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

EJPPS Vol 30.4A

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, Australian Swiss and USA regulatory authorities.

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

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

·       Medicines that you cannot export from the UK or hoard

·       New Commission to help accelerate NHS use of AI

·       Designated standards prioritisation

·       MHRA and partners unite to reaffirm prescription weight-loss medicine advertising rules

The Association of the British Pharmaceutical Industry (ABPI)

·       Accelerated review of VPAG concludes without agreement

EU

European Medicines Agency (EMA)

·       Warning about sharp rise in illegal medicines sold in the EU

·       Reflection paper on patient experience data

·       Quality of medicines Q&A

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

·       Reference Standards

·       Certification monthly report of activities: End of August 2025

·       Heparin low-molecular-mass for calibration CRS batch 6

·       New guidelines on the classification of active pharmaceutical substances as regards their supply

Ireland

The Health Products Regulatory Authority (HPRA)

·       2024 Annual Report

USA

The US Food and Drug Administration (USFDA)

·       Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for Industry

·       Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications

·       Safety Labeling Changes

International

Australia

Therapeutic Goods Administration (TGA)

·       Safety concerns over imported melatonin products

·       Multiple sunscreens recall - Lower than claimed SPF levels

Pharmaceutical inspection convetion / system. PIC/S

·       Draft guidelines: Revised Chapter 1 - Pharmaceutical Quality System

Switzerland – (Swissmedic)

·       Disposal information to be added to Patient Information

Conferences

·       PHSS - QP Forum Conference 2025

·       EDQM webinar on how to read a CEP

RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS

UK

Medicines and Healthcare products Regulatory Agency (MHRA)

Medicines that you cannot export from the UK or hoard

This document lists the medicines that cannot be exported from the UK or hoarded because they are needed for UK patients. The list is updated regularly.

Hoarding or exporting a medicine on the list is considered a breach of regulation 43(2) of the Human Medicines Regulations 2012 and a contravention of the wholesale dealer licence, and may lead to regulatory action by the Medicines and Healthcare products Regulatory Agency (MHRA), which could include immediate suspension of the wholesale dealer licence.

New Commission to help accelerate NHS use of AI

The new National Commission will help accelerate safe access to AI in healthcare and across the NHS by advising on new regulatory rulebook – set to be published next year.

With expertise from global AI leaders, clinicians and regulators, the Commission will immediately review tech that’s being held back by regulatory uncertainty, like AI assistants for doctors.

It follows new tech being trialled to speed up discharges and let GPs focus on patients instead of taking notes, as tech plays central part in transforming the NHS under the Plan for Change.

Designated standards prioritisation

MHRA is working to deliver a future regulatory framework for medical devices that prioritises patient and public safety, gives patients access to the medical devices they need, and ensures the UK remains an attractive market for medical technology innovators.

In line with this objective, MHRA are committed to enhancing patient safety and harmonisation by more closely aligning with international standards and best practices.

The MHRA is seeking input through this survey on the prioritisation for designation of important medical device standards

[Included for information only, as the document was published 5 Sept 2025 and the comment period closed 30 Sept 2025!! – MBH]

MHRA and partners unite to reaffirm prescription weight-loss medicine advertising rules

An updated joint Enforcement Notice provides important clarity on the kinds of claims and images in an ad that are likely to break the rules.

The updated notice is directed at businesses, primarily pharmacies, that make these medicines available to the public and provides important clarity on the kinds of claims and images in an ad that are likely to break the rules. This year to date, the MHRA has taken action against >25 businesses that promoted to the public prescription-only medicines for weight loss.

The Association of the British Pharmaceutical Industry (ABPI)

Accelerated review of VPAG concludes without agreement

In April 2025, the ABPI and government agreed to bring forward a planned mid-scheme review of the 2024 Voluntary Scheme for Branded Medicines Pricing, Access, and Growth (VPAG).

This review was tasked with finding a mutually agreed way to address soaring VPAG payment rates, which now require pharmaceutical companies to make record payments up to a quarter to a third (23.5%-35.6%) of their revenue from sales of branded medicines to the NHS

Despite good faith and best efforts on both sides, industry and government have not been able to reach an agreed way forward that will meaningfully deliver on:

·       the UK government’s ambition for the life science sector and wider economic growth

·       industry's ambition to ensure the latest medical breakthroughs and treatments can reach all the NHS patients who can benefit from them

·       the commitments set out in the UK-US Economic Prosperity Deal

While no other country has an identical scheme to the UK, the 2025 payment rate has left the UK significantly out of line with comparable countries, with France’s average payment rate at 5.7%, Italy at 6.8%, Germany at 7%, Spain at 7.5%, Belgium at 7.9%, and Ireland at 9%.

Over the past decade, growth in the UK branded medicine market has been capped at between 1.1% (2014-2018) and 2% (2019-2023) per year. After accounting for inflation, this growth has declined by over a tenth (11%). In the same period, the NHS budget grew by a third in real terms (33%).

The UK’s decades of disinvestment in medicines and vaccines have left the NHS lagging international peers in terms of access to and use of innovative treatments. Unless something changes, these trends will continue.

[Pharmacoeconomics is not usually a topic covered in our Regulatory Update, but this issue affects us all – Regulator, Industry and patients- in so many ways. MBH].

Europe

European Medicines Agency (EMA)

Warning about sharp rise in illegal medicines sold in the EU

In recent months there has been a sharp rise in the number of illegal medicines marketed as GLP-1 receptor agonists such as semaglutide, liraglutide and tirzepatide for weight loss and diabetes. These products, often sold via fraudulent websites and promoted on social media, are not authorised and do not meet necessary standards of quality, safety and efficacy.

Such illegal products pose a serious risk to public health. They may not contain the claimed active substance at all and may contain harmful levels of other substances.

People who use these products are therefore at a very high risk of treatment failure, unexpected and serious health problems and dangerous interactions with other medicines.

The online sale of prescription only medicines is not allowed in all Member States.

To help the public identify legitimate online medicine retailers, the EU introduced a common logo which appears on the websites of all registered online pharmacies and retailers. Clicking on the logo takes buyers to a national register of authorised retailers.

If a website does not have this logo or is not listed on a national register, the website is fraudulent and operating illegally.

The national flag and the text are an integral part of the logo. Only national flags of an EU Member State, as well as those of Norway, Iceland and Liechtenstein, can be displayed.

Reflection paper on patient experience data

EMA aims to ensure that medicines deliver optimal treatment outcomes. Successful individualised medical treatment relies on three key factors: 1) an understanding of the disorder and treatment options, 2) comprehensive patient data (e.g., demographic details, medical history, lab results) and 3) consideration of the patient's expectations, preferences and values.

Patient experience data (PED) address this third factor and provide a framework for its qualitative and quantitative analysis. Recent years have seen efforts by regulators internationally to steer medicine development towards programmes that not only meet the requirements for quality, safety and efficacy of individual products, but also incorporate the broader perspectives of patients and carers. This is because patients may value different aspects of their disease and available treatments than medicine developers, including the type of relevant outcome measures to be assessed (e.g., quality of life; QoL), populations or stages of disease to be studied or risk tolerability. An optimal patient-relevant medicine development programme incorporates patients’ perspectives and documents their experience. Such PED are directly collected from patients or carers experienced in managing the disease and capture their needs and preferences.

These efforts could help to better understand the impact of a medicine on a patient’s condition and treatment outcomes, and can allow more informed assessment and decision making by medicine regulators, health technology assessment (HTA) bodies, healthcare professionals and patients.

The reflection paper is open for comment until 31 Jan 2026.

Quality of medicines Q&A

A new Q&A has been added to the section relating to the level of histamine in Gentamycin produced by fermentation for use in parenteral solutions indicated for horses. (see Q&A 3 in the section on Use of peptones in the manufacture of active substance).

Histamine in gentamicin active substance has been identified as the root cause of allergic reactions to parenteral solutions administered to horses. A limit of 8 ppm should be applied to histamine in the gentamicin active substance specification of parenteral solutions for horses. 

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

Reference Standards

1 new European Pharmacopoeia reference standard and 17 replacement batches released in August 2025

Certification monthly report of activities: End of August 2025

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

Heparin low-molecular-mass for calibration CRS batch 6

In addition to the above standards, Ph. Eur. Heparin low-molecular-mass for calibration Chemical Reference Substance (CRS) batch 6 has been established for use for determination of molecular mass distribution as prescribed in the Ph. Eur. monograph on Heparins, low-molecular-mass (0828). The fitness for use of the material was confirmed in a study conducted under the aegis of the EDQM’s Biological Standardisation Programme, a joint programme of the Council of Europe and the European Commission.

The batch was adopted by the European Pharmacopoeia Commission and is available in the online catalogue

New guidelines on the classification of active pharmaceutical substances as regards their supply

These guidelines are intended to help national competent authorities (NCAs), marketing authorisation holders (MAHs) and other interested parties establish whether a medicinal product should be available with or without a prescription, a decision that depends on several factors. The characteristics of the active substance and pharmaceutical form, the therapeutic indications and the safety profile are considered, as well as the extent to which healthcare professionals’ expertise is needed to diagnose and treat the condition for which the medicinal product is to be used. The nature and degree of any potential risk of misuse or incorrect use are also considered. The CD-P-PH/PHO issues a recommendation for a non-prescription status or exemptions to a prescription-only status if the benefits clearly outweigh the risks, as demonstrated by in-depth Evidence-Based Classification Reviews (EBR)

Ireland

The Health Products Regulatory Authority (HPRA)

2024 Annual Report

The HPRA has published its 2024 annual report, detailing a wide-ranging programme of work undertaken to regulate health products in Ireland for the benefit of people and animals. The report outlines the HPRA’s core priorities and key achievements throughout the year, while also highlighting its proactive response to external developments affecting the broader health landscape. These included challenges around medicines availability, changes to national and EU regulatory systems, and the detention of unauthorised or illegal medicinal products. 

United States of America

The US Food and Drug Administration (USFDA)

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for Industry

This guidance describes the Agency’s recommendations on the design and evaluation of comparative analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product licensed under section 351(a) of the Public Health Service Act (PHS Act). Additionally, this guidance is intended to provide recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing, and controls (CMC) portion of a marketing application for a proposed product submitted under section 351(k) of the PHS Act. This guidance finalizes and replaces the draft guidance of the same title issued on May 22, 2019, and replaces the final guidance “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product” issued on April 30, 2015.

Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications

This guidance provides information to applicants on how FDA intends to use alternative tools to assess drug manufacturing facilities identified in a marketing application (i.e., a new drug application (NDA), an abbreviated new drug application (ANDA), a biologics license application (BLA), or a supplement to any of these types of applications). FDA agreed to issue guidance on the use of alternative tools to assess manufacturing facilities named in pending applications and to incorporate best practices from the use of such tools during the Coronavirus Disease 2019 (COVID-19) pandemic. This guidance finalizes the draft guidance of the same title issued on September 22, 2023.

The following alternative tools were used during the COVID-19 public health emergency:

• Requesting records and other information, pursuant to section 704(a)(4) of the FD&C Act (21 U.S.C. 374(a)(4)), directly from facilities and other entities subject to inspection

• Performing remote interactive evaluations (RIEs) (e.g., remote livestreaming video of operations, teleconferences, screen sharing)

• Requesting existing inspection reports and other information from trusted foreign regulatory partners through mutual recognition agreements and other agreements.

FDA has strategically used these tools within the context of decisions related to preapproval inspections (PAIs) or prelicense inspections (PLIs) to maximize facility evaluation efficiency as part of appropriate, risk-based assessments. Given the success of these innovative approaches, the Agency intends to continue risk-based use of these alternative tools and to apply certain virtual technological capabilities within a specific inspectional context defined within this guidance, such as collaborative inspections conducted by foreign regulators with FDA remote participants and supporting PAIs and PLIs with FDA remote subject matter experts. When used in advance or in lieu of PAIs and PLIs or to support PAIs and PLIs, the appropriate use of these approaches helps FDA maintain operational flexibility to support timely facility evaluations and application decisions.

Safety Labeling Changes

This draft guidance provides information on the implementation of the statutory provision that authorizes FDA to require application holders for certain drug and biological products to make labeling changes based on new safety information that becomes available after approval of the drug that FDA determines should be included in the labeling of the drug. This guidance is being updated and reissued in draft to, among other things, include the addition of information related to Congress’ 2018 changes to the definition of adverse drug experience regarding reduced effectiveness and make other changes to reflect current Agency processes and procedures regarding safety labeling changes. This draft guidance revises and, when finalized, will replace the guidance for industry entitled "Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C Act" issued in July 2013.

Once FDA has determined that there is new safety information that should be included in labeling, FDA sends an SLC notification letter to the application holder(s).

International

Australia

Therapeutic Goods Administration (TGA)

Safety concerns over imported melatonin products

TGA is issuing a safety advisory regarding imported unregistered melatonin products following testing by TGA Laboratories.

The results indicate significant discrepancies in the actual melatonin content compared to the labelled amounts. One product contained more than 400% of the labelled content and another containing no melatonin at all.

Multiple sunscreens recall - Lower than claimed SPF levels

Consumers are advised that several sunscreen products are being recalled by sponsors. This follows preliminary testing evidence indicating that the SPF levels of their products may be lower than what is claimed on their labels.

There is a risk that a low SPF rating may increase the risk of sunburn during use and reduce the long-term effectiveness of preventing skin cancer.

Pharmaceutical inspection convetion / system. PIC/S

Draft guidelines: Revised Chapter 1 - Pharmaceutical Quality System

PIC/s has now published this draft guideline

Alongside other recently revised (annex 11 & Chapter 4) and new (annex 22) guidelines on the PIC/S website. 

Switzerland – (Swissmedic)

Disposal information to be added to Patient information

In the interests of environmental protection, information on the correct disposal of medicinal products will be added to Patient information from 1 September 2025. The aim is to prevent medicinal product residues entering and polluting the environment.

The information will be phrased as follows: “Do not throw away any medicines via wastewater or household waste. Expired or no longer needed medicines from households can be returned to pharmacies or collection points.

Marketing authorisation holders are requested to implement this requirement voluntarily at the next possible opportunity.

[If your company supplies the Swiss market, then you need to be aware of and perhaps have plans to come into compliance ASAP -MBH]

Conferences

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.

EDQM webinar on how to read a CEP

EDQM will hold a free webinar on 25 November 2025 for all interested users of Certificates of suitability to the monographs of the European Pharmacopoeia (CEPs), following up on the recently revised guideline

Places are limited, so register now

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.