UK/EU Regulatory Developments Review 2023

Introduction

The year 2023 has been remarkable in terms of regulatory developments within the UK and EU, characterised by substantial changes, innovative approvals, and strategic initiatives in the healthcare and pharmaceutical sectors. This review aims to provide a comprehensive overview of these pivotal developments, offering insights into their implications and future directions.

MHRA

MHRA Product Approvals

Standout Approval

The Medicines and Healthcare products Regulatory Agency (MHRA) has played a key role in advancing healthcare this year. The most notable approval was the innovative treatment, Casgevy (exagamglogene autotemcel; Vertex), for sickle-cell disease and transfusion-dependent β-thalassemia. Casgevy is the first medicine to be licensed that uses the innovative gene-editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020. Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long. In the clinical trial for sickle-cell disease, 45 patients have currently received Casgevy but only 29 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these eligible patients, 28 (97%) were free of severe pain crises for at least 12 months after treatment.

In the clinical trial for transfusion-dependent β-thalassemia, 54 patients have currently received Casgevy but only 42 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these, 39 (93%) did not need a red blood cell transfusion for at least 12 months after treatment. The remaining three had more than a 70% reduction in the need for red cell transfusions¹.

Other Significant Approvals

In addition to authorising the world-first gene therapy aimed to cure sickle-cell disease and transfusion-dependent β-thalassemia, MHRA has also played a significant part in providing patients access to many other crucial forms of treatments. Litfulo (ritlecitinib; Pfizer) for severe alopecia areata in adults and adolescents 12 years and older²; Jemperli (dostarlimab, GlaxoSmithKline) for patients with a tumour abnormality called mismatch repair deficient (dMMR) / microsatellite instability-high (MSI-H) in advanced stage cancer³; Mounjaro (tirzepatide; Eli Lilly) for weight loss and weight management in adults⁴; Krazati (adagrasib; Mirati Therapeutics) for a type of non-small cell lung cancer (NSCLC) with a KRAS G12C mutation⁵; and Tepkinly (epcoritamab; AbbVie) for diffuse large B-cell lymphoma in adults⁶. These approvals represent a significant step in addressing unmet medical needs and enhancing patient care, highlighting the MHRA's commitment to facilitating timely access to effective and safe treatments.

New Regulatory Guidelines, Legislation, and Initiatives by MHRA in 2023:

Focus on Patient Access and Innovation:

• International Recognition Framework (IRP): Launched in March 2023, the IRP allows expedited access to safe and effective medicines already approved by trusted international partners like Australia, Canada, EU, Japan, Switzerland, Singapore, and the US. This initiative aims to reduce duplication and streamline licensing procedures.
• Read our previous blog post: International Recognition Framework (IRF): Are You Ready?
• Innovation Pathway: This existing pathway continues to offer early regulatory advice and health technology assessment support for novel medicines, fostering innovation and bringing promising treatments to patients faster.

Regulatory Framework Evolution:

• Medical Devices (Amendment) (Great Britain) Regulations 2023: Introduced in March 2023, these regulations extend the grace period for certain CE-marked medical devices to ensure continued market access while manufacturers adapt to the UK's independent regulatory framework.
• Future Regulations for Medical Devices: Ongoing work focused on developing a robust future regulatory framework for medical devices, expected to launch in 2024. This framework is expected to strengthen safety, transparency, and overall product quality.
• Post-Market Surveillance Requirements: Recognising its importance for patient safety, the MHRA announced strengthened post-market surveillance requirements for medical devices in July 2023. This includes enhanced vigilance activities and manufacturer responsibilities for continued monitoring and reporting of safety concerns.

Strengthening Scientific and Regulatory Excellence:

• MHRA Science Strategy: Announced in July 2023, the Science Strategy outlines plans to leverage partnerships and research to support robust regulatory decision-making, particularly in areas of emerging science and technology.
• Clinical Trial Recognition Pathway: Ongoing efforts to simplify the process for recognising clinical trials conducted in other countries, promoting research and development efforts within the UK.

Additional Initiatives:

• Guidance Development: MHRA actively publishes new guidance documents to clarify regulatory requirements and best practices for the industry.
• Stakeholder Engagement: The MHRA prioritizes open communication through regular consultations, webinars, and engagement initiatives with industry, healthcare professionals, and patient groups.

MHRA – COVID-19 Pandemic Response

The MHRA authorised adapted COVID-19 vaccines targeting the Omicron XBB.1.5 subvariant, marking a significant advancement in the UK's pandemic response. Both Moderna's Spikevax and Pfizer/BioNTech's Comirnaty vaccines, suitable for individuals from 6 months of age, have met the MHRA's stringent standards for safety, quality, and effectiveness⁷,⁸.

In response to the evolving nature of the COVID-19 pandemic, particularly with the emergence of new variants, the UK has intensified its efforts in antiviral development and deployment. The rapid mutation of the SARS-CoV-2 virus, leading to variants with potential viral escape mechanisms, has underscored the necessity for swift action. The Antivirals and Therapeutics Taskforce, established by the UK's Department of Health and Social Care, held a workshop on 12 September 2022, involving expert pharmacologists, the UKHSA, and the MHRA. This initiative aimed to address knowledge gaps and enhance the evaluation of antiviral drugs and monoclonal antibodies. This comprehensive approach signifies the UK's proactive stance in managing the pandemic and adapting to its challenges⁹.

EMA

EMA Product Approvals

Standout Approval

European Commission (EC) has granted conditional marketing authorisation for Tepkinly (epcoritamab; AbbVie) as a standalone treatment for adult patients facing relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after undergoing two or more lines of systemic therapy. This marks a significant milestone as Tepkinly becomes the first and only subcutaneous bispecific antibody to receive approval for treating this patient group within the European Union (EU) and in Liechtenstein, Norway, and Iceland.

The benefits of Tepkinly were evaluated in a study involving 157 adults with DLBCL or a related lymphoma whose cancer had returned or was not responding after at least two other treatments. In this study, Tepkinly was given for an average of four months and was not compared with other medicines or placebo. Of the patients with DLBCL, 62% (86 out of 139) had either a complete response (no sign of cancer) or a partial response to Tepkinly; they maintained these responses for an average of around 16 months.

Crucially, the safety profile of Tepkinly across the entire LBCL patient cohort (which included DLBCL patients, totalling 167) was manageable¹⁰.

Other Significant Approvals

Alongside the MHRA, the EMA has also played a key role in advancing healthcare this year. There have been 23 new (non-orphan) medicinal approvals, 22 orphan medicine approvals, 8 biosimilar products and 16 Generic/ Hybrids/ Informed Consent. Notable approvals include Jaypirca (pirtobrutinib; Eli Lilly) for relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor¹¹; Apretude (cabotegravir; ViiV Healthcare) for Pre-exposure prophylaxis of HIV-1 infection¹²; Enrylaze (crisantaspase; Jazz Pharmaceuticals) for adults and children aged one month and older to treat acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL)¹³; Orserdu (elacestrant; Stemline Therpaeutics) for the treatment of postmenopausal women, and men, with estrogen receptor (ER) positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor¹⁴. These approvals represent a significant step in addressing unmet medical needs and enhancing patient care, highlighting the EMA’s commitment to facilitating timely access to effective and safe treatments.

New Regulatory Guidelines, Legislation, and Initiatives by EMA in 2023

Electronic Patient Information

The EU has seen a wave of regulatory transformations this year. The adoption of electronic Patient Information (ePI) for selected medicines marks a digital shift in patient communication, aiming to improve accessibility and understanding of medicinal information¹⁵.

Medicine Shortages

The EMA has also published guidance for industry to mitigate medicine shortages. The guidance describes the various stakeholders involved in the medicine supply chain and their responsibilities and role in the prevention and management of medicine shortages. It provides ten recommendations for marketing authorisation holders, wholesalers, distributors and manufacturers to minimise the occurrence of medicine shortages and their impact¹⁶. This is alongside the significant reforms in pharmaceutical legislation. These developments reflect the EU's commitment to ensuring the availability, safety, and efficacy of medicines across member states.

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

The revised transparency rules for the EU CTIS in 2023 brought significant changes to the handling of clinical trial data and documents. A notable amendment is the removal of the deferral mechanism, which previously allowed sponsors to postpone the publication of specific data for up to seven years to protect personal data and commercially confidential information (CCI).

These updated rules achieve a balance between ensuring transparency and safeguarding CCI. They are advantageous for patients by ensuring early publication of key clinical trial information deemed crucial by them. For sponsors, the rules simplify processes related to the protection of CCI and personal data. Healthcare professionals also benefit from a more user-friendly system, which improves access to clinical trial information and enhances awareness of potential treatment options. Overall, these revisions represent a pivotal development in EU clinical trial regulation, prioritising transparency while maintaining necessary protections¹⁷.

Reform of the EU Pharmaceutical Legislation

The European Commission's recent proposal to overhaul EU pharmaceutical legislation marks a substantial advancement. This proposal aims to update both the general pharmaceutical laws (Regulation 726/2004 and Directive 2001/83/EC) and specific regulations for paediatric and rare disease medicines (Regulation 1901/2006 and Regulation 141/2000/EC).

Key objectives of this revision include ensuring equitable access to safe, effective, and affordable medicines for all EU patients, reinforcing the supply chain to guarantee medicine availability across the EU, and promoting an innovative environment for medicine research and production in Europe. Moreover, the proposal places a strong emphasis on environmental sustainability within the pharmaceutical sector and tackles critical health concerns such as antimicrobial resistance (AMR) through a holistic One Health approach¹⁸.

• Reducing temporal exclusivity and allowing earlier availability of generics and biosimilars
• One of the most important changes brought about by the new legislation proposal is the reduction of the period of exclusivity for a drug. The minimum period of regulatory protection will be lowered from 10 to 8 years. However, pharmaceutical companies will still be able to benefit from an extended period of exclusivity (up to 12 years in total, or 4 additional years) if:
• The drug meets an unmet medical need.
• Comparative clinical trials are conducted.
• Products are launched in a larger number of countries.
• Multiple indications are considered in the development.

Thus, manufacturers will have to review their research, development, and marketing strategies to meet these eligibility criteria for the extension of the duration of protection.

• The EC’s evaluation identified that shortages of medicinal products are an increasing problem in the EU. According to the explanation of the proposal for the new Regulation, all MAHs should have shortage prevention plans in place, to prevent shortages. The EMA should provide guidance to marketing authorisation holders on approaches to streamline the implementation of those plans. The national competent authorities should be empowered to monitor shortages of medicinal products that are authorised through both national and centralised procedures, based on notifications of marketing authorisation holders.
• One further significant issue of the EU pharmaceutical legislation reform is the reduction of the administrative burden. The overhaul proposes to speed up the scientific evaluation and authorisation process for medicines, thus reducing the average time for EMA authorisation procedures from 400 days to 180 days. In addition, the regulatory revision aims to create a regulatory environment that fosters innovation and provides better regulatory and early scientific support.
• Simplified procedures will be introduced for promising medicines and digitisation will be adopted, such as electronic submission of applications and electronic product information.
• Finally, the legislation revision will also introduce transparency in public funding of drug development, and the production of comparative clinical data will be encouraged. It will then be interesting, once this data has been collected, to see which players receive the most public funding for their R&D in Europe.

In summary, this legislative update represents a significant stride towards a more cohesive, environmentally conscious, and patient-focused pharmaceutical system in the EU, aligning with modern health imperatives and the drive for innovation.

Innovation in Medicine

The year 2023 has been pivotal in embracing technological advancements in healthcare. The increasing use of artificial intelligence (AI) in medicine and the integration of real-world evidence in regulatory decision-making have been notable trends. These innovations are not only enhancing drug development and patient care but also paving the way for more personalised and efficient healthcare solutions. The EMA has published a draft reflection paper outlining the current thinking on the use of AI to support the safe and effective development, regulation and use of human medicines¹⁹. The paper highlights the need for a risk-based approach in AI/machine learning tool development and deployment, ensuring data integrity and compliance with regulatory standards. It emphasises the importance of data protection, ethical considerations, and the implementation of AI in a manner that respects fundamental rights and promotes trustworthiness.

Paediatric Medicine Developments

Special attention has been given to paediatric medicine development, with initiatives aimed at fostering research and approval of paediatric treatments. A major outcome of this work is the launch of a pilot phase for a ‘stepwise PIP’ agreement: under this framework, it will be possible in certain cases to agree on a partial development programme, conditional on the development of a full PIP once evidence becomes available over time. This will allow more flexibility as the agency will agree PIPs for innovative medicines where crucial information needed to define certain parts of the plan is not yet available, while planning the conditions and milestones for companies to return to EMA’s paediatric committee (PDCO) and discuss the uncertainties once more data are available²⁰. Currently the agency is assessing the pilot project, and we look forward to seeing how this will progress.

COVID-19 Regulatory Flexibilities

The EMA, the EC and the Heads of Medicines Agencies (HMA) are gradually phasing out of COVID-19 regulatory flexibilities which signals a transition towards a post-pandemic regulatory environment. These changes underscore the importance of adapting regulatory frameworks to meet evolving healthcare challenges²¹.

Conclusion

The developments in the UK and EU regulatory landscape in 2023 have laid a foundation for future advancements in healthcare. These changes not only address current needs but also demonstrate a proactive approach towards embracing innovation and improving patient outcomes. As we look forward, these regulatory developments will undoubtedly continue to shape the future of healthcare and pharmaceutical industries.

ProPharma experienced regulatory team is here to support you from early nonclinical testing through complex clinical trials and marketing authorisation. With a track record of success across various therapies and product types, our team offers top-quality, tailored support. Contact us to bring your vision to life.

References

1. MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia Return to reference
2. MHRA authorises Litfulo as a treatment for severe alopecia areata in adults and adolescents 12 years and older Return to reference
3. MHRA authorises monoclonal antibody treatment, Jemperli, to be used with chemotherapy for endometrial cancer Return to reference
4. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss Return to reference
5. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss Return to reference
6. MHRA authorises bispecific antibody therapy Tepkinly as a treatment for diffuse large B-cell lymphoma in adults Return to reference
7. MHRA approves Moderna’s adapted COVID-19 vaccine (Spikevax) that targets Omicron XBB.1.5 - GOV.UK (www.gov.uk) Return to reference
8. MHRA approves Pfizer/BioNTech’s adapted COVID-19 vaccine (Comirnaty) that targets Omicron XBB.1.5 - GOV.UK (www.gov.uk) Return to reference
9. Responding to emerging COVID-19 variants of concern - GOV.UK (www.gov.uk) Return to reference
10. Tepkinly | European Medicines Agency (europa.eu) Return to reference
11. Jaypirca | European Medicines Agency (europa.eu) Return to reference
12. Apretude | European Medicines Agency (europa.eu) Return to reference
13. Enrylaze | European Medicines Agency (europa.eu) Return to reference
14. Orserdu | European Medicines Agency (europa.eu) Return to reference
15. First electronic product information (ePI) published for selected human medicines | European Medicines Agency (europa.eu) Return to reference
16. Guidance for industry to prevent and mitigate medicine shortages | European Medicines Agency (europa.eu) Return to reference
17. Revised transparency rules for the EU Clinical Trials Information System (CTIS) | European Medicines Agency (europa.eu) Return to reference
18. Reform of the EU pharmaceutical legislation - European Commission (europa.eu) Return to reference
19. Reflection paper on the use of artificial intelligence in the lifecycle of medicines | European Medicines Agency (europa.eu) Return to reference
20. Actions to support the development of medicines for children | European Medicines Agency (europa.eu) Return to reference
21. Phasing out of extraordinary COVID-19 regulatory flexibilities | European Medicines Agency (europa.eu) Return to reference