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

EJPPS vol 30.2C 

EJPPSVol 30.2C.pdf

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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 and Australian regulatory authorities.

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

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

·         GMP & GDP Certificates- blog

·         Webinar – decentralised manufacturing regulations update

EU

European Medicines Agency (EMA)

·         Concept paper on the revision of Part IV Guidelines on GMP specific to Advanced Therapy Medicinal Products

·         Regulatory acceptance of new approach methodologies (NAMs) to reduce animal use testing

·         SME office annual report 2024

·         Minutes – Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG)

·         Q&A for biological medicinal products

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

·         Validation of eCTD submissions for CEP applications

·         EPC adopts mycoplasmas general chapter and monographs, updated to incorporate latest analytical developments

·         Reference standards monthly newsletter – April 2025

·         All-digital launch of the 12th edition of the Ph. Eur.

·         “How to read a CEP” – Revised guideline.

Ireland

The Health Products Regulatory Authority (HPRA)

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

USA

Presidential decree

·         Regulatory Relief to promote domestic production of Critical Medicines

The US Food and Drug Administration (USFDA)

·         Replacing Color Additives in Approved or Marketed Drug Products

International

Australia

Therapeutic Goods Administration (TGA)

·         Updated GMP clearance information

Products

·         Vimkunya vaccine approved

·         vaccine to protect against pneumococcal infections such as pneumonia and meningitis

·         First UK treatment for congenital thrombotic thrombocytopenic purpura (cTTP)

·         MHRA approves world’s first low-carbon version of COPD inhaler Trixeo Aerosphere

·         First UK treatment for adults with moderate to severe Thyroid Eye Disease (TED)

·         Guselkumab for Crohn’s disease and ulcerative colitis

·         New treatment for adults with acute lymphoblastic leukaemia

Conferences – web based events

·         MHRA webinar on Decentralised Manufacturing Regulations-Update

·         European shortages monitoring platform (ESMP): updates and question and answer (Q&A) clinic for marketing authorisation holders (MAHs

·         “Certified for success” –CEP conference

·         PHSS Sterile Product Conference 2025

·         PHSS Annual Conference

·         PHSS - QP Forum Conference 2025

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

GMP & GDP Certificates - blog

The purpose of this blog is to describe the MHRA approach to the validity date of UK issued certificates confirming compliance with Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP).

Webinar – decentralised manufacturing regulations update

See Conferences – web based events section of this report’

Europe

European Medicines Agency (EMA)

Concept paper on the revision of Part IV Guidelines on GMP specific to Advanced Therapy Medicinal Products

This concept paper aims to outline the rationale, objectives, and proposed changes for updating Part IV – GMP specific to ATMP of the good manufacturing practice (GMP) guide Eudralex Volume 4 following the revision of Annex 1 which came into operation in August 2023.

As the Part IV is an EU standalone guideline and that the sector is to abide solely for reference, it should be revised independently to address recent developments in the manufacture of sterile medicinal products.

Since the introduction of the revised GMP Annex I for the manufacture of sterile products has modified and clarified some requirements compared to the current ATMP guideline, the proposed revision of the ATMP guideline is to align with the current Annex 1 while maintaining a flexible approach for the production of ATMPs.

The current ATMP guideline does not reflect the advances of new technologies in the manufacture of advanced medicinal products; the proposed revision will give further clarifications on the expectations how to qualify, control and manage clean rooms and closed systems (isolators and Restricted Access Barriers Systems (RABS) in order to prevent detrimental impact on product but it will maintain open to the use of biosafety cabinets due to of the numerous manual manipulations associated with the individualized batches .

The proposed revision will embrace the use of new technologies that are not currently covered in the current version (e.g. automated advanced technology, (closed) single use systems, fast rapid microbiological testing methods).

It is noted that the current revision will only focus on the sterile manufacture sections related to the updated version of the Annex 1 and not to update any other topics/sections outside of that scope.

Comments should be submitted by 8 July 2025

Regulatory acceptance of new approach methodologies (NAMs) to reduce animal use testing

New approach methodologies (NAMs) refer to novel methods that are compliant with the so-called 3Rs principles for the ethical use of animals in medicine testing across the European Union (EU). '3Rs' stands for replacement, reduction and refinement of animal use. The European Medicines Agency (EMA) supports the regulatory acceptance of these new approach methodologies. This ensures NAMs are scientifically sound and can be used in regulatory decision-making.

This document covers:-

·         Regulatory acceptance of new approach methodologies: how to interact with EMA

·         Achieving regulatory acceptance of new approach methodologies: what to consider

SME office annual report 2024

The SME Office was set up to address the particular needs of smaller companies.

Highlights of 2024:-

• Increased success rates for marketing authorisation applications for human and veterinary medicines.

• Greater figures of SMEs in the veterinary medicines sector registered with EMA.

• Higher figures of regulatory assistance provided by the SME Office.

• Increased support to innovative developments through Innovation Task Force (ITF) briefing meetings.

• Higher figures of PRIME designations and uptake of scientific advice for orphan designated medicines.

• Continued training & education of SMEs including EIC-funded beneficiaries.

Minutes – Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG)

The European Commission (EC) presented the Critical Medicines Act - a proposal for a regulation of the European Parliament and the Council, establishing a framework to strengthen the availability and security of supply of critical medicinal products, as well as the availability and accessibility of medicinal products of common interest. This proposal, which amends Regulation (EU) 2024/795, was published on 11 March 2025.During the meeting some concerns were raised about the potential workload and resources from the MSSG, NCAs and EMA to perform the activities foreseen in the Critical Medicine Act.

EMA also presented draft MSSG recommendations to address vulnerabilities in the supply chain of radiopharmaceuticals which includes recommendations to the EC, Member States, EMA and companies.

It was also announced that the MSSG Secretariat had received a request from one Member State to include a specific class of medicinal products in the Union list of critical medicines. The procedure to review the Union List of critical medicines is being drafted and this request will be used to pilot the procedure.

Q&A for biological medicinal products

This Q&A was updated on 8 May 2025: in relation to ' Low Endotoxin Recovery, Endotoxin masking effect (3.2.P.5.3)' section

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

Validation of eCTD submissions for CEP applications

Compliance with EU M1 v3.1 and validation criteria v8.1 has been mandatory for all eCTD submissions since 1 March 2025.

It has recently become apparent that submissions to the EDQM that do not contain the now mandatory tracking table in the correct location would be in breach of rule 15.11 and 15.12, despite these rules not applying to EDQM submissions (the EDQM does not use this tracking table).

It has therefore been decided that, until a new version of the EU eCTD M1 package is issued, the EDQM will accept submissions made using validation criteria v8.1, despite the fact that they will not be compliant with the above-mentioned rules.

Furthermore, the EDQM will continue to accept submissions made using validation criteria v7.1 until 31 May 2025

EPC adopts mycoplasmas general chapter and monographs, updated to incorporate latest analytical developments

During its 181st session in March 2025, the European Pharmacopoeia Commission (EPC) adopted general chapter 2.6.7. Mycoplasmas and 11 monographs referring to it, all of which have been revised to reflect the new European Pharmacopoeia (Ph. Eur.) approach to the detection of mycoplasma contaminants. These revised texts now describe a less prescriptive testing strategy based on a risk assessment.

The revised general chapter specifies that both the culture method and the indicator cell culture method (or, alternatively, a NAT method) should be used conjointly to ensure the detection of both “cultivable” and “non-cultivable” mycoplasmas, unless otherwise prescribed in a monograph or unless justified by a risk assessment and authorised by the competent authority. It has also been clarified that, whenever possible, the samples should contain both cells and supernatant. Furthermore, the text now states that suitable strains may be selected from the proposed list and additional strains can be used, based on a risk assessment, taking into account the type of product and manufacturing process.

Reference standards monthly newsletter – April 2025

1 new European Pharmacopoeia reference standard and 20 replacement batches released in April 2025

All-digital launch of the 12th edition of the Ph. Eur.

This significant transition marks the end of the print version and the beginning of a new era for the European Pharmacopoeia. EDQM invite you to follow this landmark event in real time on its social websites and social media channels

“How to read a CEP” – Revised guideline.

This revised guideline describes in detail the information that Certificates of suitability to the monographs of the Ph.Eur. (CEPs) convey.

This document is intended to clarify specific issues for industry and competent authorities, such as the meaning of statements figuring in all types of CEPs, but it also describes the three different CEP formats (CEP 2.0, Hybrid CEP and old CEP) resulting from the implementation of changes in the content of the CEP documents in September 2023.

Please read this document in conjunction with other applicable Certification policy documents and guidelines, available on the EDQM website

Ireland

The Health Products Regulatory Authority (HPRA)

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

A 14% increase compared to numbers detained in 2023.

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 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.

In 2024, the HPRA undertook several significant enforcement actions, including: 

·         Two prosecution cases initiated, one relating to the importation or distribution of anabolic steroids and one relating to the importation or distribution of the weight loss product Saxenda;

·         2,553 websites, e-commerce listings and/or social media pages amended or shutdown.

United States of America

Presidential decree

Regulatory Relief to promote domestic production of Critical Medicines

Despite a previous Executive Order 13944 dated 6 Aug 2020 in President Trump’s first term of office, the President considers that too little has been done in the intervening years to achieve the goals set within that Executive Order. Consequentially on May 5 2025 President Trump has issued a new Executive Order which requires the FDA, the U.S. Environmental Protection Agency (EPA), and the U.S. Army Corps of Engineers to assess and improve their regulations and guidance in certain areas to encourage, and to reduce duplicative or unnecessary barriers to, domestic pharmaceutical manufacturing.

The EO also calls on FDA:-

·         evaluate the current risk-based approach to prior approval of licensure inspections, including when such inspections are necessary

·         identify and undertake existing programs that provide early technical advice before a facility is operational

·         undertake measures necessary to improve enforcement of data reporting including consideration of publicly displaying the list of facilities, including foreign facilities, that are not in compliance;

·         develop and advance improvements to the risk-based inspection regime that ensures routine reviews of overseas manufacturing facilities involved in the supply of United States medicines, which shall be funded by increased fees

·         to increase the frequency of the agency’s unannounced inspections of foreign drug manufacturing facilities.

The President also announced, outside of the Executive Order that the Administration would be imposing tariffs on the importation of pharmaceuticals to the USA.

Prior to the issue of this Executive Order several large pharma organisations had already commenced moves towards on-shoring certain operations to the USA.

The US Food and Drug Administration (USFDA)

Replacing Color Additives in Approved or Marketed Drug Products

FDA is announcing the availability of this draft guidance for industry.

This draft guidance provides recommendations for replacing color additives in approved or marketed drug products. If a color additive is replaced in a drug product, information to support the change should be retained and available at the manufacturing facility. Additionally, this draft guidance recommends that new drug application (NDA) and abbreviated new drug application (ANDA) holders submit information to support color additive replacements in changes being effected in 30 days (CBE-30) supplements. Although a qualitative or quantitative change to an inactive ingredient is generally considered a major change, in many cases, replacing a color additive with one that is listed in the color additive regulations is unlikely to adversely affect the identity, strength, quality, purity, or potency of the drug product.  Therefore, this draft guidance recommends a CBE-30 for such a change.

Comments should be submitted by 27 July 2025.

International

Australia

Therapeutic Goods Administration (TGA)

Updated GMP clearance information

Good Manufacturing Practice (GMP) Clearance information resources have been updated with new information for Sponsors Published on 21 May 2025

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]

Vimkunya vaccine approved

MHRA has approved a vaccine (Vimkunya) used to prevent disease caused by the chikungunya virus in people 12 years of age and older. 

This vaccine has been approved through the International Recognition Procedure (IRP). The IRP allows the MHRA to take into account the expertise and decision-making of trusted regulatory partners for the benefit of UK patients.  The MHRA conducts a targeted assessment of IRP applications and retains the authority to reject applications if the evidence provided is not considered sufficiently robust. 

vaccine to protect against pneumococcal infections such as pneumonia and meningitis

MHRA has approved the vaccine Capvaxive for people aged 18 years and older to help protect against illnesses caused by bacteria called Streptococcus pneumoniae or pneumococcus.

Illnesses caused by Streptococcus pneumoniae bacteria include pneumonia, meningitis and infection in the blood (bacteraemia).

This vaccine has been approved through the International Recognition Procedure (IRP).

The marketing authorisation was granted to Merck Sharp & Dohme (UK) Limited.

First UK treatment for congenital thrombotic thrombocytopenic purpura (cTTP)

MHRA has approved rADAMTS13 (ADZYNMA), to treat congenital thrombotic thrombocytopenic purpura (CTTP) in patients of all ages.  

CTTP is a very rare inherited blood disorder in which blood clots form in small blood vessels throughout the body. These clots can block the flow of blood and oxygen to the body’s organs.

This medicine has been approved through the International Recognition Procedure (IRP). The marketing authorisation was granted to Takeda UK Ltd. 

MHRA approves world’s first low-carbon version of COPD inhaler Trixeo Aerosphere

MHRA has approved a low-carbon version of Trixeo Aerosphere, a triple combination inhaler for adults with moderate to severe chronic obstructive pulmonary disease (COPD.The newly approved version of Trixeo Aerosphere replaces the propellant HFA-134a with HFO-1234ze(E) – a fluorinated gas with near-zero global warming potential.

This new version will be available in the UK from the second half of 2025.The variation to the existing marketing authorisation of Trixeo Aerosphere was granted to AstraZeneca.

First UK treatment for adults with moderate to severe Thyroid Eye Disease (TED)

MHRA has approved teprotumumab (Tepezza). for adult patients with moderate to severe Thyroid Eye Disease.

TED is an autoimmune condition where the immune system attacks the muscles and fat around the eyes. This medicine is administered via an intravenous drip directly into a vein by a healthcare professional.

The new marketing authorisation was granted to AMGEN LIMITED

Guselkumab for Crohn’s disease and ulcerative colitis

MHRA has approved guselkumab (Tremfya) to treat Crohn’s disease and ulcerative colitis (UC).

Guselkumab is currently approved to treat plaque psoriasis and psoriatic arthritis. However, clinical studies have shown that guselkumab is also efficacious in treating adults with moderately to severely active Crohn’s disease and UC who have not responded well to other treatments or experienced unacceptable side effects.

The approval was granted to Janssen-Cilag Limited and the product was submitted and approved via national procedure.

New treatment for adults with acute lymphoblastic leukaemia

EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Aucatzyl (obecabtagene autoleucel) to treat adults from 26 years of age with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B ALL).

Aucatzyl is a genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy, a type of personalised cancer immunotherapy that is based on collecting and modifying the patient's own immune cells to treat their cancer. The modified T cells attach to and kill the cancer cells, thereby helping to clear the cancer from the body.

Aucatzyl 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. Aucatzyl is recommended for a conditional marketing authorisation, one of the EU’s regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.

The applicant for Aucatzyl is Autolus GmbH.

Conferences Web based events

MHRA webinar on Decentralised Manufacturing Regulations-Update

This is the second webinar (14:00 - 15:30 (BST) on Tuesday 17 June 2025) about the MHRA’s new, world-leading regulatory framework for the manufacture of innovative medicines near to or at the point of patient care.

Amongst topics covered will be:-

·         content of the Decentralised Manufacture (DM) hub on gov.uk, to be published in early June

·         guidance to existing GXP areas, clinical trial, marketing authorisation and pharmacovigilance.

·         Illustrative examples of the of treatments that we anticipate that this new regulation will enable,

·         Work with international regulators through the ICMRA to develop an aligned position 

European shortages monitoring platform (ESMP): updates and question and answer (Q&A) clinic for marketing authorisation holders (MAHs)

Tuesday, 24 June 2025, 09:30 - 11:00 British Summer Time (GMT+1)

In this updates and Q&A clinic session, the team will provide a short update on recent ESMP developments and will be available to answer questions from marketing authorisation holders (MAHs).

This session is aimed at MAHs and the scope are questions on the platform in general and clarifications on recent updates.

MAHs can submit their questions ahead of the event and during the session through a dedicated slido channel. A recording of this session is made available a few weeks after the event.

“Certified for success” –CEP conference

Registrations are now open for this international conference,

This is a unique opportunity to explore the latest developments and future directions of the Certification of suitability to the monographs of the European Pharmacopoeia (CEP) Procedure.

Date: 23-24 September 2025

Venue: Larus Event Centre, Csörsz u. 18/b, 1124 Budapest, Hungary (in-person only)

PHSS Sterile Product Conference 2025

This major PHSS conference will address the key challenges in sterile product manufacture and processing of intermediates that require low bioburden control following risk-based initiatives from a regulatory, Pharmaceutical-/-Biopharmaceutical industry, and healthcare pharmacy perspective. AstraZeneca will offer a site tour on the afternoon of June 25th, there will be a networking dinner at Shrigley Hall.

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 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.