Latest Regulatory Updates

April 2024

Hello and welcome 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 ICH.

Food and Drug Administration (FDA)

Artificial Intelligence (AI)

FDA published a new paper “Artificial Intelligence and Medical Products: How CBER, CDER, CDRH, and OCP are Working Together,” which outlines specific focus areas regarding the development and use of AI across the medicinal product lifecycle. This multi-centre effort promotes responsible innovation, health equity, and patient-centricity and supports the safe, secure, ethical, and trustworthy development and use of AI.

See also the agency’s AI initiatives.

Final guidance released:

The following guidance replaces the draft version issued in February 2022 and aims to facilitate the development of antibody-drug conjugates (ADCs) and ensure their safety and efficacy.

Final guidance released:

The final guidance on Providing Regulatory Submissions in Electronic Format: IND Safety Reports is now available. This is relevant for all commercial investigational new drugs (INDs) currently submitted through the Electronic Submissions Gateway (ESG) and will apply to 7-day and 15-day suspected unexpected serious adverse reactions (SUSARs) including single occurrences, one or more occurrences not commonly associated with drug exposure, and aggregate analyses.

Draft guidance out for comment

Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products. This guidance discusses topics Sponsors should consider regarding the design and analysis of non-interventional studies before developing the protocol and statistical analysis plan.

Submit Comments by 20 June 2024.

Draft guidance out for comment

Two draft guidance documents were released on bioavailability (BA) and bioequivalence (BE) studies. The first, Handling and Retention of BA and BE Testing Samples, highlights how the test article and reference standard for such studies should be distributed to the testing sites, how to randomly select samples for testing and select material to maintain as reserve samples, and how the reserve samples should be retained.

The second,  Data Integrity for In Vivo BA and BE Studies, provides recommendations to applicants and testing site management on achieving and maintaining data integrity for the clinical and bioanalytical portions of BA and BE studies submitted in support of IND and new drug applications (NDAs), abbreviated NDAs (ANDAs), plus the bioanalytical portion of clinical pharmacology studies supporting CDER-regulated biologics license applications.

Submit Comments by 28 May 2024 for the first and 03 July 2024 for the second guidance.

New Center of Excellence

FDA’s CDER announced its new Quantitative Medicine (QM) Center of Excellence (CoE) to spearhead QM-related policy development and best practices to facilitate the consistent use of QM approaches during drug development and regulatory assessment, facilitate systematic outreach to scientific societies, patient advocacy groups, and other key stakeholders, and to

coordinate CDER’s efforts around QM education and training.

To register for a public introductory workshop on QM (25 April 2024) see here.

European Medicines Agency (EMA)

Clinical Trial Information System (CTIS)

The Clinical Trials Coordination Group (CTCG) published another update of the best practice guide and cover letter template for Sponsors transitioning trials to the Clinical Trials Regulation (CTR), and published a new Recommendation paper on principles of GLP for clinical trial applications under the CTR. A template table has also been made available for Sponsors to use when providing the required information on GLP compliance.

Centralised procedure 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 and updated 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 marketing authorisation (MA), post‑authorisation safety studies, and the transfer of MAs.

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

Real World Data (RWD)

EMA and the Heads of Medicines Agencies (HMA) launched two public electronic catalogues for  RWD sources and for RWD studies to identify the most suitable data sources to address specific research questions and support the assessment of study protocols and results. The aim is to promote transparency, encourage the use of good practices, and build trust in research‑based on RWD.

Environmental risk assessment (ERA)

The revised Guideline on the environmental risk assessment of medicinal products for human use was adopted by the Committee for Medicinal Products for Human Use (CHMP) and will come into effect on 01 September 2024.

An ERA is required for all new MA applications (MAAs) for a medicinal product submitted through a centralised, mutual recognition, decentralised or national procedure. This guideline does not apply to medicinal products (MPs) consisting of genetically modified organisms (GMOs).

Draft guidance out for feedback

The multidisciplinary Guideline on quality, non-clinical and clinical requirements

for investigational advanced therapy medicinal products (ATIMP) in clinical trials addresses development, manufacturing, and quality control as well as non-clinical and clinical development of ATIMPs. Considerations on genome editing tools are included. Its focus is on the requirements for exploratory trials, but it also concerns first in human studies and confirmatory trials.

Submit comments by 01 August 2024.

Draft guidance out for feedback

Guideline on allergen products development for immunotherapy and allergy diagnosis in moderate to low-sized study populations. Although other guidelines applicable to allergen products are available, these assume a sufficient number of patients participating in the respective clinical trials. This guidance focuses on products for allergen immunotherapy and in vivo diagnosis of allergies where only moderate to low-sized study populations are available. Recommendations are made on clinical development, potential study designs and safety considerations.

The deadline for comments is 31 May 2024.

Advanced Therapy Medicinal Products (ATMP)

Following its launch in 2022 EMA published a progress update on the  pilot for academic and non-profit developers of ATMP and highlights that it is looking to add another two developers to this pilot by the end of 2024. The pilot supports non-profit developers navigating the challenging regulatory requirements to MAA for a product.

Newsletter:  Human medicines highlights – Issue 178, March 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: SME Office – Issue 61, February 2024

The bulletin highlights news, documents, and activities of interest to SMEs and their stakeholders.

Fees for applications

A reminder for applicants and marketing authorisation holders that adjusted fees for all applications, except for pharmacovigilance procedures, came into effect on 1 April 2024.

Medicines and Healthcare products Regulatory Agency (MHRA)

Press release – Medical devices

The government announced New action to tackle ethnic and other biases in medical devices as it accepts recommendations from a UK-first independent review into equity in medical devices.

Podcasts – Transforming clinical trials

The MHRA and HRA “combined review” team are producing a series of podcasts with the New Scientist. The episodes shine a light on the UK’s landscape for life sciences research and development post-Brexit. Read more about the first podcast with Lord James O'Shaughnessy, the chair of the UK review into commercial clinical trials, here.

European Commission (EC)

New guidance for clinical investigation plans (CIP) with medical devices

The Medical Device Coordination Group published Guidance on content of the Clinical Investigation Plan for clinical investigations of medical devices and a Template for Clinical Investigation Plan Synopsis. This is an essential guide on the approach to CIP setting out content such as rationale, objectives, design methodology, monitoring, conduct, record-keeping, and the method of analysis for the clinical investigation. It is based on section 3 of chapter II of annex XV of the Medical Device Regulation (MDR) and follows the numbering of the MDR, to facilitate cross-referencing with the legal requirements.

Changes to marketing authorisations

In March the EC adopted the Delegated Regulation thereby amending Regulation 1234/2008 as regards the examination of variations to the terms of marketing authorisation.

This targeted revision aims to reduce the number of variations required, shorten the preparation time for companies and decrease the assessment time for regulators due to classifying some variations into lower categories. The risk-based approach to variation categorisation is now also extended to biological products.

Auxiliary Medicinal Products (AxMP)

The Clinical Trials Coordination and Advisory Group (CTAG) updated its 2017 guidance on Recommendations on the use of Auxiliary Medicinal Products in Clinical Trials.

The revision includes the documentation required for unmodified authorised AxMP, recommendations for challenge agents that are MPs, an update on the classification of investigational MPs (IMPs) versus AxMP, plus the addition of a flowchart on labelling requirements.

International Council for Harmonisation (ICH)

Pharmaceutical Product Lifecycle Management

Following the Q12 Guideline reaching Step 4 in November 2019, a comprehensive training programme and associated materials are available to facilitate its interpretation and harmonised implementation. The latest additions include the publication of the ICH Q12 Module 8 in February 2024 plus an introductory video on “Regulatory and Technical Considerations for Pharmaceutical Product Lifecycle Management” in March 2024.

To watch the video or download the training materials, see the Quality Guidelines webpage.

Podcast: Conversations in Drug Development

In our latest podcast episode of Conversations in Drug Development, we take a deeper dive into US Drug Development: The latest regulatory trends and initiatives.

Host Harriet Edwards is joined by Katy Rudnick and Dr Julie Warner from Boyds to discuss US regulatory trends and initiatives at the FDA.

Join us for another Conversation in Drug Development, exploring the dynamic landscape of regulatory trends expected in 2024 and beyond, with a key emphasis on the US scope.

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).