Dental devices would likely strike most observers as fairly simple items, but an FDA employee said on a recent webinar that these filings have a refuse-to-accept (RTA) rate in excess of 80%, suggesting sponsors have a lot of regulatory homework to do.
The FDA finalized the RTA policy for 510(k) devices in September 2019, wrapping up a draft that originated in 2012, but which is on the second iteration. The first final guidance for this policy was posted in January 2018, and the latest final guidance was immediately in effect for special 510(k) filings. However, the agency indicated it would default to the legacy final guidance for all other 510(k)s through Nov. 13, 2019, to give industry and reviewers at the agency sufficient time to implement the terms of the guidance. (See BioWorld MedTech, Sept. 13, 2019.)
High volume of dental 510(k) filings
Dental 510(k) submissions are hardly the darlings of Wall Street, but the FDA's acting assistant director for the restorative and surgical devices office, Michael Adjodha said on a recent webinar that the agency receives "a high volume of 510(k) submissions" for dental devices every year. Adjodha pegged the number at an average of 240 such applications annually over the past few years, suggesting that at least 190 such applications have to be redrafted by device makers each year.
Of the nearly 220 dental devices cleared in calendar year 2018, 66 were for dental abutments under product code (procode) NHA, while endosseous implants under procode DZE accounted for another 44 clearances. Another five clearances were for orthodontic software under procode PNN, and Adjodha reminded attendees that some of these clearances were for files received in a previous calendar year. The agency is receiving an increasing volume of applications for snoring and sleep appliances of late, as well as for treatment planning software under the PNN procode.
Of the five PNN applications cleared in 2018, only two were filed that year, Adjodha said, noting that those two consumed an average of 187 total days to process (90.5 FDA days and 96.5 sponsor days). The eight applications for dental handpieces didn't go much more smoothly as they took on average nearly 175 days to process (87 FDA days and 88 sponsor days), while the dozen applications for snoring/sleeping devices rang in at 143 days. Sponsors were relatively prompt with their responses to the FDA's reaction to the snoring/sleeping device filings, but those sponsors still needed an average of 54 days to handle their regulatory business after the date of the 510(k) application.
Adjodha said there are a number of conspicuous repeat problems with these applications that lead to an RTA designation. These include that sponsors frequently fail to adequately describe the applicant device. Many applications lack engineering drawings as well, but Adjodha said, "we often see the submission does not address the recommendations of a device-specific guidance."
Among the existing guidances for this category are the October 2005 guidance for dental composite resin devices and the May 2004 special controls guidance for endosseous implants and abutments. Dental amalgams will be on tap at the FDA's Nov. 13-14, 2019, hearing of the immunology devices advisory committee to review the safety evidence associated with the use of amalgams.
Sponsors are prone to erratic characterization of their substantial equivalent claims, largely due to inconsistent citation of predicates. Adjodha said also that device makers working this terrain frequently fail to justify the use of the predicate's characteristics in performance testing of the applicant device.
Another area in which these applications are lacking – and one about which the FDA is notoriously impatient – is sterilization. Adjodha said such information is often insufficient, including on the question of validation of the sterilization method. Cleaning and disinfection methods are likewise short in many applications, but applications are often deficient in instructions for use and contra-indications. The same holds for information on hazards, warnings and precautions.
Among the oft-seen problems for biocompatibility testing is a lack of such testing as well as a failure to explain why such testing is necessary. Material identification is another running sore spot for dental device applications, but Adjodha said performance testing is similarly problematic.
Performance testing data omit test results
Adjodha said these 510(k) filings often lack information on the sponsor's performance testing. In some instances, the sponsor has provided specifications for the testing without providing the results. He said some sponsors engage in irrelevant testing, but the larger picture is that the testing frequently fails to demonstrate substantial equivalence to the predicate device.
Performance test data is a tripwire at the substantive review stage as well, Adjodha said, stating, "performance statements and the selection of appropriate predicate[s] continue to present grievous challenges to clearance." One of the issues the agency sees is that sponsors may not anticipate that performance statements indicative of enhanced clinical outcomes "may need to be substantiated with clinical data."
Sponsors need to be more selective with their choice of predicate, Adjodha said, suggesting that sponsors select a predicate that is closest to the applicant device in terms of intended use, allowing technological similarity to play a secondary role. He noted that a number of performance standards are available to sponsors, and reminded attendees that ISO 10993 is still the relevant biocompatibility standard.
The 510(k) summary "is very often missing key information," Adjodha said, adding that some applications lack sufficient data to make a compelling substantial equivalence argument.
"We recommend that you avoid absolute statements that your device is safe and effective because the 510(k) process is based on substantial equivalence," Adjodha said, recommending that sponsors default instead to claims that the applicant device is as safe and as effective as the predicate. He also urged applicants to avoid including any trade secrets or confidential information in the applications inasmuch as a cleared 510(k) is publicly available.
Malvina Eydelman, FDA's director of dental devices, acknowledged that there are a number of guidances for dental devices and that the agency is "taking a comprehensive look at everything that is currently available." Eydelman said the agency would like to hear from sponsors about guidance needs, including updates to existing documents.