Monday, March 31, 2008

Novartis and FDA Complete Two-year Cooperative Research & Development Agreement to Define &Test a Process for Qualifying Preclinical Safety biomarkers

Novartis Pharmaceuticals Corporation announced today the successful completion of a cooperative research and development agreement (CRADA) with the Food and Drug Administration (FDA), one of the first projects conducted under the FDA's Critical Path Initiative.

The Critical Path Initiative was launched by FDA in 2004 to refine the science and processes through which FDA-regulated drugs, biologics, and devices are translated from a discovery or "proof of concept" to a medical product. The research produced under the CRADA led to a number of key achievements that will enhance the development and application of preclinical biomarkers to evaluate drug safety. "In working together with FDA, we have demonstrated the progress that can be achieved in the biomarker field, and in the science of drug development in general, through public-private partnerships," according to John Orloff, MD, Senior Vice President, US Medical and Drug Regulatory Affairs at Novartis Pharmaceuticals Corporation.

"We have developed both a process for defining biomarkers of safety and real-world data that can support regulatory decision making regarding renal safety." The FDA-Novartis CRADA had two primary objectives: 1) To define a process for qualifying preclinical safety biomarkers for regulatory decision making; and 2) to test this pilot process by submitting kidney-related safety biomarkers identified and characterized through preclinical studies to the FDA for qualification. Efforts conducted under the CRADA have resulted in the publication of the first pilot framework for a preclinical regulatory biomarker qualification process(1).

The development of this process will have a broad impact on the understanding of the qualification of safety biomarkers far beyond this partnership. In addition, the preclinical data identified thus far have demonstrated evidence for the superiority of new renal biomarkers over the current standards used to assess renal injury in drug testing, namely serum creatinine and blood urea nitrogen (BUN). Further efforts will focus on the extended clinical qualification of biomarkers that could allow clinicians to detect kidney injury in patients earlier than current clinical practice allows. Relevant safety biomarker data generated by Novartis as part of the CRADA has been shared with the Critical Path Institute's Predictive Safety Testing Consortium (PSTC).

The PSTC is a larger public/private partnership between industry, academia, and regulatory health authorities intended to serve as a neutral body for coordinating activities related to biomarker qualification in drug development. The CRADA data, together with data generated by other partners in the PSTC has been submitted to FDA and the European Medicines Agency (EMEA) as part of a Voluntary Exploratory Data Submission (VXDS). The two regulators are now considering whether to approve use of these biomarker data in support of particular aspects of regulatory decision making. As a result of this data submission,

FDA and EMEA have utilized appropriate internal boards and worked to refine the process to qualify such preclinical safety biomarker data. Further joint evaluation of additional data under the auspices of the PSTC is expected to lead to additional submissions of peripheral biomarkers representing additional renal pathologies. "The Biomarker CRADA is a significant step in bridging the gap between basic scientific research and the medical product development process," said Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research. "The FDA was pleased to work with Novartis to further the development of renal safety biomarkers that can be used to prevent drug-induced kidney damage." The data generated by Novartis under the CRADA will continue to have an impact despite the agreement's conclusion. Novartis intends to submit additional data on genomic- and proteomic-based renal safety biomarkers to FDA and EMEA in the summer of 2008.

No comments: