Latest Regulatory Updates

July 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 and EMA.

Food and Drug Administration (FDA)

Modernizing the New Drugs Regulatory Program (NDRP)

Back in 2017, the Center for Drug Evaluation and Research (CDER) began an initiative to modernize its NDRP to continuously improve regulatory science and review. A new report is now available reviewing the strategic objectives, impact and progress of modernization, and the continued efforts toward reaching the program goals.

Final guidance published

FDA issued the Small Entity Compliance Guide applicable to in vitro diagnostic (IVD) products, including laboratory-developed tests (LDTs). Along with this amendment, the LDT Final Rule includes a policy under which FDA will phase out its general enforcement discretion approach for LDTs over the course of four years so that IVDs manufactured by a laboratory will fall under the same enforcement approach as other IVDs. The phaseout includes targeted enforcement discretion policies for specific categories of IVDs manufactured by laboratories.

Final guidance published

FDA states that a drug or device is “deemed to be adulterated” if the owner, operator, or agent of the factory, warehouse, or establishment at which the drug or device is manufactured, processed, packed, or held delays, denies, or limits an FDA inspection or refuses entry or inspection. FDA has now released guidance that defines the types of  Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection, which replaces the draft guidance of the same title issued in December 2022.

Draft guidance out for consultation

Since publication of the guidance on interchangeability in 2019, experience has shown that for biosimilars the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product. This updated guidance on Considerations in Demonstrating Interchangeability With a Reference Product therefore provides FDA’s current thinking and experience gained over the years.

Comments on both draft guidance documents can be submitted until 20 August 2024.

Draft guidance out for consultation

Bioresearch Monitoring (BIMO) is a comprehensive portfolio of programmes designed to assess and monitor the conduct and reporting of FDA-regulated research plus certain post-marketing activities. The draft guidance on Processes and Practices Applicable to BIMO Inspections discusses the conduct and best inspection practices, such as the types of records and information required to be provided in advance of or during an inspection.

See also the draft guidance document Standardized Format for Electronic Submission for Marketing Applications Content for the Planning of BIMO Inspections on data from pivotal studies used to support safety and efficacy claims in biologics license applications (BLAs) and new drug applications (NDAs) regulated by the Center for Biologics Evaluation and Research (CBER).

Comments on both draft guidance documents can be submitted until 05 August 2024.

Artificial Intelligence (AI) in medical devices

FDA published links to six research areas where its AI Programme will conduct regulatory science research.

European Medicines Agency (EMA) and the European Union (EU)

Two new advice pilots initiated

As part of the Accelerating Clinical Trials in the European Union (ACT EU) initiative, two new advice pilots were initiated in June with the aim of improving the quality of applications for clinical trials. The first pilot offers harmonized scientific advice to support the submission of marketing authorization (MA) and clinical trial authorization (CTA) applications, and the second pilot provides technical and regulatory support for the CTA dossier prior to its submission through the Clinical Trials Information System (CTIS). The duration of both pilots will be evaluated over time based on data and feedback collected from applicants.

An information and training webinar is planned on the consolidated advice pilots (17 July 2024).

Scientific advice (SA) and protocol assistance (PA)

EMA webpages on SA and PA were updated with a new section on SA for clinical trials highlighting the two pilots mentioned above.

Also new on this webpage is the updated Questions and Answers (Q&A) document with tailored SA to support step-by-step development of new biosimilars, plus the publication of the dates of 2025 Scientific Advice Working Party (SAWP) meetings.

Simultaneous National Scientific Advice (SNSA)

When SA is sought it is often requested in parallel from more than one national competent authority (NCA). To optimize Agency resources and to enhance the quality and consistency of such advice, the SNSA approach was developed back in 2020. Following a positive evaluation of the first pilot phase, the Heads of Medicines Agencies (HMA) entered into the second pilot phase which is open until the end of 2024. To support applicants an updated guide was published in June alongside the revised list of NCAs participating in SNSA.

Chimeric Antigen Receptor (CAR) T-cell risk of secondary malignancies

The latest meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) report that the committee evaluated data on 38 cases of secondary malignancy of T-cell origin, including T-cell lymphoma and leukemia, reported among approximately 42,500 patients who have been treated with CAR T-cell medicines. For the six CAR T-cell products approved in the EU, the product information and the risk management plans will be updated to include the new information. Direct healthcare professional communications (DHPC) are also required and will include a reminder about the need for life-long monitoring of patients for secondary malignancies.

ICH M12 Guideline

The ICH M12 Guideline on drug interaction studies, plus accompanying Q&A guide, were adopted by the Committee for Medicinal Products for Human Use (CHMP) in June. Coming into effect on 30 November 2024, ICH M12 will supersede the EMA Guideline on the investigation of drug interactions. A future Q&A document will address drug interactions in the gastrointestinal tract.

Updated guidance

The Q&A guidance on EMA’s pre-authorization procedural advice for users of the centralized procedure was updated in June. The revisions cover questions around the acceptability and justification of combination packs; the notification of change of intended marketing authorization application (MAA) submission date and/or the intention to withdraw the request for submission of a MAA, and GLP compliance. A new section is also available on the declaration in the Letter of Intent for a product in scope of the Joint Clinical Assessment (JCA) under the Health Technology Assessment (HTA) regulation.

New guidance on the clinical evaluation of orphan medical devices

The Medical Device Coordination Group (MDCG) published new guidance for manufacturers and notified bodies outlining criteria for determining when a medical device or an accessory for a medical device should be regarded as ‘orphan device’ under the Medical Devices Regulation 2017/745 (MDR).

What EMA publishes and when

The guide to information on human medicines evaluated by EMA: What the Agency publishes and when describes the different types of information the Agency currently publishes for both centrally and non-centrally authorized medicines and includes publication times and the location on its website. The update in June provides information on medicines granted an orphan designation. Also available is the quick guide on the revised CTIS transparency rules, highlighting changes that came into effect on 18 June 2024 and explaining what is published from CTAs submitted before that date.

Consultation: Post-authorisation changes to the terms of a MA

The European Commission has published its proposed changes to the rules governing the procedures for post-authorisation changes to the terms of a MA, upon which stakeholders are

invited to comment on the proposed amendment. This refers specifically to the guidelines on the details of the different categories of variations and the operation of the variations procedures. The consultation period ends on 23 August 2024.

Paediatric applications

Since the beginning of June, paediatric applications (initial and modified investigation plans [PIPs], waivers, compliance checks, annual reports on deferred measures, or discontinuation of paediatric development) are to be submitted via the IRIS platform. The previous process continues to apply for ongoing applications submitted before that date.

An updated guide with procedural advice, plus new templates and forms are now available for the relevant applications.

Newsletter: SME Highlights – Issue 62, June 2024

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

Newsletter: Clinical Trials Highlights – Issue June 2024

Provides insights on clinical trial topics, including ACT EU and CTIS.

Podcast: Conversations in Drug Development

Exploring Genome Editing Technologies in Drug Development

In this episode, host Dr. Katherine Bowen, is joined by Harriet Edwards, Associate Director in Regulatory Affairs, to explore the fascinating world of genome editing technologies.

Together, they delve into the ethical considerations of editing somatic versus germline cells and trace the historical progression of these technologies from agriculture to healthcare. Join us as we discuss the complexity of genome editing methods, the irreversible nature of genetic changes, and the associated risks.

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).