Regulatory Round-up - November 2024

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

Statement of policy intent: relaunch of the Innovative Licensing and Access Pathway (ILAP)

This statement from the MHRA sets out the plans for the new ILAP for innovative medicines in England, Scotland and Wales. The ILAP partnership is preparing to relaunch its offer in response to the evolving needs of the fast-paced life sciences ecosystem. The new ILAP will be open to applications in March 2025, with full details of the pathway to be published in January 2025. Some of the key improvements that the new ILAP will bring compared to the existing pathway are: 

• Better quality bespoke service through more selective entry and dialogue between the ILAP partner organisations and the developers.
• Simpler roadmap and more predictable timelines, enabling developers to plan more effectively.
• The NHS will be involved as a core partner and will bring a focus on operational planning and system preparedness for the introduction of innovative new medicines into the NHS for the benefit of patients.
• Prioritised scheduling of the ILAP Joint Scientific Advice, the ILAP Access Forums, the MHRA scientific advice and pre-submission meetings and access to Clinical Practice Research Datalink (CPRD).
• The ILAP will be future-proofed to accelerate access of transformational products by broadening to drug-device combinations.

MHRA Case Study: The importance of giving patients a voice in the approval of a new sickle cell treatment

A case study carried out by the MHRA has looked at the potential benefits of patients providing their lived experience for the pre-authorisation stage of the benefit-risk review of Casgevy. The MHRA collaborated with the Sickle Cell Society to identify three patients living with sickle cell disease and worked with these patients between April and August 2023. This began with introductory briefing sessions, before a meeting took place between each patient and an assessment team. The questions in these meetings focused on understanding the patient’s quality of life and experience of living with sickle cell disease, their expectation of a new treatment, and their views on gene therapies. The MHRA incorporated the patients’ contribution into its assessment of the product, and ahead of the approval of Casgevy in November 2023, the patients were kept abreast of developments as the product went through the regulatory system. Please find further information here.

Consultation on Medical Devices Regulations: Routes to market and in vitro diagnostic devices

MHRA is inviting members of the public to provide their views on proposals to update the regulatory framework for medical devices. It welcomes the views of patients, medical device researchers, developers, manufacturers and suppliers, clinicians, other healthcare professionals and the wider public on the following four areas: 

• International reliance 
• UKCA marking 
• In vitro diagnostic devices 
• Assimilated EU law

The deadline for responses is 5^th January 2025. Please find further information here.

MHRA Consultation on the International Council for Harmonisation ICH E6 (R3) Guideline for Good Clinical Practice (GCP) Annex-2

MHRA are seeking views of UK stakeholders on the draft of the ICH E6 (R3) Guideline for GCP Annex-2. The deadline for responses is 14^th February 2025.

The update of ICH E6 is to address the application of GCP to new trial designs, technological innovations and to strengthen a proportionate risk-based approach of its application for clinical trials of medicines. This was set out in the ICH Reflection paper on Renovation of Good Clinical Practice and the ICH E6(R3) Concept Paper and a Business Plan was developed. ICH E6(R3) has been restructured and is composed of Annex 1 (interventional clinical trials) and Annex 2 (additional considerations for non-traditional interventional clinical trials), Glossary and Appendices.Annex 2 was endorsed by the ICH Management Committee on 28 April 2023 and has now reached Step 2b public consultation stage. MHRA became a full regulatory member of ICH in May 2022, and whilst feedback on the ICH E6(R3) Annex 2 guidance can be provided via the ICH website, MHRA is consulting directly with UK stakeholders to compile and co-ordinate their comments to the ICH Expert Working Group. Please find further information here.

EUROPE

European Directorate for the Quality of Medicines (EDQM)

European Pharmacopoeia to be online-only from June 2025

EDQM will launch the online-only European Pharmacopoeia (Ph. Eur.) in June 2025, providing subscribers with legally binding European pharmacopoeial standards in a user-friendly format. Please find further information here.

European Medicines Agency (EMA)

Highlights - 6th EMA-EuropaBio bilateral meeting 

Please find the highlights of the 6^th EMA-EuropaBio meeting including EuropaBio’s priorities and vision for future biotechnology industry and pipeline trends in Europe. A study detailing the Impact of the EU's General Pharmaceutical Legislation on Europe’s innovation ecosystem and biotechnology companies has been published by EuropaBio and it is available to download here. 

New fee regulation from 1 January 2025

As of 1 January 2025, EMA's fees are governed by Regulation (EU) 2024/568, known as the 'New Fee Regulation'. Current rules still apply until 31 December 2024. Please find further information here. EMA has provided a Questions & Answers (Q&As) document regarding Annex I to Regulation (EU) 2024/568.

USA

Food and Drug Administration (FDA)

FDA approval: Kebilidi 

FDA has approvedeladocagene exuparvovec-tneq (Kebilidi) a recombinant adeno-associated virus serotype 2 (rAAV2)-based gene therapy, containing the human DDC  gene (dopa decarboxylase) indicated for the treatment of adult and paediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. It is designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production. AADC deficiency is a rare genetic disorder that affects the production of some neurotransmitters. Affected individuals may experience symptoms such as delays in gross motor function (head control, sitting, standing, and walking), hypotonia (weak muscle tone), and developmental and cognitive delays. Kebilidi is the first FDA-approved gene therapy for treatment of AADC deficiency.

FDA approval: Aucatzyl

FDA has approvedobecabtagene autoleucel (Aucatzyl) a CD19-directed chimeric antigen receptor (CAR) T cell therapy indicated for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. Aucatzyl is the first CAR-T cell therapy approved by the FDA with no requirement for a Risk Evaluation Mitigation Strategy (REMS) program. However, the FDA has added a boxed warning for cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and T cell malignancies to the prescribing information.

Important information for human cell, tissue, and cellular and tissue-based product (HCT/P) establishments regarding the Oropouche virus and HCT/P donation

The FDA hasprovided information regarding Oropouche virus (OROV) and considerations for donor eligibility determinations for human cells, tissues, and cellular and tissue-based products (HCT/Ps).

The Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory in August 2024 to notify clinicians and public health authorities of an increase in OROV disease in the Americas region, originating from endemic areas in the Amazon basin and new areas in South America and the Caribbean. Due to the robustness of existing donor screening measures and taking into consideration the current small number of OROV disease cases among U.S. travellers, and no reports of OROV transmission by HCT/Ps, screening donors by asking them specific questions about exposure to OROV or travel to areas with OROV outbreaks is not warranted at this time. FDA will continue to monitor cases of Oropouche in the U.S. and worldwide and available information about potential risks of Oropouche virus transmission by HCT/Ps.

Patient and care partner perspectives on safety considerations for approved gene therapy treatments for rare diseases 

The FDA Center for Biologics Evaluation and Research (CBER) hosted a public patient listening meeting on the 20^th September 2024 and opened a docket to better understand patient and care partner perspectives on safety considerations and long term follow-up for approved gene therapy treatments for rare diseases. The video recording of this meeting is available here.

FDA CBER Office of Therapeutic (OTP) town Hall: Cell therapy CMC readiness for late-stage INDs

During the September 5^th September 2024 CBER OTP Town Hall, subject matter experts answered questions regarding development and readiness of chemistry, manufacturing, and controls (CMC) data and information for late-stage investigational new drug applications (INDs) intended to collect primary evidence of effectiveness to support a marketing application for both cell therapy and tissue-engineered products. Transcript for the FDA CBER OTP Town Hall: Cell Therapy CMC Readiness for Late-Stage INDs is now available here.

Developing potential cellular and gene therapy products - frequently asked questions 

The FDA has issued a draft guidance intended to provide industry with answers to frequently asked questions (FAQs) and commonly faced issues that arise during the development of cellular and gene therapy products. Comments are due by 18^th February 2025.

Split Real Time Application Review (STAR)

Under the Prescription Drug User Fee Act (PDUFA) VII Commitment, FDA is creating the STAR pilot program which aims to shorten the time from the date of complete submission to the action date, in order to allow earlier patient access to therapies that address an unmet medical need.

FDA will consider an application eligible for the STAR pilot program if each of the following criteria are met:

1. Clinical evidence from adequate and well-controlled investigation(s) indicates that the drug may demonstrate substantial improvement on a clinically relevant endpoint(s) over available therapies.
2. Breakthrough Therapy Designation (BTD) or Regenerative Medicine Advanced Therapy Designation (RMAT) is not required, but above criteria must be met.
3. The application is for a drug intended to treat a serious condition with an unmet medical need.
4. No aspect of the submission is likely to require a longer review time (e.g., requirement for new REMS, etc.)
5. There is no chemistry, manufacturing, or control information that would require a foreign manufacturing site inspection (i.e., domestic site inspections may be allowed if it does not affect the expedited timeframe).

Please find further information here.

Workshop on integration site analysis during long term follow-up for gene therapies with integrating viral vectors

The FDA’s CBER Office of Therapeutic Products (OTP) hosted a virtual scientific public workshop on 14^th November 2024 to discuss the clinical use of integration site analysis (ISA) during long term follow-up following administration of gene therapies with integrating viral vectors. In this workshop, FDA convened a panel of external experts to discuss the risk of insertional mutagenesis and best practices for ISA method design, data analysis, and clinical interpretation. The video recording of this workshop is available here.

INTERNATIONAL

International Council for Harmonisation (ICH)

ICH Pharmaceutical Quality Knowledge Management (PQKM) Task Force

ICH is issuing a Request for Information as a means of conducting a market consultation to determine interest and potential approaches to support the ICH PQKM Task Force’s initial assessment for a secure, standardised technology platformfor CMC-related post-approval changes, submissions, products, and facilities. For further information about this effort please refer to the ICH PQKM home page. The deadline for consultation is 8 January 2025, 2:00 PM EST. 

ICH Q9(R1) implementation working group updated training materials

ICH has announced the publication of the updated training materials related to ICH Q9(R1) Quality Risk Management (QRM). These materials, include a Q9(R1) Introduction Presentation replacing five presentations in the current ICH Q9 Briefing Pack and updated ICH Q8/Q9/Q10 Training Material which replaces 12 presentations developed in 2006-2010. The training material is available here.

ICH E6(R3) Annex 2 draft Guideline presentation available now on the ICH website.

The ICH E6(R3) Annex 2 draft Guideline on Good Clinical Practice reached Step 2b of the ICH Process on 6 November 2024 and entered the public consultation period. A Step 2 Informational Presentation has also been developed by the E6(R3) Annex 2 Subgroup. The presentation is available here.

Public consultations

Medicines and Healthcare products Regulatory Agency (MHRA)

European Medicines Agency (EMA)

Food and Drug Administration (FDA)

International Council for Harmonisation (ICH)

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