GAO Says Device Reviews Are Taking Longer…and FDA Says It Is Because Your Submission had Quality Issues

By Carmelina G. Allis –

In a report released last week, the U.S. Government Accountability Office (“GAO”) provides the results from a study it conducted to determine whether FDA has met timeframe performance goals related to the completion of reviews for premarket notification (510(k)) submissions and premarket approval (“PMA”) applications. 

The study found that while FDA met performance goals for 510(k)s and the average number of submissions per year remained generally steady during fiscal year (“FY”) 2003 through FY 2010, the review times for 510(k)s increased.  Likewise, review times for PMAs also increased despite FDA meeting most performance goals for PMA applications.  There has also been a decrease in the number of 510(k) clearance determinations and PMA approvals.  In sum, FDA is taking longer to complete the reviews of 510(k)s and PMAs when the purpose of the user fee program was to streamline the regulatory process.

And who is responsible for this unintended effect?  While assuming some responsibility, FDA points a heavy finger at industry stakeholders.  We will explain this further below, after first providing a brief overview of the device user fee program and discussing the noteworthy GAO study results.

FDA’s Performance Goals.  FDA’s performance goals are defined in terms of “tiers.”  The goals required FDA to complete the review process for 90% of the 510(k)s within 90 days of submission (“Tier 1” goals), and complete the review process for 98% of 510(k)s within 150 days (“Tier 2” goals).  FDA completes the review process for a 510(k) if it issues an order declaring the device substantially equivalent (“SE”), not substantially equivalent (“NSE”), or advises the submitter that a 510(k) is not required.  Regarding PMAs, the FDA had to complete the review of 60% of original PMAs within 180 days of submission (“Tier 1” goals) and 90% of reviews within 295 days (“Tier 2” goals).  The review of a PMA is completed if the agency issues an approval order, an approvable letter, a major deficiency letter, a not approvable letter, or a denial order.  The agency committed to those goals as part of Congress’s enactment of the Medical Device User Fee and Modernization Act of 2002 (“MDUFMA”) (reauthorized in 2007), which authorized the FDA to collect user fees to support its medical device review process.  The user fee program is intended to streamline the review process.

The GAO Study and Performance Results.  The GAO study looked at performance goals for FY 2003 through FY 2010, and also at stakeholders’ concerns with FDA’s review processes and the steps FDA is taking to address those concerns.  Congress requested the study, because it is preparing to reauthorize the medical device user fee program this year.

In a nutshell, here are the most significant GAO findings:

510(k) Performance Goals:

• The time to final decision for 510(k)s has increased substantially, a rise of approximately 61 days.  When GAO added FDA’s time spent reviewing a submission (“on-the-clock FDA review time”) to the time where FDA waited for the sponsor to provide additional information (“off-the-clock time”), the resulting time to final decision increased 61% (from 100 days to 161 days) from FY 2005 through FY 2010.

• The average number of review cycles and requests for additional information have increased by 39% (1.47 cycles for FY 2003 to 2.04 cycles for FY 2010).

• The percentage of 510(k)s receiving a first-cycle decision of SE decreased from 54% for FY 2003 to 20% in FY 2010.

• The percentage of 510(k)s that received a final SE decision decreased from a high of 87.9% for FY 2005 to 75.1% in FY 2010.  Likewise, the percentage of NSE decisions increased from 2.9% in FY 2003 to 6.4% in 2010.

PMA Performance Goals:

• The review times for both original and expedited PMAs, as well as time to final decision, generally increased.  For example, average FDA review time for original PMAs increased from 211 days in FY 2003 to 264 days in FY 2008, but then fell in FY 2009 to 217 days.  Likewise, the average time to final decision for FY 2003 through FY 2008 fluctuated year to year, but increased form 462 days for FY 2003 to 627 days for FY 2008.

• The percentage of original PMAs approved at the end of the first review cycle fluctuated throughout the review period, but generally decreased from 16% in FY 2003 to 9.8% in FY 2009.

• The percentage of original PMAs that were ultimately approved also fluctuated throughout the years, but exhibited an overall decrease.  In FY 2003, 74% of original PMAs were approved, compared to 68.8% in FY 2008.

And why is it that review times have increased?  Why has the number of 510(k) clearances and PMA approvals decreased?  Industry is to blame, according to written comments from the Department of Health and Human Services (“HHS”) to the GAO report.  For example, the HHS written response states that, based on FDA reports, review cycles have increased because “more than 50 percent of 510(k) applications” have “quality issues,” which “require agency staff to prepare and issue additional information letters, resulting in additional review cycles.”  (No explanation – at least that was obvious to us – was offered as to why the review times for PMAs have increased.)

Certainly, it is true that issues with the quality of a submission can delay the review process.  However, Figure 3 on page 16 of the GAO report shows that from FY 2000 to about FY 2005, the average time to final decision for 510(k)s remained fairly steady at an average of about 100 days per FY.  After FY 2005, those times rose steadily peaking at about 160 days on average for FY 2010.  Were 510(k)s of better quality before FY 2005?  Or is it that starting at around FY 2005 FDA changed its standards for reviewing submissions?

We share the industry stakeholders’ views expressed to GAO that FDA has become more stringent in its review process.  The industry stakeholders interviewed by GAO stated that reviewers may be “requesting additional information more often due to a culture of increased risk aversion at FDA,” and noted that the “additional information being requested is not always critical for the review of the submission.”  This results in longer overall review times, because the sponsors’ time to gather information to address FDA’s requests increases with the number and complexity of FDA requests.  Moreover, industry stakeholders noted that review criteria sometimes change after a sponsor has submitted an application, or that reviews are inconsistent between reviewers and review groups.  Inconsistencies in the regulatory process also increase review times, because these often result in sponsors having to conduct additional studies in order to satisfy FDA’s new criteria for clearance or approval.

Concurrently, consumer advocacy groups have also vocally raised concerns with FDA’s regulatory process.  In particular, consumer advocates find objectionable the 510(k) “substantial equivalence” process under which most medical devices are authorized for marketing.  Because 510(k) devices are cleared on the basis of their equivalence to a legally marketed device, consumer critics say that the regulatory process does not require the stringent data gathering and testing that is required of PMA devices.  According to consumer advocacy groups, this lack of stringent oversight of 510(k) devices puts patients’ health at risk.

And the agency has listened to both industry and consumer advocacy groups, and is attempting to accommodate both their perspectives.  The FDA has embarked on an effort to evaluate and bolster the 510(k) program in a manner that has often seemed to give primary weight to alleviating consumers’ concerns.  For example, late last year the agency issued a draft document that updates predecessor guidance for when to submit a new 510(k) for modifications to a legally marketed 510(k) device.  As discussed in a prior post, the draft guidance makes substantive changes to existing policy and will result in more 510(k) submissions.

Simultaneously, the agency is trying to accommodate industry stakeholders’ concerns, and has been instituting changes to “improve the predictability, consistency, and transparency of both the 510(k) and [PMA] review programs,” as HHS explained in its written response to GAO.  For example, according to HHS’s letter, the agency “is developing an SOP for requests for additional information that clarifies when these requests can be made for 510(k)s . . . and the management level at which the decision must be made.”  No statements, however, were made on what FDA says is a major shortcoming: the quality of industry stakeholders’ submissions.

We do not know when the FDA will become more predictable, consistent, transparent, and efficient, or whether its current initiatives and guidance development practices will rightly balance both industry and consumer advocacy stakeholders’ interests.  In the meantime, as a quick solution, because FDA and industry “bear shared responsibility for the increase in [review] time[s] and will need to work together to achieve improvement,” should FDA offer submission writing workshops to industry stakeholders?  Just a thought. . . .