Literature Screening


Literature report is any adverse drug reactions reported in
  • Published abstracts or
  • Articles in medical/scientific journals
  • Unpublished manuscripts involving case reports
  • Important safety findings or clinical studies including posters, letters to the editors, and associated communication from scientific meetings.

Regulatory Guidance of EMA and FDA

According to the European Medicines Agency (EMA), marketing authorization holders (MAHs) are obligated to monitor scientific and medical publications in countries where they have marketing authorization, regardless of the commercial status of their products.
In the United States, the Food and Drug Administration (FDA) requires the submission of reports on serious and unexpected adverse drug reactions (ADRs) described in scientific literature for products with the same active ingredient as those marketed in the US, even if there are variations in excipients, dosage forms, strengths, routes of administration, and indications.
The “literature” section of the periodic benefit-risk evaluation report (PBRER) necessitates a summary of significant safety findings from published peer-reviewed scientific literature or unpublished manuscripts during the reporting period.
EMA guidelines also mandate the inclusion of relevant safety information for other active substances within the same class as the marketed drug. Therefore, any potentially significant event identified in the literature may be considered an emerging safety issue, requiring immediate analysis and, if necessary, corrective and preventive action.
Marketing authorization holders are expected to stay informed about possible publications through systematic literature reviews of widely used reference databases, such as Medline, Excerpta Medica or Embase, and Eudravigilance, at least once a week.
Each MAH should regularly screen global scientific literature using widely used systematic reviews or reference databases, adhering to local requirements or at least every two weeks.
Cases of ADRs reported in scientific and medical literature, including relevant abstracts from meetings and draft manuscripts, may qualify for expedited reporting. A regulatory reporting form with relevant medical information should be completed for each identifiable patient, citing the publication reference(s) as the source of the report. Additionally, the local regulatory authority may request a copy of the article to accompany the report. All company offices are encouraged to stay vigilant regarding publications in local journals and inform the company’s safety department when necessary.
The regulatory reporting timeframe begins as soon as the MAH becomes aware that the case meets the minimum criteria for reportability.
If the specific product source, brand, or trade name is not specified, the MAH should assume that it pertains to their product, while indicating in the report that the specific brand was not identified.
If multiple products are mentioned in an article, a report should only be submitted by the applicant whose product is suspected, as determined by the article’s author.

Regulatory Guidance of China NMPA

Per the China GVP1, MAH’s responsibility relative to ICSR generated from the literature is depicted as below:
Chapter IV Monitoring and Reporting Section 1 Collection of Information
Article 36 The holder shall conduct periodic screening on academic literatures, develop rational screening strategy and determine the frequency of such screening according to the safety characteristics of the product, etc., and the time range of the searches shall be continuous.
Chapter IV Monitoring and Reporting Section 3 Submission of Report
Article 50 For adverse drug reactions reported in the literature, if the suspected drug is the holder’s product, the reaction shall be reported as an individual adverse drug reaction. If it is uncertain whether it is the holder’s product, the reaction shall be analyzed in the periodic safety update report and may not be reported as an individual adverse drug reaction.

Processing of Confirmed ICSRs

  1. For literature reports of confirmed cases which can generate ICSRs, a full text of the citation is obtained and, if not in English, translated into English though it is not specified how/who does this or how long this takes).
  2. The article is reviewed and the number of valid ICSRs is determined, and seriousness/non-seriousness is noted.
  3. An ICSR is then created along with a case narrative for serious cases. No narrative is prepared for non-serious ICSRs.
  4. Causality assessment and relatedness also performed.
A regulatory reporting form with relevant medical information should be provided for each identifiable patient. The regulatory reporting time clock starts as soon as the MAH has knowledge that the case meets minimum criteria for reportability.
Reference: 1. China Good Pharmacovigilance Practice Announcement of the NMPA on the Publication of China Good Pharmacovigilance Practice (No. 65 of 2021)
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