Euro Roundup: EMA sees slight improvement in approval submission predictability, reversing trend

The trend for the timing of initial marketing authorization applications (MAAs) to be less predictable is slowly reversing but there remains room for improvement, the European Medicines Agency (EMA) said.

EMA and industry representatives formed a focus group to look at submission predictability in 2022. By then, the recurrent problem of unreliable long-term planning for initial MAAs for centralized procedures had become unsustainable because the pandemic had stressed regulatory resources. The focus group’s initial report found actions taken in 2023 failed to significantly improve submission predictability.

This week, the focus group published a report about the impact of actions taken after the failure of the initial attempts to reverse the trend. The focus group closely monitored the MAA pipeline in the second half of last year to inform the report.

EMA reported a slight improvement in the predictability of MAA submissions compared to 2023 and an increase in communication engagement by applicants. During the period, 57% of applications were submitted on time, compared to 48% of MAAs in 2023. The proportion of MAAs delayed but submitted within the year fell from 13% to 8%.

About one-quarter of filings were delayed to the next year in both periods. Applicants gave EMA 3 to 146 days’ notice of the delays, with an average of 51 days. Fifteen applications were delayed once, on average by 5.7 months. Seven applications were delayed twice, with the second delay pushing the filing back by 3.4 months, on average.

EMA found applicants gave less than 60 days’ notice of more than 60% of the delays. The agency received at least 90 days’ notice, a period it called more acceptable, in less than 10% of cases. EMA said the failure to give sufficient advance warning to regulators to adjust their workplans causes “major disruption in the workload allocation of the assessors.”

The agency emails prospective applicants three months before the planned submission date, requesting confirmation and, if changes occur, a justification. More than 90% of companies responded, and 73% of applicants changing their filing date provided a justification. While more companies are justifying changes, EMA said the lack of information on the real reasons for delays hinders efforts to improve predictability.

EMA cited the high percentage of companies failing to fully justify changes in their submission plans and the very short advance notice provided by applicants as evidence that communication can improve. Lacking legal powers to enforce stricter measures, EMA will focus on communication activities that draw attention to the problem and the consequences to the network while waiting for new legislation.

“Further systematic monitoring to assess the effectiveness of the adopted measures is not envisaged,” EMA said. “Instead, the Agency will focus on potential new approaches that could be implemented to improve submission predictability as part of the work towards the implementation of the New Pharmaceutical Legislation.”

EMA Report

EDQM gives manufacturers recommendations for supporting traceability in hospitals

The European Directorate for the Quality of Medicines and HealthCare (EDQM) has published best practices for the traceability of medicines in hospital settings.

EDQM created the guidance for policymakers, payers, and hospitals. Yet the directorate also included proposed actions for pharmaceutical manufacturers to take with the support of their solution providers and other industry third parties. EDQM recognized industry’s existing efforts to support patient safety but called for the sector to implement additional actions to enable medicine traceability in hospitals.

The directorate proposed that drugmakers implement the regulatory requirements for barcoding at the primary packaging level, facilitating full in-hospital traceability. The Falsified Medicines Directive imposes coding of secondary packaging but does not require manufacturers to barcode primary packaging.

Only some medicines entering hospitals are barcoded at the primary packaging level, EDQM said, and the proportion varies by country. Hospitals that implement point-of-care scanning need to relabel packs without barcodes at a pharmacy, a procedure that EDQM said requires dedicated staff.

EDQM also proposed that manufacturers establish monitoring systems in packaging lines and in quality control to guarantee that hospitals can scan barcodes. The monitoring would check if the barcodes meet applicable quality standards, EDQM said, and ensure that they are located in an appropriate place on the packaging. EDQM said manufacturers would need to discuss exceptions with regulatory agencies.

The directorate’s final proposal for drugmakers addressed the data encoded by barcodes. EDQM wants barcodes to include the product code, batch number, and expiry date because hospitals need to include that information in their traceability systems. Primary packaging should also state at least the product, dose, and batch number in human-readable text to ensure patient safety, EDQM said.

EDQM Notice

EMA answers questions about clinical data work-share initiative with Health Canada

EMA has shared information on its work with Health Canada to reduce duplication by jointly assessing documentation.

The partners are accepting requests for single reviews of common procedures from companies filing initial marketing authorization applications to both agencies. EMA and Health Canada will only accept a submission for their work-share program if there is about a 70% overlap in the list of documents and the planned outcome dates for both agencies fall in a six-month period.

EMA and Health Canada will assign a lead agency based primarily on regulatory timelines. The lead agency performs the primary assessment of the redaction package, coordinates the joint review process, and interacts with the applicant.

Other questions address package preparation and timelines, and assessment and publication. EMA said applicants do not need to reformat documents submitted to Health Canada to reapply redaction labels that meet European requirements. The work-share process leads to publications in EMA’s clinical data portal, which does not distinguish Health Canada collaborations from internal procedures.

EMA Q&A

UK MHRA seeks feedback on guidance about clinical trial roles and responsibilities

The Medicines and Healthcare products Regulatory Agency (MHRA) has published draft guidance on the roles and responsibilities of people involved in medicine clinical trials in the UK.

MHRA published the guidance to accompany amendments to UK clinical trial legislation that will come into force on 28 April. The legislation expands the definition of who may act as a clinical trial investigator to include a broader range of healthcare professionals who have appropriate qualifications, experience, and training and are supported by medically trained professionals as required.

The draft guidance states sponsors are responsible for appointing an investigator and ensuring they have the required training and qualifications. MHRA said it is “strongly suggested” that organizations running trials consider what training and support is required for investigators, especially where they do not have prior experience.

MHRA is accepting feedback on the draft until 30 April.

Draft Guidance

Other News:

MHRA has extended its fee waiver program for micro- and small-sized enterprises studying innovative medical devices in humans. After closing the previous pilot, MHRA decided to resume granting waivers. The agency plans to run the program until April 2027 and grant 10 waivers. Developers of Class III devices are now eligible for fee waivers. MHRA Update

The European Commission authorized the first combined COVID-19 and influenza vaccine for people 50 years and older. The vaccine, Moderna’s mCombriax, contains mRNA to train the immune system to recognize proteins found on the COVID-19 virus and three seasonal influenza viruses. Moderna withdrew an application for approval of the vaccine in the US last year. Press Release