Medical Device Daily Washington Editor

Donna-Bea Tillman, PhD, is the director of the Office of Device Evaluation (ODE) at FDA's Center for Devices and Radiological Health, a post that gives her a great insight into device approvals, which have been the subject of seemingly endless controversy of late.

According to the annual report for ODE for fiscal years 2006 and 2007, the average number of days needed to review PMAs and panel-track PMAs has remained more or less flat since 2001, but that does not address the number of reviewer hours required. Regarding whether a PMA typically takes more person-hours to review, Tillman said, "it's hard to generalize too much, but our sense is that PMAs are getting more complex. We don't have any data on the number of people are on a [typical] review team," which might suggest something about the actual number of hours applied to the typical PMA.

However, Tillman noted that this complexity is "one of the reasons we renegotiated the user fee program, to have it based on registration listings because that's a somewhat more fixed rate" as compared to the number of PMA filings, which is "more variable from year to year. But it's our sense that devices are getting more complicated and the issues are getting harder to resolve."

Device makers would argue that it's getting tougher to get through the FDA process, partly because the amount of clinical data required is increasing, not to mention post-market requirements. On the other hand, some recent controversies seem to suggest there is a culture shift at work, but Tillman said she does not see this as the case.

"The standard for PMAs for approval hasn't changed. It's still a reasonable assurance of safety and effectiveness," Tillman said, adding that when industry comes up with new technologies, "I think there is an expectation in those situations that a sponsor needs to provide a little more data" because reviewers are unfamiliar with the technology. "The kinds of data we need for a first-of-a-kind product may be more than we need for the tenth coronary stent," she pointed out.

However, Tillman acknowledged "a perception that we get easier, then harder, and maybe there's a political tie to that depending on the administration," but nonetheless said that evolving technology means that "sometimes the science [behind an application] changes and so the bar has to change, too."

Tillman declined to directly address the controversy over the Sprint Fidelis lead and the fact that it was not tested clinically, but said that in general, the agency's position is that "there are some questions that are better answered on the bench than in a clinical study" in part because "you're limited in terms of how big it can be." This fact limits the agency's ability to "look at device failure modes from clinical studies, so you do bench testing, where you can take a device and stress it [repeatedly] and see where it fails," she said.

Tillman said that in many instances, "bench testing is a better way to get at device performance than a clinical study," but FDA's approach is consistently that "we look at the particular device, we look at the issues and the questions and the risks, and based on a consideration of that, we work with the company to decide on an appropriate set of tests to be done."

The flap over the Menaflex 510(k) has generated a hefty amount of coverage and the device's maker, ReGen Biologics (Franklin Lakes, New Jersey), concluded that reviewers had a mindset about the application that led them to ignore what the company saw as fairly plain facts about the application. Tillman said her office expects reviewers "to do reviews based on the appropriate scientific and regulatory considerations and not on their personal views of the device." She noted that if FDA management "felt a reviewer was unable to be objective and make a decision based on science and regulatory policy, then it would be within that manager's right and responsibility to assign [the application] to another reviewer." On the other hand, she also noted that while she cannot say it has not happened, she is "not personally aware of an instance in which that occurred."

The GAO report on the 510(k) program listed no discernible misgivings other than that some devices that predate the Medical Device Amendments of 1976 (MDA) still have not been classified, and Tillman noted that in a few instances, these are device categories that are technologically outdated. However, getting the remaining device types classified will not happen overnight.

Tillman said that FDA has "competing priorities, and the ones we [reclassified] first were the ones with the biggest public health impact and the ones there were the most concerns about. What's left are some things we certainly need to deal with but once again, it's a competing priority issue."

The process, Tillman noted, involves filing "section 515 requests for information about these remaining pre-amendment class III devices so we can make a decision about what we're going to do with them." She said an advisory panel may be convened for some pre-Amendments devices that defy easy categorization. In any event, the agency will have to propose a classification for each device in the Federal Register and take in comments. "Realistically, it's not going to happen within the next year," she said. Among the obsolete devices on the list are "single-chamber, non-rate responsive pacemakers and pulse generators," she noted.

The media have been replete lately with reports that describe the 510(k) program as a "fast-track" program for devices without noting that there is not just one type of 510(k), as anyone who has ever filed a de novo 510(k) can attest.

"I think that's a really common misconception out there in the press that this notion that the 510(k) is a fast-track process," Tillman said, adding that the program "was designed to be a risk-based way to account for the fact that there's a wide variation of risk to medical devices [and] that we need to have an approach that balances public health protection with public health promotion, and it doesn't make sense to ask for the same amount of data for a stethoscope as it does for a drug-eluting stent."

Tillman said that the concept of substantial equivalence (SE) has proven somewhat elastic over time, but said that this principally is a function of the mounting number of legacy devices upon which SE is based. She noted that with the passage of the MDA in 1976 "and for the first couple of years [after that], substantial equivalence was a new device compared to a pre-Amendments device." Subsequently, however, "if you look at the chain, you have 510(k) devices that are equivalent to something that's equivalent to this and equivalent to this." Tillman pointed out that "as more time elapses, the substantial equivalence tree gets bigger and broader because there are simply more devices out there to serve as predicates."