By: Mark Crawford
Medical device manufacturers (MDMs) know all too well how the FDA 510(k) review process of premarket applications for devices can seem to take forever. Although it’s easy to blame the FDA, there is a lot MDMs can do to expedite the process.
According to a new FDA guidance, total review time—the time it takes FDA to review an application and for companies to respond to the FDA’s questions—has increased, primarily due to companies taking more time to respond to requests for additional information. In addition, the number of Additional Information (AI) letters per submission the FDA sends out (“cycles”) has also increased.
After analyzing several hundred AI letters, the FDA determined the main reason for the increase in AI letters and cycles was the poor quality of submissions (usually incomplete information). Interestingly, this was the same cause for follow-up AI letters. The FDA’s analysis indicated that about 85% of all submissions contained deficiencies related to quality that triggered AI letters and follow-up letters.
If that wasn’t enough, about half of the remaining 15% of submissions that weren’t sunk by quality issues had other deficiencies, such as not enough information on the device description or inconsistent descriptions.
The FDA’s second AI letter was most often sent because the applicant failed to fully provide what was asked for in the first AI letter, and/or provided a response that raised new questions, such as testing results that identified a new safety risk or changing the indication for which the device is intended to be used.
Even though the FDA can easily trip up the process by itself (such as asking for new information or wrong information), there is enough evidence to show that many of the submissions are simply lacking the basics (if these were term papers the teacher would send them back).
The FDA defines a poor quality submission as having at least one of the following deficiency categories:
- Inadequate device description
- Discrepancies throughout submission (most often related to description or indications for use)
- Unclear indications for use statement
- Failure to follow or otherwise address current guidance document(s) or recognized standards
- Missing performance testing
- Missing clinical data
- The most common reasons for second-round AI letters are:
- Information submitted did not address all deficiencies completely
- Information submitted did not support labeling claims
- Test results submitted in response to first AI letter indicated problems with device design or function
- Testing was not performed correctly
- Justification for omission of response to first AI letter raised additional questions or was insufficient
- Information submitted to address deficiencies, but corresponding changes to update the 510(K) summary, labeling, or other aspects of submission were still needed
- Predicates used were not suitable
- Sponsor did not agree with request in first AI letter
- Reviewer unable to determine device design or new issues regarding device design raised by response to first AI letter
- The sponsor’s response to the first round AI letter raised issues for follow-up by FDA
- The FDA reviewer raised new questions that should have been raised previously
The FDA should be commended for analyzing hundreds of these letters. The results are revealing. The key mistakes that companies make are clearly identified. The best part is that they are easy to fix—personnel need to take more time to analyze the submission and be certain all the required information is supplied and consistent. Even though the FDA can take some blame for the slowdown, it’s mostly related to sloppy submissions that result from miscommunication or lack of time for overworked staff.
The first step is learning FDA requirements for its submission processes. A good way to do this is with a software program that provides complete lifecycle management for regulatory submissions. For example, whether managing NDAs, ANDAs, MAAs, INDs, BLAs, PMAs, or 510(k)s and other submissions, Pilgrim’s “Regulatory Submissions” solution provides all the elements needed for global electronic submissions needs, including eCTD or non-eCTD electronic submission (NEES); it is also valuable for helping global organizations prepare for the global mandates by regulatory agencies.
Knowing something is one thing; doing it is something else. As a final check, find employees who have a good eye for detail and good writing skills, educate them the submission process, and turn them into final reviewers/proofreaders to find mistakes and inconsistencies. Or hire a third-party consultant to review the submission before submitting it. Either way, cleaning up the final copy should eliminate those annoying AI letters and save months of backtracking and rewriting during the 510(k) process.
To read the complete FDA guidance, visit http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm263385.htm.