675device outweigh risks; and (b) an already approved product exists, but labeling for
that product must be revised to address serious safety concerns, and use of an unap-
proved/uncleared companion device may address such concerns.
If safe and effective use of a therapeutic product depends on use of a companion
diagnostic device, the device should be available once the FDA approves the prod-
uct. Thus, the FDA will apply a “risk-based approach” to determine regulatory path-
ways for IVD companion diagnostic devices, where the level of risk to patients and
available controls to mitigate risks dictate whether the device will require PMA
(premarket approval) or 510(k) clearance. Except in certain situations, such as (a)
and (b) discussed above, the FDA intends to approve/clear a therapeutic product and
its corresponding companion diagnostic device at the same time. Therefore, the
FDA encourages sponsors to time clinical studies and regulatory submissions to
facilitate concurrent approval.
In a situation where a relevant device is already legally marketed, but the device
manufacture intends to market the device for a new use as a IVD companion diagnos-
tic device for a new therapeutic product, the FDA considers this to be “a major change
in the intended use of the device, raising new questions of safety and effectiveness.”
Thus, the FDA must approve/clear the new use of the device with the new product.
Regarding labeling of a relevant therapeutic product, the Draft Guidance notes
that existing regulations (21 CFR 201.56 and 21 CFR 201.57) indicate that product
labeling must include information relating to relevant laboratory tests. For example,
if a therapeutic product is only safe and effective in a patient subpopulation identi-
fi ed by a diagnostic test, the Indications and Usage section of the labeling must
defi ne the patient subpopulation. Likewise, if a diagnostic test is essential for moni-
toring benefi cial or adverse effects, the Warnings and Precaution section must iden-
tify the type of test. In addition, labeling must include information about the type of
device (i.e., intended use of the device), rather than a specifi c manufacturer’s device.
Also, if the FDA approves/clears a companion diagnostic device after it approves a
relevant therapeutic product, sponsors must update product labeling accordingly.
Regarding labeling of IVD companion diagnostic device, the Draft Guidance states
such labeling should specify the intended use of the device, as well as relevant
therapeutic products. When appropriate, the labeling can name a class of therapeu-
tic products, rather than specifi c products within the class. Device labeling should
be expanded (i.e., approved/cleared) to refl ect use in a new disease or setting, or
with a different/new therapeutic product.
The FDA will consider any diagnostic device used to make treatment decisions
in a clinical trial to be an “investigational device,” unless the device is used in a
matter already approved/cleared. A sponsor must comply with investigational
device exemption (IDE) regulations that address signifi cant risk devices, if one uses
a diagnostic device to make critical treatment decisions, such as patent selection,
treatment assignment, or treatment arm.
A diagnostic device and therapeutic product may be studied in the same investi-
gational study, as long as the study otherwise meets IDE and IND regulations.
Sponsors should include information about a planned use of an IVD companion
diagnostic device and its use in clinical trials in an investigational submission.
Evaluation of Companion Diagnostics/Therapeutic