Since 1992, FDA has received numerous Request for Designation (RFD’s) for combination product diagnostic breath tests in which the drug component is an isotope-labeled (typically 13C) substrate and the device components capture and/or analyze exhaled breath for detection of labeled carbon dioxide or other gases. These RFD’s have addressed the use of breath test combination products for the diagnosis of H. pylori, gastric emptying disorders, carbohydrate malabsorption, intestinal bacterial overgrowth, insulin resistance, liver function, for monitoring enzyme activity, for assessment of small intestinal function, and for use in pharmacological research. In some cases, such as diagnosis of H. pylori, the substrate is metabolized by bacteria present in the stomach or gut; in others, the substrate is metabolized by the patient when a particular disease or condition is present. Upon metabolism of the substrate, labile metabolites are exhaled that can be uniquely traced to the substrate. Thus, for example, the presence, absence, or rate of release of isotope-labeled carbon dioxide in exhaled breath is intended to be indicative of the presence or absence of the disease or condition in question.
In these cases, FDA determined that the primary mode of action (PMOA) of such combination products was attributable to the device components’ role in the in vitro diagnosis of the disease or condition in question, while the drug component plays a secondary role in acting as the diagnostic substrate. FDA assigned the Center for Devices and Radiological Health (CDRH) to be the lead agency center for reviewing these products.
In a recent case, FDA determined that two marketing applications were not necessary for a diagnostic breath test combination product. In this recent case, FDA determined that the premarket approval (PMA) provisions of the Act (21 CFR 814) would enable the Agency to determine the safety and effectiveness of both the device and drug components of the combination product. CDRH will consult or collaborate with CDER as appropriate on issues such as chemistry and manufacturing, pharmacology and toxicology, and clinical issues related to the drug component.
Sponsors wishing to discuss the regulation of a particular breath test combination product may contact the Office of Combination Products at 301-796-8930, or CDRH’s Office of In Vitro Diagnostic Evaluation and Safety, Division of Chemistry and Toxicology Devices, at 301-796-5450.