Breaking Stereotypes of Local Literature Review

Under the requirements for the EU pharmacovigilance system, the Marketing Authorization Holders (MAH) must ensure the performance of medical literature monitoring in international and local sources.

While the international literature review is described quite detailed in GVP, local literature search remains hot topic in pharma industry because even though the requirement for MAHs to conduct local literature search came into force long time ago, there are still no clear guidelines with regards to this activity. In the whole GVP there are only few sections where this topic is mentioned and this leaves room for varying interpretations for MAHs, Competent Authorities, and Service Providers.

As a standard stereotype the local literature search typically begins with the Marketing Authorization approval, with no other factors usually considered at this stage. However, it is not true. Below are the considerations that companies should anticipate ensuring the most robust local literature screening process:

• Start date: it is commonly understood that the local literature search should begin once the Marketing Authorization is approved, as stated in the EU GVP (VI.B.1.1.2.). However, research conducted by Insuvia with National Competent Authorities has revealed that, in some cases, Local Authorities may have different expectations for scientific literature screening. For example, some authorities expect Marketing Authorization Holders to initiate local literature screening simultaneously with international literature screening, i.e., after the submission of the Marketing Authorization Application (MAA). Since the MAA submission is handled by the Regulatory Affairs division, maintaining regular communication and information exchange with RA colleagues is critical to ensure that PV staff receive the most up-to-date information on submitted dossiers.
• Database of local journals: as there is no EMA approved list of non-indexed sources in each country, and only few NCAs have it, Marketing Authorization Holders need to define and maintain the sources by themselves. This can be challenging due to language barrier and the large amount of literature sources in each country. To keep up with constant changes in local journals there should be efficient process in place to monitor the release of new publications and discontinuation of not relevant sources.
• Product commercial status: the requirement for literature searching is not dependent on a product market status. Literature searches should be conducted for all products, irrespective of commercial status. Here are a few reasons why:
  1. Regulatory compliance: ensuring your product complies with local regulations from the start can prevent costly delays and legal issues when you decide to market it.
  2. Risk management: identifying any potential safety concerns at early stage can help mitigate the risks and address them proactively before the product reaches the market.
  3. Market insights: local literature searches can provide valuable insights into the current market landscape, competitor activities, and tailor the product to meet local need

Key Highlights:

• Local literature monitoring remains in a grey zone, making it more complex than it appears.
• NOT always local literature review begins with MA approval.
• Depending on country specifics, local literature search shall be applied after the submission of MAA, even before the approval.
• Product commercial status is NOT the reason to omit local literature search.
• Local literature search is NOT “stand alone” activity – collaboration with other company departments and sharing insights are very valuable tools in ensuring regulatory compliance.
• Development of local journals database is NOT “one off” task – constant supervision is needed.