AdvaMed, Device Companies Claim FDA's 510(k) Pre-Review Guidance Lacks Objectivity

Several prominent members of the medical device industry, including its largest trade group, have voiced their concerns about a new guidance document released by the US Food and Drug Administration (FDA) that would consolidate and expand the agency's pre-review policies for some medical device applications submitted through the 510(k) pathway.

The guidance, Refuse to Accept (RTA) Policy for 510(k)s, is intended to make it easier for FDA to filter out inadequate submissions by updating two existing guidances and allowing it to use a checklist of specific criteria to refuse to accept 510(k) applications.

"In order to enhance the consistency of our acceptance decisions and to help submitters better understand the types of information FDA needs to conduct a substantive review, this guidance, including the checklists included in the appendices, clarifies the necessary elements and contents of a complete 510(k) submission," explained FDA.

510(k) submissions are used to show a medical device is substantially equivalent to an already-approved medical device under the theory that if the prior device has been shown to be safe and effective, a similar device should typically be as well.

Is FDA's Guidance Objective?

Though FDA's guidance contends the pre-review assessment is not intended to review the products-just assess whether it has all required components and has been submitted correctly-the Advanced Medical Technology Association (AdvaMed) and manufacturers Zimmer, Inc and Abbott Laboratories both took issue with this assessment.

"Despite these very clear and concise explanations of the purpose of the acceptance review stated in the draft guidance, some items in the Acceptance Checklists require responses that could only be provided if a substantive review has been conducted," wrote Ruey Dempsey, AdvaMed's associate vice president for Technology and Regulatory Affairs in a 27 September 2012 letter to FDA.

A letter on behalf of Abbott Laboratories written by April Veoukas, director of Regulatory Affairs, made a similar observation. While Veoukas said the company applauded FDA for the development of the checklist and agreed many of its elements would "facilitate an administrative review," she said other elements of the checklist, "Are more subjective and begin to cross into a substantive review."

Zimmer's general comments were more succinct, noting only "specific concerns about the level of detail in the checklists," but those concerns were shared by both Abbott and AdvaMed as well.

Potentially Time-Consuming Pre-Review

One of the most prominent examples cited by the companies referred to Item G, a checklist item intended to assess whether the storage conditions of a product affect its safety or efficacy.

"It would be very difficult for the reviewer conducting the acceptance assessment to determine if the device could be adversely affected by the storage conditions," argued AdvaMed's Dempsey. Zimmer's own assessment also noted problems, albeit different ones than AdvaMed. Zimmer recommended that some metal implant products and other products should be exempted from the guidance so long as they meet sterile packaging validation requirements, such as those established in a prior device submission being used as the standard for the 510(k) submission.

AdvaMed's letter makes clear it believes a lower bar for acceptance criteria should be used. "The acceptance review should determine that the required elements of a 510(k) are present, that they are legible and provided in English. It should verify that the submission is organized in a manner that allows efficient substantive review."

"It is critical that FDA limit its acceptance review to prescreening of 510(k) submissions, that is, to determining whether an element is present and not whether it is substantially acceptable," concluded AdvaMed.

Abbott, meanwhile, said it believes the checklist could be beneficial with some tweaks to ensure it promotes a, "More objective and administrative focus," and both its letter and Zimmer's each include more than a dozen mostly minor recommendations.