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Regulatory Focus™ > News Articles > FDA Guidance: So you've Royally Messed up the Submission of your ICSR - Now What?

FDA Guidance: So you've Royally Messed up the Submission of your ICSR - Now What?

Posted 24 July 2013 | By Alexander Gaffney, RAC

A new guidance document released by the US Food and Drug Administration (FDA) is intended to clarify the process by which postmarket non-expedited individual case safety reports (ICSRs) on adverse drug experiences are reported by the agency in electronic format.


The final guidance, Providing Submissions in Electronic Format -Postmarket Non-Expedited ICSRs Technical Questions and Answers, was released by FDA on 24 July 2013 after an earlier Federal Register notice foreshadowed its release.

Per FDA regulations under 21 CFR 314.80(c)(2) and 600.80(c)(2), manufacturers of pharmaceutical and biological products are required to submit reports of adverse drug experiences that occur after regulatory approval. Those reports are divided into two primary types: expedited and non-expedited reports. Expedited reports must generally be reported to FDA within 15 days, and relate to adverse drug experiences that are serious, life-threatening or deadly.

Non-expedited reports, by contrast, encompass all adverse events that are less serious, and are generally those that would make their way into a periodic adverse drug experience report (PADER), a periodic adverse experience report (PAER), a periodic safety update report (PSUR) or a periodic benefit-risk evaluation report (PBRER)-all reporting forms used to inform regulators.

The reports are required by FDA at varying intervals, depending primarily on how new a drug product is to the market. Generally, newly approved drugs must report once per quarter for the first three years, and then annually thereafter.

Currently, the reports may be submitted to FDA either in paper form or in electronic form. In recent years, increasing numbers of companies have been shifting to electronic submissions, which are built on an extensive markup language (XML) backbone, as directed by the International Conference on Harmonisation's (ICH) standards for database transmission.

"When submitted in this compatible electronic format, non-expedited ICSRs can be downloaded into the FDA Adverse Event Reporting System (FAERS) database through the Electronic Submission Gateway," the agency explained in the guidance.

So you've Messed Up… Now What?

The problem, FDA continues, is that some companies are meeting their duty to submit ICSRs to the agency in a timely manner, but are submitting the data in a non-XML file format that renders it unable to be processed into the FAERS database, making it effectively useless for its given purpose.

The guidance, then, is intended as a sort of "so you've messed up horribly-now what?" document that explains the remediation steps companies can take to rectify the situation.

The first of those steps involves sending a general correspondence letter to FDA to inform the agency about previous submissions, including the data of those submissions, the products involved in the reports and the number of ICSRs contained in the report on a product-by-product basis.

FDA will then reportedly contact each firm to verify the need for resubmission of the ICSRs, according to the guidance.

"In most cases, FDA will instruct firms that previously submitted non-expedited ICSRs of serious adverse experiences in the PDF format to resubmit these ICSRs in the XML format, or in paper form, if firms do not have XML-format capability," the agency explained.

The agency also directs companies to refer to information on its website on how to submit ICSRs in electronic format, and notes that companies can refer to the ICH E2B standard (now in its third revision). However, "Submission of ICSRs to the electronic common technical document (eCTD) is not acceptable because these ICSRs cannot be processed into the FAERS database," FDA cautioned.

FDA Guidance on ICSR Submissions

Federal Register Notice

Tags: guidance

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