NEW YORK (GenomeWeb News) – The US Food and Drug Administration and the European Medicines Agency have agreed to accept data for seven kidney toxicity biomarkers as part of the drug approval process, the FDA said today.
The agencies will now accept the results of tests that measure the levels of seven proteins found in urine -- KIM-1, albumin, total protein, β2-microglobulin, cystatin C, clusterin, and trefoil factor-3 -- that are indicative of drug-induced damage to kidney cells.
The agreement is the “first use of a framework allowing submission of a single application to the two agencies,” FDA said in a statement.
To date, both FDA and EMEA have required drug companies to submit the results of two blood tests -- blood urea nitrogen and serum creatinine -- to evaluate renal toxicity. Now, in addition to those tests, the agencies will accept results from the seven biomarker-based tests as part of the drug-review process.
Drug makers are not required to collect this biomarker data, but if they do, “it must be submitted to FDA,” the agency said.
The biomarkers were developed by the Predictive Safety Testing Consortium, an initiative led by the Critical Path Institute that kicked off around two years ago.
Under the auspices of the consortium, researchers from Merck and Novartis identified and validated the biomarkers and then shared their findings with the other PSTC members for further study. The consortium submitted applications for use of the biomarkers to FDA and EMEA last year.
The project is the “first in which a group of drug companies has worked together to propose and qualify new safety tests and then present them jointly to the FDA and EMEA for consideration,” FDA said.
This process allowed the PSTC to submit a single biomarker data application to both regulatory agencies, and then to meet jointly with scientists from both agencies for discussion. The FDA and EMEA reviewed the application separately and made independent decisions on use of the new biomarkers, FDA said.
FDA said that the seven new tests “may provide important advantages over the BUN and creatinine tests.” For example, in experiments using rats, current tests can only detect kidney damage a week after it has begun to occur. The new tests, on the other hand, “can detect cellular damage within hours,” FDA said.
In addition, BUN and serum creatinine can only indicate that damage has occurred somewhere in the kidneys, but the new tests can “pinpoint which parts of the kidney have been affected,” the agency said.
The seven new tests will initially be carried out in rat studies, but FDA said that the PSTC has begun to qualify the biomarkers for use in human studies.
If successful, the consortium will present a new application to the two agencies to seek acceptance of the human biomarkers, FDA said.
"We hope these biomarkers will lead to human tests that detect drug-induced kidney injury in people earlier than is now possible, and help health care professionals better manage potential kidney damage from drugs." said Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, in a statement.
Further information on the Predictive Safety Testing Consortium is available here.