A new draft guidance document published by the US Food and Drug Administration (FDA) is intended to assist sponsors in the application of electronic regulatory submissions for products regulated by the Center for Drug Evaluation and Research (CDER), part of an ongoing series of guidances meant to move the industry away from paper-based submissions.

CDER regulates nearly all pharmaceutical products, including branded and biologic medicines, as well as many biological products and some combination products, depending on their primary mechanism of action.

For a novel product, usually submitted in the form of either a new drug application (NDA) or a biologics licensing application (BLA), the center requires the submission of clinical data in order to show that it is both safe and efficacious before considering it for approval.

Background

The point of the guidance, Providing Submissions in Electronic Format - Summary Level Clinical Site Data for CDER's Inspection Planning, "is to assist applicants in the submission of a clinical dataset that describes and summarizes the characteristics and outcomes of clinical investigations at the level of the individual study site (summary level clinical site data)," FDA explained.

That data, in turn, is intended to facilitate CDER's ability to take what regulators called a "risk-based approach" for conducting on-site inspections, which FDA says is necessary to evaluate the integrity of data submitted in support of an NDA or BLA. Inspected entities might include the institutional review board (IRB), the clinical investigation site, the contract research organization (CRO), the sponsor or the clinical investigators.

While this responsibility is not new, FDA said its increasingly tight deadlines under the new Prescription Drug User Fee Act (PDUFA) reauthorization mean that in order for it to meet its review performance goals, it must accomplish its duties to inspect even faster. "To facilitate timely selection of inspection sites, CDER must have sufficient data from the sponsor to identify which sites will provide the necessary information for the review of the application," FDA explained.

The present format of these data, FDA continued, is inefficient in that it presents the data at the subject, rather than site, level. "CDER has determined that to plan efficiently for clinical site inspections and to meet the PDUFA goal dates for marketing applications, CDER prefers to receive summary level clinical site data."

These data are typically submitted to CDER during the filing determination and review planning phases.

The New System

CDER said that it has already experimented with the submission of such data in a pilot program, and that the use of summary level clinical data has facilitated a "more efficient site selection" for inspections.

Under the new system, CDER said it "anticipates that site inspections will be conducted earlier in the review cycle," allowing for a faster and more efficient review by FDA, as well as more time and opportunities for sponsors to address regulatory issues earlier in the review process.

So what should the clinical data application include?

"A single summary level clinical site dataset should contain data from all major (e.g., pivotal) studies used to support safety and efficacy in the application, including studies with different treatment indications," FDA explains in the draft guidance. "For each major study used to support safety and efficacy, data should be submitted by clinical site and treatment arm for the intent-to-treat (ITT) population.  For clinical investigator sites involved in multiple studies in support of an application, applicants should provide the data independently for each study within the dataset."

"When in doubt about what constitutes a 'major' study, applicants should consult the relevant review division," FDA concluded. Regulators said sponsors should refer to a number of other guidance documents for additional requirements related to the submission of clinical data.