Data obtained from the medical and scientific literature is a key aspect of monitoring the safety profile and risk-benefit balance of medicines, as it can help identify new safety signals or safety issues. Literature searches form an important part of pharmacovigilance for Sponsors or Market Authorisation Holders (MAHs) and are also a regulatory requirement in many countries.

Regulatory requirements for approved medicines

In Australia, the Therapeutic Goods Administration (TGA) requires that all Sponsors of registered medicines and listed medicines on the Australian Register of Therapeutic Goods (ARTG) perform regular, at least weekly, global and local literature reviews. Any identified serious adverse drug reactions (ADRs) occurring in Australia, whether expected or unexpected must be reported to the TGA within 15 calendar days from initial receipt, where Day 0 is the date when the Sponsor becomes aware of a publication containing the four minimum data elements for a valid report.

The minimum 4 data elements are:

1. one or more identifiable reporters (the primary source), such as their qualification, name, initials, address or contact details (for follow-up).
2. an identifiable patient, such as their initials, gender, patient identification number, date of birth, age or age group.
3. one or more suspected medicines.
4. one or more suspected reactions.

Similarly, regulatory authorities in other countries require regular literature searches. The US Food and Drug Administration (FDA) requires reporting of serious, unexpected ADRs within 15 days. The European Medicines Agency (EMA) requires all serious ADRs (expected and unexpected) occurring worldwide to be reported within 15 days and all non-serious ADRs occurring within the European Union (EU) to be reported within 90 days.

Below are links to the regulatory guidelines, which include details on literature reviews:

• TGA Pharmacovigilance responsibilities of medicine sponsors: Australian recommendations and requirements
• FDA Draft Guidance for Industry: Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines
• EMA Guideline on good pharmacovigilance practices (GVP) Module VI: Collection, management and submission of reports of suspected adverse reactions to medicinal products

Literature search strategy

An appropriate search strategy is required to ensure that all relevant articles are retrieved for regulatory purposes, while not obtaining too many articles that are unrelated to pharmacovigilance.

Consideration should be given to the following:

• Sources of literature to be used, e.g. large (indexed) reference databases, such as Embase, Medline, and Pubmed, as well as local (non-indexed) journals specific for the marketed product in that country.
• Search terms, e.g. the brand name versus the generic name for a product
• Boolean operators (“AND”, “OR”, and “NOT”) and search syntax (e.g. wild cards and proximity operators) can broaden or narrow a search
• Search filters, e.g. date restrictions
• Medical review of the list of returned articles.

Datapharm Australia, an experienced CRO, can help you with designing the optimal
literature search strategy for your products, as well as conduct literature reviews of your
products on your behalf.