, and more rigorous supplier qualification.
• Qualification Stages: concepts such as User Requirements Specifications (URS) and Factory/Site Acceptance Testing (FAT/SAT) will be formally extended to AS manufacturing.
• Transport and Distribution: in line with Good Distribution Practices (GDP), the revision will provide guidance on verifying transportation to ensure that the quality of active substances is not compromised during transit.

Implementation Timeline

The revision process is already underway. A public consultation period is scheduled from February 9 to April 9, 2026. Following the review of comments and final endorsements, the European Commission is expected to publish the finalized guideline by December 2026.

SOURCES:

concept-paper-revision-guidelines-good-manufacturing-practice-medicinal-products-annex-15-qualification-validation_en.pdf

The Committee of Experts on the Classification of Medicines as Regards their Supply (CD-P-PH/PHO), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), has just published five new evidence-based classification reviews (EBRs) on herbal medicines.

The five new ERBs, drafted in 2025, concern the following herbal substances:

• castor oil (Ricinus oleum);
• St John’s wort (Hypericum herba);
• capsicum (Capsicum);
• ivy leaf (Hedera helix folium);
• agnus castus fruit (Agni casti fructus).

The CD-P-PH/PHO adopted a new format for EBRs following the roll-out of the recently developed assessment approach described in the new guidelines on the classification of active pharmaceutical substances as regards their supply.

The CD-P-PH/PHO issues a recommendation for a non-prescription status or exemptions to a prescription-only status if the benefits clearly outweigh the risks, as demonstrated by in-depth Evidence-Based Classification Reviews (EBR).

The EBRs are published on the CD-P-PH/PHO Programme results web page, maintained by the EDQM. More information is available in the EDQM Newsroom.

SOURCES:

https://www.edqm.eu/en/-/cd-p-ph/pho-publishes-5-new-evidence-based-classification-reviews

On October 27, 2025, the European Commission released two new implementing regulations on good manufacturing practices (GMP) in the veterinary field:

• Commission Implementing Regulation (EU) 2025/2091(for GMP of finished products)
• Commission Implementing Regulation (EU) 2025/2154(for GMP of active substances used as starting materials).

The new Implementing Regulations set out the Good Manufacturing Practice (GMP) requirements introduced by Regulation (EU) 2019/6 on veterinary medicinal products and will have to be fully applied from July 16, 2026.

The Regulations apply to manufacturers, importers, repackagers, and relabelers of active substances and medicinal products for veterinary use.

These regulations provide a specific framework and GMP requirements with their own separate legal basis within veterinary legislation, replacing the current GMP provisions for veterinary medicinal products and their active substances laid down in Volume 4 of EudraLex, which are currently aligned with the GMP framework for medicinal products for human use.

To support stakeholders, the European Commission has also issued correlation tables linking each Implementing Regulation to the existing GMP requirements for veterinary medicinal products and active substances, providing clear indication on how the new rules relate to the current regulatory framework.

The regulation applies to manufacturers, importers, repackagers, and re-labellers of active substances for veterinary use.

SOURCES:

https://eur-lex.europa.eu/oj/daily-view/L-series/default.html?&ojDate=27102025