Regulatory Round-up - July 2024

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

Regulatory Assessment of Casgevy for the Treatment of Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-Occlusive Crises

In November 2023, MHRA approved exagamglogene autotemcel (Casgevy) for treatment for sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT). Casgevy is the first licensed therapy globally to utilize CRIPSR/Cas9 technology and induces an increase in expression of γ-globin chains to compensate for the reduction in functional β-globin. The MHRA’s evaluation of the data to support the approval are presented and discussed in this article by the MHRA assessors.

EUROPE

European Commission (EC)

EU publishes regulation governing use of AI in medical devices and IVDs

The EU has published the Artificial Intelligence Act (AIA; Regulation (EU) 2024/1689), which will enter into force on 1 August 2024, and most of the Act will apply from 2 August 2026. The AIA establishes a common regulatory and legal framework for AI for medical devices, in vitro diagnostic devices (IVDs) and other products within the European Union (EU). It does not apply to research or testing activities prior to placing products on the market. The regulation also mandates that providers and deployers of AI systems provide a “sufficient level” of AI literacy to their staff.

The Act aims to improve the functioning of the internal market, prohibits certain AI practices, and adds specific requirements for high-risk AI systems. The text is unchanged from the AI Act adopted by the European Parliament on 13 March 2024

Publication of Political Guidelines for the Next European Commission 2024-2029

The Political Guidelines 2024-2029 sets out the EC plan for Europe’s sustainable prosperity and competitiveness. The European Federation of Pharmaceutical Industries and Associations (EFPIA) has welcomed the ambition to support European life sciences through a dedicated life sciences strategy which includes a plan for a new European Biotech Act proposal expected in 2025. The aim of the European Biotech Act will be to make it easier to bring biotech from the laboratory to the factory and then onto the market. The plan also includes an increase of research spending and the expansion of the European Research Council and the European Innovation Council.

European Medicines Agency (EMA)

Development and manufacture of oligonucleotides - Scientific guideline

This draft guideline addresses aspects regarding the manufacturing process, characterisation, specifications and analytical control for synthetic oligonucleotides which are not covered in the Guideline on the Chemistry of Active Substances (EMA/454576/2016) or Chemistry of Active Substances for Veterinary Medicinal Products (EMA/CVMP/QWP/707366/2017). The document contains requirements and considerations related to conjugation, the active substance in solution, medicinal product development, oligonucleotide generics development, oligonucleotide personalised medicine approaches and clinical trial applications (human products only). The deadline for comments is 31 January 2025.

USA

Food and Drug Administration (FDA)

Purpose and Content of Use-Related Risk Analyses for Drugs, Biological Products, and Combination Products Guidance for Industry and FDA Staff

This draft document provides guidance to industry and FDA staff on the purpose and content of a use-related risk analysis (URRA) and how a URRA, along with other information, can be used to determine human factors (HF) data needs during product development and to support a marketing application. This guidance applies to drug- and biologic-led combination products that include a device constituent part and are the subject of an investigational new drug application (IND), a new drug application (NDA), or a biologics license application (BLA) and supplements to these applications. Comments can be submitted until 9 September 2024.

Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies

Diversity Action Plans are intended to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population. FDA has issued a draft guidance intended to assist sponsors conducting certain clinical studies involving drugs, biological products, and devices to meet requirements for the submission of Diversity Action Plans under section 505(z) and section 520(g)(9) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as added by section 3601 of the Food and Drug Omnibus Reform Act of 2022 (FDORA). Comments can be submitted until 27 September 2024.

Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products

This draft guidance addresses key aspects of drug delivery performance information for devices, and combination products that include device constituent parts, intended for delivery of a human drug, including a biological product. It describes FDA’s recommendations related to the device design outputs that are essential for establishing and assessing drug delivery performance. The guidance provides recommendations for the information and data to submit in investigational, marketing, and postmarket change applications. Essential drug delivery outputs (EDDO) refer to the design outputs necessary to ensure delivery of the intended drug dose to the intended delivery site. This guidance recommends an approach to identifying EDDOs, provides examples of EDDOs for specific types of devices, and describes the information and data related to EDDOs provided in an application. Comments can be submitted until 30 September 2024.

Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies Modified to Minimize Burden on Healthcare Delivery System

In line with section 505-1(g)(4)(B) of the Federal Food, Drug, and Cosmetic Act (FDCA), the FDA has determined that the approved risk evaluation and mitigation strategies (REMS) for autologous chimeric antigen receptor (CAR) T cell immunotherapies (listed below), must be modified to minimize the burden of complying with the REMS on the healthcare delivery system. Therefore, REMS have been modified to remove requirements for educational and training materials. Please find further information here.

The currently approved autologous CAR T cell immunotherapies, available only through a restricted program under a REMS due to the risks of cytokine release syndrome (CRS) and neurological toxicities are:

Abecma (idecabtagene vicleucel)

Breyanzi (lisocabtagene maraleucel)

Carvykti (ciltacabtagene autoleucel)

Kymriah (tisagenlecleucel)

Tecartus (brexucabtagene autoleucel)

Yescarta (axicabtagene ciloleucel)

OTP Events, Meetings, and Workshops

The Office of Therapeutic Products (OTP) hosts a variety of events to share information about OTP-regulated products and bring together important stakeholders to discuss the development and advancement of these products. Please find event details below.

• FDA | NIH : Regulatory Do’s and Don’ts: Tips from FDA – 4 September 2024. This webinar is intended for early-stage companies (small businesses) new to the regulatory landscape at the FDA. It aims to provide an overview on resources and programs that FDA has developed across Center for Biologics Evaluation and Research (CBER), CDER, and Center for Devices and Radiological Health (CDRH) that can help academic life-science accelerators and early-stage, oncology-related companies, develop new anticancer-therapeutics, devices, and diagnostics.
• OTP Town Hall: Cell Therapy CMC Readiness for Late-Stage INDs – 5 September 2024.
• In this event, experts from OTP’s Office of Cellular Therapy and Human Tissue CMC will answer questions regarding development and readiness of chemistry, manufacturing, and controls (CMC) data and information for late-stage investigational new drug applications (INDs) – INDs intended to collect primary evidence of effectiveness to support a marketing application for cell therapy and tissue-engineered products.
• Meeting 1: Patient and Care Partner Perspectives on Safety Considerations for Approved Gene Therapy Treatments for Rare Diseases – 20 September 2024.

CBER will host a public patient listening meeting and opening 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.

International

International Conference on Harmonisation (ICH)

Press Release: New collaboration between WHO International Classification of Diseases (ICD) and MedDRA launched

On 27 June 2024, the World Health Organization (WHO) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) announced a new collaboration to enhance registry and sharing of regulatory information on medical products worldwide. The collaboration aims to establish a unified language that streamlines global regulatory decision-making concerning the safety and efficacy of medical products by connecting the WHO International Classification of Diseases (ICD-11) with the ICH Medical Dictionary for Regulatory Activities (MedDRA). Please find further information here.

World Health Organization (WHO)

MeDevIS platform announced to boost access to medical technologies and devices

WHO has created a medical device database to encourage data consistency across borders. An online platform, called MeDevIS (Medical Devices Information System) is the first global open access clearing house for information on medical devices. It is designed to support governments, regulators, and users in their decision-making on selection, procurement, and use of medical devices for diagnostics, testing and treatment of diseases and health conditions. MeDevIS references two international naming systems for medical devices - the European Medical Device Nomenclature (EMDN), mostly used in European countries for registration in the European database, and the Global Medical Device Nomenclature (GMDN) used in regulatory agencies in Australia, Canada, the United Kingdom and the USA and other Member States. Please find further information here.

Public consultations

European Directorate for the Quality of Medicines (EDQM)

European Medicines Agency (EMA)

Food and Drug Administration (FDA)

Click here to download the PDF.