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by a particular use. In this instance, a test for the prognosis of breast cancer would
require different data than a test used to diagnose the disease. A number of tumor
markers have already cleared as Class II devices.
Evaluation of Companion Diagnostics/Therapeutic
Until recently there was no development pathway for FDA approval of the necessary
companion diagnostic tests and their associated targeted therapies. In 2007, the Critical
Path Institute (Tempe, AZ) used a $2.1 million Arizona state grant to work with the
FDA and the NCI to standardize how companion diagnostics and therapies for cancer
are evaluated. The goal of this collaboration was to establish the performance stan-
dards that would serve as the model for future FDA co-submissions of companion
diagnostic tests and cancer drugs. The ultimate goal of the project is to guide the
choice of targeted therapy so that patients receive the most effective treatments.
The FDA issued guidance for “In Vitro Companion Diagnostic Devices” on 6
August 2014 after the release of the draft in 2011.. The development of therapeutic
products that depend on the use of a diagnostic test to meet their labeled safety and
effectiveness claims has become more common. These technologies – including
IVD companion diagnostic devices – are making it increasingly possible to indi-
vidualize, or personalize, medical therapy by identifying patients who are most
likely to respond, or who are at lower or higher risk for a particular side effect. This
guidance defi nes IVD companion diagnostic devices, provides information for
industry and FDA on possible premarket regulatory pathways and FDA’s regulatory
enforcement policy, and describes certain statutory and regulatory approval require-
ments relevant to therapeutic labeling.
The FDA recognizes that contemporaneous development of a therapeutic prod-
uct and corresponding diagnostic device, although ideal, is not always possible.
Along these lines, an IVD companion diagnostic device may be (1) a new device,
(2) a new version of existing device, or (3) an existing device approved/cleared for
another purpose. For a new device, the FDA recommends that a therapeutic product
and its corresponding companion diagnostic should be developed and approved
contemporaneously. In most cases, assuming device/test results are essential for
product safety and effi cacy, the FDA will not approve the product or use of the
product with the device if the FDA has not also approved/cleared the device itself.
However, the FDA has discretion to approve a therapeutic product for use with a
companion device, even if the FDA has not yet approved/cleared the device. In this
situation, the FDA expects it will approve/clear the device subsequently, and that
sponsors will revise relevant therapeutic product labeling accordingly. The FDA
will also consider whether additional protections are necessary.
In this context, the FDA refers to two scenarios where it may approve a therapeutic
product for use with an unapproved/uncleared companion device: (a) a new product
will treat a serious or life-threatening condition for which no satisfactory alternative
treatment exists, and benefi ts from using the unapproved/uncleared companion
22 Regulatory Aspects of Personalized Medicine