Euro Roundup: EMA posts draft guideline on approval dossiers for biomarker-guided therapies
The European Medicines Agency (EMA) is seeking feedback on the information needed for the approval of biomarker-guided medicinal products.
Linking medicinal products to predictive biomarkers allows physicians to identify the patients most likely to benefit from a treatment. EMA published a draft concept paper on predictive biomarkers in 2017, reflecting the need to clarify the rules ahead of the In Vitro Diagnostic (IVD) Regulation. The draft guideline released this week builds on the concept paper.
EMA’s guideline details the scientific requirements for developing and validating predictive biomarkers and their corresponding assays to support medicinal product applications. The document outlines the evidence that companies should generate throughout the clinical development program. While primarily aimed at medicinal product developers, the document may also be useful for diagnostic manufacturers.
The agency expects companies to submit data supporting the context of use (CoU) in their approval applications. The CoU includes the proposed indication of the medicinal product, the intended purpose of the IVD, the target population, and the conditions for use.
EMA outlined three potential stages of biomarker development, while noting that not all stages are sequential or mandatory. The first stage covers research settings, while the other two stages focus on early and mature companion diagnostic candidates.
Another section of the guideline addresses the scientific rationale for predictive biomarkers and their corresponding assays. Companies should thoroughly explore the characteristics of the biomarker, including its prevalence in the target patient population and relationship to disease pathogenesis, EMA said.
The guideline also addresses analytical and clinical validation of biomarker assays, the collection of samples for biomarker analyses, bridging studies, and the summary of product characteristics. EMA included a brief section on post-approval follow-up, explaining that companies with uncertainties about predictive biomarkers at the time of authorization may need to address them post-approval.
EMA is accepting feedback on the draft until 31 March.
MHRA shares 5-year public engagement strategy for patient-centred regulation
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has set out how it will engage the public in drug and device regulation through 2030.
Building on its strategy for 2021 to 2025, MHRA has outlined plans to strengthen its feedback monitoring and reporting system to show how public input influences its work. MHRA will also expand membership of its patient and public community to reflect the diversity of the UK population and use deliberative engagement to ensure public perspectives shape the assessment of medicines’ risks and benefits.
Other objectives include involving patients and the public in work to make information on medicines clearer and more accessible, and collaborating with the National Institute for Health and Care Excellence to reduce the duplication of patient involvement in 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,” Anthony Harnden, chair of MHRA, said.
The priorities reflect MHRA’s wider objectives around advancing patient-centered regulation, addressing evidence gaps, supporting proactive regulation, and ensuring patient safety. MHRA’s patient-centered regulation objectives include having “structured digital content that can be accessed through a range of tools and services” by 2030.
Officials developed the priorities in response to MHRA’s assessment of the progress on its first patient involvement strategy. The assessment showed “clear progress in embedding patient involvement more systematically across the agency and demonstrated the value of lived experience in informing regulatory thinking,” MHRA said. However, the agency also uncovered areas for improvement.
EMA seeks feedback on assessing drugs’ reproductive and developmental risks
EMA has released a draft guideline on assessing the risks of medicinal products in human reproduction and breastfeeding.
The document, which will replace a guideline that took effect in 2009, addresses how to integrate nonclinical and human data to assess reproductive and developmental risks. EMA wants to update the existing text to reflect current standards, including the option to use new approach methods (NAMs) and postmarketing data in the assessments.
NAMs, such as in vitro, ex vivo, and non-mammalian in vivo assays, may be valuable for identifying adverse effects and understanding developmental and reproductive toxicity mechanisms, EMA said. The agency sees a role for NAMs at any stage of medicinal product development, adding that the assays may allow companies to reduce or replace certain in vivo studies.
Other proposed changes include the addition of details on risk classifications and their impact on recommendations for the use of medicinal products during pregnancy and breastfeeding. The new information forms part of a stepwise process, which starts with the assessment of data on reproduction, pregnancy, and breastfeeding and moves on to classifying risks and recommending actions to mitigate them.
EMA concluded the guideline with a discussion of the product information and standard statements. The draft features updated examples of standard statements for the summary of product characteristics and new standard statements on fertility.
The agency is accepting feedback on the draft until 28 February.
MHRA posts guidance on nonclinical safety data from outside OECD framework
MHRA has shared guidance on clinical trial applications that rely on nonclinical safety data generated outside an international framework.
Countries participating in the Organisation for Economic Co-operation and Development (OECD) Mutual Acceptance of Data framework accept each other’s test results. All OECD member countries participate in the system, and several non-member countries, including India, fully adhere to the framework. China is not an OECD member or on the list of full adherents to the system.
Responding to the increasingly global nature of nonclinical drug development, MHRA has outlined how sponsors can use non-OECD data to support requests to run trials in the UK. The agency will consider the data alongside aspects of the proposed study, including the participant population, the seriousness of the condition, the unmet medical need, and the stage and design of the trial.
“In limited circumstances, the MHRA 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,” the agency said. “This provides additional scientific scrutiny of the available evidence where appropriate.”
MHRA’s framework for considering non-OECD data comprises three interconnected streams: inspection and compliance intelligence, enhanced nonclinical assessment, and weight-of-evidence use of clinical data. One or more streams may contribute to assessments, depending on the details of an application.
Publication of the framework coincided with a report showing that the number of people participating in industry clinical trials in the UK fell for a fifth year in a row. The decline happened despite “real progress on setting up industry trials faster, particularly at the regulatory stage of set-up,” ABPI said.
Press Release, MHRA Guidance, ABPI Statement
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