FDA recently released, as a part of President Obama's
Precision Medicine Initiative, two draft
guidance documents proposing what the Agency is calling a
"flexible and streamlined approach" for regulating next
generation sequencing ("NGS")-based tests. The first
guidance document, "Use of Standards in FDA Regulatory Oversight of
Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs)
Used for Diagnosing Germline Diseases," proposes, in part,
that certain NGS-based tests (those for germline, e.g., hereditary,
diseases) may be suitable for denovo
classification and, if FDA makes a class II determination,
potentially appropriate for exemption from premarket notification
requirements.
In evaluating whether a 510(k) is needed to provide reasonable
assurance of the safety and effectiveness of an NGS-based test for
germline diseases, FDA will consider, among other things,
assurances of analytical and clinical validity. These assurances
are consistent with the parameters that are assessed as part of
most IVD premarket reviews—analytical performance and
clinical performance. (For more on IVD premarket reviews, see the
Overview of IVD Regulation page on FDA's
website.)
To provide assurance of analytical validity for an NGS-based test
for germline diseases, FDA proposes that NGS-based test developers
can follow the recommendations outlined in Section VI of the
guidance document referenced above. (The section provides
"Recommendations for Design, Development and Validation of
NGS-based Tests for Germline Diseases," which "FDA
believes can help demonstrate a reasonable assurance that an
NGS-based test for germline diseases is analytically valid.")
In the future, FDA suggests it may recognize standards consistent
with those recommendations, and conformance with those standards
could support or provide reasonable assurance of a test's
analytical validity. FDA also suggests that its analytical
validity-related recommendations could also form the basis for
special controls or conditions for 510(k) exemption in the
future.
To provide assurance of clinical validity for any NGS-based test
(i.e., not limited to those for germline diseases), FDA proposes
that NGS-based test developers may utilize assertions of
genotype-phenotype correlations and underlying data from
FDA-recognized public genetic variant databases, as outlined in and
consistent with FDA's second guidance document, "Use of Public Human Genetic Variant Databases to
Support Clinical Validity for Next Generation Sequencing
(NGS)-Based In Vitro Diagnostics." In some instances, FDA
suggests that NGS-based test developers may not need to submit
additional clinical data beyond what is provided from the
recognized genetic variant database. Comments on both draft
guidances are due October6, 2016.
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