Optimizing Medical Devices' Regulatory Submissions

By Thomas Varricchione, Senior Vice President, Clinical & Regulatory Affairs

The FDA’s Center for Devices and Radiological Health recently published their “Analysis of Premarket Review Times under the 510(k) Program” in which they attribute the recent increase in total review time “primarily due to companies taking more time to respond to requests for additional information.” This analysis was prompted by recent industry-sponsored reports, which attribute problems with the 510(k) program to lack of predictability, disruptions, and delays due to staffing turnover and inconsistency in reviews.

Even more damning in the FDA’s analysis is their determination that the underlying reason for the increase in review time and number of review cycles “was the poor quality of submissions — those that did not contain required information to complete a review — from companies and companies’ failure to fully address these quality issues when raised . . .” The following problems were cited by the FDA as frequent culprits in the quality of submissions:
While there is probably room for debate on whether the FDA’s findings are entirely accurate, there’s no doubt that the FDA believes much of the responsibility lies with industry. There may not be one solution for the problems they cite, but it is critical that medical device manufacturers do everything possible to make submissions for their review as clear, free of discrepancies, and complete as possible.

• Inadequate device description
• Discrepancies in the device description or indication(s) for use
• Failure to follow or address relevant standards or guidance
• Problems with the indication for use
• Performance data missing or inadequate

Here are some pointers:
Since there’s so much about the premarket review process that the submitter can’t control, the last thing a submission should do is complicate the process by being poorly structured, unclear, or incomplete. Focus on the process steps that the submitter can control.

• Clarity: Make the submission as informative as possible with clear, concise descriptions enriched with diagrams, drawings, and photographs. FDA reviewers have no way of understanding a specific product as well as the submitter does; all they have is the information provided. Part of the submitter’s responsibility is to educate the reviewer about the product. A high-quality submission often resembles a tutorial in places, and it is a case where the success of the review is tied to the understanding of the reviewer.
• Consistency: Carefully crosscheck instances where the same information is provided in multiple places. Submissions that state critical product functions or indications for use differently in various places (e.g. the device description section, the Instructions for Use, and/or the Indications for Use Statement) place doubt in a reviewer’s mind about the overall accuracy and completeness of the submission. This step can shave significant time off an FDA review.
• Completeness: Know the standards and guidances that apply to a given product type. This is critical to providing the FDA with the information and performance data they need to complete their review. Given the pace of changes to recognized standards and issuance of new guidance, it is definitely challenging to stay current, but identifying the most recent version of relevant documents is a necessary and productive step in the development process. Learning at the time of review from the FDA that a relevant standard or guidance was not applied during development, or that an outdated version was used, is the worst time to find that out. Unfortunately, required changes to a product at that stage cause huge expense and disruption.
• Knowing FDA’s Expectations: Engage in a pre-submission dialogue with FDA staff to begin the process of familiarizing them with your product and gauging their response to proposed protocols for developing pre-clinical and/or clinical performance data. This can be enormously productive: It is an era of major innovation and technological change in the medical product arena. If the product under development utilizes a new and unfamiliar technology or if it introduces a novel way to apply an older technology, oftentimes it won’t be clear from studying standards and guidances what sort and how much performance data the FDA will require to demonstrate that the product is safe and effective.