FDA Analyzes Premarket Review Times Under 510(k) In an analysis of premarket review procedures, t

FDA Analyzes Premarket Review Times Under 510(k)

In an analysis of premarket review procedures, the U.S. Food and Drug Administration (FDA) concluded that the overall review time for 510(k) submissions isincreasing primarily because of an increase in the number of review cycles and the amount of time it takes device manufacturers to respond to the FDA’s requests for additional information.

In response to recent studies sponsored by the medical device industry thatreported delays in the FDA’s review of premarket applications submitted under the 510(k) pathway, the FDA conducted its own analysis using Additional Information (AI) letters, which are sent when moreinformation is needed—each AI letter sent stops the clock on the review time andcreates a new cycle in the review process.

Two analyses were conducted by staff familiar with but not involved in thesampled submissions. In Cohort 1, 100 submissions were assessed for incoming submission quality. In Cohort 2, 134 submissions were assessed for the drivers of the increasing numbers of review cycles. A list of deficiencies and a sub-list of those related to poor quality were created. Deficiencies indicating poor quality were identified as: inadequate device description; discrepancies throughout submission; problems with indications for use; failure to follow or otherwise address current guidance documents or recognized standards; performance data not provided; and clinical data not provided. Letters also were examined to determine how often inappropriate information was requested by the FDA, such as data not permissible as a matter of federal law or FDA policy, orunnecessary data.

Results showed that 83 percent of the submissions in Cohort 1 and 82 percent of the submissions in Cohort 2 contained at least one quality deficiency. In Cohort 1, 52 percent of quality issues were related to device description; 24 percent failed to show a current guidance document; and 22 percent showed discrepancies throughout the submission related to indications for use or device description. In Cohort 2, 50 percent of quality issues were related to device description. Almost 60 percent of submissions failed to address current guidance documents. Cohort 2 included only submissions that contained at least two AI letters, which indicated a more problematic situation.

“Although these cohorts are unrelated, the distribution of deficiencies among them is strikingly similar,” the FDA report stated. “Problems with submissions quality are contributing to an overall increase in review times.”

Less than 20 percent of submissions in each cohort contained deficiencies that were not related to quality, but still would be addressed with an AI letter, and therefore, also would stop the review clock. The Cohort 2 analysis showed that second round AI letters were sent because the sponsor did not address requests made in the first round AI letter (66 percent); the sponsor’s response to the first round AI letter raised issues for the FDA (63 percent); or the FDA reviewer raised new questions that should have been raised in the first round (4 percent).

“In 93 percent of the submissions analyzed, the sponsor had either failed to address questions raised in the initial AI letter and/or provided information in response to the deficiencies that did not support a determination that the device was substantially equivalent and, therefore, FDA sent a second AI letter to give the sponsor a second opportunity to address these problems rather than determine that the device is not substantially equivalent,” the FDA report stated.

Inappropriate requests for information were made in 12 percent of the cases in Cohort 1 and 4 percent of the cases inCohort 2. These requests included data beyond that which had been asked for in the past and were not scientifically justifiable; data not consistently required; information inconsistent with current guidance; unnecessary additional testing; and information to support a standard government form specifically created to avoid the submission of the related underlying data as part of 510(k).

The FDA has drafted Standard Operating Procedures for Notice to Industryletters to help facilitate that goal. The FDA also is enhancing training for staff and the device industry to reduce inappropriate requests and help sponsors understand when they must submit data.

“It is our hope that taking actions toincrease submission quality and avoidinappropriate requests for additional information will prevent avoidable delays and reduce review times, which will, in turn, get safe and effective devices to market faster,”the report concluded.