More Than 1.2m Adverse Drug Reactions Reported In EU In 2016; EMA Reviewed 2,000 Safety Signals
Executive Summary
The European Medicines Agency has published details of the drug safety issues it dealt with in 2016, noting that more than 1.2 million adverse drug reaction reports were received and that it reviewed in excess of 2,000 potential safety signals. A total of 118 products were withdrawn from European markets.
In 2016, more than 1.2 million adverse drug reactions were reported to the EU’s EudraVigilance database, broadly in line with 2015. In the same year, the European Medicines Agency reviewed more than 2,000 potential safety signals related to marketed drugs, of which 94 were prioritized and assessed by its Pharmaceutical Risk Assessment Committee, with 28 of these resulting in changes to the product information.
The data come from the EMA’s annual report for 2016, which notes that both the agency and national competent authorities in the EU member states are responsible for continuously monitoring data reported to EudraVigilance to identify any new or changed risks and determine whether these have an impact on a products’ overall benefit-risk balance.
Of the 2,076 potential safety signals reviewed by the EMA in 2016, 83% originated from monitoring of EudraVigilance. In 2015, the agency reviewed 2,372 signals, and in 2014 the figure was 2,030. Out of the 94 confirmed signals prioritized and assessed by the PRAC, 48 were detected and validated by the EMA and 46 by the member states.
Four of those signals led to a referral procedure to investigate the issue further, while two triggered another regulatory action, such as a recommendation to update the product’s risk management plan (RMP) or to conduct a study. Three of the 28 signals that led to updated product information also included a “Direct Healthcare Professional Communication” to highlight important new safety information, according to the annual report.
30 signals were still under PRAC review at the end of 2016, while a further 30 had led to a recommendation for routine pharmacovigilance.
A new version of EudraVigilance that will make it easier for drug companies to report individual case safety reports (ICSRs) and introduce new obligations regarding signal detection is scheduled to go live in November. Marketing authorization holders, clinical trial sponsors and national authorities will need to prepare for the transition by ensuring the compatibility of their processes and local IT infrastructure with the new system, according to the EMA. (Also see "New EudraVigilance System To Usher In Simplified Reporting of ADRs From Nov. 22" - Pink Sheet, 23 May, 2017.)
PSUR Assessments
Under EU rules, companies marketing pharmaceuticals must submit a periodic safety update report (PSUR) or a periodic Safety update single assessment (PSUSA; for more than one product containing the same active ingredient) at regular intervals following authorization.
Based on an assessment of PSURs and PSUSAs in 2016, the PRAC made 791 recommendations, an increase of 25% over 2015 that the EMA attributes to a higher number of single assessments of active substances contained in only nationally authorized medicines. This is a new activity taken on by the agency in 2015, and such assessments accounted for more than 33% of all assessments finalized in 2016. Nearly one in five assessments led to changes in the product information.
118 products were withdrawn for safety reasons last year, sharply down on the 160 seen in 2015.
Withdrawals, Referrals
Since 2014, marketing authorization holders have been required to inform the EMA whenever a product is withdrawn from the market, and the agency is responsible for coordinating withdrawal actions across the member states. 118 products were withdrawn for safety reasons last year, sharply down on the 160 seen in 2015.
Where there are safety or benefit-risk, concerns, or member states disagree on the use of a medicine, an EU referral can be made whereby the EMA conducts a scientific assessment of a specific medicine or product class, and issues a pan-EU recommendation.
In 2016, 19 referral procedures were finalized, six of which related to pharmacovigilance; five of these resulted in changes to the product information and one led to the revocation of the marketing authorization – fusafungine nasal and oral solution for upper airway infections. In that case the PRAC concluded that the risks of the product outweighed its benefits, mainly because of the risk of serious allergic reactions.
The remaining 13 referral procedures involved efficacy or quality concerns with certain medicines, a need for EU-wide harmonization of product information, or differences among the member states in the mutual recognition and decentralized procedures.
PASS, PAES, RMPs
Also in 2016, the PRAC assessed 10 imposed PASS (post-authorization safety study) protocols (such studies can be imposed on companies as part of their post-approval obligations), while six post-authorization efficacy studies (PAES) were imposed on companies to collect further data on the benefits of medicines in real-life usage.
Finally, a total of 266 RMPs were submitted in relation to new marketing authorization applications, including changes made during the evaluation process at the EMA. 739 requests to change existing RMPs were received.
The EMA also recently announced that its roadmap for improving its medical literature monitoring (MLM) service – which had been expected by the end of 2016, but was delayed to address comments and suggestions from marketing authorization holders – will be ready for publication soon. The roadmap is expected to help improve the MLM service, which industry claims has failed to meet its key objective of simplifying the monitoring and reporting of adverse events by companies. (Also see "Roadmap To Improve EMA’s Medical Literature Monitoring Service Due Soon" - Pink Sheet, 25 May, 2017.)
From the editors of Scrip Regulatory Affairs.