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

EJPPS vol 30.3A

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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 regulatory authorities.

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

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

·         Helping bring phage medicines to UK patients – guidance for industry

·         Decentralised manufacture hub

·        Decentralised Manufacture: Marketing Authorisation application

·        Decentralised manufacture: The designation step

·        First major overhaul of medical device regulation comes into force across Great Britain

·        AI breakthroughs drive expansion of ‘Airlock’ testing programme to support AI-powered healthcare innovation

·        UK MHRA leads safe use of AI in healthcare as first country in new global network

·        Final Business Plan for 2023-2026 Corporate Plan

·        MHRA seizes illegal medicines as part of an annual global coordinated operation

·        GLP-1 medicines and patients hospitalised by acute pancreatitis

EU

European Medicines Agency (EMA)

·        EMA Management Board: highlights of June 2025 meeting

·        Annual activity report 2024

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

·        Certification monthly report

·        EDQM reference standards monthly newsletter – May 2025

·        Ph.Eur 12^th Edition

·        EDQM-on air 8th edition- Removal of rabbit pyrogen test

Ireland

The Health Products Regulatory Authority (HPRA)

·        Over 1 million units of illegal medicines detained by the HPRA in 2024

USA

The US Food and Drug Administration (USFDA)

·        Recommendations for Complying With Over-the-Counter Monograph Procedure for Minor Changes C001: Minor Changes to Solid Oral Dosage Forms for Certain Over-the-Counter Monograph Drugs

·        ANDAs: Pre-Submission Facility Correspondence Related to Prioritized Generic Drug Submissions

·        Post-Warning Letter Meetings Under GDUFA

·        Q1 Stability Testing of Drug Substances and Drug Products

International

Products

·        MHRA approves aumolertinib to treat non-small cell lung cancer

·        MHRA approves UK’s first anti-PD-1 monoclonal antibody for treatment of aggressive form of lung cancer

·        Chikungunya vaccine temporarily paused in people aged 65 and over.

·        New stem cell therapy to treat patients with blood cancers

Conferences

·        PHSS Annual Conference

·        PHSS - QP Forum Conference 2025

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

Helping bring phage medicines to UK patients – guidance for industry

MHRA has published the UK’s first official guidance to support the safe development and use of phage therapies – treatments that use viruses to target and destroy harmful bacteria. The guidance covers both combined phage products designed for common infections and circulating strains, as well as personalised phage therapies that are tailored for individual patients with rare or highly resistant infections.

While some patients in the UK have already received phage therapy under compassionate use – with phages imported from abroad – there are currently no licensed phage medicines on the UK market.

Phage therapies use bacterial viruses – called bacteriophages – that attack specific bacteria without harming human cells. They have received increased interest in recent years as a potential way to treat antibiotic-resistant infections. Bacteriophages are naturally occurring viruses that infect specific bacteria. Unlike antibiotics, which can harm helpful bacteria too, phages typically target only one species or strain of bacteria. They work by attaching to the bacteria, injecting their genetic material, and destroying it. In medicine, phages can be tailored to attack the bacteria causing an infection, with less impact on the body’s healthy bacteria.

Companies interested in developing bacteriophage treatments can access scientific advice from the MHRA at any stage of development.

Decentralised manufacture hub

Point of Care (POC) and Modular Manufacture (MM) are collectively described as Decentralised Manufacture (DM).

DM processes allow medicinal products to be made close to or at the location of the patient for administration of the medicine. DM medicines encompass a wide and diverse array of different manufacturing techniques which may not be utilised in conventional centralised manufacturing.

All DM manufactured products will be based on a ‘hub and spoke’ manufacturing model with a Control Site at the hub and manufacturing sites at the spokes. The Control Site will be the only location named on the manufacturers licence and will manage overall aspects of manufacturing,

To support DM, the UK has amended the Human Medicines Regulations 2012 and the Medicines for Human Use (Clinical Trials) Regulations 2004 through Statuatory Instrument 2025.87.

Decentralised Manufacture: Marketing Authorisation application

Guidance on applying for a Marketing Authorisation for Decentralised Manufacture, including eligibility, process, and requirements.

Decentralised manufacture: The designation step

This Guidance is MHRA’s mechanism for evaluating the justifications supplied by applicant organisations who plan to utilise decentralised manufacture.

First major overhaul of medical device regulation comes into force across Great Britain

From 16 June 2025, a landmark reform of how medical devices are regulated in Great Britain takes effect, as part of the MHRA’s broader transformation of the UK’s medical device regulatory framework.

The new Post-Market Surveillance (PMS) regulations require device manufacturers to actively track the safety and performance of products already in use. This will help identify potential safety issues earlier and strengthen protection for patients and the public through faster responses to incidents and emerging risks.

The regulations will ensure all manufacturers have an effective system in place to monitor devices once they are in use, collect comprehensive safety data, report serious incidents, and take swifter action when issues arise. New trend reporting requirements will help the MHRA and industry spot patterns and intervene earlier to protect patients.

AI breakthroughs drive expansion of ‘Airlock’ testing programme to support AI-powered healthcare innovation

MHRA opens a second round of applications to test cutting-edge AI medical technologies following successful pilot phase.

A £1 million boost to the MHRA’s pioneering AI Airlock programme will expand access to a first-of-its-kind regulatory testing ground where companies can work directly with regulators to safely test new AI-powered medical devices and explore how to bring them to patients faster, through streamlined regulations.

This programme is backed by the Government’s new Regulatory Innovation Office (RIO), which is supporting regulators to test more agile, flexible ways of working that can keep pace with emerging technologies like AI. By cutting unnecessary red tape and making the UK a more innovation-friendly environment

UK MHRA leads safe use of AI in healthcare as first country in new global network

The move puts the MHRA at the centre of global efforts to get trusted AI tools safely into clinics faster – supporting earlier diagnosis, cutting NHS waiting times, and backing growth in the UK’s health tech sector.

The MHRA will draw on its leading work at home to help shape the network from the ground up. That includes AI Airlock, a global leading example of a regulatory sandbox for AI medical devices – which lets companies test new tools with the regulator before wider NHS roll-out.

The MHRA has updated guidance and begun reforming medical device safety regulations, and continues to adapt them for fast-developing areas such as adaptive and generative AI. The MHRA is also working with researchers, National Institute for Health and Care Excellence (NICE) and the NHS to strengthen real-world evidence on how these tools perform in practice.

Final Business Plan for 2023-2026 Corporate Plan

The new Business Plan sets out priorities for 2025–26 and includes commitments towards:-

·        Strengthening patient safety further, by making safety monitoring faster, more efficient, and more data driven

·        Implementing an agile and risk-proportionate regulatory environment that enables growth

·        Embedding changes needed to continue maintaining consistent performance and efficient delivery of core services within predictable timeframes.

MHRA seizes illegal medicines as part of an annual global coordinated operation

Operation Pangea, coordinated by Interpol and involving around 90 countries, is the world’s largest initiative of its kind. This year’s operation took place between December 2024 and May 2025.

Working with law enforcement partners, the MHRA’s Criminal Enforcement Unit (CEU) seized 7.7 million doses of illicit medicines with an estimated value of £17.2m. Among the products seized in the UK were various prescription-only medications including powerful painkillers, anti-depressants and sleeping pills.

The CEU also coordinated several arrest operations, denied gangs access to almost £1.4m in criminal profits, and removed 367 websites and social media accounts offering medical products to the public illegally.

GLP-1 medicines and patients hospitalised by acute pancreatitis

The Yellow Card Biobank, launched by the MHRA and Genomics England, will start investigating whether the risk of acute pancreatitis from GLP-1 injections for weight loss and Type 2 diabetes may be influenced by an individual’s genes.

Patients are being asked to report it to the MHRA’s Yellow Card Scheme. Healthcare professionals are also being asked to help recruit for the study by reporting Yellow Cards on behalf of patients experiencing acute pancreatitis while taking GLP-1 medicines.  

When a Yellow Card report is received, the MHRA will contact patients to ask if they would be willing to take part in the Biobank study. This would involve providing further information and submitting a saliva or spit sample which will be used to explore whether some people are at a higher risk of acute pancreatitis when taking these medicines due to their genetic makeup.

[Rather an unusual item to include in these pages (and also I was unsure whether to include it here under MHRA or under the products section). Nevertheless, I thought it important to raise awareness here. MBH.]

Europe

European Medicines Agency (EMA)

EMA Management Board: highlights of June 2025 meeting

Highlights include:-

·        Management Board meets the African Medicines Agency Governing Board

·        Positive assessment of EMA activities in 2024

·        Update from CHMP chair

·        Election of new vice-chair

·        Progress with clinical trials in the EU

·        EMA code of conduct

Annual activity report 2024

The main focus areas of the Agency for the year 2024 comprised enhancing the assessment of key medicines, translating innovation into medicines that reach and provide benefits to more patients based on better data and evidence generation, and preparing for the review of the EU pharmaceutical legislation to seize the opportunity to future-proof medicines regulation in the EU.

In terms of assessment of key medicines, the Agency continued to use haematology and oncology products as pathfinders to enhance assessments, provided regulatory training for oncologists, and strengthened international partnerships.

Regarding translating innovation into medicines, achievements included the growth of the real-world data network DARWIN EU®, and the ACT EU initiative to strengthen the generation of clinical evidence. In preparation for the revision of the Pharmaceutical Legislation, various activities and initiatives were undertaken by EMA and the Heads of Medicines Agencies (HMA). The new European medicines agencies network strategy (EMANS 2028) developed in the course of 2024, lays the groundwork for future implementation of the Legislation.

In the area of international cooperation, EMA supported the establishment of the African Medicines Agency, in close collaboration with African and European regulators. EMA continued fostering international regulatory cooperation, by leveraging its position as Chair of the International Coalition of Medicines Regulatory Authority (ICMRA) and by hosting and coordinating the 2024 Steering Committee and 7th conference of the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH).

[This is a 245 page report. Most of our readers could perhaps start at page 12 and then look at section 1 Achievements. I suspect this will cover most points of interest for our members. MBH]

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

Certification monthly report

The report for the period ending May 31 2025 is available.

EDQM reference standards monthly newsletter – May 2025

Two new European Pharmacopoeia reference standard and fifteen replacement batches released.

Ph.Eur 12^th Edition

The launch of the European Pharmacopoeia (Ph.Eur online platform marks the beginning of a new era for the Ph. Eur. When you renew your licence you will be able to consult the Ph. Eur. texts you need on a redesigned, user-friendly platform launched alongside the 12th Edition. In the new publication cycle, each edition consists of three issues published over a 12-month period. The first of these issues, 12.1, will be published at the end of June 2025.

The new Ph. Eur. 365-day licence is available now and will provide a year’s access to the Ph. Eur. Online platform from the date of activation of a licence key (EPID).

EDQM-on air 8th edition- Removal of rabbit pyrogen test

The rabbit pyrogen test (RPT), a standard safety test designed to determine the presence of certain fever-inducing contaminants, called pyrogens, in medicines, was added to the European Pharmacopoeia in the 1970s. Today, it is estimated that some 400 000 rabbits are used worldwide each year to perform this test. Viable alternatives exist, however, and the EDQM has been at the forefront of efforts to promote their use.

In June 2024, the RPT was definitively removed from the European Pharmacopoeia texts. How was this accomplished? Gwenaël Cirefice and Emmanuelle Charton from the European Pharmacopoeia Department explain how the EDQM’s commitment to animal welfare in Europe and beyond led to such an important milestone being achieved.

[If you can spare 24 minutes it’s a worthwhile listen, particularly if you are not aware of the background. Certainly, it is good to see the EU eliminating this animal test for medicinal products in the EU.

For those wanting more background reading see meeting report ex Biologicals journal vol 84 November 2023. MBH]

Ireland

The Health Products Regulatory Authority (HPRA)

Over 1 million units of illegal medicines detained by the HPRA in 2024

Announcing its annual enforcement data, the HPRA confirmed that it detained 1,000,984 dosage units of falsified and other illegal medicines in 2024. The data highlights that anabolic steroids, sedatives and erectile dysfunction products are consistently the most detained categories of medicines year on year.

The HPRA states that the supply of online prescription medicines into and within Ireland is illegal and that consumers are taking a risk with their health if they seek to buy outside of the regulated pharmacy setting or via the internet.

The HPRA detention figures for 2024 include:-

·        Anabolic steroids - 203,088 units detained (20%^)

·        Sedative medicines - 146,686 units detained (15%)

·        Erectile dysfunction - 119,289 units detained (12%)

·        Analgesic medicines - 113,555 units detained (11%)

The HPRA also noted an upward trend in detentions of GLP-1 products including, predominantly, semaglutide and liraglutide. While overall numbers remain low, 1,582 units of GLP-1 products were detained in 2024 compared to 568 units in 2023 and just 40 units in 2022.

United States of America

The US Food and Drug Administration (USFDA)

M13B Bioequivalence for Immediate-Release Solid Oral Dosage Forms: Additional Strengths Biowaiver

This draft guidance for industry was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

The intent of this draft guidance is to provide harmonized criteria and data that support waivers for drug applications with multiple strengths when in vivo BE has been demonstrated for at least one strength using the principles outlined in the final guidance M13A  published in October 2024.

This document is not for implementation and is issued for comment only. Comments should be submitted by 1 Aug 2025

Recommendations for Complying With Over-the-Counter Monograph Procedure for Minor Changes C001: Minor Changes to Solid Oral Dosage Forms for Certain Over-the-Counter Monograph Drugs

This proposed order, if finalized, will specify the requirements that must be met for a minor change in dosage form of an OTC monograph drug from a capsule or tablet to a chewable tablet, ODT, or film.

Comment by 3 Oct 2025

ANDAs: Pre-Submission Facility Correspondence Related to Prioritized Generic Drug Submissions

This final guidance describes the facility information to be submitted in a pre-submission facility correspondence (PFC) and how FDA will use this information to set a review goal for a priority abbreviated new drug application (ANDA).

This guidance incorporates a program enhancement agreed upon by the Agency and industry as part of the negotiations relating to reauthorization of the Generic Drug User Fee Amendments (GDUFA). This guidance finalizes for implementation the draft guidance of the same title issued on December 5, 2022.

Post-Warning Letter Meetings Under GDUFA

This final guidance provides information on the implementation of the Post-Warning Letter Meeting process for certain drug manufacturing facilities, a program enhancement agreed upon by the Agency and industry.

Specifically, this guidance describes the process detailed in the GDUFA III commitment letter for how an eligible facility may request a Post-Warning Letter Meeting with FDA regarding the facility’s ongoing remediation efforts to address current good manufacturing practice (CGMP) deficiencies described in a warning letter, how to prepare and submit a complete meeting package, and how FDA intends to conduct the Post-Warning Letter Meeting.

Q1 Stability Testing of Drug Substances and Drug Products

This draft guidance for industry was prepared under the auspices of the ICH.

The draft guidance outlines stability data expectations for drug substances and drug products to support drug product marketing, including marketing authorization applications and, where applicable, drug master files.

The revision also provides stability related guidance for product categories such as advanced therapy medicinal products, vaccines, and other complex biological products including combination products that were not previously covered under the existing stability guidances.

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 aumolertinib to treat non-small cell lung cancer

Aumolertinib can be used in patients who have tested positive for a mutation in a gene called epidermal growth factor receptor (EGFR) and who have not yet received treatment for their cancer which has spread to other parts of the body. In certain circumstances it can be used even if the metastatic cancer has been treated before.

This medicine is administered in tablet form, to be taken orally.

The new marketing authorisation was granted to SFL Pharmaceuticals Deutschland GmbH. This product was submitted and approved via a national procedure.  

MHRA approves UK’s first anti-PD-1 monoclonal antibody for treatment of aggressive form of lung cancer

MHRA has approved serplulimab (Hetronifly) to treat adults with extensive-stage small cell lung cancer (ES-SCLC), which has not previously been treated, and has spread within the lungs or to other parts of the body.

SCLC is a fast-growing cancer that typically develops in the airways of the lungs. It accounts for 10-15% of lung cancer cases and is often diagnosed at a late stage when the cancer has already spread. Serplulimab is a monoclonal antibody that supports the immune system by blocking PD-1, a receptor some cancer cells use to avoid detection.

Chikungunya vaccine temporarily paused in people aged 65 and over.

This is a precautionary measure while the MHRA conducts the safety review.

Following global reports of serious adverse events in older people, the government’s independent expert advisory body, the Commission on Human Medicines (CHM), has temporarily restricted use of a chikungunya vaccine called IXCHIQ in people aged 65 and over until a further safety review has been concluded.

The MHRA is working with the manufacturer of the vaccine, Valneva.

This vaccine was approved by the MHRA in February 2025. There will be no impact on operational issues as this vaccine is not yet available in the UK and therefore there is no immediate safety concern.

New stem cell therapy to treat patients with blood cancers

EMA has recommended granting a conditional marketing authorisation in the EU for Zemcelpro (dorocubicel / unexpanded umbilical cord cells) to treat adults with haematological malignancies (blood cell cancers).

Zemcelpro can be used in patients requiring an allogeneic haematopoietic stem cell transplantation (allo-HSCT, transplantation of stems cell from a donor) following myeloablative conditioning (chemotherapy and/or radiotherapy) for whom no other type of suitable donor cells is available.

Zemcelpro is a cell therapy containing stem cells from a donor’s umbilical cord blood, some of which have been grown and multiplied (dorocubicel). By increasing the number of cells, Zemcelpro makes the stem cells from a small cord blood unit more effective.

Zemcelpro was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.

Conferences

PHSS Annual Conference

This year's PHSS Annual Conference is in association with BioMerieux.

There will be a site tour locally (TBC) and a networking dinner, which BioMerieux is sponsoring.

The conference day on the 17th of September, is packed with keynote speakers, industry SME, and MHRA (TBC).

PHSS - QP Forum Conference 2025

The Conference is designed for all QPs and aspiring QPs. Listen and interact on topics and the latest developments regarding the duties and responsibilities of QPs.

This annual event has proved valuable to those in the QP role.

And finally…

We hope that our eaders 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 cmpiled by Malcolm Holmes C.Chem. MRSC, a member of the PHSS Management Committee.