The Ides of March was eventful this year at FDA. The White House nominated acting commissioner Andrew von Eschenbach to take
over the top job permanently. Then Health and Human Services (HHS) secretary Mike Leavitt joined him and deputy commissioner
Janet Woodcock in unveiling a long-awaited list of "scientific projects" to accelerate the development of new medical products.
Although Woodcock has been the prime force behind Critical Path, von Eschenbach gets credit for keeping it on the table. But
his good efforts may not overcome the political issues blocking his confirmation (see "Nomination on Hold").
FDA launched Critical Path two years ago to reverse a downward trend in new drug approval (see "What Ever Happened to Critical
Path," Pharmaceutical Executive, January 2006). The initiative aims to identify new research practices and biomarkers in order to streamline clinical studies
and better ensure the safety and efficacy of new treatments.
Nomination on Hold
"We now have the science and technology to support a powerful engine for drug development," says James Shannon, head of
pharmaceutical development at Novartis, "but the science has not been allowed to flourish in the current regulatory environment;
the rules of the road say we can't drive more than 30 miles per hour."
FDA intends for many individual components of Critical Path to be carried out by consortia. One early model is the Predictive
Safety Testing Consortium, established by the non-profit Critical Path Institute (C-Path) and eight pharma companies. The
participants have agreed to cross-test each other's pre-clinical laboratory methods to determine which are most effective
in detecting kidney, muscle, and liver toxicity.
C-Path will submit the resulting data to FDA, which will weigh whether the information supports new guidance on detecting
kidney or liver safety problems during development. The goal is to identify the most informative tests—animal, in vitro, or
clinical—for predicting toxicity, explains C-Path president Ray Woosley.
With early insight into which compounds have unacceptable side effects, companies can avoid spending on unpromising drug candidates
and spur efforts to find safer compounds. Consortium members will have access to data on test methods—and opportunities to
license resulting patentable technologies.
Another consortium, the Oncology Biomarker Qualification Initiative, was formed by FDA, the National Cancer Institute (NCI),
and the Centers for Medicare and Medicaid Services (CMS). The group's first project is to evaluate whether PET scans can provide
a marker for early drug response in non-Hodgkin's lymphoma. The project could create a new tool for assessing how well molecular
imaging technology reveals drug interaction with a target. The results may be useful, moreover, for tumor staging and helping
providers, payers, and patients make treatment and coverage decisions.
Woodcock regards the opportunities list as an evolving document and expects to issue an update of activities underway this
summer. One project on the table is an FDA–industry effort to identify biomarkers that already exist, to demonstrate the practical
value of such measures.
FDA participated in an Institute of Medicine workshop on cancer biomarker development in March and plans to hold a workshop
on what type of evidence is needed to qualify biomarkers for different purposes. This should lead to a general biomarker qualification
guidance describing ways to link biomarker validation to intended uses. Additional guidances on specific qualified markers
will follow, possibly starting with documents on testing for liver and kidney toxicity. Also on the agenda is draft guidance
on drug–diagnostic co-development.