Comments from John Jenkins, director of CDER's Office of New Drugs (OND), provide a clear view into FDA's dilemma. He gave
review division chiefs "discretion" to reduce work on some activities to deal with a high-priority requirement, even if that
means missing user-fee deadlines. Jenkins explained to reporters that his office cannot keep up with a growing volume of requests
to meet with sponsors, provide Special Protocol Assessments for innovative therapies, supply the reams of information demanded
by Congressional committees, and still perform routine tasks. Jenkins thus advised OND office and division directors to assess
where it will be difficult to meet application-review goals set by the latest Prescription Drug User Fee Act (PDUFA IV) and
to notify sponsors of anticipated delays.
Jenkins noted that there is "no specific end date" to the possibility of missing PDUFA deadlines because it may take FDA years
to hire the necessary personnel to remedy the situation. Under PDUFA IV, CDER has resources to add some 400–500 additional
staffers, but the task of hiring and training a whole new team of reviewers and analysts will consume considerable time and
energy (see sidebar, "Seeking scientists").
For pharmaceutical companies, this development raises the prospect of added costs and delays in bringing new drugs to market,
a trend evident in FDA's declining drug-approval rate. The agency approved only 19 innovative new drugs in 2007, 17 new molecular
entities, plus two novel biotechnology therapies. Those numbers are way down from the peak of 53 new drugs in 1996, but in
line with a steady decline in new-drug approvals since 2002. Another analysis indicates that FDA approved only 64% of all
New Drug Applications (NDAs) in 2007 and issued more nonapprovable and approvable letters that request additional data and
information from sponsors for final approval.
Manufacturers say these trends reflect a cautious environment at the agency in approving new drugs. FDA officials maintain
that they have not changed standards or become more risk-averse, but now have better tools for detecting safety problems,
especially for drugs that treat chronic conditions. At the same time, FDA officials acknowledge that new treatments in crowded
drug classes will have to show an efficacy or safety advantage to gain market approval.
One factor interfering with CDER's review process is the need to spend more time and resources implementing new postmarket
surveillance programs. CDER's new "Safety First" initiative reflects the prominence CDER will give to safety issues in evaluating
NDAs. The aim is to better integrate pre- and postapproval safety assessments to avoid clashes between OND and CDER's Office
of Surveillance and Epidemiology (OSE). A Safety First steering committee is clarifying internal processes for managing "significant
safety issues," Woodcock said in a staff memo. A safety director and managers in each new-drug review office will oversee
and coordinate safety assessment, which will be performed by interdisciplinary teams that include staffers from both offices.
Woodcock notes that OSE will have lead regulatory responsibility for observational epidemiologic studies and medication error
prevention, including review of proprietary names, packaging, and container labeling. But safety officers won't get a veto
over approvals, as some critics both inside and outside the agency have recommended.
OSE is reorganizing to handle its growing portfolio of postmarket surveillance activities. It has expanded from three to five
divisions to better monitor adverse events and weigh safety issues in applications. And OSE Director Gerald Dal Pan heads
expanded management, communications, and policy development staffs. One new task for OSE is to develop summaries of adverse
drug events within 18 months of market approval or after a new drug is used by 10,000 patients, as stipulated by FDAAA (see
sidebar, "Postmarket safety evaluation"). Such summaries will identify new and potential product risks and increased incidence
of known risks.
Postmarket safety evaluation