6:11 PM
 | 
Jun 28, 2018
 |  BC Innovations  |  Tools & Techniques

QT replacement plan

How stem cell-based assays could help fix the problem with clinical QT testing

FDA has completed validation of a preclinical assay system that could replace clinical QT testing, a move it hopes will lower development costs and reduce false alarms of arrhythmia risk.

The question for drug developers is when the new tests will be required for all IND submissions, and how long they’ll have to be performed on top of existing QT testing.

The assay is the result of five years’ work on the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative, which came out of a 2013 FDA-led meeting of stakeholders to discuss technologies that could eliminate the need for thorough QT (tQT) studies.

The CiPA initiative was led by FDA’s Division of Cardiovascular and Renal Products and the Health and Environmental Sciences Institute (HESI), and involved a precompetitive consortium of drug companies, CROs, academics and regulators.

“This new cellular assay is being introduced across all drug programs, across all FDA divisions, and we plan to have it replace the old QT study requirements.”

Scott Gottlieb, FDA

In remarks to the U.S. House Subcommittee on Agriculture, Rural Development on April 17, FDA Commissioner Scott Gottlieb described the new assay system as “a faster, less expensive and more accurate method to screen drugs for this safety issue,” referring to QT prolongation, and said the system will become incorporated into the regulatory pathway for drug development.

“This new cellular assay is being introduced across all drug programs, across all FDA divisions, and we plan to have it replace the old QT study requirements,” said Gottlieb. “FDA will recommend the use of this new QT method in a new guidance for drug sponsors,” he added. He did not give a timeline.

FDA introduced tQT studies in 2005 as one of multiple solutions to a rash of 14 drug withdrawals caused by arrhythmia deaths in the ‘90s and early 2000s. The studies use electrocardiograms (ECGs) to assess arrhythmia risk early in clinical development and inform decisions about whether and how to proceed to Phase III testing.

But concern began to build that tQT testing, despite being highly sensitive, was not sufficiently specific and was producing false positives that were killing promising drug candidates and leading to unwarranted warnings on labels.

The CiPA initiative was designed to find ways of replacing tQT with in...

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