GMP Tag

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