Guidance Breakdown: Electronic Submission of Expedited Safety Reports From IND-Exempt BA/BE Studies
New final FDA guidance mandates electronic submission of expedited serious adverse event reports for IND-exempt BA/BE studies, detailing technical specifications, submission methods, etc.
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On April 1st, the FDA published final guidance for the electronic submission of expedited serious adverse event reports from IND-exempt bioavailability (BA)/bioequivalence (BE) studies. This guidance is designed to facilitate and standardize the electronic reporting of adverse events, improving the efficiency and accuracy of data submission to the FDA Adverse Event Reporting System (FAERS). The document specifies the technical requirements and submission methods, including database-to-database transmissions and the Safety Reporting Portal (SRP) use.
“This guidance provides instructions for the electronic submission of expedited individual case safety reports (ICSRs) from investigational new drug (IND)-exempt bioavailability (BA)/bioequivalence (BE) studies conducted to support abbreviated new drug applications (ANDAs) to FDA Adverse Event Reporting System (FAERS). An ICSR captures information necessary to support the reporting of an adverse event related to an individual subject that is associated with the use of an FDA-regulated product. The electronic submission of the ICSRs from IND-exempt BA/BE studies is a voluntary option for submitting these required reports.”
The guidance sets out detailed procedures for the submission of individual case safety reports (ICSRs), providing clear instructions on the identification, classification, and reporting of adverse events. By establishing these requirements, the FDA aims to streamline the reporting process, enhance the monitoring of drug safety, and ensure compliance with regulatory obligations.
This guidance finalization marks a critical step towards optimizing pharmacovigilance practices and aligning them with international reporting standards. It underscores the importance of robust safety reporting mechanisms.
In case your time is short, here's a quick summary of its policy contents, along with our recommendations for action.
Who’s impacted by this guidance
The following entities must use the specified electronic methods for submitting ICSRs to ensure that all serious adverse events are promptly and accurately reported to the FDA.
Investigators: Those who conduct the clinical studies and are directly responsible for collecting and reporting data on adverse events.
Pharmaceutical Companies: Organizations that sponsor and oversee the BA/BE studies. They are responsible for ensuring compliance with FDA regulations regarding adverse event reporting.
Institutional Review Boards (IRBs) and Ethics Committees: These bodies oversee the ethical aspects of clinical studies to ensure that the rights and welfare of study participants are protected. They need to be aware of any serious adverse events that occur.
CROs: These organizations may manage clinical studies on behalf of pharmaceutical companies and thus must adhere to the reporting requirements outlined in the guidance.
ANDA Applicants: Manufacturers submitting ANDAs must include adverse event information from BA/BE studies as part of their application, irrespective of whether the study was conducted inside or outside the United States.
Introduction and background
The guidance outlines instructions for submitting expedited ICSRs electronically for IND-exempt BA/BE studies that support ANDAs. The guidance explains that BA and BE studies, which meet certain conditions for exemption under 21 CFR 320.31, do not require an IND and are not subject to IND safety reporting requirements. However, they are subject to safety reporting requirements under § 320.31(d)(3) specifically for persons conducting exempt BA or BE studies.
Electronic Submission of Expedited Serious Adverse Event Reports from IND-Exempt BA/BE Studies
Methods for Electronic ICSR Submission
Two methods for electronic submission are provided:
Database-to-Database Transmission (E2B): This allows direct submission of ICSRs in XML format via the Electronic Submissions Gateway (ESG), which processes these reports into the FAERS.
Safety Reporting Portal (SRP): For those without database-to-database transmission capability, ICSRs can be manually entered into a web-based form on the SRP, then uploaded to FAERS.
Identification of the ICSRs
The FDA has developed business rules for the system to ensure accurate identification and management of ICSRs within the FAERS. These rules are designed to:
Distinguish between premarket and postmarket reports: The rules ensure that ICSRs from IND studies (premarket) and those not requiring INDs (postmarket), like BA/BE studies, are correctly processed within their respective pathways.
Prevent Misrouting: By using these rules, the system can identify and reject premarket submissions if they are mistakenly sent to the postmarket pathway, ensuring that the submitter corrects such errors.
ICSR Attachments
Attachments to ICSRs are crucial for providing comprehensive details about the adverse event and can include:
Study Protocols: Detailed plan or methodology of the study in which the adverse event occurred.
Case Report Forms (CRFs): Documented forms that record information about each participant's study data, including adverse event details.
Medical Records: Relevant patient medical records that provide background and context to the adverse event.
Autopsy Reports: If applicable, autopsy reports that may provide critical insights into the cause of death linked to an adverse event.
Exceeding Character Limitations: In cases where the narrative of the adverse event is too long for the standard ICSR data fields, attachments can provide a full description without being constrained by character limits.
Initial and Follow-up ICSRs
For managing ICSRs effectively:
Unique Case Identification Number: When initially reported, each ICSR must be assigned a unique identification number. This number is essential for tracking and referencing the case throughout its lifecycle.