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

EJPPS vol 30.2C 

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INTRODUCTION

This month reported issues have come from the UK, EU, Australian & Swiss regulatory authorities.

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

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

• USFDA Warning Letters

• Public advised to stop using certain non-sterile alcohol-free wipes

• Recruitment for new digital roles at Leeds hub to drive innovation and smarter regulation

• Patients will receive medicines 3-6 months faster under 10-Year Health Plan, as regulators set out plans

• MHRA Performance Data July 2025

• MHRA crackdown on illegal ‘Botox’ after victims left seriously ill

• MHRA approves UK’s first new type of antibiotic for urinary tract infections in nearly 30 years

EU

European Commission, Directorate-General for Health & Food Safety

• Titanium dioxide

European Medicines Agency (EMA)

• Feedback from EMA to the EU Commission request to evaluate the feasibility of alternatives to replace titanium dioxide (TiO2) in medicinal products

• Quality Innovation Group (QIG) Listen and Learn Focus Group (LLFG) meeting on personalised medicines

• Open consultation ICH Q3E extractables and leachables - scientific guideline

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

• Major Revision to General Chapter Q-09: Particulate Contamination

• Certification

• Reference standards

Ireland

The Health Products Regulatory Authority (HPRA)

• Further deferral of prescription requirement for antiparasitic veterinary medicines in food-producing animals

International

Australia

Therapeutic Goods Administration (TGA)

• Focus on compliance of AI and software-based medical devices

Switzerland

Swissmedic

• Hospital Inspections Annual Report 2024

Products

• MHRA approves teplizumab to delay progression of type 1 diabetes

• Zuranolone to treat moderate or severe postnatal depression

• MHRA approves UK’s first new type of antibiotic for urinary tract infections in nearly 30 years

Conferences – web based events

• “Pharmaceutical Reference Standards” – Joint EDQM-USP International Symposium

• PHSS Annual Conference

• PHSS - QP Forum Conference 2025

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

USFDA Warning Letters

This Blog relates to actions which licence holders should do following the issuing of USFDA Warning Letters.

The MHRA’s Inspection Action Groups (IAG) are responsible for recommending and implementing regulatory action against companies for breaches across all GxPs, and its Defective Medicines Report Centre (DMRC) provides an emergency assessment and communication system for manufacturers and regulatory authorities in regard to defective medicines. The IAG and DMRC regularly receives USFDA Warning Letters (also Official Action Indicated, OAI, and Import Ban letters) and currently contacts UK licence holders who may be implicated.

The MHRA has reviewed its current approach. IAG and DMRC note that these letters are in the public domain and takes the view all manufacturing and wholesale licence holders, as well as API (Active pharmaceutical ingredient) registration holders should be reviewing these Warning Letters as part of their ongoing quality assessment of suppliers and contract manufacturers. In future, MHRA will not be contacting licence holders as a matter of routine and companies should ensure they have measures in place to review and risk assess USFDA Warning Letters. Should this risk assessment require notification to MHRA then this could be via the DMRC (if medicines are defective) and to IAG (in regard to ongoing regulatory compliance).

Public advised to stop using certain non-sterile alcohol-free wipes

The UK Health Security Agency (UKHSA) and the MHRA are advising the public to stop using certain non-sterile alcohol-free wipes and to dispose of them.

During investigation of an outbreak, certain wipes were found to be contaminated with Burkholderia stabilis. These products which may have been used for ‘skin cleansing’ and cleaning in or around wounds have been withdrawn from sale but may still be found in some first aid kits and in people’s homes. These products are not routinely used in the NHS. If you have these products (listed in the MHRA Notice), you are advised not to use them and to dispose of them in your household waste as a precautionary measure given the potential for contamination.

This notice relates only to the products listed. However, the public are reminded that non-sterile alcohol-free wipes should not be used for the treatment of injuries, wounds or on broken skin, nor should they be used for cleaning intravenous lines, as they are not appropriate for these purposes and their safety cannot be guaranteed.

[I note the comment from Dr Alison Cave, MHRA Chief Safety Office, “We consider wipes which are intended for a medical purpose to be medicines. These products do not have a medicines authorisation, and we are taking appropriate action to ensure compliance with the requirements of the applicable legislation governed by MHRA”.

If you are not sure of the classification of your product e.g. is it a medicine, or a device, or if the claims you make for it constitute a medical claim, then it is always sensible to seek clarification from the regulator before going ahead. MBH]

Recruitment for new digital roles at Leeds hub to drive innovation and smarter regulation

New jobs to strengthen innovation, safety and smarter regulation across the UK health and life sciences sector.

MHRA has begun recruiting for a first wave of new, highly skilled digital and data roles at its newly launched Digital Hub in Leeds. This marks a key step forward in the agency’s programme to modernise the regulation of medicines and medical devices in the UK.The new hub, will play a vital role in building the MHRA’s digital capability and expanding its national presence.

[Fancy a change of career? This looks like a great opportunity, If you have the right skills, to start an exciting new career, in a new field, with MHRA. It’s in a nice part of the country too (despite me being a Lancastrian by birth!) MBH]

Patients will receive medicines 3-6 months faster under 10-Year Health Plan, as regulators set out plans

Under a joint information sharing agreement, pharmaceutical companies will be invited to register early with the MHRA and NICE to allow parallel decision making over licencing and value.

Under a joint information sharing agreement, pharmaceutical companies will be invited to register early with both agencies to allow parallel decision making over licencing and value. It will mean more medicines receive approval for use on the NHS in England at the same time as they are licensed for use in the UK.

The enhanced coordinated approach offers medicine developers an integrated advice service and an aligned pathway to help them streamline both regulatory and Health Technology Assessment (HTA) requirements and provides a clearer route to help get their treatments to patients.

To benefit from this service, companies should register their products onUK PharmaScan, the national horizon scanning database, at least three years before their expected marketing authorisation.

MHRA Performance Data July 2025

The priority is to maintain performance to predictable and statutory timeframes, while delivering against MHRA’s ambition to accelerate patient access to life-changing medicines and medical technologies. MHRA will continue to publish monthly updates providing applicants with transparent information on expected timescales.

MHRA crackdown on illegal ‘Botox’ after victims left seriously ill

Between 4 June and 6 August 2025, 41 confirmed cases of botulism – a rare but potentially life-threatening condition causing paralysis – were reported across several regions in England, including the North East, East Midlands, East of England, North West, and Yorkshire and Humber. The Criminal Enforcement Unit has seen evidence that some sellers and practitioners – often untrained – are obtaining unlicensed botulinum toxin products illegally and offering injections in unsafe, unregulated settings.

Anyone caught selling or supplying unlicensed botulinum toxin faces up to two years in prison and unlimited fines under the Human Medicines Regulations 2012.

Almost all of the seized products originated in South Korea, including brands such as Botulax, reNTox, Innotox, and Toxpia, which are not authorised for sale in the UK.

Europe

European Commission, Directorate-General for Health & Food Safety

Titanium dioxide

The European Commission DG for Health & Food Safety has published a Commission staff working document on the use of titanium dioxide in medicinal products which concludes that titanium dioxide should be allowed to continue to be used in medicines.

[This risk based conclusion should now bring the topic to closure, at least for the forsee-able future MBH].

[See also the updated / closing Impact statement on the PHSS website.which provides additional information.MBH.]

European Medicines Agency (EMA)

Feedback from EMA to the EU Commission request to evaluate the feasibility of alternatives to replace titanium dioxide (TiO2) in medicinal products

Despite extensive efforts by the pharmaceutical industry to investigate a number of alternative formulations the feasibility of replacing TiO2 cannot be confirmed without negatively impacting the quality, safety and efficacy of medicines.

QWP concludes that a transition period of more than 12 years would be required for the phasing out of TiO2 in medicines in the hypothetical scenario that an alternative for TiO2 would be found. Even with such a transition period, a considerable negative impact on availability of medicines due to withdrawal of products and medicines shortages is inevitable. The resultant capacity and supply chain issues are also considered likely to hinder the development of new medicines addressing unmet medical need.

 Quality Innovation Group (QIG) Listen and Learn Focus Group (LLFG) meeting on personalised medicines

This meeting with representatives from academia and industry on manufacturing of personalised medicines is aimed to go through case studies proposed by stakeholders (e.g. ATMPs, antisense oligonucleotides, 3D printing) and focus on scientific challenges and solutions that can support development of these medicines in the future.

Selected case studies will be presented and discussed at the meeting. The meeting is invitation based only to discuss these case studies and a meeting report will subsequently be published.

Open consultation ICH Q3E Extractables and leachables - scientific guideline

EMA has posted this guideline which presents a holistic framework and process for the assessment and control of extractable and leachable impurities and complements existing ICH guidelines on impurities, including impurities in 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).

The framework of this guideline follows the principles of risk management as described in ICH Q9. While the guideline includes materials characterization and process understanding, its primary purpose is to protect patient safety and product quality through assessment and control of leachables in the drug product.

The guideline and supporting documentation for class 3 leachables are open for consultation until 18 Dec 2025.

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

Major Revision to General Chapter Q-09: Particulate Contamination

The revised harmonised general chapter “Particulate Contamination (Q-09)” was signed-off by the Pharmacopeial Discussion Group (PDG) on 2 May 2025.

The revision of Q-09 represents a significant step forward in standardised testing procedures for sub-visible particulate matter in all injectable products applied in the PDG regions. This update makes the process more robust and adaptable to different product types, including biologicals.

Major changes include:

• Definition clarification

• Guidance on sample preparation, especially for formulations with a volume of 25 mL or less

• Method 1 (light obscuration particle count test) updates

• Method 2 (microscopic particle count test) updates

Certification

The certification monthly report as of the end of July is now available.

Reference standards

6 new European Pharmacopoeia reference standard and 19 replacement batches released in July 2025

Ireland

The Health Products Regulatory Authority (HPRA)

Further deferral of prescription requirement for antiparasitic veterinary medicines in food-producing animals

The Minister for Agriculture, Food and the Marine, has further deferred the requirement for a veterinary prescription for anti-parasitic veterinary medicines used in food-producing animal species until 1 December 2025. The deferral is stated to allow time for stakeholders in moving to digital prescribing nationally.

International

Australia

Therapeutic Goods Administration (TGA)

Focus on compliance of AI and software-based medical devices

TGA is stepping up its efforts to make sure that software-based medical devices meet Australia’s regulatory requirements. This includes those using artificial intelligence (AI). Ccurrent focus includes reviewing AI digital scribes, some of which are introducing more advanced features such as diagnostic and treatment suggestions. These features may cause the software to become a medical device under the Therapeutic Goods Act 1989.

Switzerland

Swissmedic

Hospital Inspections Annual Report 2024

In 2024, Swissmedic inspected the reprocessing, maintenance and vigilance – in other words monitoring and reporting of serious incidents – of medical devices in 23 Swiss hospitals. The report shows that many hospitals still have considerable challenges to overcome to ensure compliance with legal requirements. Particular attention is paid in the report to root cause analysis and the resulting recommendations.

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 teplizumab to delay progression of type 1 diabetes

MHRA has approved teplizumab (Tzield) to delay the onset of Stage 3 type 1 diabetes (T1D) by an average of three years in adults and children aged 8 years and older with Stage 2 T1D.

Teplizumab is the UK’s first-ever approved immunotherapy for type 1 diabetes.

This medicine has been approved through the International Recognition Procedure (IRP). The approval was granted to Aventis Pharma Limited.

Zuranolone to treat moderate or severe postnatal depression

MHRA has approved zuranolone (brand name: Zurzuvae) to treat moderate or severe postnatal depression (PND) in adults following childbirth.

Zuranolone is the first oral treatment for postnatal depression approved in the UK.

This product was submitted and approved via the International Recognition Procedure.

The approval was granted to Biogen.

MHRA approves UK’s first new type of antibiotic for urinary tract infections in nearly 30 years

MHRA has approved gepotidacin (Blujepa), a new kind of oral antibiotic pill to treat uncomplicated urinary tract infections (UTIs) in females aged 12 years and older, weighing at least 40 kg. Uncomplicated UTIs are the most common bacterial infection in women, affecting around half of females in the UK. With drug-resistant bacteria increasing, new treatment options are critical in preventing treatment failure and complications, including sepsis or permanent kidney damage. The active ingredient in the antibiotic targets and blocks two enzymes that bacteria need to replicate and multiply, making it effective against many drug resistant infections such as E. coli.

The MHRA’s national approval is supported by evidence from two multicentre, randomised, active-controlled Phase 3 trials in females with uncomplicated UTIs, where 1572 participants were given gepotidacin and 1564 received nitrofurantoin, the frontline antibiotic currently used to treat uncomplicated UTIs.

The new marketing authorisation was granted on 27 August 2025 to GSK plc.

[Well done GSK! But I would say that wouldn’t I, having worked for them for 42 years. Interestingly my first role with them at their Glaxo Ulverston Cumbria API facility was as an analytical technician working on another first group of antibiotics, the cephalosporins, which proved to be a giant leap forward. MBH].

Conferences

“Pharmaceutical Reference Standards” – Joint EDQM-USP International Symposium The symposium will take place in Strasbourg (France) on 23 and 24 September 2026, in a hybrid format, allowing both in-person and online participation.

Key topics will include best practices for the establishment and lifecycle management of pharmaceutical reference standards. While ICH Q6 and other pharmaceutical regulations provide a foundational framework, they offer limited technical details on the subject.

The symposium agenda will explore applicable regulations and guidance that apply to pharmaceutical reference standards. In addition, the symposium will highlight recent scientific and technical developments in the field.

PHSS Annual Conference

This year's PHSS Annual Conference is in association with BioMerieux, which is also sponsoring the networking dinner

There will be a site tour locally (Cell & Gene Therapy Catapult, Stevenage).

The conference day on the 17th of September, is packed with keynote speakers, industry SME, and HPRA.

PHSS - QP Forum Conference 2025

The Conference held this year in USK, 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.