Justification Memo for 83C Change Request 9-18-14

“Electronic Submission Gateway and the Safety Reporting Portal”

(OMB Control Number 0910-0645)

CHANGE REQUEST (83-C)

Date: September 18, 2014

FDA receives information regarding postmarketing adverse drug experiences from safety reports submitted to the agency. For nearly 35 years, FDA has received these postmarketing safety reports on paper. In recent years, many companies have voluntarily submitted these reports to the Agency in electronic format.

Data from both electronic and paper reports are entered into FDA’s Adverse Event Reporting System (FAERS) database. FAERS is a computerized information database designed to support FDA's postmarketing safety surveillance program for drug and biological products. The FAERS database is used to store and analyze data received in postmarketing safety reports. Safety reporting data submitted on paper must first be converted into an electronic format before being entered into AERS.

The June 10, 2014, final rule “Postmarketing Safety Reports for Human Drug and Biological Products; Electronic Submission Requirements,” requires the use of an electronic format for the submission of postmarketing safety reports, which is an important step toward improving the agency’s systems for collecting and analyzing these reports. The rule: (1) Eliminates the time and costs associated with submitting paper reports (for industry) and converting data from paper reports into electronic format for review and analysis (for the agency); (2) Expedites the agency’s access to safety information and provide data to the agency in a format that would support more efficient and comprehensive reviews; and (3) Enhances our ability to rapidly communicate information about suspected problems to health care providers, consumers, applicants, and sponsors within the United States and internationally in support of FDA’s public health mission.

FDA currently accepts all postmarketing individual case safety reports (ICSRs) in either a paper format or an electronic format. Sections 310.305(d), 314.80(f), and 600.80(f) authorize use of a paper FDA Form 3500A for reporting of single cases of adverse drug experiences for human drug and biological products. The regulations also permit use of the form introduced by the World Health Organization’s (WHO’s) Council for International Organizations of Medical Sciences (CIOMS) Working Group I for reporting single cases of foreign adverse drug experiences that are serious and unexpected (CIOMS I form).

Section 11.2(b)(2) currently provides that regulatory submissions may be voluntarily provided to the agency in electronic form if the submissions are identified by FDA in its electronic submissions public docket as submissions the agency will accept in electronic form. Postmarketing safety reports for drug and non-vaccine biological products have been identified in the docket as submissions the agency can accept in electronic format. If the reporter elects to file the safety report in electronic format rather than on paper, current §§ 310.305(d), 314.80(f), and 600.80(f) require that the ICSRs in the electronic report include the same information as the paper FDA Form 3500A or CIOMS I form. Accordingly, under current regulations, an ICSR submission can take the form of a paper FDA Form 3500A, a paper CIOMS I form, or comparable information submitted in electronic format. Each of these is a different method of transmitting to FDA the same basic elements of the ICSR, whether on paper or in electronic format. ICSR attachments and the descriptive information portions of periodic safety reports may also be submitted electronically.

Adverse experience reporting for vaccine products may be submitted to the Vaccine Adverse Event Reporting System (VAERS). VAERS is co-managed by the Center for Biologics Evaluation and Research and the Centers for Disease Control and Prevention (CDC). Vaccine manufacturers may submit postmarketing ICSRs for vaccines using the FDA eSubmitter system or through the FDA Electronic Submissions Gateway. Reports from healthcare providers and patients may be submitted to VAERS using a secure web-based system. Each of these is a different method of transmitting to CDC/FDA the same basic elements of the ICSR.

FDA is requiring that all postmarketing safety reports for human drugs and biological products be submitted in electronic format. Requiring submission of these reports in electronic format will expedite access to safety information and facilitate international harmonization and exchange of this information. This, in turn, will lead to more efficient reviews of safety data and enhance our ability to rapidly disseminate safety information to health care providers, consumers, applicants, sponsors, and other regulatory authorities in support of FDA’s public health mission. In addition, the agency will recognize a significant cost savings by converting the safety reporting system from a paper submission process to a fully electronic submission system that would increase the accuracy of information and reduce the need for manual data entry. The final rule will expedite the identification of emerging safety problems, improve the speed and efficiency of industry and agency operations, and further the international harmonization of safety reporting.

The final rule amends FDA's postmarketing safety reporting regulations for human drug and biological products under parts 310, 314, and 600, and adds part 329, to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. Under §§ 310.305, 314.80, 314.98, and 600.80, manufacturers, packers, and distributors, and applicants with approved NDAs, ANDAs, and BLAs and those that market prescription drugs for human use without an approved application must submit postmarketing safety reports to the Agency. Section 760 of the FD&C Act requires manufacturers, packers, or distributors whose name appears on the label of nonprescription human drug products marketed without an approved application to report serious adverse events associated with their products. Under § 600.81, applicants with approved BLAs must submit biological lot distribution reports to the Agency. In this rule, FDA is requiring that these postmarketing reports be submitted to the Agency in an electronic format that FDA can process, review, and archive. The final rule also states that FDA will issue guidance on how to provide the electronic submissions (e.g., method of transmission, media, file formats, preparation and organization of files). This rule does not change the content of these postmarketing reports. It only requires that they be submitted in an electronic format.

We currently have OMB approval for submission of postmarketing safety reports to FDA under parts 310, 314, and 600. The information collection for part 310 and part 314 is approved under OMB control numbers 0910-0291 (Form FDA 3500A) and 0910-0230. The information collection for part 600 is approved under OMB control numbers 0910-0291 (Form 3500A) and 0910-0308. The burdens currently estimated under parts 310, 314, and 600, for submission of postmarketing safety reports to FDA for human drugs and biological products do not change as a result of this final rule. This is because: (1) Current burden estimates associated with these regulatory requirements have taken into account voluntary submission of these reports in an electronic format and those applicants, manufacturers, packers, and distributors that already submit these reports in an electronic format would have no new reporting burdens and (2) new burdens for establishing the means for submitting postmarketing safety reports in electronic form to comply with this final rule, including obtaining an electronic certificate, revising SOPs, and becoming familiar with the system, would be negated by the savings in burden from not having to print out the report and mail it to FDA. These assumptions also apply to applicants submitting biological lot distribution reports under § 600.81. OMB has approved the burden associated with submissions required by section 760 of the FD&C Act under OMB control number 0910-0636.

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