Review of Developments in GMP and the Regulation of Medicines December 2025 

EJPPS Volume 30.4C

INTRODUCTION

During the last 4 weeks there have been a number of developments in the regulation of the pharmaceutical industry. This month reported issues have come from the UK, EU, USA and Swiss regulatory authorities.

The topics covered in this edition of the “Update” include:

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

·       Three convicted in major MHRA investigation into illegal online supply of medicines

·       New MHRA-supported research reveals patterns of vaccine-derived poliovirus spread and implications for global eradication efforts

EU

European Medicines Agency (EMA)

·       Q&A on impact of EU-USA Mutual Recognition Agreement on marketing authorisation applications and relevant variations - Revised 1st October 2025

·       Fighting medicine shortages: It takes a team

·       Meeting Summary — Medicine Shortages SPOC Working Party

·       How the safety of medicines is ensured in the European Union

·       Quality of medicines Q&A: Part 1

·       Abbreviation of names of days on calendarised blisters

·       Combination Products Operational Group

·       Acceleration of regulatory procedures during public health Emergencies (Annex 1 of the EMA Health Threats Plan)

·       Q&A on classification of a product (veterinary) as intended for a limited market according to Article 4(29) and/or eligibility for authorisation according to Article 23

·       Notification on arrangements for requesting EMA certificates through urgent and standard procedure for December 2025

·       Variations revised Q&As

The European Directorate for the Quality of Medicines & HealthCare (EDQM)

·       Certification monthly report of activities: End of October 2025

·       EDQM end-of-year closure

·       EDQM clarifies the stepwise process to getting a CEP or having a change approved

·       Reference standards monthly newsletter – October 2025

·       EDQM contributes to article on NGS for adventitious virus detection.

·        

Ireland

The Health Products Regulatory Authority (HPRA)

·       2024 annual report on the sale of veterinary antimicrobials in Ireland

USA

The US Food and Drug Administration (USFDA)

·       Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use

·       CGMP for Medical Gases

·       ICH Q3E Guideline for Extractables and Leachables

United states Pharmacopia (USP)

·       〈661.1〉 Plastic Materials of Construction

·       〈382〉 Elastomeric Component Functional Suitability in Parenteral Product Packaging /Delivery Systems

·        

International

The Pharmaceutical Inspection Co-operation Scheme (PIC/S)

·       New PIC/S Chairperson and Executive Bureau. 

·       Jordan JFDA joins PIC/S

Switzerland

Swissmedic

·       Swissmedic confirms its decision on use of titanium dioxide in medicines

Products

·       MHRA approves Siiltibcy as a diagnostic aid for Mycobacterium tuberculosis infection, including disease

·       MHRA approves inavolisib for the treatment of breast cancer

Conferences / webinars

·       Pyrogen testing 2.0: Ethical, Evolving and Eco-friendly

·       2025 EDQM virtual training programme

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

Three convicted in major MHRA investigation into illegal online supply of medicines

Operation Lamborghini disrupts a multimillion-pound criminal network supplying controlled drugs and unauthorised medicines online

Three individuals have been convicted for their roles in an organised criminal group responsible for the large-scale unlawful supply of unauthorised medicinal products online, one individual was found not guilty. A fifth pleaded guilty at an earlier hearing.

Everton Reynolds, Paul Billingham, and Junior Ranger, were convicted by a jury of conspiracy to supply controlled drugs (Class B and C), and conspiracies to supply unauthorised medicines, prescription only medicines, following a 6-week trial at Wolverhampton Crown Court. Anita Rama had pleaded guilty to all the charges at an earlier hearing.

The investigation identified almost two million doses of medicinal controlled drugs and other medicines linked to the criminal group.

New MHRA-supported research reveals patterns of vaccine-derived poliovirus spread and implications for global eradication efforts

This study provides crucial insights for targeting rapid response strategies and improving polio surveillance worldwide Analysis shows that whilst most outbreaks remain relatively contained – with a median of just 4.5 cases – some have spread extensively, affecting up to 14 countries.

The research also demonstrates that historic wild-type poliovirus spread patterns closely resemble current cVDPV2 transmission routes, with movement largely sustained through unidirectional flow between adjacent countries.

Since March 2021, a novel type-2 oral poliovirus vaccine (nOPV2), engineered to be more genetically stable. has been deployed under WHO Emergency Use Listing. The vaccine achieved full WHO prequalification in December 2023. The novel vaccine nOPV2 was designed in large part by scientists at the MHRA.

Europe

European Medicines Agency (EMA)

Q&A on impact of EU-USA Mutual Recognition Agreement on marketing authorisation applications and relevant variations - Revised 1st October 2025

Following an evaluation through a pilot programme the EU GMP/GDP Inspectors Working Group agreed to enable the voluntary provision of the EU-US MRA foreseen in Article 3(1) of the agreement to rely on the outcome of US FDA inspections conducted outside the US as of 1 October 2025.

Following a case-by-case assessment and the application of a risk-based approach EU national competent authorities may decide to apply reliance and to postpone the conduct of an EU inspection that would normally be required during the assessment timelines of a Marketing Authorisation Application or variation. A proactive provision of FDA inspection reports by applicants in the pre- submission phase or with the filing of the MAA or variation will facilitate the application of this provision.

Fighting medicine shortages: It takes a team

EMA), together with consumer and healthcare professional organisations, is running the #ItTakesATeam campaign to highlight how different actors work together to help patients during medicine shortages. Medicine shortages are a complex issue with no single solution. Fighting them takes a team. Through the #ItTakesATeam campaign, EMA and its partners aim to raise awareness of the actions taken at EU level to prevent and manage medicine shortages, and to highlight the role of each actor involved.

EMA, together with consumer and healthcare professional organisations, is running the #ItTakesATeam campaign to highlight how different actors work together to help patients during medicine shortages. Medicine shortages are a complex issue with no single solution. Fighting them takes a team. Through the #ItTakesATeam campaign, EMA and its partners aim to raise awareness of the actions taken at EU level to prevent and manage medicine shortages, and to highlight the role of each actor involved.

Meeting Summary — Medicine Shortages SPOC Working Party

Minutes of the 25 Sept 2025 SPOC working party have been published as of 31 October.

How the safety of medicines is ensured in the European Union

EMA and the EU Member States work together to supervise the safety of medicines through a unique collaborative network that draws on expertise from across the EU. The Member States conduct a wide range of activities at national level, such as supervising the collection of suspected side effects or collecting safety signals for authorised medicines. For some activities, one Member State may carry out assessments on behalf of the EU.

Data gathered from across the EU are centralised and analysed by EMA’s safety committee (the Pharmacovigilance Risk Assessment Committee; PRAC), which plays a key role in this system. Each EU Member State, as well as Iceland and Norway, appoints safety experts to the PRAC. The European Commission also nominates six independent

scientific experts, as well as members representing patient and healthcare professional organisations. The PRAC meets monthly to provide scientific expertise on all aspects of human medicines’ safety.

Quality of medicines Q&A: Part 1

This Q&A was updated 10 November 2025, whereby 'Novel or complex manufacturing process in Q.II.b.1 and Q.II.b.4' section was added

Abbreviation of names of days on calendarised blisters

Rev. 2 Changes since publication: All abbreviations for Malta revised; Tuesday abbreviation for Iceland revised.

[assuring artwork compliance can be pretty troublesome when you supply multiple markets. This useful table provides a good tool for you to check against- and it’s probably worth checking for all markets listed, not just Malta & Iceland. MBH.]

Combination Products Operational Group

The Combination Products Operational Group (COMBO) fosters dialogue and addresses regulatory challenges for combination products. These are medicinal products used in combination with a medical device.

The group aims to facilitate dialogue on regulatory challenges at the intersection of pharmaceutical and medical device frameworks.

It engages stakeholders across medicine, medical device, and in vitro diagnostic sectors to promote a shared understanding of respective regulatory frameworks, roles, and assessment processes.

This aims to foster alignment and coordination in the assessment of products at the interface of medicines and medical devices.

It also explores potential solutions to technical and procedural challenges for combination products in a collaborative way, with the aim to develop and update guidance.

Acceleration of regulatory procedures during public health Emergencies (Annex 1 of the EMA Health Threats Plan)

This document provides an overview of EMA’s rapid formal review procedures in response to public health emergencies. Outside public health emergency context, acceleration of procedures remains possible (e.g. based on shortened procedural timetable agreed with the Rapporteurs and respective scientific body) on case-by-case basis in exceptional cases, when EMA considers that acceleration of the procedure will help to tackle an important public health threat.

For accelerated procedures that are expected to be used extensively, upon declaration of a public health emergency more detailed acceleration process descriptions (e.g. as standard operating

procedures or working instructions) may be developed or updated based on those used during a past public health emergency, for internal use by the EMA.

Q&A on classification of a product (veterinary) as intended for a limited market according to Article 4(29) and/or eligibility for authorisation according to Article 23

This Q&A document is aimed at providing guidance to assessors and applicants on relevant key criteria for classifying a product as intended for a limited market and confirming that the product is eligible for a marketing authorisation for a limited market.

The document addresses aspects not covered by the European Commission Notice:Guidance to Applicants - Veterinary Medicinal Products (Corrigendum, C/2024/90009) in order to facilitate intended marketing authorisation applications for limited markets.

Notification on arrangements for requesting EMA certificates through urgent and standard procedure for December 2025

The EMA will be closed from 23 December 2025 to 4 January 2026.

The arrangements for issuing certificates of medicinal products submitted through urgent procedure and through the standard procedure in December 2025 are detailed in this document,

Variations revised Q&As

Sections of these Q&As have been updated as of November 2025

The European Directorate for the Quality of Medicines & HealthCare (EDQM)

Certification monthly report of activities: End of October 2025

The latest monthly activity report for the Certification of Substances Department (DCEP) is now available.

EDQM end-of-year closure

Order and shipment deadlines have been established for publications and reference standards, taking into account the closure of the EDQM offices from Tuesday 23 December 2025 (12 noon CET) to Monday 5 January 2026 (8 a.m. CET).

EDQM clarifies the stepwise process to getting a CEP or having a change approved

This document is intended to clarify, for all types of application, the process and steps for obtaining a certificate of suitability (CEP) or having a change approved, from the submission of the application to the communication of the final decision. The steps and the associated timelines are unchanged, but are now explained in greater detail and accompanied by descriptive flowcharts.

This document also clarifies the interactions between evaluation and Good Manufacturing Practice (GMP) inspection activities of the CEP procedure.

Reference standards monthly newsletter – October 2025

2 new European Pharmacopoeia reference standard and 10 replacement batches released in October 2025

EDQM contributes to article on NGS for adventitious virus detection.

EDQM continues its collaboration on next-generation sequencing (NGS, also called high-throughput sequencing, or HTS), contributing directly to the 4th Conference on NGS for Adventitious Virus Detection held on 4 and 5 December 2024, and to the subsequent report published in Biologicals. The report summarises the outcomes of the conference and underlines the growing interest in NGS for adventitious virus detection, particularly in view of its recent introduction in the ICH Q5A (R2) and the new Ph. Eur. general chapter.

NGS is a powerful technology for broad virus detection, developed to complement conventional techniques that have failed to detect novel or even known viruses in certain cases. The complexity of this recent technique has created several challenges in regulation, standardisation and validation, among others, that are being addressed by a diverse array of stakeholders, including the U.S. FDA, the EDQM, the World Health Organization and numerous regulatory bodies and pharmaceutical companies worldwide.

Ireland

The Health Products Regulatory Authority (HPRA)

2024 annual report on the sale of veterinary antimicrobials in Ireland

The HPRA has released its yearly report on the sale of antimicrobials used in animals. Collecting and publishing this data is required by European veterinary medicines legislation, which aims to address the public health issue of antibiotic resistance. This information helps us understand the volume and types of veterinary antibiotics sold every year. 

In 2024, approximately 76 tonnes of antibiotics for animals were sold in Ireland. This is similar to the amounts sold in 2022 and 2023.

United States of America

The US Food and Drug Administration (USFDA)

Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use

This guidance is intended to assist abbreviated new drug application (ANDA) applicants that reference a drug product intended for parenteral, ophthalmic, or otic use in seeking approval of a drug that is qualitatively (Q1) different or quantitatively (Q2) different from the reference listed drug (RLD) with respect to the pH adjuster(s). This guidance describes how FDA intends to evaluate a request for a waiver of Agency requirements for a Q1 or Q2 difference in pH adjuster, including recommendations on the type of information to provide in support of such a waiver request. This guidance finalizes the draft guidance of the same title issued on April 14, 2022.

CGMP for Medical Gases

This guidance is intended to assist manufacturers of medical gases in complying with regulations CGMP that become effective on December 18, 2025 (note, the conforming amendments to the CGMP requirements for combination products become effective February 2, 2026). These regulations are specific to medical gases for human and animal use and, like all CGMP requirements, contain the minimum requirements to ensure that manufacturing processes operate under a state of control to meet prespecified quality standards for identity, strength, quality, and purity, but are tailored more narrowly to how medical gases are manufactured, packaged, labeled, stored, and distributed.

ICH Q3E Guideline for Extractables and Leachables

The draft guidance and supporting document were prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The draft guidance presents a holistic framework and process for the assessment and control of extractables and leachables (E&L) for pharmaceutical products. The draft guidance builds upon ICH impurity guidances on new drug substances (ICH Q3A) and new drug products (ICH Q3B), residual solvents (ICH Q3C), and elemental impurities (ICH Q3D), as well as DNA reactive (mutagenic) impurities (ICH M7). In addition to outlining E&L safety assessment principles, the draft guidance includes draft supporting documentation of Class 3 leachable monographs. The draft guidance is intended to provide approaches to risk-based assessment and control of E&L to ensure patient safety and pharmaceutical product quality.

United states Pharmacopia (USP)

〈661.1〉 Plastic Materials of Construction

In accordance with the Rules and Procedures of the Council of Experts, the General Chapters—Packaging and Distribution Expert Committee has revised the 〈661.1〉 Plastic Materials of Construction chapter.

Comments were received indicating that a revision to the Stabilizers in the Polyvinyl Chloride section was needed.

The 〈661.1〉 Plastic Materials of Construction Revision Bulletin supersedes the to be official chapter.

〈382〉 Elastomeric Component Functional Suitability in Parenteral Product Packaging /Delivery Systems

The General Chapters–Packaging and Distribution Expert Committee intends to revise 〈382〉 Elastomeric Component Functional Suitability in Parenteral Product Packaging /Delivery Systems.

Stakeholder comments noted that the Needle Self-Sealing Capacity Test requires 1.5 penetrations of elastomeric closures, differing from ISO 11608-3’s 1.0 penetration. The USP requirement could cause excessive punctures—up to 252 per cartridge—which may lead to leak test failures not representative of typical patient use.

To address this, USP will revise the requirement to a maximum of 1.0 scheduled penetration.

It is anticipated that the revision will be posted as a Revision Bulletin on January 30, 2026 pursuant to the Rules and Procedures of the Council of Experts.

[I’m unsure as to how the figure of 252 punctures per cartridge was derived. MBH]

International

The Pharmaceutical Inspection Co-operation Scheme (PIC/S)

New PIC/S Chairperson and Executive Bureau.

A new PIC/S Chairperson and Executive Bureau were elected as from 1 January 2026 by the PIC/S Committee, the PIC/S Committee unanimously elected Ms Kathleen Sinninger (US FDA) as Chairperson for the period 2026-2027. Ms Sinninger will be assisted by Mr Gwylim Janssens (Netherlands / IGJ), PIC/S Deputy Chairperson.

Jordan JFDA joins PIC/S

The PIC/S Committee has invited the Jordan Food and Drug Administration (JFDA) to join the PIC/S Scheme. JFDA will become the 57th Participating Authority as from 1 January 2026.

Switzerland

Swissmedic

Swissmedic confirms its decision on use of titanium dioxide in medicines

Swissmedic has noted the European Commission’s analysis and considers a coordinated international approach to be appropriate. The use of titanium dioxide in medicinal products therefore also continues to be permitted in Switzerland.

Products

[This section makes reference to some of the most notable new products approved during the past month and focuses on approvals of medicines for which there is a previously unmet need and / or where approvals have been made using shared information from other trusted regulators.MBH]

MHRA approves Siiltibcy as a diagnostic aid for Mycobacterium tuberculosis infection, including disease

MHRA has approved Siiltibcy, a diagnostic aid for detection of Mycobacterium tuberculosis infection, including tuberculosis disease, in adults and children.

Siiltibcy is given as an injection in the skin of the forearm. It contains two active substances, rdESAT-6 and rCFP-10, which are proteins specific of Mycobacterium tuberculosis that have been produced in a laboratory. If a person has been infected with Mycobacterium tuberculosis, her/his immune system will respond by producing cytokines (inflammatory proteins) which cause induration (hardening) at the site where SIILTIBCY was injected

Siiltibcy has been evaluated in 3 main studies involving over 2000 participants, including children.

This product was submitted and approved via an international recognition procedure.

The approval was granted to Serum Life Sciences Ltd.

MHRA approves inavolisib for the treatment of breast cancer

MHRA hasapproved inavolisib (Itovebi) for the treatment of adults with a type of breast cancer called HR-positive, HER2-negative breast cancer. Inavolisib is a film-coated tablet which is to be administered orally. The approval of inavolisib provides a new targeted treatment for people with advanced breast cancer that has returned or spread after hormone therapy.

The approval was granted to ROCHE PRODUCTS LIMITED.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Conferences

Pyrogen testing 2.0: Ethical, Evolving and Eco-friendly

Registration is now open for this upcoming joint EDQM-EPAA symposium to be held 25-26 February 2026.

This symposium will be of particular interest to professionals from the pharmaceutical and biopharmaceutical industries, contract laboratories and health authorities. Participation is free of charge.

2025 EDQM virtual training programme

This on-line virtual training programme comprises of nine independent modules on the Ph. Eur., reference standards and the CEP Procedure designed to enhance your expertise.

The training modules will focus on chemically defined active substances and medicinal products. Dates: 01-12 December 2025

And finally…

We hope that our readers find our reviews to be both informative and helpful in keeping up to date with pharmaceutical legislation and regulatory guidance.

Further information on these and other topics can be found in recent versions of the “Regulatory Update” on the PHSS website (members area) by utilising the hyperlink within that particular Update.

GMP Update is compiled by Malcolm Holmes C.Chem. MRSC, a member of the PHSS Management Committee.