The Problem

The tests used to determine drug safety have not changed in decades. Although companies have developed newer methods to test drug safety, these are not globally accepted by the FDA or EMA as proof of safety. This is, in part, because the methods used for testing are often different from company to company. That discrepancy leaves regulatory scientists uncertain about which methods should be preferred. Another key factor is the tests have not, in the past, been independently validated.

The Solution

PSTC was formed and officially announced by Health and Human Services (HHS) Secretary Michael Leavitt, Food and Drug Administration (FDA) Commissioner Dr. Andrew von Eschenbach and FDA Deputy Commissioner Dr. Janet Woodcock. Upon its inception, Woodcock described the consortium as “unprecedented” and a “shining example” of the type of work the FDA would like to see conducted.

PSTC’s goal is to obtain regulatory acceptance of novel drug safety tests. PSTC brings together pharmaceutical companies to share and validate innovative safety testing methods under advisement of the U.S. FDA, its European counterpart, the EMA (European Medicines Agency), and PMDA (Japanese Pharmaceutical and Medical Devices Agency).  Currently, PSTC is focused on developing and obtaining regulatory qualification of improved clinical safety biomarkers for use in drug development.

The Impact

Since PSTC’s launch, the consortium achieved qualifications for kidney safety biomarkers from the EMA, PMDA, and FDA for nonclinical use of the biomarkers, summarized in this article. In 2018, the FDA qualified a panel of six kidney safety biomarkers for use in phase one clinical trials. Two recent articles summarize the impact on drug development of the qualified kidney safety biomarkers: Troth et, 2019; Chen et al, 2018. In addition to qualifications, PSTC received several Letters of Support for safety biomarkers to detect drug-induced kidney, skeletal muscle, liver, and vascular injury from the EMA and FDA. Within the consortium, members shared data to support these Qualifications and Letters of Support totaling more than 90 nonclinical studies and more than ten clinical studies.

The kidney safety biomarker Qualifications received by PSTC have enabled more specific and sensitive detection, monitoring and reversibility of potential kidney injury as described by Dr. Stefan Sultana (AstraZeneca) and Dr. Warren Glaab (Merck & Co., Inc.) during the PSTC 15-year anniversary workshop.

In addition to improving detection and monitoring drug-induced organ injury, where possible, PSTC works with disease-specific consortia across C-Path to provide initial evidence of applicability of the safety biomarkers for future use as diagnostic, prognostic, or efficacy biomarkers.