Euro Roundup: EMA outlines processes for accelerating drug development in health emergencies
The European Medicines Agency (EMA) has set out actions to improve scientific advice and accelerate regulatory processes in public health emergencies.EMA shared details of the changes in two documents. One document provides guidance for applicants seeking advice from the Emergency Task Force (ETF). The ETF provides scientific advice on clinical trial authorization (SA-CTA) to clarify requirements for clinical trial and marketing authorization applications.
Through the updated approach to SA-CTA, sponsors can apply for combined scientific advice from EMA and clinical trial and ethics experts at a national level. The advice is available to developers of medicines falling within the scope of the ETF’s activities, including drugs for antimicrobial resistance.
Marco Cavaleri, co-chair of the ETF, said the new approach is intended to give developers “clear input on the design of clinical trials to allow generation of adequate evidence, and how these trials should be conducted according to both regulatory and ethical considerations.” Enabling input on science and ethics at the same time could speed up medicine development and approval, Cavaleri said.
Sponsors will receive one consolidated opinion. EMA sees the consolidation as a way to promote the harmonization of scientific expectations between different Member States. That harmonization could result in greater consistency in the interpretation and application of scientific requirements for CTAs and marketing authorization applications.
Developers of eligible medicines, which include products against threats that could cause public health emergencies, can apply for an ETF SA-CTA by following the usual EMA scientific advice submission route. The validation phase for emergency and standard scientific advice procedures is the same. EMA has updated the application form in IRIS to address whether advice on clinical trials is requested.
EMA published the SA-CTA guidance alongside an annex to its health threats plan. The annex covers the rapid formal review procedures EMA can adopt in response to public health emergencies, including the acceleration of the scientific advice process. EMA can reduce the total review time for scientific advice to 20 days in emergencies, compared to 40 to 70 days under its regular timeline.
Other sections of the annex address rapid agreement of pediatric investigation plans and compliance checks, rolling reviews, marketing authorizations, label extensions, and compassionate use. The annex only provides a high-level overview of each of the mechanisms. EMA plans to provide standard operating procedures for processes it expects to use extensively when a public health emergency is declared.
Press Release, SA-CTA Guidance, Annex
EMA seeks feedback on clinical trial non-inferiority and equivalence comparisons
EMA has released a draft guideline on non-inferiority and equivalence comparisons in clinical trials for consultation.
Currently, the use of non-inferiority and equivalence comparisons is governed by guidelines that were published in 2000 and 2005. EMA is planning to replace the two documents with the guideline that it has released for consultation. The draft addresses all the topics that are covered in the older documents and provides updated recommendations to reflect changes in European and international frameworks.
EMA’s guideline covers three objectives of non-inferiority comparisons. The typical aim in the regulatory context is to show absolute efficacy, EMA said. Sponsors compare the test treatment to another active therapy to show it is better than no treatment or placebo.
“This situation arises when a trial would ideally be placebo controlled but an active comparator is selected for ethical reasons,” EMA said. “The analysis is essentially an indirect comparison between the test treatment and a putative placebo arm.”
Other studies assess relative efficacy. Such trials compare a test treatment to another active therapy to show the study drug “is not worse by more than a clinically acceptable amount,” EMA said. Scientifically, it is best for relative efficacy comparisons to include a placebo cohort alongside the two treatment arms. Yet EMA said the three-arm design is often difficult to justify ethically.
The third objective of non-inferiority comparisons is to assess safety. EMA said sponsors can compare test treatments to active therapies, placebo, or no treatment to show that the study drug “does not lead to an unacceptably large increase in the risk of an adverse drug reaction.”
The rest of the guideline provides detailed advice on performing non-inferiority comparisons, covering topics including assay sensitivity, selecting the margin of non-inferiority, and estimands. EMA’s section on estimands reflects concepts that the International Council for Harmonisation introduced in ICH E9(R1).
EMA is accepting feedback on the draft until 31 May.
Draft Guideline
MDCG shares advice on implementing master UDI-DI solution for vision glasses
The Medical Device Coordination Group (MDCG) has published guidance on implementing the master unique device identifier (UDI-DI) solution for vision glasses.
Officials amended the Medical Device Regulations (MDR) in 2023 to introduce master UDI-DIs for highly individualized devices. Master UDI-DIs group highly individualized devices with specific similarities to cut the number of UDI-DIs in the database. The European Commission later introduced a regulation on a master UDI-DI for spectacle frames, spectacle lenses, and ready-to-wear reading spectacles.
Months after sharing a timeline for complying with the master UDI-DI, MDCG has published advice on how to implement the solution. The guidance defines various spectacle designs and lens technologies.
Other sections explain how different parameters, such as spectacle frames’ design and material, inform the assignment of basic and master UDI-DIs. MDCG has provided examples of the labels various devices should have and the information they should present.
Spectacle frames, spectacle lenses, and ready-to-wear reading spectacles produced prior to 1 November 2028 do not need to include the master UDI-DI on the label. MDCG previously said manufacturers of the devices must implement the master UDI-DI solution from September 2028.
The transition timeline means the devices may not be registered in the UDI/Devices Eudamed module when it becomes mandatory. MDCG wants manufacturers to act as soon as the issuing entities master UDI-DI codification standard becomes fully available, and at least before the Vigilance and Post-Market Surveillance module of Eudamed becomes mandatory.
MDCG Guidance
Team-NB posts position paper on moving MDR applications to new notified bodies
Team-NB has adopted a position paper on transferring MDR applications and legacy device surveillance activities between notified bodies.
The European Commission addressed transfers in a question and answer document about the extension of the MDR transitional period. Officials said that the withdrawal of a conformity assessment filing or the ending of an agreement with a notified body would leave legacy device manufacturers noncompliant with MDR, unless they simultaneously entered into a written agreement with another notified body.
Notified body trade group Team-NB has created the position paper to explain how manufacturers can transfer the regulatory status of the MDR application and the formal written agreement. The document includes an agreement that specifies the terms of transfers between outgoing and incoming notified bodies that manufacturers can use to remain compliant with MDR while switching between providers.
Position Paper
Other News:
ABPI and the UK government have agreed to a third extension to the deadline for leaving the 2024 voluntary scheme for branded medicines pricing, access, and growth (VPAG). The extension pushed the deadline back by one month, giving manufacturers until 16 December to decide if they want to stay in the scheme. ABPI said the VPAG delay reflects ongoing global uncertainty. ABPI Notice
×
Welcome to the new RAPS Digital Experience
We have completed our migration to a new platform and are pleased to introduce the updated site.
What to expect: If you have an existing login, please RESET YOUR PASSWORD before signing in. After you log in for the first time, you will be prompted to confirm your profile preferences, which will be used to personalize content.
We encourage you to explore the new website and visit your updated My RAPS page. If you need assistance, please review our FAQ page.
We welcome your feedback. Please let us know how we can continue to improve your experience.