This chapter presents the US Food and Drug Administration (FDA) regulatory process as it relates to in vitro therapeutic drug monitoring devices. The increasing use of nonisotopic immunoassay systems is likely to have the greatest impact on standardization and total quality assurance of the system. To enable sponsors of new drugs to conduct the necessary studies, Congress permitted the FDA to exempt a drug from this prohibition and certain other requirements of the Act for the limited purpose of conducting clinical studies. In the US, FDA approval is required for a new drug for the indications specified in the New Drug Application. The FDA has, among its responsibilities, the regulation of medical devices. In the semantic framework of the FDA device evaluation process, a determination of whether a device is considered old or new is made based on whether it was in the commercial marketplace at the time of passage of the Medical Device Amendments of 1976.