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Name of Guidance
Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Postmarketing Individual Case Safety Reports

Status of Guidance
Draft guidance

Date of Guidance
June 10, 2008

Link to the Guidance
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072369.pdf

Target audience
Individuals charged with making postmarketing individual case safety reports to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA).

Laws and Regulations Referenced
21 CFR 314.98 Abbreviated new drug applications (ANDA)
21 CFR 310.305 prescription drug products marketed for human use without an approved new drug application or ANDA
21 CFR 600.80 biological products marketed for human use with biologic license applications and submission tracking numbers
21 CFR 1271.350(a) section 361 human cells, tissues, and cellular and tissue-based products
21 U.S.C. 379aa section 760 nonprescription human drug products marketed without an approved application

Summary and Rationale
Since 1997 the FDA has encouraged the use of electronic submissions for regulatory documents. Over the years, the agency has issued several guidances regarding premarketing and postmarketing submissions. These submissions become part of the the FDA’s Adverse Event Reporting System database.

The rationale for this draft guidance is to simplify FDA guidance for industry by consolidating 2 existing draft guidances. The draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Postmarketing Individual Case Safety Reports supersedes and consolidates draft guidances Providing Regulatory Submissions in Electronic Format – Postmarketing Expedited Safety Reports issued in May 2001 and Providing Regulatory Submissions in Electronic Format – Postmarketing Periodic Adverse Drug Experience Reports issued in June 2003.

This guidance applies to submissions of postmarketing individual case safety reports (ICSRs) of adverse events related to drugs, biologics, therapeutic vaccines, human cells, tissues, and cellular and tissue-based products that have been approved under a new drug application, abbreviated drug application, or a biologic license application, as well as nonprescription drugs marketed without FDA approval. The draft guidance explains how to submit an electronic ICSR and any attachments, which may be electronic or paper documents. It also explains when and how a report receipt will be issued and what to do if the FDA’s Electronic Submission Gateway is temporarily unavailable.

Resulting Recommendations
1. Each adverse events experienced by a patient should be reported to the CDER as an invidudual case report. Any relevant documents should be submitted separately as attachments. This means that if a report has attachments, 2 submissions should be made: 1 for the report and 1 for the attachments. The information required in a report can be found on FDA form 3500A.

2. Each report should have its own identification number that would allow the CDER to match follow-up reports with the original report. All reports with the same identification number will be linked in the adverse event database. If the initial report is an electronic submission and follow-up reports are made on paper, the paper reports should have the same identification number as the original report. If the identification number is the manufacturer’s control number, follow-up reports should use that number as well.

3. Data elements and electronic transport format can be found in the FDA guidance document, Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachements.

4. Before submitting your first electronic ICSR, contact the FDA’s Adverse Event Reporting System coordinator by e-mail in order to send a test file. This only needs to be done before the first submission.

5. Electronic ICSRs should be sent through the FDA’s Electronic Submission Gateway because it’s the most efficient way for the CDER to process submissions. The ICSR should be sent first, followed by any attachments in subsequent dispatches. When the electronic gateway recognizes the message, the gateway will send a receipt, which will serve as the FDA receipt date of the report and its attachments.

6. If you do not receive a receipt of a submission within 24 hours, check the Web site (www.fda.gov/esg/default.htm) to see if the system is temporarily unavailable. If the system is available, contact the system coordinator by e-mail. If the system is down and you decide to send the report and attachments on paper, do not resend the report later as an electronic submission. For paper submissions, the date the paper documents arrive at CDER will be the FDA receipt date.

Impact
Individuals who submit ICSRs electronically should have good working knowledge of the format for submission as well as the protocols for sending the submissions electronically. They will need to be familiar with the guidance Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachments in order to include all the needed information in the proper format. Once the electronic submission is prepared, the submitter should have good knowledge of how to use the Electronic Submission Gateway, how to create a identification number for the case, and what to do if the electronic gateway is not working. In order to achieve this, drug firms, research institutions, hospitals, investigative sites, and contract research organizations should have appropriate training courses.