Translating Biomarker Discovery into Companion Diagnostics through Validation and Regulatory Consideration - Genomic Biomarkers for Pharmaceutical Development - page 159

glance at the regulatory pathway to commercial use of an in vitro diagnostic in association
with a therapeutic agent, it is meant to present the complexity of approval of an in vitro diag-
nostic in multiple geographic locations under the authority of a number of regulatory bodies.
It is critical to understand the requirements of the specific geographic location in which you
seek approval or clearance of the diagnostic to ensure appropriate planning and design of
analytical and clinical validation studies.
7.3.6 510(k) vs PMA
There are two types of device approvals and clearances. The distinction for a device is
made as either Premarketing Notification or a 510(k), or a Premarket Approval or PMA.
The key distinction from the FDA viewpoint is the level of risk of the device. A 510(k) is for
lower risk devices where the FDA requires only substantial equivalence to a currently mar-
keted device for which a PMA is not required [10] . The FDA defines substantially equivalent
in the following manner:
● has the same intended use as the predicate; and
● has the same technological characteristics as the predicate; or
● has the same intended use as the predicate; and
● has different technological characteristics and the information has been submitted
to the FDA;
● does not raise new questions of safety and effectiveness; and
● demonstrates that the device is at least as safe and effective as the legally marketed
device [10] .
The FDA may require different information from different sponsors depending on the
intended use of the device, the technology involved, the therapeutic area to which it is
being applied, etc., so there is no uniform data package to ensure demonstration of sub-
stantial equivalence. The ultimate decision from the FDA on a 510(k) submission is a clear-
ance decision, not an approval decision. The 510(k) definition is important to understand
in the diagnostic development process if you are developing a device similar to a currently
marketed device. The FDA has in numerous public meetings and also has specified in the
most recent draft guidance [1] that devices intended to inform a clinical decision on a ther-
apeutic are considered high-risk devices and are therefore subject to the PMA process. The
PMA 'is the most stringent type of device marketing application required by the FDA [11] .'
Rather than a clearance decision, the PMA is either granted or refused approval. As the
FDA states:
'PMA approval is to be based on a determination by FDA that the PMA contains sufficient valid scien-
tific evidence that provides reasonable assurance that the device is safe and effective for its intended use or
uses [11] .'
Due to this distinction, much more thorough data are required in the PMA submission.
The burden for PMA approval stated above should be strongly considered when develop-
ing, validating, and applying a companion diagnostic with a therapeutic product.