FDA's "Critical Path" initiative will redirect the agency's research funding towards identifying and alleviating some major barriers to drug development.

The initiative, outlined in a ¹ report titled "Innovation or Stagnation? - Challenges and Opportunity on the Critical Path to New Medical Products," aims to identify the key problems that hold up innovative products.

"FDA is planning an initiative that will identify and prioritize (1) the most pressing development problems and (2) the areas that provide the greatest opportunities for rapid improvement and public health benefits," the report states.

"At FDA, we are going to be reallocating and redirecting some of our limited applied research funding to reflect these new challenges," Commissioner McClellan said in detailing the plan at a Research! America meeting in Washington, D.C. March 16.

"FDA will refocus its internal efforts to ensure that we are working on the most important problems, as well as intensifying our support of key projects," the report states.

Without any new funding, it appears the agency could have about $135 mil. at its disposal for the "Critical Path" project. Total agency research funding requested for fiscal year 2005 is $150.6 mil., $16 mil. of which is designated for orphan drug development by Congress. That would leave $134.6 mil. for FDA to potentially redistribute.

The report suggested FDA may use the orphan products grants program as a model for solving problems identified along the "critical path."

"This program is widely viewed as a major success in assisting in development of treatments for rare diseases, at a very modest investment," the report states.

"FDA is conducting an internal review of how the success of the Orphan Products development research might be applied to other kinds of critical path programs."

Under the new initiative, FDA aims to develop new "toolkits" for industry in three areas of drug development: "assessing safety"; "demonstrating medical utility"; and "characterization and manufacturing."

The first concrete step will be the creation of a "Critical Path Opportunities List" by FDA, meant to identify and clarify the major goals of the project in "extensive consultation will all public and private stakeholders," including industry, the National Institutes of Health and academia, the report says.

NIH has been developing improved analytical tools for clinical trials as part of its "roadmap" (² Also see "Biotechs Must Work With NIH To Tackle “Complexity,” NIH Director Tells BIO" - Pink Sheet, 8 March, 2004., p. 36).

McClellan said the project would involve "a series of workshops" and conferences. The agency also plans to devote its April Science Board meeting to the initiative.

The announcement was met with approval by industry, including a statement in support of the program by the Biotechnology Industry Organization.

At the Research! America meeting, Lilly CEO Sidney Taurel also lent his support. "FDA is in a unique position of having access in a holistic way to all the information coming from companies on new platforms for pharmaceutical products," Taurel said. Such information could help other companies avoid "the same pitfalls," he said.

McClellan vowed the agency would not divulge proprietary information revealed during consultations with industry on the initiative. "I'm confident that there are many ways to address these problems without getting into proprietary concerns of companies," he said.

The commissioner will presumably hand off the project to his successor at FDA; McClellan is expected to begin his new post as Centers for Medicare & Medicaid Services administrator shortly (³ [A#00660110002], p. 4).

FDA's report reviews some of the problems in drug development identified by the agency.

In the area of safety, for example, FDA noted that issues uncovered during clinical trials can contribute significantly to high R&D costs.

The point was reiterated by Center for Drug Evaluation & Research Medical Policy Director Robert Temple, MD. "One of the things that needs to be done is to help explain the high failure rates" in drug development, he said during a conference call on the report.

FDA identified liver toxicity issues as one example. "One pharmaceutical company estimates that clinical failures based on liver toxicity alone have cost them more than $2 bil. in the last decade - dollars that could potentially be directed toward successful new product development."

An earlier approach to the hepatotoxicity problem not unlike the "Critical Path" proposal included the formation of an FDA/industry working group (⁴ Also see "Post-Marketing Hepatotoxicity Drug Withdrawals Subject Of FDA Study" - Pink Sheet, 5 November, 2001., p. 11).

For improving safety determination overall in drug development, FDA identified opportunities in proteomic and toxicogenomic approaches, as well as computer modeling. "Some believe that extensive use of in silico technologies could reduce the overall cost of drug development by as much as 50%," the report states.

The report also describes an "urgent need" to create tools that accurately assess the risk of heart rhythm abnormalities in new drugs.

For demonstrating medical utility, FDA noted the utility of biomarkers and surrogate markers to speed drug development.

In addition, imaging technologies "may provide powerful insights into the distribution, binding, and other biological effects of pharmaceuticals."

In the area of manufacturing, FDA highlighted process analytical technologies "that can improve efficiency and increase flexibility while maintaining high-quality standards." FDA expects to issue a final PAT guidance this summer.

FDA Will Fund Research On “Critical Path” Of Drug Development

More from Archive

More from Pink Sheet