Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 96

The federal regulations noted above describe what the FDA expects to receive from biopharmaceutical companies regarding the reporting of drug safety information. In all cases, sponsors are expected to be 100% compliant with regulations, i.e., submit complete reports on time and do follow-up with due diligence to get complete medically-relevant information:

Clinical trials — AEs reported to the IND

In 7 calendar days: deaths/life-threatening (at presentation), serious, unexpected, associated with the drug;

In 15 calendar days: serious, unexpected, associated with the drug;

For both 7- and 15-day reports: FDA requests that sponsors submit one ICSR to the “parent” IND rather than to all open INDs. (The “parent” IND is the open IND for the subject active substance that has the earliest filing date.) This is to avoid duplicate reports that could confound safety signal detection; and

In annual periodic reports: summary of all studies, tabular summary of the most serious and most frequent serious AEs, deaths, discontinuations due to AEs, and the 15-day reports submitted since the last aggregate report.

Marketed biopharmaceuticals — AEs reported to the NDA

In 15 calendar days: serious, unexpected. Note that all spontaneous reports are considered to be “associated with the drug”. The reasoning is that if the reporter did not believe there was at least some level of association (causality) with the drug, he or she would not have reported it. This comes from an earlier CIOMS recommendation.

In 15 calendar days: Reports from the medical literature that are serious and unexpected.

In the quarterly or annual periodic reports (PADERs) or PSURs: A narrative summary and analysis of the 15-day alert reports submitted since the last periodic report plus all other reports that are not serious and not unexpected. Foreign non-serious AEs do not have to be reported. In general, clinical trial AEs do not have to be reported to the NDA. Note that, currently, ICH E2C PSURs are not required by FDA and PADERs are required by regulations. FDA does accept PSURs with the PADER-specific appendices; the ICH PSUR (PBRER format) may be made obligatory at some point in the future.

Solicited reports: AEs that are received from customer engagement programs with the possibility of two-way communication, e.g., disease management programs, patient support programs, etc., should be reported as 15-day reports to the NDA if they are serious, unexpected, and associated with the drug. It is the latter causality assessment that differentiates solicited reports from spontaneous reports (FDA Guidance for Industry, August 1997).