PMA Denials: Why so Few?

Regulatory NewsRegulatory News | 15 November 2018 |  By 

In the pharmaceutical industry, complete response letters, or rejections, are a common occurrence. And though they aren’t frequently explained in detail publicly, the public is still usually notified that the company has received such a letter. But in the world of medical devices, failing to win approval for a high-risk device is a much more closely held secret, and companies can withdraw their applications rather than be denied approval.
A Federal Register notice on Thursday listing approved premarket approval (PMA) applications for Class III devices from 1 January through 18 September, noted: “There were no denial actions during this period.”
The sentence kick-started a search for why, not only in this notice, but in just about every other notice dating back decades, there was hardly a sign of a PMA denial. In fact, searches in turned up only two PMA denials – one in 2011 and one in 2014.
The dearth of denials seemed odd, especially considering how for a decade, more than 50% of PMAs have received a major deficiency letter on the first cycle of review. And in about half of those years, more than 80% have received a major deficiency letter on the first cycle of review.
However, despite such deficiencies in the first cycle – more than 80% of PMAs still received final approvals in each of the last six years. And in those same years, between 5% and 16% of PMAs are withdrawn, according to the latest medical device user fee program statistics.


So where do all the rest of the applications go?
FDA explained to Focus that there are actually two categories for PMAs that do not win approval (in addition to a sponsor withdrawing an applicaton): FDA can decide to not approve a device in its current form or there’s a denial.
The total number of denials (here’s what would cause a denial) has been “very small since 1976,” a spokeswoman confirmed. And devices that are not approved in their current form are not disclosed publicly, FDA said.

Lakshman Ramamurthy, principal at DxDevice Strategies, noted that the PMA process is long and deliberative and that PMA denials only come when there is a safety issue or a particularly recalcitrant sponsor. "Most sponsors are keen to take FDA’s feedback, and FDA has been incredibly communicative," he added.

But some think FDA could do more to be transparent about high-risk devices that fail to win approval.

Madris Tomes, a medical device post-market surveillance expert, told Focus that it “seems like denied PMAs should be made public but that would not be in the manufacturer’s best interest. If the file of denials were available then perhaps if the device was being used abroad, it would be recalled.”

Research from 2008 found that from December 2002 through 2007, there were seven PMA applications that were disapproved by FDA based in part on disapproval recommendations by the FDA-appointed scientific advisory panels. Of these seven PMA applications, five of the devices were found to have received prior European CE marking. Though the research said that no safety-related problems had been reported in France, Germany or the UK for the five devices that had received CE mark approval but PMA denial.


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