Biology Reference
In-Depth Information
samples utilized to bridge the assay would be those samples comprising the training and test
sets. This allows for accurate setting of the classifier in each iteration of the test. Each time a
test is bridged from one version to another, amounts of sample are consumed in the process.
A number of bridges of an assay can quickly utilize all of the available samples. This point
cannot be understated, as sample availability can be a limiting factor in the ability to opti-
mize an assay. If all sample material has been exhausted, the accuracy of the bridge can be
brought into question, or additional samples may be needed to strengthen the migration to
the updated version of the assay. Given the importance of sample availability, it is key to col-
lect sufficient samples from early clinical development programs to support the development
of the diagnostic. This often includes collecting as many aliquots from each patient as possi-
ble. Because collecting as many samples from each patient is of such importance, the clinical
material utilized in the assay must be readily available. Therefore, it is important to ensure
either correlation between disease site information and a surrogate tissue, or sufficient access
to the disease site tissue itself. However, often obtaining multiple biopsies to access disease
site tissue samples is not a safe or logistically feasible option. In most indications, this means
developing assays in more readily available biofluids such as whole blood, serum, or plasma,
or utilizing paraffin embedded tissues as starting material for diagnostic assays after estab-
lishing correlation with the diseased tissue. Utilization of these more readily available tissues
helps improve the potential for having sufficient clinical material for assay development and
validation, and also eases the transition to commercial clinical testing laboratory implemen-
tation. A diagnostic requiring disease site tissue to function properly will likely be limited
not only by sample for assay development, but also availability of sample from patients in
the commercial clinical testing setting. Many patients may elect not to have the sample taken
unless the test has an extremely powerful predictive value.
7.4.2.6 Technical Considerations
In addition to the aforementioned general considerations for diagnostic development,
there are also a number of technical considerations that must be addressed to ensure suc-
cessful translation of a diagnostic from discovery through clinical validation.
According to feedback obtained by interaction via pre-IDE meetings with the FDA, it has
been noted that most changes to an assay are considered major or substantive changes and
therefore repeat validation following these changes would be necessary. This includes, but
is not limited to, enzymes, buffers, software, algorithm, and instrument changes. With this
definition in mind, the companion diagnostic developer must be aware of the status of each
component of the assay.
7.4.2.7 Testing Volume
Extensive marketing research is required to determine the expected volume of testing for
a particular companion diagnostic device. The components of this include the therapeutic
disease prevalence, physician-required turnaround time, current standard of care treatment,
competition in the market, availability of platform in testing market, and configuration of the
assay itself, as well as additional factors. It is important to conduct this research early in the
development of the companion diagnostic assay, as feedback from this research can guide the
development of a more market-ready assay. For example, if the test will be relatively low vol-
ume due to low disease prevalence and a less time-sensitive turnaround, then multiplexing
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