The Good Old Days: FDA's Jenkins Instructs Reviewers To Meet Original User Fee Review Time Standard

After an almost two-year hiatus from strict adherence to the review timeframes set forth in the Prescription Drugs User Fee Act, Office of New Drugs Director John Jenkins has told the drug review staff that, once again, they should strive to meet the user fee deadlines.

"In October of this year, recognizing the increased staffing in the last couple years, I instructed the OND managers to move back to the prior posture of meeting PDUFA goals whenever possible," Jenkins told a Dec. 3 session of Elsevier Business Intelligence's FDA/CMS Summit in Washington, D.C.

Jenkins had issued an internal memorandum in November 2007, allowing reviewers to miss user fee deadlines for FDA decisions because of workload issues, as the agency faced the immense task of implementing the FDA Amendments Act of 2007 and a crisis of understaffing. (¹ (Also see "The New User Fee Rules: FDA Sacrifices Timeliness, Tries to Save Predictability" - Pink Sheet, 1 Mar, 2008.).)

As part of the 2007 memo, FDA reviewers could delay their reviews by two months. Instead of six-month priority drug reviews and 10-month standard drug reviews, the deadlines were extended to eight- and 12-month reviews, respectively.

"They listened," Jenkins said, noting that FDA data indicate that review times did indeed slip following the internal policy memo.

The performance goal set in PDUFA is that FDA meets 90 percent of user fee deadlines; for the cohort of applications submitted in FY08 (FY09 numbers are not yet mature), the performance statistics generally were in the 70 to 80 percent range.

However, since the October directive, reviewers already are making headway on hitting the 90 percent target. "In November, we met all of our goals," Jenkins said. "So hopefully the tide has turned."

He cautioned that the return to meeting PDUFA goals did not necessarily include granting meeting requests or special protocol assessments.

Jenkins also provided confirmation that in terms of novel drug approvals, FDA has cleared more new molecular entities in 2009 than in 2008: 25 so far compared to 24 in 2008 (² Pharmaceutical Approvals Monthly, October 2009).

Though the calendar year count of novel approvals is the most closely followed (and accessible) measure for FDA watchers, Jenkins stressed that it is an imperfect marker. The better metric is to look at cohorts of submissions in a fiscal year, although that figure takes longer to mature.

Along those lines, he presented preliminary data showing that 2009 is looking consistent with 2008, both in terms of approvals and submissions.

Jenkins also broke out data on the submission cohorts for previous fiscal years, which demonstrate that FDA has improved on delivering first-cycle approvals for priority NMEs over the last three PDUFA five-year cycles.

For example, under PDUFA I, FDA approved 46 percent of priority NMEs during the first cycle, 58 percent under PDUFA II, and 68 percent under PDUFA III. For 2008, the first year of PDUFA IV, 69 percent of priority NMEs were cleared in one review period.

Where the real problem continues to appear is first-cycle standard NME applications (³ (Also see "Priority Review's Luster Dims In "Safety First Era" But Retains Value - Parexel" - Pink Sheet, 1 Sep, 2009.)). Under PDUFA I, 30 percent of standard applications were approved on the first cycle. That decreased to 22 percent over the five years of PDUFA II, then increased to 30 percent under PDUFA III. It is also 30 percent for the FY08 cohort.

First-cycle approvals can also be difficult to attain if there are complicating elements that need to be factored into the review. Jenkins noted that the new drug regulations under FDAAA have added broad new responsibilities to FDA reviewers, most notably the Risk Evaluation and Mitigation Strategies.

Failure to incorporate a REMS program that goes beyond a MedGuide from the very early phase of drug development would make it "almost impossible" to meet a review deadline if a more complicated REMS program is needed for a given drug.

- Ramsey Baghdadi ( ⁴ [email protected] ) and Mary Jo Laffler ( ⁵ [email protected] )