EMA Tackles Complexities Introduced By Literature Monitoring Service

The European Medicines Agency is exploring how to address the challenges companies face when they use its medical literature monitoring (MLM) service.

The MLM service, since it was launched last year, has triggered concern among companies that it is not fulfilling its objectives in respect of cutting administrative burden for them. Under the MLM service, the EMA monitors medical literature for reports of suspected adverse drug reactions (ADRs) from drugs containing certain active substances and then submits case reports into the EudraVigilance database on behalf of drug companies. While it is available for use by both branded and generics companies, it is more relevant for the generics industry as it covers substances with the greatest number of marketing authorizations. (Also see "EMA to scour medical literature for potential safety concerns from popular drugs " - Pink Sheet, 26 Jan, 2015.)

When it was first introduced, the hope among generic marketing authorization holders was that it would significantly reduce the burden associated with their literature monitoring obligations, said Katarina Nedog, safety and regulatory manager at Medicines for Europe (formerly, the European Generic Medicines Association).

"Companies don't see that just yet in practice and the service still needs to bear its fruit," Nedog told the Pink Sheet.

At an industry conference last year, companies had pointed out that they continue to perform literature checks to ensure that the EMA has not missed any qualifying cases or has wrongly categorized an ADR (e.g., serious or non-serious), which has created complexities and has led to duplication of effort. (Also see "EMA's Medical Literature Monitoring Service Creates New Complexities For Pharma" - Pink Sheet, 3 Nov, 2015.)

The EMA told the Pink Sheet that it has recently expanded the service to cover non-serious non-EEA reactions. This was done to address a major concern that companies initially had with the MLM service – that its scope was restricted to identifying suspected ADRs that only met the EU reporting criteria. As a result, companies were still monitoring the same literature sources for the same active substances to fulfil their reporting obligations to regulators outside the EU and also to comply with other EU pharmacovigilance requirements.

The EMA is now organizing a workshop on Sept. 13 that will explore, among other things, possible enhancements to the operation or scope of the MLM service. Earlier this year, respondents to a pharmaceutical industry survey suggested to that the MLM service should be expanded to cover aspects of literature monitoring beyond just ADR reports. For example, they said it should also cover such things as off-label use and medication errors that do not result in harm.

The September workshop is also expected to look at "what MLM work marketing authorization holders still have to perform for the substances covered by the service" and "whether there is any overlap with the work being performed by the EMA's MLM service and industry", the EMA said.

Companies are also worried that the complexities introduced by the MLM service may result in problems during inspections. The EMA said that its pharmacovigilance inspectors would be invited to attend the workshop, and that they "have been routinely informed of the activities of the MLM service.

The agency expects the workshop to help develop recommendations "that can help shape the future direction of the MLM service" for the benefit of safety monitoring and the efficient operation of the EU pharmacovigilance system.

Good, But Could be Better

Earlier this year, the EMA conducted its own survey of the MLM service and most of the marketing authorization holders that responded agreed that the service had improved since it was first launched. Nedog also endorsed this opinion and highlighted some of the other improvements made to the service over time, such as:

• changes to the daily Excel sheets, including highlighting cases newly available to download and preparation of monthly cumulative spreadsheets;
• improvement in case quality; and
• better availability of the MLM helpdesk service.

The EMA survey highlighted that there were “still areas for significant improvement", most notably the data quality of individual case safety reports (ICSRs). (Also see "EMA Survey To Gauge Pharma's Satisfaction With Its Medical Literature Monitoring Service" - Pink Sheet, 8 Mar, 2016.)

To further improve the service, Nedog said that a joint industry-EMA advisory board should be created that would:

• take a step-by-step approach to solving challenges;
• monitor closely any improvements made to the service and have an open dialogue; and
• help achieve the five key objectives of the MLM service - ie to make the system of adverse reaction reporting more efficient, provide simplification for the industry, improve data quality by reducing the number of duplicates in the system, contribute to resource savings for the industry and support signal detection activities by national competent authorities and marketing authorization holders.

Under the MLM service, the EMA monitors thousands of medical journals to check for suspected ADRs to 400 active substance groups (300 chemical active substance groups and 100 herbal active substance groups) and submits relevant valid cases to the EudraVigilance database in the correct E2B format on behalf of the companies.

From the editors of Scrip Regulatory Affairs.