Regulatory Round-up - December 2023

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA supports launch of Innovate UK’s first-of-its-kind initiative to fund new Regulatory Science and Innovation Networks

Innovate UK, part of UK Research and Innovation, will invest up to £7.5 million, up to 2025, to support the creation of regulatory science and innovation networks across the UK. Applications are now open for UK academic institutions wishing to bid for funding of up to £50,000 to collaborate with others to establish new Regulatory Science and Innovation Networks (RSINs) in innovative sectors. Please find further information here.

MHRA New Notification Scheme

The MHRA’s new Notification Scheme enables a more streamlined and risk-proportionate approach to processing clinical trial authorisation (CTA) for “initial” applications. The scheme applies to CTA applications for Phase 4 and certain Phase 3 clinical trials deemed to be of lower risk; it does not include CTA applications for first in human, Phase 1 or Phase 2, or amendments. MHRA acceptance of an application under the new Notification Scheme will be confirmed within 14 calendar days from the application receipt. Authorisation by the MHRA will be granted unless any criterion is not met. If the MHRA considers the application does not meet the new Notification Scheme criteria, an objection decision will be communicated within 14 calendar days from the application received effective date, and the application will continue under full CTA assessment with a decision communicated within the 30-day statutory timeframe. Please find further information here.

Access Consortium Promise Pilot Pathway New Active Substance Work-sharing Initiative (NASWSI)

The New Active Substance Work-Sharing Initiative (NASWSI) is an innovative work sharing procedure for the coordinated assessment of new chemical entity or new biological entity applications, or new indication applications that are submitted to two or more Access agencies.The Access Consortium working group for new active substances has established an aligned process for priority review, which includes the decision on priority status. Creating the Promise Pilot Pathway, the Access partners sought consesus on their respective criteria for priority review. Applications for new active substances fulfilling the following criteria are eligible for the Promise Pilot Pathway:

• diagnoses, treats or prevents a condition that is serious, life-threatening or severely debilitating and
• for which no other treatment is currently registered and marketed in participating jurisdictions for the proposed indication

The scope of the Promise Pathway will be further reviewed after the pilot.

This document outlines operational procedures and recommendations for the planning and implementation of the NASWSI for the regulatory agencies within the Access Consortium:

• Therapeutic Goods Administration (TGA) – Australia
• Health Canada (HC) – Canada
• Health Sciences Authority (HSA) – Singapore
• Swissmedic (SMC) – Switzerland
• Medicines and Healthcare products Regulatory Agency (MHRA) – United Kingdom

Genomics England

Pilot launched to support children with rare conditions to access personalised therapies

The UK government has announced its support for the Rare Therapies Launch Pad, a new programme that will develop a pathway for children with rare conditions to access individualised therapies. The programme’s first project will explore the use of individualised therapies known as antisense oligonucleotides (ASOs) to treat children with ultra-rare and life-threatening brain conditions.

In the future, the Rare Therapies Launch Pad will support access to other types of individualised therapies across a wider range of rare conditions. Please find further information here.

EUROPE

European Commission (EC)

EU and MHRA extend GMP and GDP Certificates

EMA, the EC and the Heads of Medicines Agencies (HMA) had allowed the flexibility arrangements for medicines introduced during the COVID-19 pandemic to expire in order to address the regulatory and supply challenges created by the pandemic. Although no-site GMP and GDP inspections resumed after being postponed or conducted remotely during the pandemic, a significant number of postponed inspections still need to be carried out. The validity of the GMP and GDP certificates has been further extended by the GMP/GDP inspectors' working group from the end of 2023 to 2024 or until the completion of the next on-site inspection, whichever comes first, unless otherwise stated in the document. During this period, competent authorities will conduct risk-based surveillance of sites, either through on-site inspections or distant assessments, and depending on the outcome, they may continue to issue, withdraw or restrict GMP and GDP certificates. Please find further information here.

Cloud Computing: Assessment of Cloud Suppliers from an authority's point of view

There is a trend in the pharmaceutical industry towards the use of cloud computing which brings financial and organizational advantages. However, potential dangers and regulatory restrictions should be considered. Nine experts from the pharmaceutical industry and regulatory authorities have answered questions from the following GxP-relevant topics:

• Basics of Cloud Computing Technology
• Regulations and Expectations of Inspectors
• Customer-Supplier-Relationship
• Requirements for Cloud Service Providers (CSP)
• Requirements for Supplier Evaluation and Supplier Audits
• Requirements for Qualification / Validation

Please find further information here.

European Directorate for the Quality of Medicines (EDQM)

The CEP 2.0 guideline on requirements for the content of the dossier has been updated

The guideline on requirements for the content of the CEP dossier according to the CEP 2.0 has been revised to include updated requirements and clarifications related to sections 3.2.S.4.1 & 3.2.S.4.2. and an updated Annex 1. The revised requirements apply to newly submitted applications for a new dossier, a sister file and a renewal. Please find link to the guideline here.

New general chapter on comparability of alternative analytical procedures published in European Pharmacopeia

A new general chapter, Comparability of alternative analytical procedures (5.27), has been published in Supplement 11.5 of the European Pharmacopoeia (Ph. Eur.). This new general chapter describes how to demonstrate the comparability of an alternative analytical procedure to a pharmacopeial analytical procedure, in line with the requirement laid down in section 1.1.2.3. of the Ph. Eur. General Notices. General chapter 5.27. does not introduce any new requirements, but the text provides practical guidance on how users who wish to rely on an alternative analytical procedure instead of the pharmacopoeial procedure for their testing strategy can demonstrate comparability and indicates that this comparability must be maintained over the lifecycle of both analytical procedures. The new general chapter, which may also be useful to assessors during their evaluation, mphasizes that other approaches to demonstrating comparability may also be appropriate. Please find further information here.

European Medicines Agency (EMA)

Global regulators strengthen efforts to ensure continuous availability of safe and high-quality medicines

Collaboration between medicines regulators worldwide enable the development of a global Pharmaceutical Quality Knowledge Management System (PQ KMS) which aims to help patients benefit from a continuous supply of life-saving medicines. The collaborative assessment pilots aim to enable greater cross-regional access to high-quality, critical medicines through parallel assessments and approvals in different regions. The pilots focus on two parts of medicines evaluation: collaborative assessments of post-approval changes and hybrid inspections. In the first pilot, regulators had the opportunity to develop reliable mechanisms and approaches that enhance regulatory convergence, mutual recognition and trust. According to participants, it brought significant benefits, with same-day approval from both FDA and EMA, with no delays to timelines and no significant additional workload. Work continues to further develop and optimise logistical and technological requirements to support collaborative assessments. The next step is to complete further pilot cases, with the involvement of additional regulators. The pilot is open for new applications from industry. Please find further information here.

EMA Management Board: highlights of December 2023 meeting

Please find the highlights of the EMA Management Board December 2023 meeting including the overview of Pharmacovigilance Risk Assessment Committee’s (PRAC) recent activities, progress on the Accelerating Clinical Trials in the EU (ACT EU) initiative, CTIS operation as well as update on Quality Innovation Group (QIG) achivements and HMA/EMA Joint Big Data Steering Group’s AI workplan.

CHMP positive opinion: Casgevy

Following the Committee for Advanced Therapies (CAT) assessment, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorisation for Casgevy, the cell-based gene therapy intended for the treatment of transfusion‑dependent β‑thalassemia (TDT) and sickle cell disease (SCD). Casgevy will be available as a 4-13 x 10⁶ cells/ml dispersion for infusion, one-time administration. The benefits of Casgevy are its ability to eliminate dependence on chronic red blood cell transfusions in patients with TDT and its ability to reduce the number of vaso-occlusive crises in patients with SCD.

The full indication is:

• β‑thalassemia

Casgevy is indicated for treatment of transfusion‑dependent β‑thalassemia (TDT) in patients 12 years of age and older for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)‑matched related HSC donor is not available.

• Sickle cell disease

Casgevy is indicated for the treatment of severe sickle cell disease (SCD) in patients 12 years of age and older with recurrent vaso‑occlusive crises (VOCs) for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)‑matched related HSC donor is not available.

Please find further information here.

Research and Treatment of Cancer (EORTC) workshop: How can patient-reported outcomes (PRO) and health-related quality of life (HRQoL) data inform regulatory decisions?

EMA and EORTC are organising a workshop on how patient-reported outcomes (PRO) as well as health-related quality of life (HRQoL) data can inform regulatory decisions. The event will take place on Thursday, 29 February 2024, in Netherlands. Please find furhter information including how to register here.

ACT EU PA08 multi-stakeholder methodology workshop

The ACT EU PA08 multi-stakeholder methodology workshop was held on 23 November 2023 wich offered participants the opportunity to:

• Understand different stakeholder perspectives on the development of clinical trial methodology guidance

• Discuss the status of guidance on priority clinical trial methodology topics

• Identify the need for new guidance or updates to the existing guidance for the priority methodology topics.

The presentations are now available via the following links: Complex clinical trials, enabling innovative designs (breakout session A), EFSPI perspective and Paediatric clinical trials - Setting the scene (breakout session B).

DARWIN EU Advisory Board meeting - 24 May 2023

EMA and the European Medicines Regulatory Network established a coordination centre to provide timely and reliable evidence on the use, safety and effectiveness of medicines for human use, from real world healthcare databases across the EU. This capability is called the Data Analysis and Real World Interrogation Network (DARWIN EU). A DARWIN EU Advisory Board virtual meeting will be held on 24 May 2023. Please find the agenda here.

Medicinal products development and assessment involving companion diagnostic (CDx) Q&A

This Questions and Answers (Q&As) document is intended to provide an overview of EMA’s current line of thinking on issues related to predictive biomarker-guided medicinal products development and assessment including a companion diagnostic (CDx) development. It addresses issues that may require further clarity, considering their recurrence in preauthorisation interactions and in the context of marketing authorisation/variation applications of medicinal products.

Product Lifecycle Management (PLM) Value Stream Deep-Dive Webinar 30 November 2023

On 30 November 2023 EMA held a public webinar for regulators and medicine developers interested in learning more about what the Agency's Product Lifecycle Management (PLM) value stream is working on and what it aims to achieve.The video recording of the public webinar is available here.

Artificial intelligence workplan to guide use of AI in medicines regulation

EMA and the Heads of Medicines Agencies (HMAs) have published an artificial intelligence (AI) workplan to 2028, setting out a collaborative and coordinated strategy to maximise the benefits of AI to stakeholders while managing the risks.

USA

Food and Drug Administration (FDA)

FDA approval: Casgevy

FDA has granted BLA approval for Casgevy for the treatment of sickle cell disease (SCD) in patients 12 years of age or older with recurrent vaso-occlusive crises (VOCs). Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.

FDA approval: Lyfgenia

FDA has granted BLA approval for Lyfgenia (lovotibeglogene autotemcel), a cell-based gene therapy for patients ages 12 and older with sickle cell disease and a history of vaso-occlusive events. Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification. With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease. Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient.

Advanced Manufacturing Technologies Designation Program

FDA encourages the early adoption of advanced manufacturing technologies (AMTs) that have the potential to benefit patients by improving manufacturing and supply dependability and optimizing development time of drug and biological products. AMTs can improve product quality through higher capability manufacturing designs and enhanced controls. This draft guidance provides recommendations to individuals and organizations interested in participating in FDA’s Advanced Manufacturing Technologies Designation Program, which aims to facilitate the development of drugs, including biological products, manufactured using an AMT that has been designated as such under the program. Comments can be submitted until 12 of February 2024.

Master Protocols for Drug and Biological Product Development

The primary focus of this draft guidance is on randomized umbrella and platform trials that are intended to contribute to a demonstration of safety and substantial evidence of effectiveness of a drug. The concepts discussed may also be useful to consider for early-phase or exploratory umbrella and platform trials as well as those conducted to satisfy post-marketing commitments or requirements. The recommendations and considerations in this guidance do not apply to master protocols evaluating first-in-human drugs given the unique attributes from both a trial design and regulatory perspective that must be considered. This draft guidance provides recommendations on the design and analysis of trials conducted under a master protocol as well as guidance on the submission of documentation to support regulatory review. This should be taken into consideration with FDA guidance for Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial. Comments can be submitted until 22 February 2024.

Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs

The FDA has announced the availability of a final guidance for industry entitled “Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs. The guidance covers the statutory verification systems requirements which include the quarantine and investigation of a product determined to be suspect and the quarantine and disposition of a product determined to be illegitimate. The guidance also addresses the statutory requirement for notification to the Agency of a product that has been cleared by a manufacturer, repackager, wholesale distributor, or dispenser (also referred to as “trading partners”) after a suspect product investigation because it is determined that the product is not an illegitimate product. Finally, the guidance addresses the statutory requirement for responding to requests for verification and processing saleable returns.

FDA Creates New Advisory Committee for Evaluation of Genetic Metabolic Disease Treatments

The purpose of the new Committee is to review and evaluate data on the safety and effectiveness of marketed and investigational human drug and biologic products for use in the treatment of genetic metabolic diseases and makes appropriate recommendations to the Commissioner of Food and Drugs. Please find further details here.

Registration for FDA's Rare Disease Day 2024

The Virtual Public Meeting will be held on 1 March 2024 from 9AM - 4:30PM EST. This year’s Rare Disease Day is dedicated to patients and health care professionals. Panels will discuss:

• The legal framework for approving studies and medical products at FDA
• What FDA does during review processes to approve medical products
• Decentralized clinical trials and digital health technologies
• Where to find important information and documents related to clinical trials
• Information that can be obtained from medical product labels
• Legal and ethical requirements for consent forms in clinical trials
• FDA initiatives to advance medical product development for rare diseases
• Ways for patients to engage with FDA

Please find information on how to register here.

WCBP Symposium 2024 - FDA California Separation Science Society (CaSSS) Interface of Regulatory and Analytical Sciences for Biotechnology Health Products

The Symposium, organised by CASSS & FDA will be held on 23-25 of January 2024 in Washington D.C. It addresses the role of current and emerging CMC analytical technology among evolving US and international regulatory perspectives. The topics include CMC development strategies, innovative analytical characterization, global submission strategies, next-generation therapeutics & vaccines, as well as the challenges and promises of CRISPR-based therapeutics, which are poised to revolutionize the future of medicine. Please find further details including agenda and how to register here.

Public consultations

EUROPEAN MEDICINES AGENCY (EMA)

Food and Drug Administration (FDA)

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