Regulatory issues on breath tests and updates of recent advances on [13C]-breath tests.

Over the last decade non invasive diagnostic phenotype [(13)C]-breath tests as well as tests using endogenous volatile organic compounds (VOCs) in breath have been researched extensively. However, only three breath tests have been approved by the FDA over the last 15 years. Despite the potential benefits of these companion diagnostic tests (CDx) for evaluation of drug metabolizing enzyme activities and standalone diagnostic tests for disease diagnosis to personalize medicine, the clinical and commercial development of breath tests will need to overcome a number of regulatory, financial and scientific hurdles prior to their acceptance into routine clinical practice. The regulatory agencies (FDA and EMEA) need to adapt and harmonize their approval process for companion diagnostic tests as well as standalone diagnostic breath tests for personalized medicine. The Center for Devices and Radiological Health has deemed any breath test that involves a labeled (13)C substrate/drug and a device requires a Pre Market Approval (PMA), which is analogous to an approved New Drug Application. A PMA is in effect, a private license granted to the applicant for marketing a particular medical device. Any breath test with endogenous VOCs along with a device can be approved via the 510(k) application. A number of (13)C breath tests with clinical applications have been researched recently and results have been published in reputed journals. Diagnostic companies will need to invest the necessary financial resources to develop and get regulatory approval for diagnostic breath tests capable of identifying responders/non responders for FDA approved drugs with narrow therapeutic indices (personalized medicine) or for evaluating the activity of drug metabolizing P450 polymorphic enzymes or for diagnosing diseases at an early stage or for monitoring the efficacy of medications. The financial success of these diagnostic breath tests will then depend entirely on how the test is marketed to physicians, healthcare organizations, payers (reimbursement), insurance companies and most importantly to patients, the eventual beneficiaries.