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PSTC Slides

New testing methods!

Predictive Safety Testing Consortium (PSTC)

The PSTC is a unique public-private partnership, led by the non-profit Critical Path Institute (C-Path), that brings together pharmaceutical companies to share and validate each other's safety testing methods under advisement of the Food and Drug Administration ("FDA") and its European counterpart, the European Medicines Agency ("EMA"). The 16 corporate members of the consortium share internally developed pre-clinical safety biomarkers in five workgroups: carcinogenicity, kidney, liver, muscle and vascular injury.

The PSTC was officially announced on March 16, 2006 by Health and Human Services Secretary Michael Leavitt, FDA Commissioner Dr. Andrew von Eschenbach, and FDA Deputy Commissioner Dr. Janet Woodcock, who identified the consortium as "unprecedented" and a "shining example" of the type of work the FDA would like to see conducted.

Background

The tests that are used to determine drug safety today have not changed in decades. Companies have developed newer safety testing methods, but these are not generally accepted by the FDA or EMA as proof of safety because the tests have not been independently validated by a third party. Also, the methods used by companies are often different, leaving regulatory scientists unclear about which methods should be preferred.

In order to find improved testing methods, C-Path has invited pharmaceutical companies to join the PSTC in which they share their internally developed methods and then test the methods developed by another member of the Consortium. Ten EMA and nineteen FDA scientists participate as advisors, along with more than 250 participating scientists, with C-Path serving as the "trusted third party," leading the collaborative process, collecting and summarizing the data.

Process

Consortium members are sharing their new pre-clinical biomarker tests for examination and cross-validation by other members of the Consortium. The process is expected to enable the FDA and EMA to write new Guidances for industry that identify more accurate methods to predict drug safety. Notably, the FDA and EMA scientists are not acting in their usual role as regulators. Instead, they are active participants, providing assistance and advice to the Consortium.

Early Results

This unprecedented sharing of data by the industry facilitated the FDA's and EMA's piloting of data submission processes to receive, review and approve new methods as qualified for use in drug development. In May 2008, the FDA and EMA confirmed their joint review and acceptance of seven new laboratory tests on urine which signal kidney injury. The protein signals, known as biomarkers, were confirmed in data from rat studies submitted to the FDA and EMA by the PSTC. The FDA and EMA jointly came to the conclusion that:

• the kidney biomarkers are acceptable in the context of non-clinical drug development for the detection of acute drug-induced kidney toxicity;
• the kidney biomarkers provide additional and complementary information to the currently available standards;
• the use of kidney biomarkers in clinical trials is to be considered on a case-by-case basis in order to gather further data to qualify their usefulness in monitoring drug-induced kidney toxicity in man.

The newly accepted biomarkers are KIM-1, Albumin, Total Protein, B2-Microglobulin, Cystatin C, Clusterin and Trefoil factor-3. The use of these new tests can now be used in laboratory research to predict the safety of experimental drugs, allowing drugs to reach market faster and with greater confidence in their safety. The PSTC is actively involved in research to further qualify the biomarkers for use in clinical drug development.

EMA announces first EMA-FDA joint biomarker qualification review
FDA announces joint EMA/FDA biomarker review
PSTC's technical summary of the biomarker review

Current PSTC Members:

• Abbott
• Amgen Inc.
• AstraZeneca Pharmaceuticals LP
• Boehringer Ingelheim Pharmaceuticals, Inc.
• Bristol-Myers Squibb Company
• ClinXus
• Daiichi Sankyo
• Eli Lilly and Company
• GlaxoSmithKline
• Johnson & Johnson Pharmaceutical Research & Development, LLC
• Merck and Co., Inc.
• Mitsubishi Tanabe Pharmaceutical Corporation
• Novartis Pharmaceutical Corporation
• Pfizer, Inc.
• Roche Palo Alto, LLC
• sanofi-aventis U.S., Inc.

C-Path PSTC leadership team:

• Elizabeth Gribble Walker, PhD, Director
• Eric Thompson, PhD, Assistant Director
• Phil Rossi, Database & Collaborative Tools Administrator

An overview of the PSTC is linked here. Information for those interested in interacting with or participating in the PSTC is linked here.