FDA To Provide Updates On Critical Path Opportunities List Projects

FDA will highlight the agency's involvement in Critical Path projects in the coming months, Deputy Commissioner for Operations Janet Woodcock said March 16.

"We are going to issue a report on what projects we're involved in - probably within a month or two - to show what FDA is currently working on," Woodcock said.

The agency will also update its Critical Path opportunities list, which was released March 16. The list identifies 76 projects "that could be undertaken by industry or academia and could be sponsored by patient groups, foundations or government agencies" (see chart: " ¹ Spirit of 76: Critical Path Opportunities List ").

"We will update the list, and we will also update what we're working on and the progress so people will know how we're doing against this list," Woodcock said.

FDA described the opportunities list as a "living, evolving document" that lays out specific science projects that could modernize the drug development process.

The agency also solicited feedback about barriers to effective collaboration on Critical Path projects.

"We'd be interested to hear from people's experiences as they move into these consortia what barriers" there are, Woodcock said. "We don't really know yet because we are so early in this process."

In its Critical Path report, FDA identifies six priority areas for drug development research: developing new biomarkers and disease models, streamlining clinical trials, harnessing bioinformatics, modernizing manufacturing, developing products to address urgent public health needs, and the pediatric population.

One highlighted project to improve evaluation tools is to modernize predictive toxicology. Specifically, FDA suggests developing safety biomarkers for liver or kidney toxicity.

Novartis has partnered with FDA to look at the development and use of preclinical biomarkers in the evaluation of renal toxicity (² (Also see "Novartis Sets Out On The Critical Path; Will Others Follow?" - Pink Sheet, 10 Oct, 2005.), p. 9). The project may serve as a model for other collaborative efforts between industry and regulatory agencies seeking to develop a validation process.

FDA also announced the formation of the Predictive Safety Testing Consortium March 16. As part of the collaboration, companies will evaluate testing methods to detect nephrotoxicity.

Another area the agency highlights as an opportunity to improve evaluation tools is through advancing the use of new imaging technologies, including improving imaging biomarkers for cardiovascular disease.

Pfizer's torcetrapib/ Lipitor combination could be an example of an upcoming submission dependent upon cardiovascular imaging data.

The company has suggested that cardiovascular imaging data could act as a surrogate for outcomes and expects imaging to show the arterial remodeling capability of its cholesterol combo (³ , p. 14).

FDA identifies active-controlled trials, enrichment designs and use of adaptive trial designs as ways to streamline clinical trials.

The agency has recently expressed interest in adaptive trial designs, which allow for the adjustment of trial parameters based upon results observed in interim analyses (⁴ (Also see "The Next Phase: FDA Looks Beyond Three-Stage Drug Development Model" - Pink Sheet, 13 Feb, 2006.), p. 10).

FDA noted that sponsors need consensus and clarification on questions related to when adaptive trial design is appropriate.

Under a section on bioinformatics, FDA said that clinical trial simulations may reduce the number of trials and patients and improve decisions on dosing and increase informativeness.

In addition, biologics manufacturing is given prominent placement among identified opportunities.

The proposed project "Novel Approaches to Characterizing and Standardizing Biological Products" could assist the agency in developing regulatory standards for generic biologics.

The Critical Path report also identifies a need to develop a national infrastructure for conducting Critical Path research.