EMA opens feedback on biomarker-guided drug approval dossiers

The European Medicines Agency is taking comments on a draft guideline setting out the scientific requirements for developing and validating predictive biomarkers and the assays that pair with them. The document builds on a 2017 concept paper that flagged the need to clarify the rules ahead of the In Vitro Diagnostic Regulation. Companies are expected to submit data supporting the context of use in their applications — covering the proposed indication, the IVD's intended purpose, the target population and the conditions for use. Feedback runs until 31 March.

EMA lays out three possible stages of biomarker development, and notes they are not necessarily sequential or mandatory: one for research settings, then two for early and mature companion diagnostic candidates. Developers should dig into the biomarker's characteristics, including how common it is in the target patient population and how it relates to disease pathogenesis, the agency said. The guideline also covers analytical and clinical validation, sample collection, bridging studies and the summary of product characteristics, plus a short section on post-approval follow-up for uncertainties that survive authorization.

A second EMA draft tackles reproductive and developmental risks, replacing a guideline that took effect in 2009. It focuses on weaving nonclinical and human data together, and for the first time leaves room for new approach methods — in vitro, ex vivo and non-mammalian in vivo assays — at any stage of development, potentially letting companies cut back or replace some animal studies. The update adds detail on risk classifications and how they feed recommendations for use during pregnancy and breastfeeding, plus new standard statements on fertility. Comments close 28 February.

The UK's Medicines and Healthcare products Regulatory Agency set out how it will bring the public into drug and device regulation through 2030, building on its 2021-2025 strategy. Plans include a beefed-up system for tracking how public feedback changes the agency's work, a wider patient and public community reflecting the UK's diversity, and deliberative engagement on weighing medicines' risks and benefits. MHRA also wants to work with the National Institute for Health and Care Excellence to stop patients being asked the same things twice across regulatory and health technology assessments. “Through this plan, we will involve people earlier, hear from a broader range of communities and patient demographics, and explain how their contributions have influenced our work,” chair Anthony Harnden said.

MHRA also published guidance on clinical trial applications leaning on nonclinical safety data generated outside the OECD's Mutual Acceptance of Data framework. All OECD members take part and several non-members, including India, fully adhere — China does neither. The agency will weigh such data alongside the participant population, the seriousness of the condition, unmet need and the trial's stage and design, and said it “may consider an enhanced nonclinical assessment, including for first-in-human trials in patients with advanced cancers or other serious or life-threatening conditions where there is significant unmet medical need.” Its framework runs on three streams: inspection and compliance intelligence, enhanced nonclinical assessment, and weight-of-evidence use of clinical data. The guidance landed alongside an ABPI report showing UK industry clinical trial participation fell for a fifth straight year, despite what the group called real progress on faster regulatory set-up.

Elsewhere, EMA agreed to swap information on the safety, efficacy and quality of medicines and medical devices with Singapore's Health Sciences Authority, in a deal that also brings in Europe's Directorate-General for Health and Food Safety and includes training and knowledge-sharing. And the Dutch competition regulator has opened an investigation into Biogen, according to raps.org.