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Updated: 6 days ago

Review of Developments in GMP and the Regulation of Medicines November 2023




EJPPS Vol 28.4B (1)
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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 Australia and WHO regulatory authorities. In addition there are a number of interesting items covered under the ‘Product’ section of the report.


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

UK 

  • Medicines that you cannot export from the UK or hoard – Updated  

  • MHRA warns of unsafe fake weight loss pens  

  • Safety warnings to be provided to all patients with every valproate-containing medicine they receive under new law 

  • New streamlined notification scheme for lowest-risk clinical trials marks start of MHRA overhaul of regulation  

  • MHRA and international partners publish five guiding principles for machine learning-enabled medical devices  

  • MHRA to launch the AI-Airlock, a new regulatory sandbox for AI developers 

  • 15 years of Operation Pangea 

 

EU 

  • Revised transparency rules for the EU Clinical Trials Information System (CTIS) 

  • CTIS newsflash 

  • Post-authorisation procedural advice for users of the centralised procedure 

  • Notifying a change of marketing status 

  • Stability testing for applications for variations to a marketing authorisation for veterinary medicinal products - Scientific guideline 

  • Guideline on the calculation of dose factor to be submitted to the Union Product Database (UPD) 

  • DNA and host cell protein impurities, routine testing versus validation studies - Scientific guideline 

  • EMA Mid-year report 2023 

  • Further steps to address critical shortages of medicines in the EU 

  • Revised general chapter 2.7.24 Flow cytometry in Pharmeuropa 35.4 

  • EDQM joins efforts to tackle medicine shortages 

  • Pharmacopoeial Discussion Group (PDG) welcomes Indian Pharmacopoeia Commission as a member 

  • Implementation of the European Pharmacopoeia Supplement 11.4 – Notification for CEP holders  

  • Ph. Eur. pre-publishes Cannabis flower monograph 

  • European Paediatric Formulary: Chloral hydrate oral solution monograph published 

  • Pharmeuropa 35.4 released  

  • Ph. Eur. Supplement 11.4  

USA 

  • Quality Considerations for Topical Ophthalmic Drug Products  

  • Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol 

  • Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products. Q&A 

  • Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities 

International 

Australia – Therapeutic Goods Administration (TGA) 

  • TGA seizes 70,000 vapes in NSW 

 

World Health Organisation (WHO) 

  • Bioanalytical method validation and study sample Analysis 

 

Products 

  • EMA alerts EU patients and healthcare professionals to reports of falsified Ozempic pens 

  • UK MHRA authorises monoclonal antibody treatment, Jemperli, to be used with chemotherapy for endometrial cancer  

  • New treatment option for heavily pre-treated multiple myeloma patients 

  • MHRA authorises bispecific antibody therapy Tepkinly 

  • GLP-1 receptor agonists: available evidence not supporting link with thyroid cancer 

  • Treatment with isotretinoin for patients under 18 must be approved by two prescribers, under new MHRA rules  

Conferences 

  • Awareness session for SMEs on the reform of the EU pharmaceutical legislation 

 

 

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 – Updated  

As of 9 Oct2023 the following products have been added to the list of medicines: Hyoscine hydrobromide (strength: 1.5mg, pharmaceutical form: patches); Bumetanide (strength: all, pharmaceutical form: tablets); Methylphenidate hydrochloride (strength: all, pharmaceutical form: all); Atomoxetine (strength: all, pharmaceutical form: all); Lisdexamfetamine mesylate (strength: all, pharmaceutical form: all); Dexamfetamine sulfate (strength: all, pharmaceutical form: all); and Guanfacine (strength: all, pharmaceutical form: all) 

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 MHRA, which could include immediate suspension of the wholesale dealer licence. 

See also the October 2019,  letter to holders of a wholesale dealers licence which was sent out about the restrictions on parallel exports. 

MHRA warns of unsafe fake weight loss pens  

Fake, potentially harmful Ozempic and Saxenda pens have been found in the UK: you should only access weight loss medicines via a medical prescription. MHRA) is warning the public not to buy pre-filled pens claiming to contain Ozempic (semaglutide) or Saxenda (liraglutide) but to consult a healthcare professional qualified to prescribe medicines and obtain a prescription. 

Semaglutide and liraglutide are prescription only medicines. 

Saxenda (liraglutide), is authorised in the UK for weight loss, with diet and exercise. Ozempic (semaglutide) has been authorised for the treatment of adults with type 2 diabetes, also with diet and exercise. It is not authorised for weight loss, but it is commonly used off-label for that purpose. 

The MHRA has seized 369 potentially fake Ozempic pens since January 2023, and has also received reports of fake Saxenda pens that have been obtained by members of the public in the UK through non-legitimate routes Buying prescription-only medicines online without a prescription poses a direct danger to health. The MHRA has received reports of a very small number of people who have been hospitalised after using potentially fake weight-loss pens. Serious side effects reported of those hospitalised, including hypoglycaemic shock and coma, indicate that the pens may contain insulin rather than semaglutide 

Safety warnings to be provided to all patients with every valproate-containing medicine they receive under new law 

Valproate-containing medicines will be dispensed in the manufacturer’s original full pack, following changes in regulations coming into effect on Wednesday, 11 October 2023.  

MHRA has published new guidance for dispensers to support this change. 

This change to legislation has been made to ensure that patients always receive specific safety warnings and pictograms, including a patient card and the Patient Information Leaflet, which are contained in the manufacturer’s original full pack. The changes follow a consultation on original pack dispensing and supply of medicines containing sodium valproate led by the Department of Health and Social Care (DHSC), in which there was overwhelming support for the introduction of the new measures. 

MHRA notes that these amendments currently apply in England, Scotland and Wales, and the guidance should be regarded as good practice by pharmacists in Northern Ireland. 

New streamlined notification scheme for lowest-risk clinical trials marks start of MHRA overhaul of regulation  

UK patients, the healthcare system and the life sciences sector are set to benefit from a new scheme that will see the time taken by the Medicines and Healthcare products Regulatory Agency (MHRA) to approve the lowest-risk clinical trials reduced by more than 50%. 

Initial applications for the lowest-risk Phase 3 and 4 trials will be processed by the MHRA within 14 days instead of the statutory 30 days, 

MHRA and international partners publish five guiding principles for machine learning-enabled medical devices  

The MHRA, FDA and Health Canada have published five guiding principals for the development of PCCPs for MLMD manufacturers.  

These guiding principles aim to support manufacturers of MLMDs by reducing the regulatory burden of reassessment following certain changes and updates to their devices.the five guiding principles for MLMD manufacturers outline that a PCCP must be: Focused and Bounded, Risk-based, Evidence-based Transparent, Total Product Lifecycle Perspective.  

Currently, in the UK, when a manufacturer makes any significant updates or changes to their medical device, they must notify their conformity assessment body and their device may be reassessed to ensure these changes have not had a negative impact on performance and safety. 

Medical devices using AI and machine-learning can require frequent updates and therefore potentially lengthy reassessment every time a change is made. This could create significant regulatory burden for both developers and assessors. 

PCCPs allow manufacturers of MLMDs to demonstrate which changes and updates would be made, and how they would ensure safety and effectiveness are maintained, without the need for regulatory intervention. 

MHRA to launch the AI-Airlock, a new regulatory sandbox for AI developers  

This new ‘regulatory sandbox’, the AI-Airlock, will provide a regulator-monitored virtual area for developers to generate robust evidence for their advanced technologies. 

Artificial Intelligence in healthcare represents the exciting potential to improve patient outcomes in many ways, for example through improving diagnoses and treatment selections, optimising medication dosages, and providing enhanced personalised care for patients. 

This world-leading partnership between government, regulators and industry will see advanced AI technology used in NHS settings, with strict safety controls, ahead of navigating regulatory approval. 

Where successful the AI-Airlock will help NHS patients to benefit earlier from emerging technologies before they are available anywhere else in the world. 

This initiative demonstrates the MHRA’s commitment to building on its existing capabilities and investing its regulatory expertise to enable highly innovative areas of medical product development, bringing cutting-edge products to UK patients faster, without compromising on its robust standards of safety and performance. 

15 years of Operation Pangea 

This year marks 15 years since the Medicines and Healthcare products Regulatory Agency (MHRA) launched Operation Pangea, an initiative cracking down on medicines crime. So far, over 25 million illegally traded medicines and devices have been seized in the UK valued at more than £84m 

Pangea is now coordinated by Interpol, and the MHRA’s Criminal Enforcement Unit (CEU) joined 89 countries for this year’s operation. Working with law enforcement partners, the CEU seized over two million doses of medicines this year valued at nearly £5 million. 

Among the products seized in the UK were several prescription-only medicines including anti-depressants, pain medication and human growth hormones. 

 

Europe 

European Medicines Agency (EMA) 

Revised transparency rules for the EU Clinical Trials Information System (CTIS) 

The updated rules strike a balance between transparency of information and protection of commercially confidential information. They benefit patients, because key clinical trial information, that patients flagged as being most relevant for them, is published early. They also introduce process simplifications that benefit clinical trial sponsors who have to protect commercially confidential information and personal data. Finally, they benefit healthcare professionals because the resulting system is more user-friendly, facilitating access to information about clinical trials and enrolment in clinical trials, and also increasing awareness of possible treatment options. 

The updates were triggered by feedback from stakeholders and experience after the launch of the system.  

The revised transparency rules will apply after their technical implementation in CTIS, including its public portal, which is expected to be finalised in the second quarter of 2024. The effective date of completion of the process and the entry into application of the new rules will be communicated to the users of the system before they become applicable. 

CTIS newsflash 

This regular CTIS newsflash provides key updates on CTIS and links to useful reference materials.  

This edition contains a reminder on transitioning trials to CTIS, By 30 January 2025, any ongoing trials approved under the Clinical Trials Directive will fall under the CTR. Therefore, any ongoing trials will need to be transitioned to CTIS and approved by 30 January 2025. Sponsors have submitted around 390 transitional trials to CTIS, out of an estimated total of 4,000-6,000 trials that need to be transitioned. 

Post-authorisation procedural advice for users of the centralised procedure 

A number of changes have been made in this revised document (v105) and are best viewed from the ‘track changes’ pdf version. 

Notifying a change of marketing status 

A change has been made in the Marketing status updates and withdrawals section of this document concerning Q&A#9 “how should I request the withdrawal of my central marketing authorisation?”  

Stability testing for applications for variations to a marketing authorisation for veterinary medicinal products - Scientific guideline 

This concept paper has been developed to address the need for a new guideline on stability testing for variations to a marketing authorisation for veterinary medicinal products in which the new classification system for variations under Regulation (EC) 2019/6 will be used. The proposed guideline will replace the 'Guideline on stability testing for applications for variations to a marketing authorisation' (EMA/CHMP/CVMP/QWP/441071/2011-Rev.2) for veterinary medicinal products only. 

The guideline will provide general guidance on the stability data which have to be generated in order to support a variation to a marketing authorisation for veterinary medicinal products. 

The consultation period ends 5 Jan 2024. It is not expected that the new guideline will result in increased data requirements for marketing authorisation holders. 

Guideline on the calculation of dose factor to be submitted to the Union Product Database (UPD) 

This guideline provides additional guidance to marketing authorisation holders (MAHs) that are  

required to submit annual volume of sales data, including dose factor for each veterinary medicinal product (VMP), to the Union Product Database (UPD). The data submitted by MAHs will be used to calculate an estimated number of treated animals (ENTA), and subsequently, in combination with the total number of animals displaying a suspected adverse event recorded for VMPs in EudraVigilance Veterinary (EVV), to derive an annual reporting incidence. In accordance with Regulation (EU) 2019/640, these annual reporting incidences of reported suspected adverse events will be made publicly accessible by 2024. 

The overall objective of this guideline is to provide specific guidance on the considerations and calculations related to dose factor. The aim being to generate a simple, pragmatic, and harmonised approach to dose factor. This in turn should provide consistence, stability, and comparability in the subsequent calculation of the reporting incidence. 

DNA and host cell protein impurities, routine testing versus validation studies - Scientific guideline 

This document has been superseded. A new Q&A (Sept 2023) has been published. The Q&A page is developed and maintained by the CHMP Biologics Working Party (BWP) and provides agreed positions by the Biologics Working Party position on issues that can be subject to different interpretation or require clarification, typically arising from discussions or correspondence during assessment procedures of biological human medicinal products. 

EMA Mid-year report 2023 

This report is prepared by the Executive Director of the EMA and presented to the Agency's Management Board on 5 October 2023. 

[I would recommend a read of this document to help in understanding of EMAs current targets and progression. Our readers may be particularly interested to note that: 

  • The number of good manufacturing practice (GMP) inspections have more than doubled, from 89 in the first half of 2022 to 210 in 2023.  

  • Good clinical practice (GCP) inspections remained stable compared to the previous year 

  • Plasma Master File (PMF) inspections, showed a notable growth in the first half of 2023 with 88 inspections, representing 340% increase against the same period in 2022 

  • Standard certificate requests marked a significant increase again in the first half this year compared to the previous year first half (2,486 vs 2,012), while urgent certificate requests remained stable compared to the first half of 2022 (612 vs 591). 

MBH] 

Further steps to address critical shortages of medicines in the EU 

The solidarity mechanism, which is based on an informal setup during COVID-19, will enable any Member State facing a critical shortage that has been escalated to the MSSG for coordination at European level to request assistance from other Member States in obtaining medicine stocks. This mechanism can only be used under very limited conditions and was developed as a last resort for Member States after they have exhausted all other possibilities. 

The toolkit includes recommendations for monitoring supply and demand, an approach that was used to tackle the widespread critical shortages of antibiotics in the autumn and winter seasons of 2022 / 2023. The toolkit also provides guidance on interactions with marketing authorisation holders and manufacturers to increase and redistribute existing stocks and the implementation of regulatory flexibilities, such as the exceptional supply of certain medicines that may not be authorised in a particular EU Member State, or full or partial exemptions to certain labelling and packaging requirements for medicines. 

The two documents are part of a clear set of actions announced by the European Commission today to protect Europe against medicines shortages in the future. 

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

Revised general chapter 2.7.24 Flow cytometry in Pharmeuropa 35.4 

The revision of this general chapter is of high importance since it will facilitate the use of a major technique, flow cytometry, to detect and analyse the chemical and physical attributes of a population of cells or particles.  

The general chapter 2.7.24 Flow cytometry has been updated to reflect current techniques. The text provides important information on technical considerations (including equipment description and system selection), sample preparation and data analysis. It also supports users by giving examples of flow cytometry applications, as well as recommendations regarding qualification and validation. Additional information has been inserted throughout the text. For instance, the chapter now covers the analysis of small particles (e.g. exosomes and viral particles) and includes a table summarising fluorescent dyes and fluorochromes commonly used in flow cytometry, together with an example of a stepwise procedure to establish compensation. 

EDQM joins efforts to tackle medicine shortages 

Medicine shortages are a growing problem that compromises patient care. Two key committees at the European Directorate for the Quality of Medicines & HealthCare (EDQM), the European Committee on Pharmaceuticals and Pharmaceutical Care (CD-P-PH) and the European Pharmacopoeia Commission (EPC), are working together to alleviate shortages through the use of unlicensed pharmaceutical preparations prepared in pharmacies. These have already proven to be an effective tool during specific medicine shortages in some countries. 

The initiative consists of two recently launched projects :- 

  • Methodological guide for selecting essential medicines at risk of shortage 

  • European Drug Shortages Formulary 

Pharmacopoeial Discussion Group (PDG) welcomes Indian Pharmacopoeia Commission as a member 

PDG announced the Indian Pharmacopoeia Commission (IPC) as a PDG member.  

The World Health Organization (WHO) also continues to serve as observer of the group. 

Implementation of the European Pharmacopoeia Supplement 11.4 – Notification for CEP holders  

Supplement 11.4 of the European Pharmacopoeia (Ph. Eur.) is now available. Holders of Certificates of suitability to the monographs of the Ph. Eur. (CEPs) are invited to update their applications according to the revised monographs that will be implemented on 1 April 2024 

It is the responsibility of the manufacturer to comply with the current version of a Ph. Eur. monograph, and therefore to update the specification when a revised monograph is issued. In addition, the EDQM ensures that CEPs refer to the most recent version of a Ph. Eur. monograph at any time. 

The need to submit information to the EDQM following a revised monograph depends on the changes made to the monograph.  

Ph. Eur. pre-publishes Cannabis flower monograph 

The new monograph on Cannabis flower (3028) was adopted at the 176th session of the European Pharmacopoeia. Given the exceptionally high interest from stakeholders in having access to the new text as soon as possible, the Ph. Eur. decided to make the monograph immediately available on the EDQM website for information. The monograph will be published in Ph. Eur. Supplement 11.5 in January 2024. 

Note - The EDQM will hold a webinar on 14 December 2023 (15:30 – 17:00 CET) to present the new monograph to its stakeholders to help them prepare for implementation of the text. 

European Paediatric Formulary: Chloral hydrate oral solution monograph published 

EDQM has published its fifth new monograph, Chloral hydrate 100 mg/mL oral solution, in the European Paediatric Formulary. The monograph was published for public consultation in Issue 5 of Pharmeuropa PaedForm in January 2023, approved by the European Pharmacopoeia Commission at its 176th session in June 2023 and recently adopted by the European Committee on Pharmaceuticals and Pharmaceutical Care (CD-P-PH). 

Pharmeuropa 35.4 released 

Users and interested parties are welcome to comment on these drafts. The deadline for comments on Pharmeuropa 35.4 is 31 December 2023. 

Ph. Eur. Supplement 11.4 

The European Pharmacopoeia (Ph. Eur.) Supplement 11.4 is now available and will be applicable in 39 European countries as of 1 April 2024. 

 

United States of America 

The US Food and Drug Administration (USFDA) 

Quality Considerations for Topical Ophthalmic Drug Products  

This draft guidance discusses certain quality considerations for ophthalmic drug products (i.e., solutions, suspensions, emulsions, gels, ointments, and creams) intended for topical delivery in and around the eye. Specifically, the guidance discusses: 

• Approaches to evaluating visible particulate matter, extractables and leachables, and impurities and degradation products. 

• Use of in vitro drug release/dissolution testing as an optional quality control strategy for certain ophthalmic dosage forms. 

• Recommendations for design, delivery, and dispensing features of container closure systems (CCSs). 

• Recommendations for stability studies. 

Comments should be submitted by 12 Dec 2023 

Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol 

This guidance is intended to alert pharmaceutical manufacturers and pharmacists in State-licensed pharmacies or Federal facilities who engage in drug compounding to the potential public health hazard of alcohol (ethyl alcohol or ethanol) or isopropyl alcohol contaminated with or substituted with methanol. During the Coronavirus Disease 2019 (COVID-19) public health emergency (PHE), the Food and Drug Administration (FDA) became aware of reports of fatal methanol poisoning of consumers who ingested alcohol-based hand sanitizer products that were manufactured with methanol or methanol-contaminated ethanol. FDA has also received numerous reports of dermal toxicity associated with such products. 

FDA also is concerned that other drug products containing ethanol or isopropyl alcohol (pharmaceutical alcohol), which are widely used ingredients in a variety of drug products, could be similarly vulnerable to methanol contamination. For example, certain inhalation products, mouthwashes, cough and cold products, and many topical drug products include pharmaceutical alcohol. As the COVID-19 pandemic increased the demand for hand sanitizer products, the demand for pharmaceutical alcohol as the active ingredient of those products also increased. In the past, increased stress on supply chains has made ingredients more vulnerable to economically motivated adulteration. 

For these reasons, the policy outlined in this guidance applies to pharmaceutical alcohol used as an active or inactive ingredient in a drug product regardless of whether the drug product is a hand sanitizer product.  

This guidance replaces the guidance for industry Policy for Testing Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19) published in January 2021. 

Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products. Q&A 

This revised draft guidance, when finalized, will provide FDA’s current thinking on common questions regarding certain communications by firms to health care providers (HCPs) of scientific information on unapproved use(s) (SIUU) of approved/cleared medical products. 

Specifically, this guidance relates to firms sharing the following types of communications with HCPs:- 

  • Published scientific or medical journal articles (reprints) 

  • Published clinical reference resources, as follows: 

-Clinical practice guidelines (CPGs) 

-Scientific or medical reference texts (reference texts) 

-Materials from independent clinical practice resources  

-Firm-generated presentations of scientific information from an accompanying published reprint 

The Federal Food, Drug, and Cosmetic Act (FD&C Act), the Public Health Service Act (PHS44 Act), and their implementing regulations (collectively, the FDA Authorities) prohibit, among other things, the introduction (or causing the introduction) into interstate commerce of a medical product that fails to comply with applicable premarket requirements or is otherwise misbranded or adulterated. This prohibition includes introducing (or causing the introduction) into interstate commerce a medical product that is intended for a use that has not been approved or cleared by FDA, even if that same product is approved or cleared for a different use. In certain circumstances, however, HCPs may be interested in scientific information about unapproved uses of approved/cleared medical products to inform clinical practice decisions for the care of an individual patient. In developing this draft guidance, FDA has sought to strike a careful balance between supporting HCP interest in scientific information about unapproved uses of approved/cleared medical products to inform clinical practice decisions for the care of an individual patient, and mitigating the potential that the government interests advanced by these statutory requirements will be undermined. 

Comments to be submitted by 24 Dec 2023 

Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities 

FDA is issuing this draft guidance to describe how we request and conduct voluntary remote interactive evaluations at facilities where drugs are manufactured, processed, packed, compounded, or held, and at drug facilities covered under FDA’s bioresearch monitoring (BIMO) program. 

 

International 

 

Australia – Therapeutic Goods Administration (TGA) 

TGA seizes 70,000 vapes in NSW 

TGA executed warrants on two storage units in Sydney and seized more than 70,000 vaping products with an estimated street value in excess of $2.1 million.  

The TGA warrants were executed as part of ongoing investigations into the alleged importation of unapproved nicotine vaping products. The seized products are alleged to be prescription medicines that were not included, or otherwise exempt from inclusion, in the Australian Register of Therapeutic Goods (ARTG).  

The products will be tested at the TGA laboratories for scheduled and other dangerous ingredients. Nicotine vaping products that are not imported or supplied under a TGA-approved pathway pose a significant public health risk, with many tested by the TGA found to contain dangerous and undeclared chemicals. 

Penalties for the illegal importation or supply of counterfeit or unapproved therapeutic goods is up to five years’ imprisonment and/or a financial penalty of up to $1.25 million. 

 

World Health Organisation (WHO) 

Bioanalytical method validation and study sample Analysis 

This draft working document for comments (guideline) is intended to provide recommendations for the validation of bioanalytical methods for chemical and biological drug quantification and their application in the analysis of study samples. Adherence to the principles presented in this guideline will ensure the quality and consistency of the bioanalytical data in support of the development and market approval of both chemical and biological drugs.  

Concentration measurements of chemical and biological drug(s) and their metabolite(s) in biological matrices are an important aspect of drug development. The results of studies employing such methods contribute to regulatory decisions regarding the safety and efficacy of drug products. It is therefore critical that the bioanalytical methods used are well characterized, appropriately validated and documented in order to ensure reliable data to support regulatory decisions. 

This draft guideline intends to facilitate development of drugs in accordance with the principles of 3Rs (Reduce, Refine, Replace) for animal studies, where valid. 

[PHSS does not currently intend to coordinate comments on this document, should you wish to do so you can access the comments form from the current working documents list above. MBH] 

Products 

EMA alerts EU patients and healthcare professionals to reports of falsified Ozempic pens 

The EMA has been notified by relevant national competent authorities that pre-filled pens falsely labelled as the diabetes medicine Ozempic (semaglutide, 1 mg, solution for injection) have been identified at wholesalers in the EU and the UK. 

The pens, with labels in German, originated from wholesalers in Austria and Germany. The pens have batch numbers, 2D barcodes and unique serial numbers from genuine Ozempic packs. In the EU, each medicine pack has a unique 2D barcode and serial number so that it can be tracked in an EU-wide electronic system. When the packs of the falsified Ozempic were scanned, the serial numbers were shown to be inactive, thereby alerting operators to a potential falsification. 

There is no evidence that any falsified pens have been dispensed to patients from legal pharmacies and there are no reports of harm to patients in relation to the falsified medicine. 

The issue is currently being investigated by EU medicines regulatory authorities and the police. Wholesalers and pharmacies in the impacted countries have been warned about the suspicious offers of Ozempic to wholesalers. In addition, parallel distributors across the EU have been alerted. 

The latest reports of falsification come in the wake of an increase in demand for Ozempic which has also led to a shortage situation. 

Additionally, UK MHRA has confirmed that pre-filled pens falsely labelled as the diabetes medicine Ozempic (semaglutide, 1 mg, solution for injection) have been identified at two UK wholesalers. All affected pens have been recalled and accounted for, and none of the pens have been supplied to UK patients. 

Following investigation, the MHRA has confirmed that the products were brought in from legitimate suppliers in Austria and Germany. 

The MHRA is working closely with its regulatory partners internationally to continue to maintain the security of the wider supply chain, both at home and abroad. 

[Evidence that the verification system is working in practice. MBH] 

UK MHRA authorises monoclonal antibody treatment, Jemperli, to be used with chemotherapy for endometrial cancer  

Jemperli (GSK) is now authorised to be used together with chemotherapy to slow the progression of these cancers, increasing life expectancy for patients. This is the first medicine licensed as first line treatment for primary advanced or recurrent endometrial cancer. 

Jemperli has been authorised through Project Orbis, a global partnership between the MHRA, the Therapeutics Goods Administration in Australia, Health Canada, the Health Sciences Authority in Singapore, Swissmedic, Agência Nacional de Vigilância Sanitária in Brazil and Israel’s Ministry of Health, coordinated by the US Food and Drug Administration. This programme reviews and approves promising cancer drugs, helping patients to access treatments more quickly.  The active ingredient in this treatment, dostarlimab, is a monoclonal antibody. 

Also, On 12 October 2023, the EMA CHMP adopted a positive opinion recommending a change to the terms of the marketing Authorisation for Jemperli. The CHMP adopted a new indication for the treatment of endometrial cancer in combination with carboplatin and paclitaxel. 

New treatment option for heavily pre-treated multiple myeloma patients 

EMA’s CHMP has recommended a conditional marketing authorisation in the EU for Elrexfio (elranatamab) -Pfizer-as a monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies and whose cancer has worsened since they received their last treatment. 

(Elrexfio was accepted into the PRIME scheme on 26 March 2021and was designated as an orphan medicinal product on 19 July 2021.) 

[It is good to see these formalised risk management systems being used to facilitate early access to innovative new medicines MBH] 

MHRA authorises bispecific antibody therapy Tepkinly 

MHRA has authorised a new medicine called Tepkinly (epcoritamab), a treatment for diffuse large B-cell lymphoma (a type of blood cancer) in adults. 

It can be used to treat patients when the cancer has returned after previous treatment, or who have not responded to at least two previous treatments. 

The active ingredient in this treatment, epcoritamab, is a bispecific antibody. This is a type of protein designed to recognise and attach to a specific target substance in the body, helping a patient’s immune system fight cancer. 

In this case, it has been designed to help a patient’s immune system to attack cancer (lymphoma) cells by attaching to both their immune cells and cancer cells, bringing them together, so that their immune system can destroy the cancer cells. 

Tepkinly / Epkinly is also approved under the US FDA's Accelerated Approval program based on response rate and durability of response. Other approvals have been made in Japan and the EU (conditional marketing authorization) 

GLP-1 receptor agonists: available evidence not supporting link with thyroid cancer 

EMA’s safety committee (PRAC) has concluded that the available evidence does not support a causal association between the Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) - exenatide, liraglutide, dulaglutide, semaglutide, and lixisenatide - and cancer of the thyroid, 

GLP-1 receptor agonists are used to treat type 2 diabetes and, in some cases, for the treatment of obesity and overweight under certain conditions. The PRAC began assessing this safety signal following the publication of a stud suggesting that there might be an increased risk of thyroid cancers with the use of these medicines in patients with type 2 diabetes mellitus. 

Treatment with isotretinoin for patients under 18 must be approved by two prescribers, under new MHRA rules  

MHRA has introduced a number of regulatory changes to strengthen the safe use of isotretinoin, the acne medicine commonly known by brand names Roaccutane and Reticutan. These include additional safeguards when prescribing isotretinoin to patients under 18 years old, along with closer monitoring of a patient’s mental health and sexual well-being during treatment. 

The new safety measures, developed with input from patients and healthcare organisations, have been introduced to ensure that patients across the UK are better informed to make decisions about their treatment and so that they receive appropriate care and monitoring throughout treatment. These are: 

  • Additional oversight for patients under 18 

  • Better information on potential risks 

  • Improved monitoring and assessment of mental health and sexual wellbeing 

Conferences 

Awareness session for SMEs on the reform of the EU pharmaceutical legislation 

The SME office at EMA is organising a virtual webinar on the revision of the pharmaceutical legislation on 24 November 2023. 

The aim of the webinar is to raise awareness of the proposed changes that will mostly impact small and medium-sized enterprises (SMEs). 

The event is open to SMEs; registration enables active participation. The event will be broadcast and recorded, and the videos will be made available on the EMA website. 

 

 

And finally… 

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.  

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. 


 




 

 

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