On July 14, 2011, the Food and Drug Administration (FDA) issued a Draft Guidance on In Vitro Companion Diagnostic Devices (Guidance). The Guidance is intended to assist (1) sponsors developing a therapeutic product that depends on the use of an in vitro companion diagnostic device (Companion Diagnostic) for its safe and effective use, and (2) sponsors developing an in vitro companion diagnostic device intended to be used with a corresponding therapeutic product. The Guidance includes a narrow definition of a Companion Diagnostic and provides an overview of the FDA’s expectations for the contemporaneous development and approval of a therapeutic product and a Companion Diagnostic, with the goal of ultimately stipulating the use of the Companion Diagnostic with the therapeutic product in the instructions for use in the labeling of both the diagnostic device and the therapeutic product as well as in any generic equivalents of the therapeutic product.

The Guidance defines a Companion Diagnostic as a device that provides information that is essential for the safe and effective use of a corresponding therapeutic product.1 To be essential, the use of the Companion Diagnostic with the therapeutic products is necessary to allow the benefits of the therapeutic to exceed its risks. Tests that may be useful but are not a determining factor in the safe and effective use of the therapeutic product, and most laboratory developed tests (LDTs) for which the FDA does not currently require premarket clearance or approval, will not fall within the scope of the Guidance.2

While the FDA expects that the Companion Diagnostic and the therapeutic product will be approved at the same time, there are certain circumstances in which the FDA might approve a therapeutic product before the Companion Diagnostic designated in its labeling is cleared or approved. For example, the FDA indicated that it might approve a therapeutic product that is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists and the benefits of use of the product, even without a Companion Diagnostic, far outweigh the risks. In addition, the FDA might approve a revision to the labeling of an already approved therapeutic product when it is necessary to include use of a Companion Diagnostic to address a serious safety issue.

The review and approval of a Companion Diagnostic and the corresponding therapeutic product will be a collaborative effort of the applicable offices at the FDA. This means that approval (by way of a premarket approval application) or clearance (by way of a 510(k)) of the Companion Diagnostic will be subject to the applicable medical device regulations and approval of the therapeutic product will be subject to relevant drug or biologics product regulations. Because an uncleared or unapproved diagnostic device used to make treatment decisions in a clinical trial of a therapeutic product would be considered a significant-risk device, the clinical trial of a proposed Companion Diagnostic will have to be conducted in accordance with the investigational device exemption (IDE) regulations. It is possible, however, to study the Companion Diagnostic and the therapeutic product in the same investigational study if it meets both the IDE requirements and the investigational new drug requirements. In order to design an appropriate clinical trial, sponsors are urged to meet with the relevant product review divisions as early as possible.

The FDA already recognizes the importance of biomarkers in identifying responders and non-responders to drugs, avoiding adverse events, and optimizing drug dose, and the FDA’s website includes a table that lists FDA-approved drugs with pharmacogenomic biomarker information in their labels. However, few of these drugs have labels that stipulate the use of a Companion Diagnostic, and the only drug that is mentioned in the Guidance as an example of a therapeutic with a Companion Diagnostic is Herceptin (trastuzumab), a drug that is used to treat metastatic breast cancer and gastric cancer, and the related HER-2 test, which can identify patients for whom the drug will not be effective or will cause severe adverse effects. This Guidance is a recognition by the FDA of the potential of personalized medicine and the growing use of targeted medicines with tests that will better define the targets. It does little, however, to make the approval of therapeutics and Companion Diagnostics more predictable and does not change the need for sponsors developing such products to collaborate early in the development process and meet with the FDA.

This Guidance is a draft and begins with the FDA’s usual notice that guidance documents describe its current thinking on a topic and do not establish legally enforceable responsibilities. Comments on the Guidance, which can be accessed using the link below, should be submitted by September 12, 2011 in order to ensure consideration by the FDA before it begins work on the final version.