Latest Regulatory Updates

January 2024

Hello and welcome to the Boyds Regulatory Intelligence Digest. We are delighted to be back and kickstarting the new year by sharing the latest guidance and key updates from the regulatory agencies - FDA, EMA, MHRA and WHO.

Food and Drug Administration (FDA)

Return to In-Person Face-to-Face (FTF) Formal Meetings with FDA

Commencing 22 January 2024, the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) will expand in-person FTF industry meetings to include all meeting types. Sponsors should specify the request for a FTF meeting in their application. If agreed, FDA’s focus is on hybrid meetings, with only core participants with a primary speaking role participating in-person while others join virtually.

Final Guidance Documents Published

Rare Diseases: Considerations for the Development of Drugs and Biological Products
The selected issues discussed here are commonly encountered in rare disease drug development, for which there is often limited medical and scientific knowledge, poorly understood natural history data, sample size constraints, and lack of drug development experience. This guidance finalizes the draft guidance entitled “Rare Diseases: Common Issues in Drug Development” issued on 01 February 2019.

Data Standards for Drug and Biological Product Submissions Containing Real-World Data (RWD)
This guidance addresses considerations for the use of data standards currently supported by FDA in applicable drug submissions containing study data derived from RWD sources.

Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products
This guidance is aimed at Sponsors proposing to design a new registry or use an existing registry to support regulatory decision-making about a drug’s effectiveness or safety. It does not provide recommendations on choice of study design or statistical methods used to analyse data from registries.


Digital Health Technologies (DHT) for Remote Data Acquisition in Clinical Investigations
This guidance provides recommendations for ensuring that a DHT (hardware and/or wearable and software application) is fit-for-purpose and supports the interpretability of its data in a clinical investigation. It considers of both the DHT’s form (i.e., design) and function(s) (i.e., distinct purpose within an investigation).

Draft Guidance Documents out for Comment

Potency Assurance for Cellular and Gene Therapy (CGT) Products
This guidance includes recommendations for helping to assure the potency of CGT products at all stages of the product lifecycle and using an approach that is grounded in quality risk management. Submit Comments by 27 March 2024.

Master Protocols for Drug and Biological Product Development
This draft guidance addresses the design and analysis of trials conducted under a master protocol, as well as the submission of documentation to support their regulatory review. The primary focus is on randomized umbrella and platform trials intended to demonstrate safety and substantial evidence of effectiveness. Submit Comments by 22 February 2024.

Use of Real-World Evidence (RWE) to Support Regulatory Decision-Making for Medical Devices
FDA issued this draft guidance to clarify how to evaluate real-world data and provides expanded recommendations to Sponsors considering using RWE to support a regulatory submission for medical devices. Submit Comments by 20 February 2024.


Advanced Manufacturing Technologies (AMT) Designation Program
This draft guidance provides recommendations for those interested in participating in the AMT Designation Program. It outlines the eligibility criteria for AMT designation, the submission and assessment process for requests, and the benefits of receiving an AMT designation, plus a question-and-answer (Q&A) section covering key concepts important for program utilization. Submit Comments by 12 February 2024.

Quality Considerations for Topical Ophthalmic Drug Products
This guidance revises the draft guidance of the same name issued in October 2023. This revision adds microbiological considerations related to product sterility for all ophthalmic drug products and the prevention of contamination of products packaged in multidose containers. Submit Comments by 26 February 2024.

Breakthrough Therapies and PRIME Programs

The EMA–FDA joint Q&As on Quality and GMP aspects of PRIME/Breakthrough therapy applications document, published last month, provides general information and insight on the ongoing discussions between FDA and the EMA on this topic. The document is divided into four annexes, discussing:  control strategy considerations, process validation approaches, alternatives for determination of re-test period or shelf-life, plus good manufacturing practice (GMP) considerations for PRIME/BT applications.

European Medicines Agency (EMA)

Clinical Trials Information System (CTIS)

A reminder that the CTIS ‘winter clock stop’ will end on 8 January 2024 at 00:00:01 CET and clinical trial application evaluations will resume thereafter. More information is available in the CTIS evaluation timelines document.

Revised versions are available of the Best Practice Guide and Cover Letter Template for Sponsors transitioning multi-national clinical trials to the CTR and CTIS. The revised guide includes clarifications on background treatment and the status of non–Investigational Medicinal Products under the Clinical Trials Directive (CTD) regarded as IMPs or Auxiliary Medicinal Product under the CTR.

Personal data in CTIS

The question-and-answer document (Q&A) on protection of confidential information and personal data in CTIS has been updated and a quick guide for users has also been published. The Q&A now includes a new section on revised transparency rules.

Artificial Intelligence (AI)

The EMA and the Heads of Medicines Agencies (HMA) adopted a workplan on AI in medicines regulation through to 2028. The workplan sets out to maximise the benefits of AI while managing the risks. The focus is on key areas: guidance, policy and product support, AI tools and technology, collaboration and training, plus experimentation.

Paediatric investigation plans (PIP)

The EMA webpage guiding applicants on PIPs, waivers, deferrals or product-specific waivers has been updated to include several modified Q&As and publish the revised Guide on paediatric submissions.

Risk Management Plans (RMPs)

To increase transparency, EMA is publishing RMPs since October 2023 for all centrally authorised products. The general guidance has now been updated to support this change: Anonymisation of Protected Personal Data and assessment of Commercially Confidential Information during the preparation of Risk Management Plans (main body and annexes 4 and 6)

ICH Q2(R2) guideline on validation of analytical procedures

The ICH Q5A(R2) Guideline on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin was adopted in December and becomes legally effective on 14 June 2024. This guideline provides recommendations on how to derive and evaluate the various validation tests for each analytical procedure. It applies to new or revised analytical procedures used for release and stability testing of commercial drug substances and products and can also be applied to other analytical procedures used as part of the control strategy following a risk-based approach.

Bacteriophage Medicinal Products - Consultation

EMA published a Concept paper on the establishment of a Guideline on the development and manufacture of human medicinal products specifically designed for phage therapy for the therapeutic treatment or prophylaxis of one or more specific bacterial infection(s) or infectious disease(s). Antimicrobial resistance has become a serious problem worldwide contributing to morbidity and mortality and increasing the burden for society and hospitalisation costs. Bacteriophages are a promising alternative to antibiotics for the treatment of infections that do not respond to conventional treatment options. Deadline for comments is the 31 March 2024.

Newsletter:  Human medicines highlights – Issue 175, November-December 2023

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

Medicines and Healthcare products Regulatory Agency (MHRA)

Clinical trials best practice guide

Marketing Authorisation applicants (MAAs)

Clinical Investigations for Medical Devices

Research Model Agreements

Following feedback, the October 2023 commercial agreements and guidance have been updated.

The main changes include the clarification of expectations for archiving fees, plus a new clause in the financial appendix to ensure that NHS organisations can defer the use of funds into future financial years to build research capacity. Sponsors and CROs should use the new December 2023 versions of the agreements to ensure that there is clarity of expectation between the parties.

A new Non-commercial Hub and Spoke Agreement is available to support hub and spoke delivery models for non-commercial clinical trials. This can be adopted when using the unmodified model Non-Commercial Agreement (mNCA).

World Health Organisation (WHO)

First WHO-Listed Regulatory Agencies (WLA)

Singapore’s Health Sciences Authority (HSA), South Korea’s Ministry of Food and Drug Safety (MFDS) and the Swiss Agency for Therapeutic Products (Swissmedic) are the first three countries to receive the status of WLA. The designation of WLA is a global recognition that these regulatory authorities meet WHO, and other internationally recognised, regulatory standards.