Personalized medicine (also referred to as “precision medicine”) relies on the use of in 17 vitro diagnostic (IVD) devices to detect and measure biomarkers and other individual 18 characteristics of disease or other conditions with the goal of better directing patient 19 treatment. With the continued growth of personalized medicine, an increasing number of 20 clinical investigations of therapeutic products (also referred to here as therapeutic product 21 trials or studies) are using investigational IVDs to guide the management of subjects in 22 such investigations. In some cases this has led to the development of an in vitro 23 companion diagnostic device that is essential to the safe and effective use of the 24 therapeutic product, once approved. The information generated by the use of 25 investigational IVDs in therapeutic product trials may affect important aspects of 26 treatment for the enrolled subjects and, by doing so, directly influence the types of 27 therapeutic products or therapeutic management strategies the subjects may be exposed to 28 during the study. Therefore, use of an investigational IVD in a therapeutic product trial 29 may pose significant risk to subjects. FDA is concerned that sponsors (including sponsor-30 investigators) and IRBs may not understand that many IVDs used as a critical part of 31 therapeutic product trials are investigational. This guidance document is intended to 32 inform stakeholders, including institutional review boards or institutional review 33 committees (referred to hereafter as IRBs) reviewing clinical investigations, and sponsors 34 that therapeutic product4 trials that include investigational IVDs are subject to FDA’s 35 Investigational Device Exemption (IDE) regulation (21 CFR Part 812), regardless of the 36 source or manufacturer of the device, in addition to the Investigational New Drug (IND) 37 regulation (21 CFR Part 312).