Last week's blog post introduced our new pharmacovigilance "best practices" series that we have put forward for clinical and early stage biopharma companies. This week we discuss Best Practice #1: Understand what is reportable and know how reports are submitted to FDA.
For approved drugs, manufacturers are required to submit to FDA an individual case safety report (ICSR) for any adverse event that is reported to them, regardless of causality. In its evaluation of the event, the manufacturer must decide whether the event was serious and unexpected, serious and expected, or non-serious. If the event was serious and unexpected, the manufacturer must file the report with FDA within 15-days. All other adverse event reports may be filed periodically (quarterly for the first three years on market and annually thereafter).
The process is quite different for drugs involved in clinical trials that have not been approved for marketing by FDA. Investigators involved in the clinical trials for a development stage drug report adverse events to the study sponsor (usually the biopharma company that will become the manufacturer if the drug is approved). It is up to the sponsor to determine seriousness, expectedness, and causality. If the sponsor determines that the adverse event is serious, unexpected, and that there is a reasonable possibility that the event was caused by the drug, they must submit a case report to FDA that is attached to the drug’s investigational new drug (IND) application. Like with an approved drug, such a case report is required to be filed within 15-days.
Beyond the reporting requirement differences, how FDA actually receives adverse event reports is different between approved and clinical stage drugs as well.
All adverse event reports for approved drugs are required to be submitted by a manufacturer to FAERS electronically, specifically using the ICH E2B XML format that replicates form FDA 3500A. This database-to-database connection reduced the burden for manufactures of having to file a PDF electronic common technical document (eCTD) of form 3500A and likewise reduces the burden of FDA of having to review the ICSRs manually.
The submission process for adverse event reports on clinical stage drugs is still manual, with study sponsors submitting PDFs of the form FDA 3500A. FDA is in the process of transitioning to the use of electronic submissions for clinical stage drugs, but are not there yet. FDA published timelines that specify the goal to complete testing of electronic submissions in September 2019, and begin voluntary submissions in October 2019.
Both the criteria and the submission process in how adverse events are reported for clinical stage and approved drugs are important to understand. They dictate how standard operating procedures (SOPs) are established and how software is used to simplify SOP workflow.
Can't wait for Best Practice #2? Download the white paper, Pharmacovigilance Best Practices for Clinical and Early Post-Approval Biopharma.
Interested in signal detection best practices? Read Pharmacovigilance Signal Detection: A Complete Guide.