Latest Regulatory Updates

May 2024

Welcome back to the Boyds Regulatory Intelligence Digest. This month we are sharing the latest guidance and key updates from the regulatory agencies - FDA, EMA, MHRA, EC and IMDRF.

Food and Drug Administration (FDA)

FDA establishes Center for Clinical Trial Innovation (C3TI)

The Center for Drug Evaluation and Research (CDER) recently launched C3TI, a central hub for information on innovative approaches to clinical trials that are designed to improve the efficiency of drug development. C3TI aims to promote existing CDER programmes and spur future clinical trial innovation activities through enhanced communication and collaboration.

Two new draft guidance documents on safety testing for cell and gene therapy (CGT) products

With the publication of the draft guidance Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products the FDA provides recommendations for determining the appropriate cell safety testing to support an Investigational New Drug Application (IND) or a Biologics License Application (BLA) for products consisting of live cells, inactivated cells, cell lysates, or other cell-based materials such as cell-derived particles. 

The release of Considerations for the Use of Human-and Animal-Derived Materials in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products provides manufacturers of CGT and tissue-engineered medical products (TEMPs) with guidance to assure the safety, quality, and identity of materials of human and animal origin used in the manufacture of such products.  Recommendations are also provided regarding the chemistry, manufacturing, and control (CMC) information submitted in an IND relating to these materials.

Draft guidance out for comment

Eligibility criteria in cancer trials are sometimes more restrictive than necessary, and expanding the criteria to be more inclusive is one trial design consideration that may improve the diversity of clinical trial populations. The FDA therefore published a series of guidance documents providing recommendations for clinical trials regulated by CDER and the Center for Biologics Evaluation and Research (CBER) for the treatment of cancer:

Cancer Clinical Trial Eligibility Criteria: Performance Status

Cancer Clinical Trial Eligibility Criteria: Laboratory Values

Cancer Clinical Trial Eligibility Criteria: Washout Periods and Concomitant Medications

Submit comments by 28 June 2024.

Draft guidance out for comment

The guidance Content and Format of Composition Statements in NDAs and ANDAs and Corresponding Statement of Ingredients in Labeling describes best practices for new drug application (NDA) and abbreviated NDA (ANDA) applications and provides examples of common, recurring problems identified during FDA’s preliminary and substantive assessments.

Submit comments by 25 June 2024.

Final guidance published

FDA’s final guidance on Providing Regulatory Submissions in Electronic Format: IND Safety Reports replaces the draft guidance of the same name published in 2019 and describes the electronic format Sponsors are required to use when for electronically submitted IND safety reports to CDER and CBER for serious and unexpected suspected adverse reactions (SUSAR).  

European Medicines Agency (EMA) and European Commision (EC)

Mutual Recognition Procedure (MRP)

The Coordination Group for Mutual Recognition and Decentralized Procedures - Human (CMDh) issued advise on the Zero Day MRP. Marketing authorisation (MA) holders and Member States (MS) can initiate this procedure in exceptional cases to mitigate shortages, or issues with access to critical medicines. This procedure is only applicable when a full timetable is not considered appropriate by the proposed Concerned MS.

Paediatric investigation plans (PIPs)

From 04 June 2024 the submission of PIPs, including product-specific or class waivers, modifications, compliance checks, annual reports, or the discontinuation of paediatric development must be conducted via the IRIS platform. To access related guidance see here.

Centralised procedures pre and post authorisation

The Question and Answer (Q&A) guide on EMA’s pre-authorisation procedural advice for users of the centralised procedure has been revised with updates in the following sections: Steps prior to submitting the application, preparing the dossier, validation, and assessment of the application.

Similarly, the revised Q&A guide on EMA’s post-authorisation procedural advice for users of the centralised procedure includes updates relating to Type IA and Type II variations, extension of MAs, post authorisation safety studies, and the transfer of MAs.

Tracked and clean versions for both Q&As are available.

Medical devices – new guidance

The Medical Device Coordination Group (MDCG) issued guidance on the Investigator’s Brochure (IB) content, which is based on the requirements of both the Medical Device Regulation (MDR) and ISO14155:2020, as well as experience from the competent authorities. It describes what type of information is expected in the respective IB sections and aims to pre-empt questions from the competent authorities during the assessment of the clinical investigation application.

A Notice was also published in March highlighting the ongoing and planned guidance development and deliverables of MDCG subgroups. 

Draft guidance out for public consultation

The Heads of Medicines Agencies (HMA) and EMA published a draft guidance defining the common approach on what should be considered as personal data (PD) and commercially confidential information (CCI) in the MA application (MAA) dossier. This guidance applies to information and documents for which the procedure has been finalised under the national, mutual recognition, decentralised and centralised procedures. It also covers documents concerning the variation of a MA or documents containing information pertaining to the MAA dossier.

The deadline for comments is 28 June 2024.

Clinical Trials Information System (CTIS)

The guide to Sponsors with best practices for the first Substantial Modification (SM) for Part I after transition to the Clinical Trials Regulation (CTR), and its associated Annexes, were recently updated. For information and access visit the Key Documents List within the HMA website.

CTIS transparency rules

Revised CTIS transparency rules will become applicable on 18 June 2024, with the launch of an updated version of the CTIS public portal. To assist Sponsors a quick guide for users is available for an overview of the changes.

For all clinical trial applications (CTA) submitted on or after 18 June 2024 it will no longer be possible to defer the publication of data and documents; these will be published according to the established timelines for the trial category, population age and trial phase; and publication of documents will be focused on key documents of interest. For CTAs submitted before 18 June 2024 data will be made publicly available in line with the principles and timelines defined in the revised transparency rules.

Newsletter:  Human medicines highlights – Issue April 2024

Primarily addressed to organisations representing patients, consumers and healthcare professionals, this newsletter provides a summary of key information relating to medicines for human use.

Newsletter: Clinical Trials Highlights – Issue April 2024

Provides insights on clinical trials topics, including Accelerating Clinical Trials in the EU (ACT EU) and CTIS

Medicines and Healthcare products Regulatory Agency (MHRA)

International Council for Harmonisation (ICH) Directory

Guidance on T cell and NK cell characterisation assays

As part of the MHRA’s Strategy for pharmacopoeial public quality standards for biological medicines, the British Pharmacopoeia (BP) prepared a best practice guidance on T cell and NK cell characterisation assays for stakeholders operating in good manufacturing practice (GMP) regulated environments, research and development, academia and clinical trials.

Artificial Intelligence (AI)

Clinical investigation for a medical device

Throughout March and April, the MHRA published updates to the following guidance:

MHRA recommends that a Clinical Investigation application includes a separate document for electrical safety and electromagnetic disturbances (EMD), which is the generic International Electrotechnical Commission (IEC term) for both Electromagnetic Compatibility (EMC) and Electromagnetic Interference (EMI) – see Advice on Electrical Aspects for Clinical Investigations.

Until the functionality for investigational medical devices is introduced into the new part of IRAS, all applications for investigational medicinal product (IMP)/device trials will require applicants to complete information in both the standard and new parts of IRAS. Further information is available in the Combined review of a CTIMP and medical device section and accompanying guidance.

Clinical investigations of medical devices – guidance for manufacturers. This guidance on legislation has been updated with revised MHRA contact information and links to further guidance.

International Medical Device Regulators Forum (IMDRF)

Podcast: Conversations in Drug Development

In this episode of Conversations in Drug Development, our host Harriet Edwards, is joined by Director of Regulatory Affairs, Dr Sabine Ruehle, to discuss the challenges of navigating genetically modified organism (GMO) regulations in clinical trials within Europe.

This discussion helps decipher the nuanced environment of GMOs and their associated risks unique within the European framework. Join us as we explore the outdated definition of GMOs, the complexities of their classification, and the impact of genome editing technologies.

Tune in and listen now, search Conversations in Drug Development on your favourite streaming platform or visit Podcast | Conversations in Drug Development | Boyds (boydconsultants.com).