August, 2010

Leslie Kux,
Acting Assistant Commissioner for Policy
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville MD 20852

Dear Ms. Kux:

The Blue Cross and Blue Shield Association ("BCBSA") wishes to submit comments
regarding the Food and Drug Administration’s oversight of laboratory developed tests
(“LDTs”), as requested in the Federal Register on June 17, 2010 (75 Fed. Reg. 34463).

BCBSA represents the 39 independent Blue Cross and Blue Shield (BCBS) Plans that
collectively provide health coverage to nearly 100 million – one in three – Americans. In
addition to speaking on behalf of BCBS Plans, who need accurate, evidence-based
sources of information for researching reimbursement policy, BCBSA is also submitting
comments on behalf of BCBSA’s Technology Evaluation Center (TEC), which
conducts evidence-based health technology assessments of a variety of medical
interventions including genetic tests. Since 1997, TEC has published 24 Assessments
and Special Reports addressing various laboratory-developed genetic tests on its
publicly available website (www.bcbs.com/tec ), with documents from the most recent 3
years remaining accessible at any given time.

BCBSA strongly supports an FDA initiative to develop a program for oversight for LDTs.
We believe the FDA risk-based approach toward regulating medical devices has served
the FDA well and has helped to promote and protect public health.

While BCBSA understands the reasoning for providing enforcement discretion to

laboratory developed tests in the past, we agree with FDA that as diagnostic tests have
become more complex and of particular importance in the move toward a paradigm of
personalized health care, this regulatory exception no longer makes sense. Moving
forward, we believe that any credible risk-based approach toward regulation of
laboratory tests should rest on the planned uses and merits of the tests themselves and
not on the business model by which the tests are brought to market.

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It is our view that the current system which allows LDTs to enter the market without pre-
market review fails to provide timely pre-market assurance of both the analytical and
clinical performance of new tests, allows introduction of tests with no transparency in
performance, and allows introduction of tests that might be in some cases better
categorized as investigational rather than as clinical assays. Any new framework
developed for regulation of LDTs should take into account these current flaws in the
regulatory system.

We concur with the need for thoughtful development in any new regulatory framework.
A new system should account for the need to foster innovation in testing, must be in
tune with the rapid and iterative life cycle of diagnostic medical devices, and must
address the unique difficulties in establishing performance for tests for rare or orphan
diseases. Yet in the setting of these challenges FDA should continue to assure that
patients will obtain clinical benefit from the tests they undergo.

FDA will be challenged to develop a clear risk-based classification and to use its
resources wisely to ensure flexible, fair, but scientifically defensible requirements for all
new diagnostics. BCBSA encourages FDA to utilize its advisory panels as classification
systems are developed and to continue a robust public dialogue to ensure that all the
nuances of this new regulatory initiative are understood and addressed as FDA moves
forward.

BCBSA has three specific comments with regard to a new framework.

• First, we urge the FDA to go forward with the regulatory framework. A mechanism
of self-regulation is not sufficient to assure that clinical laboratory tests available to
the public will be beneficial. Current thinking is that tests can be just as potentially
beneficial or harmful as therapeutic interventions. In that perspective we urge the
FDA to bring the clinical framework for laboratory testing to a comparable standard.

• Second, we believe the National Institutes of Health (NIH) genetic testing registry
may be a unique resource for communicating information on all tests (LDTs and
tests in conventional multi-site distribution) to interested stakeholders. As we have
already commented to NIH in a letter dated July 14, 2010, (see attached) in order
for such a registry to be credible it must be mandatory rather than voluntary and
must have some form of standardized format and quality control of registry content.
In light of the lack of regulatory authority by NIH, we have recommended
partnerships be sought with either FDA or the Centers for Medicare and Medicaid
Services (CMS). We hope there will be discussion between government players to
ensure resources for this new endeavor are wisely used.

• Third, we assume that regulation of LDTs does not signal a change in the basic
nature of FDA review, which for high risk products is aimed at establishing “safety
and effectiveness.” We note that FDA currently defines effectiveness in 21 CFR
860.7(e)(1) by stating “there is reasonable assurance that a device is effective
when it can be determined, based upon valid scientific evidence, that in a significant

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 portion of the target population, the use of the device for its intended use and
conditions of use, when accompanied by adequate directions for use and warnings
against; unsafe use, will provide clinically significant results.” As FDA moves
forward developing guidances or new classification regulations to support its
initiative to provide a framework for LDTs, we urge the agency whenever possible
to bring its terminology and regulatory process into conformity with current best
practices such as those employed under the ACCE model
http://www.cdc.gov/genomics/testing/acce used by the Evaluation of Genomics
Applications in Practice and Prevention (EGAPP). We believe such a move will
help promote standardization in the arena of evaluation of new diagnostics and will
help clarify expectations and move the field forward.

We look forward to following the progress of FDA’s work closely and hope to continue to
have an opportunity to provide input as the agency works to continue to work to
promote public health.

Sincerely,

Justine Handelman Allan Korn, MD

Executive Director Senior Vice President and Chief Medical
Office of Legislative and Regulatory Policy Officer
Office of Clinical Affairs