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

EJPPS vol 30.2A 

EJPPSVol 30.2A.pdf

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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)

·         UK-wide licensing for human medicines

·         Supplying authorised medicines to Northern Ireland

·         Decentralised manufacture hub

·         MHRA collaboration with hospital DNA sequencing service cuts time to diagnose infections

·         Pilot on the Advice from the Expert Panels to Manufacturers of High- Risk Medical Devices.

·         New monthly safety bulletin and redesigned safety alerts

·         MHRA Performance Data

·       Dame June Raine: How innovations are transforming regulation and speeding new treatments to healthcare

EU

European Medicines Agency (EMA)

·         Guideline on the quality aspects of mRNA vaccines

·         Reflection paper on linking to electronic product information (ePI) from EU medicine packages

·         GMP/GDP Inspectors Working Group

·         EMA Management Board: highlights of March 2025 meeting

·         Unregulated advanced therapy medicinal products (ATMPs) pose serious risks to health

·         Webinar on reflection paper on the qualification of non-mutagenic impurities

·         Certificates Processing System: Demo & Q&A session for industry stakeholders

·         Joint strategy sets direction of EMA and EU medicines regulatory agencies to 2028

·         Pilot on the Advice from the Expert Panels to Manufacturers of High- Risk Medical Devices.

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

·         EDQM On Air – AI in healthcare – Innovations, ethics and the road ahead

·         EDQM On Air – The evolution of biologicals in the European Pharmacopoeia

·         Modernising excipient monographs: revised identification techniques and new CRSs

·         Ph. Eur. reference standards

·         European Paediatric Formulary: Isoniazid 50 mg/mL oral solution

·          

Ireland

The Health Products Regulatory Authority (HPRA)

·         Draft Implementing Acts on manufacturing of veterinary medicinal products (European Commission consultation)

USA

United States Pharmacopoea (USP)

·         Diethylene Glycol and Ethylene Glycol Testing Method for Finished Dosage Forms

The US Food and Drug Administration (USFDA)

·         Post election status

International

Products

·         Lazertinib approved for use in combination with amivantamab for the treatment of adults with non-small cell lung cancer 

·         Triple combination medicine approved for cystic fibrosis

·         First vaccine against (EHDV) epizootic haemorrhagic disease (veterinary)

·         World first as MHRA approves trofolastat for diagnostic imaging of prostate cancer in men 

Conferences

·         International conference on the EDQM’s CEP procedure

·         EMA’s 30th anniversary scientific conference - Medicines, regulation and the future

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

UK-wide licensing for human medicines

This guidance is designed to provide information on the implementation of changes to the licensing of medicines for human use in the UK following the agreement of the Windsor Framework. It was updated on 12 March 2025 to amend sentence in section 1 and add link to UK-wide licensing for human medicines: supplementary guidance

Supplying authorised medicines to Northern Ireland

Added information to this guidance on 20 March 2025 confirming medicines moved from Great Britain to Northern Ireland must be declared for customs or moved using the Windsor Framework simplified processes.

Decentralised manufacture hub

Information on the new regulations for decentralised manufacture, including point of care and modular manufacture, which come into effect on 23 July 2025.

This information is to help you understand and prepare for the main regulatory changes that Statutory Instrument 2025.87 will introduce for the manufacture of medicines at - or close to - the point of patient care.  Point of care (POC) and modular manufacture (MM) are collectively called decentralised manufacture (DM). DM processes allow medicinal products to be made at or close to a patient’s location for administration of the medicine.  

DM presents some new challenges compared with traditional medicinal product manufacture. MHRA are developing new regulatory guidance to provide clarity on regulatory expectations. We consulted stakeholders on draft guidance at an in-person workshop in March 2025. We will publish the guidance in early summer 2025. 

The new guidance will supplement existing guidance. You should use it in conjunction with those texts.

Internationally, work has commenced to align regulatory expectations for DM, through the International Coalition of Medicines Regulatory Authorities (ICMRA).

MHRA collaboration with hospital DNA sequencing service cuts time to diagnose infections

In a UK-first, the MHRA and Barts Health NHS Trust have developed a DNA sequencing approach that can be implemented onsite in hospitals so they can diagnose bacterial infections faster and more accurately.

This service will help doctors deliver better-targeted treatments earlier. For patients, this means a quicker recovery, fewer complications such as sepsis, and a reduced risk of spreading infections to others.

This technology is now being piloted to investigate and prevent hospital outbreaks caused by antibiotic-resistant ‘superbugs’ — a growing global threat.

The approach delivers results within two days, significantly faster than traditional methods which can take approximately seven days and, in some difficult cases, up to eight weeks.

The goal is to make rapid DNA sequencing a routine part of hospital diagnostics across the NHS, bringing faster, more accurate infection testing to patients nationwide.

Pilot on the Advice from the Expert Panels to Manufacturers of High- Risk Medical Devices.

This Interim report covers the experience with the pilot from February 2023 to December 2024.

This is the first time in the EU) that manufacturers have access via a dedicated regulatory procedure to experts that will advise on the best possible way to design and conduct clinical investigations and address questions concerning clinical development strategies to support the certification of the devices. This will help manufacturers have timely access to early consistent advice through a single EU regulatory pathway on the clinical development of their products.

This interim report provides an overview of the applications received during the pilot until the end of December 2024. A final report on the pilot will be published once all pilot procedures are finalised.

Manufacturers of class III devices and class IIb active devices intended to administer or remove medicines can now submit their request for advice via a portal and consult the medical device expert panels at different stages of the clinical development. This regular scientific advice procedure follows a pilot launched in 2023, which has helped to establish this procedure and gathered positive feedback from manufacturers and panel experts. EMA will publish a report on the pilot in the coming weeks.

There are currently no fees associated with these requests.

New monthly safety bulletin and redesigned safety alerts

The new MHRA Safety Roundup provides a monthly summary of the latest safety advice for all medicines, medical devices, and healthcare products regulated by the MHRA, as part of MHRA’s 3-year strategy to improve safety communications.

MHRA Performance Data

Performance data for MHRA key performance indicators (KPIs) and information on the expected timeline to complete a specific regulatory function.

In this report MHRA provide performance data for February 2025 for each KPI. Also provided is information on the expected timeline to complete a specific regulatory function and the current average timeline.

The aim is to help applicants with decision making, based on our performance data, and to ensure greater accountability for our service delivery.

Dame June Raine: How innovations are transforming regulation and speeding new treatments to healthcare

After nearly 40 years at the agency, the last five of which she has been CEO, Dame June Raine reflects on how new innovations are transforming regulation and how honoured she feels to have worked with such inspiring people through a period she has not just lived through but helped to shape.

[An interesting quote from this news item is “ -

AI technology is now coming on stream in regulation, with international approval of the work we are doing at MHRA. It shows how far regulation has come from the days of paper-based assessments, and how exciting regulation is today – and you don’t often hear the words ‘exciting’ and ‘regulation’ in the same sentence.”] MBH

Europe

European Medicines Agency (EMA)

Guideline on the quality aspects of mRNA vaccines

This guideline addresses the quality aspects of mRNA vaccines. It addresses specific aspects regarding the manufacturing process, characterisation, specifications and analytical control of mRNA vaccines, as well as the definition of starting materials, active substance and finished product for mRNA vaccines.

The number of clinical trial applications for human products and marketing authorisation applications for mRNA containing products significantly increased over the last few years and is expected to increase further in the future. Furthermore, significant experience with mRNA vaccines was gained during the COVID-19 pandemic.

mRNA vaccines against infectious disease have to follow the general guidelines for human vaccines, however this new technology is not specifically addressed in these general guidelines. Therefore, this guideline addresses those specific aspects regarding the manufacturing process, characterisation, specifications and analytical control as well as the definition of active substance and finished product for mRNA vaccines for the prevention of infectious disease

Additional regulatory considerations are provided for changes in existing mRNA vaccine strains, bivalent and multivalent vaccines, self-amplifying mRNA vaccines, other delivery systems and use of platform technology/prior knowledge. The scope of this guideline is applicable to mRNA vaccines against infectious diseases. Other mRNA-based medicinal products are out of scope of this guideline, although relevant parts of this guideline may be applicable to those. It is not intended to address specific requirements for mRNA vaccines to be used in clinical trials, however the scientific principles described may also be applicable during pharmaceutical development.

The document is open for comment until 30 Sept 2025.

Reflection paper on linking to electronic product information (ePI) from EU medicine packages

Development of electronic product information (ePI) for EU human medicines, compliant with a harmonised EU ePI Common Standard, is ongoing by the European Medicines Regulatory Network (EMRN) in collaboration with stakeholders. In the coming years, ePI will be created and updated for EU medicines as part of routine regulatory procedures.

The motivation for development of ePI, as outlined in the ePI key principles1, is to benefit public health. One of the ways in which this will be achieved is by expanding the dissemination of up-to-date, accessible, regulator-authorised product information for EU medicines. ePI will support provision of the latest information on a medicine’s safety, benefits and conditions of use and will enable availability of the right information at the point of need. This will support informed decision-making by patients and healthcare professionals and improve patient safety overall.

Realising these benefits requires a focus on how ePI, particularly but not exclusively the electronic package leaflet, can be accessed directly from the specific medicine in the hands of the consumer or practitioner using mobile scanning technology.

This reflection paper describes components to be put in place to realise an EU-wide solution in which ePI could be easily accessed by citizens wherever they are in Europe, in their preferred language when available.

The document is open for comment until 30 June 2025.

GMP/GDP Inspectors Working Group

EMA draws on the expertise of member states' inspectorates for the fulfilment of many of its GMP related tasks. This is primarily achieved through the GMP/GDP Inspectors Working Group (GMDP IWG). This group of senior GMP Inspectors meets on a regular basis four times a year. The meetings consider new and revised GMP and GDP - related guidance, normally developed by drafting groups, work related to Mutual Recognition Agreements, how new legislation impacts GMP and GDP inspection activity and harmonisation of GMP and GDP inspections.

The functions of inspection and assessment have always been complementary activities and there is increasing awareness of the importance of interactions between GMP inspectors and assessors. The EMA therefore arranges a joint meeting between this group and Quality Working Party at least once a year.

EMA Management Board: highlights of March 2025 meeting

Topics covered in this meeting included

·         Election of new Management Board Chair

·         EMA annual report 2024

·         European Medicines Agencies Network Strategy to 2028

·         Revised composition of EMA’s Emergency Task Force

·         Monitoring EMA’s independence policies

·         Clinical Trials in the EU

Unregulated advanced therapy medicinal products (ATMPs) pose serious risks to health

EMA and the Heads of Medicines Agencies (HMA) are warning the public about the dangers of unregulated ATMPs offered to patients in the European Union. A number of individuals, companies and clinics have been marketing unregulated ATMPs directly to patients, often when there is little or no evidence that the products work or are safe. Some of the unregulated products in the EU are sold as dendritic cell therapies, which use a type of immune cell (dendritic cell) to attack cancer cells.

Authorities are warning the public that unregulated products could put patients at risk, causing serious side effects while not providing benefits to patients.

Additionally, unregulated ATMPs present significant quality-related risks due to the lack of strict oversight and regulatory compliance in the manufacturing process, which can lead to contamination, inconsistent product composition, and improper storage.

Authorities across the EU are working together to clamp down on those supplying unregulated ATMPs.

Webinar on reflection paper on the qualification of non-mutagenic impurities

EMA has launched a public consultation on the draft reflection paper with the aim of gathering input and feedback from stakeholders.

This draft follows the earlier version that was published in 2018 and has been updated considerably.

The update focuses on alternative strategies for qualifying novel impurities or qualifying higher levels of impurities that were previously qualified at a lower level. The aim is to provide a practical reference for applicants regarding the qualification of novel impurities:

·         arising from changed manufacturing processes,

·         discovered after safety studies have been concluded, or

·         when higher levels need to be qualified and existing data from safety studies are not sufficient for qualification.

Certificates Processing System: Demo & Q&A session for industry stakeholders

From 1 January 2025, EMA certificates of medicinal product must be ordered through the Certificates Processing System (CPS). The Agency invites all human and veterinary industry stakeholders to a system demonstration session followed by Q&A on the CPS.

Thursday, 13 March 2025, 11:30 - 12:00 Greenwich Mean Time (GMT) Online

Joint strategy sets direction of EMA and EU medicines regulatory agencies to 2028

EMA and the Heads of Medicines Agencies (HMA) have published their joint EU medicines agencies network to 2028 (EMANS), following its recent adoption by the HMA and the EMA Management Board.

The strategy, titled ‘Seizing opportunities in a changing medicines landscape’, is a comprehensive update of the five-year strategy which was developed to cover the period 2021 to 2025

The six focus areas of the strategy to 2028 build upon those in the EMANS to 2025 with the updated strategy placing more emphasis on the competitiveness of the EU in the development and manufacture of medicines, as well as the use of artificial intelligence throughout the medicines’ lifecycle. The ‘One Health Approach’ is introduced as a key aspect of the strategy, recognising that the health of humans, animals and the wider environment are closely intertwined.

The strategic focus areas of the strategy to 2028 are as follows:

·         Accessibility – to facilitate pathways for access to medicines through healthcare systems in the EU.

·         Leveraging data, digitalisation and artificial intelligence – to improve decision-making, optimise processes and increase efficiency.

·         Regulatory science, innovation and competitiveness – to create a regulatory and research environment that accelerates the translation of innovation and improves competitiveness of the EU’s healthcare sector.

·         Antimicrobial resistance and other health threats – to prepare the EU for potential threats including antimicrobial resistance.

·         Availability and supply - to strengthen the availability of medicines to protect public and animal health.

·         Sustainability of the network – to ensure that the network has available resources to support its scientific and regulatory decision-making, taking full advantage of technological advances.

EMA and HMA will now implement the strategy via their respective multi-annual workplans and at national level. The network will monitor its implementation, report back and adjust as needed.

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

EDQM On Air – AI in healthcare – Innovations, ethics and the road ahead, with Eric Sutherland

Artificial intelligence (AI) is a source of great hope in healthcare. Properly applied, it has the potential to analyse images and data faster and more accurately than human beings. Its ability to perform administrative tasks can also free up medical professionals to dedicate more time to their patients.

But AI comes with certain risks. What data is being used, and from what source? Can AI respect privacy when handling personal health data? Can we really entrust our health to machines?

In this episode of the podcast, Eric Sutherland, Senior Health Economist at the Organisation for Economic Co-operation and Development (OECD)shares his insights into the developing field of AI in healthcare, addressing topics such as digital health, policy guidance and responsible analytics.

The first five episodes of EDQM On Air are already available and others will be released regularly.

EDQM On Air – The evolution of biologicals in the European Pharmacopoeia 

EDQM On Air, the podcast on public health brought to you by the EDQM of the Council of Europe, has just released a new episode!

Biological medicinal products – or biologicals– are a class of extremely powerful and versatile medicines are at the cutting-edge of pharmaceutical science and have contributed to major breakthroughs in the treatment of smallpox, diabetes and haemophilia, as well as to promising innovations such as CRISPR-Cas9 technology and CAR T-cell therapies, making us stronger in the fight against disease.

In this episode, Emmanuelle Charton from the EDQM’s European Pharmacopoeia Department walks us through the history of biologicals, from the first vaccines to the latest Nobel Prize-winning innovations.

Modernising excipient monographs: revised identification techniques and new CRSs

In recent months, several revised excipient monographs and new reference standards have been added to the European Pharmacopoeia (Ph. Eur.). The aim of the changes is to support users by promoting modern IR identification techniques and replacing reference spectra with chemical reference substances (CRS).

Several revised texts were published in Supplement 11.6, with an implementation date of 1 January 2025:

This modernisation work has continued with the monograph on Carnauba wax (0597), describing an IR identification instead of the original TLC test, and both Beeswax, white (0069) and Beeswax, yellow (0070), which now include an identification test, all published in Pharmeuropa 36.4 for comment. These follow Macrogolglycerol ricinoleate (1082) and Macrogolglycerol hydroxystearate (1083), revised to introduce an IR identification avoiding the use of the mercury-containing solutions described in one of the identification tests, and published in Pharmeuropa 36.2.

Ph. Eur. reference standards

EDQM announces the release of 1 new & 22 replacement batches of Ph. Eur. reference standards

European Paediatric Formulary: Isoniazid 50 mg/mL oral solution

EDQM has just released Issue 10 of Pharmeuropa PaedForm, containing the 11th monograph of the PaedF Working Party, Isoniazid 50 mg/mL oral solution, for public consultation. The deadline for comments is 30 June 2025.

The need for age-appropriate formulations of this medicinal product was highlighted by the EMA in 2013 and no licensed age-appropriate products are currently available.

This particular formulation, which is based on a formulation of the Spanish National Formulary, was selected because it was supported by a validated test method and stability data, both of which were provided by the University of Seville.

Ireland

The Health Products Regulatory Authority (HPRA)

Draft Implementing Acts on manufacturing of veterinary medicinal products (European Commission consultation)

The European Commission sought feedback from stakeholders on two draft Implementing Acts in accordance with Regulation 2019/6 on veterinary medicinal products. The Acts aim to ensure that good manufacturing practice for active substances and veterinary medicinal products are applied in a harmonised way throughout the EU.

In accordance with Regulation (2019/6), formal legal adoption of GMP requirements is needed for veterinary medicinal products (VMPs) and their active substances. These requirements will be specified in Implementing Regulations and will replace the existing GMP Guidelines in EudraLex Volume 4 when they come into force.

If in addition, you wish to inform the HPRA of the feedback you have provided to the Commission you can email at compliance@hpra.ie with the subject line: Comments on Draft Implementing Regulations on GMP for VMPs and APIs used in VMPs

United States of America

United States Pharmacopea (USP)

Diethylene Glycol and Ethylene Glycol Testing Method for Finished Dosage Forms

Since 1937, there have been numerous reports of diethylene glycol (DEG) and/or ethylene glycol (EG) poisoning issues. Early in 2023, WHO issued an alert regarding DEG/EG contamination and adulteration that occurred in multiple countries resulting in more than 300 fatalities, most of whom were children.

In May 2023, the U.S. U.S. Food and Drug Administration (FDA) issued a Guidance for Industry - Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol, in which seven previously revised USP-NF excipient monographs with a high risk of EG/DEG contamination/adulteration were referenced. To help address these risks, the Complex Excipients Expert Committee (CE EC) published the USP-NF PEG monograph revision proposal through an accelerated revision process.

FDA’s laboratory has developed and validated a test method using Gas chromatography-Mass spectrometry (GC-MS) for determination of EG and DEG in cough, cold, and allergy products containing Glycerin. In close collaboration with the FDA, USP intends to publish this method through the emerging standard approach for developing and sharing information with our stakeholders.

[A step forward, which I am very pleased to see. Sadly, however, I suspect that laboratories in several countries where such incidents have occurred in recent times may generally not have access to sophisticated analytical techniques such as GC-MS and we are likely to see further incidents occurring. MBH].

The US Food and Drug Administration (USFDA)

Post election status

At this time there are no issues to report whilst the internal processes are ongoing.

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]

Lazertinib approved for use in combination with amivantamab for the treatment of adults with non-small cell lung cancer 

MHRA has approved lazertinib (brand name Lazcluze) for adults with non-small cell lung cancer that has spread to other parts of the body and has undergone specific changes in a gene called epidermal growth factor receptor (EGFR). It is to be used in combination with an approved cancer medicine called amivantamab.

The lazertinib and amivantamab combination treatment was compared against treatment with lazertinib alone, and against treatment with another cancer medicine, osimertinib. Participants who received the combination treatment had a longer period without progression of their disease, as compared to patients who received the other 2 treatments.

The new marketing authorisation was granted to Janssen-Cilag Ltd.

This product was submitted and approved via a national procedure. 

Triple combination medicine approved for cystic fibrosis

MHRA has approved the triple combination medicine deutivacaftor/tezacaftor/vanzacaftor (brand name Alyftrek) to treat cystic fibrosis (CF) in people aged six years and older who have specific mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that have been shown in trials to respond to the therapy. This includes F508del, which is the most common cystic fibrosis causing mutation.  The new marketing authorisation was granted via a national route to Vertex Pharmaceuticals (Europe) Limited. 

First vaccine against (EHDV) epizootic haemorrhagic disease (veterinary)

EMA has recommended the approval of Hepizovac, the first vaccine EHD authorised in the EU for use in cattle. This new vaccine provides protection against the recently emerged serotype 8 of the epizootic haemorrhagic disease virus (EHDV), which has been responsible for recent outbreaks in Europe.

EHD is an infectious disease that primarily affects domestic and wild ruminants, like deer. The virus is transmitted through the bite of midges that have fed on infected animals. Infection with EHDV can lead to severe clinical signs in cattle, including fever, nose and mouth sores, drooling, eye inflammation, and respiratory distress. In some cases, it can result in death.

Despite the severity of the disease in affected animals, the EHDV is not a risk to human health, as it is not known to cause disease in humans under any conditions.

Hepizovac contains an inactivated form of the EHDV serotype 8 along with adjuvants to help stimulate the immune response. The vaccine is available as a ready-to-use suspension for injection.

Hepizovac was approved under exceptional circumstances considering recent outbreaks of EHD in cattle herds, for which no vaccines were previously available. The CVMP opinion will now be sent to the European Commission for the adoption of the decision on the EU-wide marketing authorisation of Hepizovac.

World first as MHRA approves trofolastat for diagnostic imaging of prostate cancer in men 

MHRA has approved trofolastat (RoTecPSMA), the first prostate-specific membrane antigen (PSMA)-targeting product authorised for use with technetium-99m to detect cancerous lesions in men with prostate cancer.

Trofolastat is combined with the radioactive tracer technetium-99m to form Technetium (99mTc) trofolastat, which is administered as a single injection. It binds to a protein called PSMA found on prostate cancer cells, helping doctors identify cancerous areas during a medical imaging technique known as single photon emission computed tomography (SPECT). This is the first PSMA-targeting diagnostic product approved with Technetium-99m, which is widely available in UK nuclear medicine facilities, this approval has the potential to expand access to prostate cancer imaging and support diagnostic pathways within the NHS.

Conferences

International conference on the EDQM’s CEP procedure

The conference is organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) and tailored to CEP applicants, holders and users, including pharmaceutical companies and authorities.

Places will be limited, so be sure to mark your calendars now. More information about the conference and registration will be released soon

23-24 September 2025, Budapest, Hungary

EMA’s 30th anniversary scientific conference - Medicines, regulation and the future

The EMA’s 30th anniversary scientific conference aims to celebrate three decades of groundbreaking achievements and advancements in the field of medicine and regulatory science. The event will bring together key partners and stakeholders, including representatives from the European institutions and agencies, the European medicines regulatory network, international partners, patient and healthcare professional organisations, industry organisations, Dutch government and other esteemed guests to discuss the latest trends, innovations, and challenges in the field of medicines regulation and public and animal health. 

The workshop will be broadcasted live, and the recording will be made available on the EMA website afterwards.

No registration is required to follow the broadcast 

Wednesday, 25 June 2025, 09:00 - 15:00 British Summer Time (GMT+1)

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.