Regulatory Literature Searches for Safety Information
Monitoring the scientific literature is critical component in understanding the safety profile of medicines and medical devices. It is a requirement mandated by regulatory authorities globally, and missing important safety information from the literature can lead to delayed and unsuccessful submissions and expensive inspection findings.
Regulatory literature searches are inherently complex, and licenses for literature databases can contribute substantial costs to the process.
Yet, there is a more cost-effective solution available today. In this article, we explore regulatory requirements for literature monitoring and how biologit offers an affordable and cutting-edge scientific literature database ready for any regulatory need.
When literature monitoring is not performed per regulatory guidance, or left too late, it can lead to missed safety information, submission failures, inspection failures and approval delays causing significant re-work.
Literature Searching in Pharmacovigilance and Materiovigilance
Regulatory authorities expect that literature searches be performed on databases of global reach, using broad searches that minimize the risk of safety events being missed, and that the process is traceable and periodically reviewed. As examples, lets take a look at the specific requirements issued by the FDA and EMA:
The FDA sets out industry guidance for monitoring and reporting of safety events for drug and biological products under clinical development in the document Sponsor Responsibilities - Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies, stating:
"sponsor-investigators are responsible for evaluating all safety information available to them, including data from reports in the scientific literature […]."
In Europe, the EMA sets out requirements for pharmacovigilance literature monitoring in the Guidelines on good pharmacovigilance practice - volume VI:
"[…] Literature searches should be conducted for all products with a marketing authorisation, irrespective of commercial status. It would therefore be expected that literature searching would start on submission of a marketing authorisation application and continue while the authorisation is active."
Medical Devices (Materiovigilance)
For medical devices the EU MDR legislation (MEDDEV 2.7.1/4) mandates literature searches for the majority of regulatory submissions and device classes. Clinical Evaluation Reports (CER) guidance for instance state that:
“Literature searching is used to identify data not held by the manufacturer that are needed for the clinical evaluation”
Meeting this requirement starts with establishing where to search by determining a suitable database (or databases) that meet your regulatory requirements.
Choosing a Database for Literature Searches
Regulatory guidance expects each marketing authorisation holder and device manufacturers to select and justify the most adequate literature databases for their products. While not mandating specific databases, existing guidance does provides useful general requirements:
Worldwide guidance emphasises broad coverage of searches, recommending that more than one database be considered:
📖 EU MDR guidance indicates “additional databases may need to be used to ensure adequate coverage of devices and therapies in use in Europe, to identify relevant clinical trials and publications of user experience”
📖 EMA GVP guidelines for global literature monitoring suggests databases that “have broad medical subject coverage. […] It is best practice to have selected one or more databases appropriate to a specific product”
📖 Finally, FDA guidance expects that “Serious and unexpected adverse experiences from all sources, whether domestic or foreign, must be submitted to the FDA. Possible sources include, for example, scientific literature, postmarketing studies, or commercial marketing experience.”
Safety monitoring requires broad searches capturing not only product brand but compounds, similar products etc. Additional safety searches may be required to focus on certain conditions, special situations, drug classes or similar product/devices in the market.
Translating those requirements into a query string requires a flexible query, ideally
consistently searching all required sources at once dispensing with having to write and validate the same query on different platforms. This can save many hours of effort in retrieving suitable results.
As with any regulated activity, full traceability of actions is a mandatory requirement. Computer systems applied to FDA regulated activities must be compliant with CFR21 Part 11 requirements; in Europe EU Annex 11 Guidance for Computerized Systems covers similar requirements.
In particular traceability requirements for literature searches extend to:
🔎 When was the search run and how many results were retrieved?
🔎 What was the specific query string executed?
🔎 When were assessments carried out (and by who)?
🔎 When were full text or translations obtained?
Are Proprietary Databases Like Embase or EBSCO Required by the EMA?
The short answer: no! It is important to use sources that are fit for purpose and well justified, as discussed in the previous section. However the use of expensive proprietary databases is not required or recommended by the EMA.
Biologit sought to clarify this with the EMA. We give an outline of the response below.
Referring to this section of the regulation:
“Marketing authorisation holders are therefore expected to maintain awareness of possible publications through a systematic literature review of widely used reference databases (e.g. Medline, Excerpta Medica or Embase) no less frequently than once a week.”
The EMA response:
"It is clear from the use of “e.g.” (“exempli gratia” or for example) in the citation above that the literature reference databases mentioned in the GVP Guideline Module VI are merely examples. […] it is immediately apparent from the wording used that these examples are not the only means of fulfilling their obligations in connection with monitoring the medical literature."
In relation to this section of the guidance:
“Medline, Embase and Excerpta Medica are often used for the purpose of identifying ICSRs. These databases have broad medical subject coverage. Other recognised appropriate systems may be used.[…].”
The EMA response again clarifies these as merely examples:
“It follows that marketing authorisation holders are free to use any “recognised appropriate systems” for their activities in connection with medical literature monitoring.”
There is thus no regulatory requirement for "lock in" with expensive proprietary database licenses, and thankfully a cost effective, ready to use solution for compliant literature searches is available today.
Compliant Literature Searches with biologit
Meeting regulatory challenges for your literature searches in pharmacovigilance and medical devices (materiovigilance) requires a comprehensive database and seamless integration of results into auditable assessment workflows.
biologit MLM-AI is a complete platform for completing regulated literature monitoring activities effectively and in full compliance. It is designed from the ground up with the needs of safety teams. To learn more get in touch and book a demo today.
biologit Database: Scientific Literature Database for your Regulatory Searches
The biologit Database is a comprehensive scientific literature resource with global and regional reach: updated daily, hosting over 50 million citations and 110,000 journals and fully integrated into the biologit platform. Broad, high quality literature searches are a few clicks away and results delivered for assessment free of duplicates.
Easy to use SaaS + Fully Configurable Workflows = Productive Teams
From a simple to use web enabled interface, assessments are easily completed in a fully auditable environment. A flexible workflow designed for safety monitoring teams supports any literature screening process, and unique AI-powered automation features ensure productive workflows for busy teams, delivering up to 70% efficiency gains compared to manual processes.
Compliance as Standard
biologit MLM-AI Platform is a fully validated and compliant platform built for strict CFR-11 traceability and security requirements. Extensive audit ready features including activity logging, reporting and fine-grained access controls.