New challenges in pharmacovigilance: the EMA’s Medical Literature Monitoring initiative

The European Medicines Agency has a new system to assess the safety of herbals and generics. How is it affecting reporting?

The European Medicines Agence (EMA) recently launched their Medical  Literature Monitoring (MLM) initiative. The intention behind this somewhat controversial project is to correct some weak spots in their ability to assess the safety of generic medications. The agency also plans new work to establish the safety profiles of herbal substances and food products.

The controversy stems from the complexities the MLM initiative may introduce into the process of reporting adverse drug reactions (ADRs) or adverse events (AEs). As with any new process, the workflow is not seamless, and the EMA and the various pharmaceutical companies will have to work out their synergies  and roles. The new initiative will certainly not decrease the workload of drug safety professionals, who will still have to screen every article detected for a given product.

Best practices

For best practices for monitoring and screening literature, read our article streamlining and improving the challenging processes in pharmacovigilance.

For herbal products, such close scrutiny of their safety is completely new. As there is no market authorization holder for these over-the-counter products, they have not fallen under the normal reporting rules for drugs. It is unclear whether scientific literature screening will actually reveal true  ADRs or AEs associated with herbals. On the one hand, the published EMA search formulas returned 406 records for herbals from Embase during a two-week test run. On the other, based on the EMA pharmacovigilance guidelines, spontaneous reporting by healthcare professionals is not expected unless the ADR or AE is extremely serious. Even then, the categorization generally  ends up being food poisoning. It remains to be seen what the MLM initiative will mean for manufacturers and the economic operators of these products.

When it comes to generics, where there is a market authorization holder, the situation is clearer although, as mentioned, the reporting procedure will be more complex.

So why did the EMA decide to change their approach to generics?

The problem faced by all regulatory bodies is that, traditionally, spontaneous ADR and AE reporting for branded generic products is completely voluntary and will probably remain so. Therefore, it is always assumed that spontaneous reports will produce individual case safety report (ICSR) counts that  do not reflect the risks of a drug proportionally much less accurately.

Previously, the EMA mandated that the market authorization holders should do literature screening and reporting for generics. There was a tendency toward misrepresentation of the literature: serious AEs were over- or underrepresented due to brand involvement. If the AE was common, then it was rare that  any marketing authorization holder took care of entering the literature case into an ICSR. Unfortunately, if nobody reported a sudden dramatic increase in occurrence of a known AE, there was the potential for a serious health problem to go unnoticed for some time. Conversely, it was also possible that  a false dramatic increase in a known AE could cause an unnecessary amount of resources to be spent investigating a large number of ICSRs only to find that it was just the same event being reported in 15 separate ICSRs. The EMA EudraVigilance  database system has procedures to handle duplicates, but the time spent on harmonization would be better used tackling real threats.

It was situations like these that led to the perception that the output for generic drugs was untrustworthy. This drove the EMA to hire a contract research organization to perform literature screening for generic drugs using several sources, and to create and deliver the completed E2B ICSRs so they  could be made available to the market authorization holders.

Even though one might think this would save the industry time and resources, the fact is that the industry professionals tasked with performing pharmacovigilance on their products will still have to screen every single article detected. Until the screening is performed, nobody will know whether an AE  is present, how serious it is and what authority it should be reported to. The market authorization holder still is responsible for due diligence until it is certain that the article has not been captured by EMA search formulas.

The complexities occur in the later reporting. If the market authorization holder finds an article reporting that an AE is not serious and happens in a country member of the EEA, or if an AE is serious, then the market authorization holder must wait for the EMA to find the article. If they discover  that the EMA found the article, then they must wait for the EMA to declare that it found the AE and that an ICSR has been created. In this case, all information — the market authorization holder article reference, the EMA article reference, the market authorization holder ICSR record and the EMA  ICSR record — must somehow be harmonized, as the EMA requires its own Case Identifier to be the Worldwide Case Identifier.

While it currently seems that there are many challenges to go through before a seamless workflow can be achieved, some positive synergies remain to be explored. Literature monitoring and screening processes can be streamlined and it falls to the EMA, information service providers such as Elsevier and industry drug safety experts to work together to find the best ways to address the new situation.

What is Embase?

Embase is the world’s mostcomprehensive international biomedical literature database. With more than 30million records and deep, full-text indexing, Embase captures all relevantinformation from biomedical literature to support pharmacovigilance andevidence-based medicine decisions.

Elsevier Connect Contributor

Júlio dos Anjos

Júlio dos Anjos implemented databases and information products for academic and hospital libraries for 20 years before joining Elsevier four years ago. Since then, he has implemented pharmacovigilance solutions for multiple companies. He is now the lead  consultant for Pharmacovigilance on the Elsevier R&D  Professional Services team.

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