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Question 13 of 20 Intermediate Practical

What are a marketing authorisation holder's literature monitoring obligations in the EU?

Short answer

The holder must search widely used reference databases such as Medline or Embase at least once a week, monitor local journals in countries where the product is authorised, and turn valid cases into ICSRs. For substances and journals covered by EMA's medical literature monitoring service, EMA enters EU cases into EudraVigilance instead.

Why

GVP Module VI calls the medical literature a significant source of safety information and expects a systematic search of widely used databases no less than once a week, using databases with the widest coverage for the product. Abstracts from meetings and draft manuscripts count too. Each identifiable patient becomes one case, with the first or corresponding author as the primary source.

Day zero is awareness of a publication with the minimum criteria. If several products are mentioned, only those the authors consider at least possibly causal need review by their holders. Under Article 27 of Regulation (EC) No 726/2004, EMA monitors selected literature for a published list of active substances and enters relevant cases into EudraVigilance, where holders can access them.

Holders remain responsible for literature outside that service, including local journals, and for cases from outside the scope. A good search strategy names the product, its active substance and synonyms, avoids filters that drop case reports, and is documented so it can be shown at inspection.

How to work it through

  1. Define search strings covering the active substance, brand names and synonyms.
  2. Run them at least weekly in databases with the widest coverage for the product.
  3. Screen hits for the minimum criteria and record day zero at awareness.
  4. Create one case per identifiable patient and submit valid cases on time.
  5. Exclude cases already handled by EMA's monitoring service where applicable.
  6. Document the strategy and any changes for inspection.

An example

A company holds an EU authorisation for an older antiepileptic. Its weekly Embase search returns 46 hits. Screening finds 3 publications with identifiable patients: a single case of DRESS, a series of 4 hepatitis cases, and a review with no patient detail.

That gives 5 ICSRs, each with day zero at the screening date. The substance is on EMA's monitored list for the journal publishing the hepatitis series, so those EU cases come from EudraVigilance, while the DRESS case from a local journal is submitted by the company.

Where the answer stops holding

Search terms can miss misspelled or new brand names, and full texts behind paywalls may delay day zero assessment. Coverage of EMA's monitoring service changes, so the list must be checked regularly. GVP will be updated to reflect Commission Implementing Regulation (EU) 2025/1466, so details may change.

A strong answer covers

  • Weekly searches in widely used databases
  • Local journals in authorised countries
  • One case per identifiable patient, author as primary source
  • EMA medical literature monitoring scope
  • Documented search strategy

Common mistakes

  • Searching only the brand name and missing generic and synonym hits.
  • Starting day zero when the full text is finally obtained rather than at awareness.
  • Assuming EMA's service covers every journal and substance.