[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
21ST CENTURY CURES: EXAMINING THE REGULATION OF LABORATORY-DEVELOPED
TESTS
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
SECOND SESSION
__________
SEPTEMBER 9, 2014
__________
Serial No. 113-171
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
____________
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COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
RALPH M. HALL, Texas HENRY A. WAXMAN, California
JOE BARTON, Texas Ranking Member
Chairman Emeritus JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky Chairman Emeritus
JOHN SHIMKUS, Illinois FRANK PALLONE, Jr., New Jersey
JOSEPH R. PITTS, Pennsylvania BOBBY L. RUSH, Illinois
GREG WALDEN, Oregon ANNA G. ESHOO, California
LEE TERRY, Nebraska ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan GENE GREEN, Texas
TIM MURPHY, Pennsylvania DIANA DeGETTE, Colorado
MICHAEL C. BURGESS, Texas LOIS CAPPS, California
MARSHA BLACKBURN, Tennessee MICHAEL F. DOYLE, Pennsylvania
Vice Chairman JANICE D. SCHAKOWSKY, Illinois
PHIL GINGREY, Georgia JIM MATHESON, Utah
STEVE SCALISE, Louisiana G.K. BUTTERFIELD, North Carolina
ROBERT E. LATTA, Ohio JOHN BARROW, Georgia
CATHY McMORRIS RODGERS, Washington DORIS O. MATSUI, California
GREGG HARPER, Mississippi DONNA M. CHRISTENSEN, Virgin
LEONARD LANCE, New Jersey Islands
BILL CASSIDY, Louisiana KATHY CASTOR, Florida
BRETT GUTHRIE, Kentucky JOHN P. SARBANES, Maryland
PETE OLSON, Texas JERRY McNERNEY, California
DAVID B. McKINLEY, West Virginia BRUCE L. BRALEY, Iowa
CORY GARDNER, Colorado PETER WELCH, Vermont
MIKE POMPEO, Kansas BEN RAY LUJAN, New Mexico
ADAM KINZINGER, Illinois PAUL TONKO, New York
H. MORGAN GRIFFITH, Virginia JOHN A. YARMUTH, Kentucky
GUS M. BILIRAKIS, Florida
BILL JOHNSON, Missouri
BILLY LONG, Missouri
RENEE L. ELLMERS, North Carolina
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee JIM MATHESON, Utah
PHIL GINGREY, Georgia GENE GREEN, Texas
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey JOHN BARROW, Georgia
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
H. MORGAN GRIFFITH, Virginia KATHY CASTOR, Florida
GUS M. BILIRAKIS, Florida JOHN P. SARBANES, Maryland
RENEE L. ELLMERS, North Carolina HENRY A. WAXMAN, California (ex
JOE BARTON, Texas officio)
FRED UPTON, Michigan (ex officio)
C O N T E N T S
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Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 2
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 3
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 5
Hon. Anna G. Eshoo, a Representative in Congress from the State
of California, prepared statement.............................. 40
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, prepared statement................................... 141
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, prepared statement.............................. 142
Witnesses
Jeffrey Shuren, M.D., J.D., Director, Center for Devices and
Radiological Health, Food And Drug Administration.............. 6
Prepared statement........................................... 9
Answers to submitted questions \1\........................... 170
Andrew Fish, Executive Director, AdvaMed Diagnostics............. 45
Prepared statement........................................... 47
Kathleen Behrens Wilsey, Ph.D., Co-Founder, Coalition For 21st
Century Medicine............................................... 66
Prepared statement........................................... 68
Answers to submitted questions............................... 171
Alan Mertz, President, American Clinical Laboratory Association.. 83
Prepared statement........................................... 85
Answers to submitted questions............................... 174
Christopher Newton-Cheh, M.D., Assistant Professor of Medicine,
Harvard Medical School, Cardiologist, Massachusetts General
Hospital....................................................... 108
Prepared statement........................................... 110
Charles Sawyers, M.D., Immediate-Past President, American
Association for Cancer Research................................ 116
Prepared statement........................................... 118
Submitted Material
S. 976 \2\....................................................... 6
Statement of the American Medical Association, submitted by Mr.
Burgess........................................................ 144
Statement of the Clinical Laboratory Improvement Amendments
program, submitted by Ms. Shakowsky............................ 152
Statement of the Small Biotechnology Business Coalition,
submitted by Mr. Pitts......................................... 155
Statement of the Association for Molecular Pathology, submitted
by Mr. Pitts................................................... 157
Statement of Invitae Corporation, submitted by Mr. Pitts......... 159
Statement of the American Association of Bioanalysts and the
National Independent Laboratory Association, submitted by Mr.
Pitts.......................................................... 162
Statement of Combination Products Coalition, submitted by Mr.
Pitts.......................................................... 164
Article entitled, ``How Bright Promise in Cancer Testing Fell
Apart,'' in The New York Times, July 7, 2011, submitted by Mr.
Waxman......................................................... 166
----------
\1\ Dr. Shuren did not respond to questions for the record.
\2\ The bill is available at http://docs.house.gov/meetings/IF/
IF14/20140909/102625/HHRG-113-IF14-20140909-SD009.pdf.
21ST CENTURY CURES: EXAMINING THE REGULATION OF LABORATORY-DEVELOPED
TESTS
----------
TUESDAY, SEPTEMBER 9, 2014
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 9:32 a.m., in
room 2322 of the Rayburn House Office Building, Hon. Joe Pitts
(chairman of the subcommittee) presiding.
Members present: Representatives Pitts, Burgess, Shimkus,
Blackburn, Guthrie, Griffith, Bilirakis, Ellmers, Pallone,
Schakowsky, Green, Barrow, and Waxman (ex officio).
Also present: Representative Eshoo.
Staff present: Clay Alspach, Chief Counsel, Health;
Leighton Brown, Press Assistant; Noelle Clemente, Press
Secretary; Sydne Harwick, Legislative Clerk; Robert Horne,
Professional Staff Member, Health; Carly McWilliams,
Professional Staff Member, Health; Tim Pataki, Professional
Staff Member; Chris Sarley, Policy Coordinator, Environment and
Economy; Heidi Stirrup, Health Policy Coordinator; John Stone,
Counsel, Health; Ziky Ababiya, Democratic Staff Assistant; Phil
Barnett, Democratic Staff Director; Eric Flamm, Democratic FDA
Detailee; Debbie Letter, Democratic Staff Assistant; Karen
Nelson, Democratic Deputy Committee Staff Director for Health;
and Rachel Sher, Democratic Senior Counsel.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. Pitts. The subcommittee will come to order. The chair
will recognize himself for an opening statement.
Today's hearing is another in a series of 21st Century
Cures hearings. Primarily focuses on FDA's July 31, 2014,
notification to Congress that it intends to issue draft
guidance on a framework for oversight of the laboratory-
developed test, the LDTs. This notification was required by
Section 1143 of the Food and Drug Administration's Safety and
Innovation Act of 2012, and provides us with an opportunity to
hear from the Agency about whether it has adequately answered
the myriad of procedural and substantive questions that were
the subject of much debate leading up to the passage of FDASIA.
It is indisputable that the draft guidance documents the
Agency recently released would fundamentally alter the
regulatory landscape for the review and oversight of LDTs and
the clinical labs that develop them. That fact alone has raised
legitimate concerns about whether FDA can or should use
guidance to promulgate a new regulatory approach. It is also
indisputable that innovative laboratories and health care
providers develop and perform tests and procedures that advance
personalized patient care. Because of the critical role they
can play in the decisions patients make with their doctors,
these tests, regardless of who develops or manufactures them,
must be accurate and reliable. Any framework adopted must not
only prioritize patient safety, which should always be
paramount, but also encourage robust investment and allow for
continued innovation. In order for that to happen, a company or
venture capitalist that invests in the development, testing,
and FDA review of a diagnostic product must have the certainty
that labs will not copy it and promote their alternatives the
next day. On the other hand, many innovative tests and
procedures are developed in labs, including continuous,
iterative improvements to FDA-approved products that often
become the standard of care. Any regulatory approach must
carefully address these complex issues.
Dr. Shuren has been a key voice throughout the 21st Century
Cures Initiative, and I thank him for his willingness to come
to the table yet again. The Committee invited CMS to testify on
its roles and responsibilities administering the Clinical
Laboratory Improvement Amendments regulations, which includes
lab practices, certification, and personnel, but they were
unable to do so.
We have a number of questions about FDA's proposed path
forward, and I look forward to hearing from all of our
witnesses on the second panel about its potential impact.
And with that, the chair yields back, and now recognize the
Ranking Member, Mr. Pallone, for 5 minutes.
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
The Subcommittee will come to order.
The Chair will recognize himself for an opening statement.
Today's hearing is another in a series of 21st Century
Cures hearings and primarily focuses on FDA's July 31, 2014
notification to Congress that it intends to issue draft
guidance on a framework for oversight of laboratory developed
tests (LDTs).
This notification was required by Section 1143 of the Food
and Drug Administration Safety and Innovation Act of 2012, and
provides us with an opportunity to hear from the agency about
whether it has adequately answered the myriad of procedural and
substantive questions that were the subject of much debate
leading up to the passage of FDASIA.
It is indisputable that the draft guidance documents the
agency recently released would fundamentally alter the
regulatory landscape for the review and oversight of LDTs and
the clinical labs that develop them. That fact alone has raised
legitimate concerns about whether FDA can or should use
guidance to promulgate a new regulatory approach.
It is also indisputable that innovative laboratories and
health care providers develop and perform tests and procedures
that advance personalized patient care. Because of the critical
role they can play in the decisions patients make with their
doctors, these tests-regardless of who develops or manufactures
them-must be accurate and reliable.
Any framework adopted must not only prioritize patient
safety-which should always be paramount-but also encourage
robust investment and allow for continued innovation.
In order for that to happen, a company or venture
capitalist that invests in the development, testing, and FDA
review of a diagnostic product must have the certainty that
labs will not copy it and promote their alternatives the next
day.
On the other hand, many innovative tests and procedures are
developed in labs-including continuous, iterative improvements
to FDA-approved products that often become the standard of
care. Any regulatory approach must carefully address these
complex issues.
Dr. Shuren has been a key voice throughout the 21st Century
Cures initiative, and I thank him for his willingness to come
to the table yet again.
The Committee invited CMS to testify on its roles and
responsibilities administering the Clinical Laboratory
Improvement Amendments regulations, which includes lab
practices, certification, and personnel, but they were unable
to do so.
We have a number of questions about FDA's proposed path
forward, and I look forward to hearing from all our witnesses
on the second about its potential impact.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts.
New technologies and advances in medicine can improve the
quality of life for millions of Americans, but the use of these
advances can also pose serious risks to individual patients if
they are not clinically accurate. And this is why we have
regulation, and it is why the FDA has proposed commonsense
changes that merely bring safety regulations up-to-speed with
medical progress.
Lab-developed tests have come a long way since Congress
gave FDA the authority to regulate all in vitro diagnostic
tests in 1976. Advances in science and technology have enabled
labs to develop more sophisticated tests that allow physicians
to identify genetic factors in diagnosing disease, and this has
allowed for early detection and more targeted medical
interventions.
Recently, genetic tests have identified specific gene
sequences which can help doctors design an approach that
patients are more likely to respond to. Identifying the HER2/
neu gene in patients allowed oncologists to target this unique
form of breast cancer with the drug Herceptin, instead of
radiation, vastly improving patient outcomes. Similarly, the
identification of mutations of the BRCA2 gene--or BRCA1 and
BRCA2 genes--can tell doctors if a patient is at an increased
risk for developing breast or ovarian cancer. Last year, the
actress Angelina Jolie revealed that she learned she was
carrying the BRCA1 gene and had an 87 percent risk of
developing breast cancer. Armed with this information, the
actress and her doctors took drastic action to prevent the
likely onset of cancer later in life, and based on the results
of this test, she took her future health into her own hands and
obtained a preventative double mastectomy. And while the
actress's actions have inspired considerable debate as to who
should get tested, and to what extent they should undertake
preventative measures, the fact remains that many of these
tests, including those used in detecting the BRCA genes, never
obtained FDA approval.
The consequences of information provided by tests like
these is great, which is why in 2010 the Subcommittee on
Oversight and Investigations and GAO explored tests directly
marketed to consumers. In its investigation, GAO found that
these tests provided individuals with a wide array of results,
with little consistency from test to test. And given the impact
on patients of the results of these tests, whether leading some
to miss real risk and others to seek treatment they don't need,
it should be clear that the information LDTs provide is of
grave consequence, and that is why many of the major cancer
advocacy groups welcome greater FDA oversight. In response to
the FDA's announcement, Calaneet Balas, Chief Executive of the
Ovarian Cancer National Alliance, said, and I quote, ``We in
the ovarian cancer community know firsthand the danger of a
test that hasn't gone through FDA approval. Oversure and early
detection tests for ovarian cancer came to market in 2008,
without independent verification and oversight, and this test
didn't accurately predict ovarian cancer cases, leading
otherwise healthy women to have their ovaries removed based on
bad information. When a test routinely provides false
positives, it is a problem, however, when that test is used to
diagnose and treat cancer, it is a potentially fatal problem
for millions of patients, and the clear demonstration of the
need for greater FDA oversight.''
I believe, Mr. Chairman, we have a responsibility to
provide patients with greater certainty. Furthermore, we want
to empower the medical community to harness these new
technologies to improve patient health and outcomes, and
eventually perhaps bend the lost curve. And while doctors have
years of training and their patients' interests at heart, they
are only as good as the tools they use. Physicians need to be
able to trust the results of diagnostic tests so they can
develop effective interventions.
It seems to me that regulating LDTs and other tests
differently based on who makes them doesn't make sense. This is
especially true given the scientific progress that has enabled
lab-developed tests to have even greater impacts, both for good
and for bad. If we want to promote the development of
personalized medicine, which I think we all recognize is the
future of medicine and the foundation of 21st Century Cures,
then we need to ensure that highly complicated and potentially
groundbreaking advances are clinically valid.
So, Mr. Chairman, this regulatory proposal has been in the
work for some time, so I think we are all eager to hear from
FDA about it. In addition, I look forward to hearing from other
stakeholders about their views of the FDA proposal, because it
is critical that its implementation ensures the safety of
patients, but also allows for the continued advancement of
cutting-edge personalized medicine, and I do not believe the
two are mutually exclusive, but rather can be mutually
supportive.
I also wanted to tell you again I enjoyed coming out to
Lancaster for the field hearing that we had a few weeks ago.
Thank you.
Mr. Pitts. Thank you. That was very productive and thank
you for coming out.
Chair now recognizes the Vice Chairman of the Subcommittee,
Dr. Burgess, 5 minutes for an opening statement.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman, and let me agree with
Mr. Pallone that the Cures roundtable that you had in Lancaster
was very worthwhile, and I think we all learned a lot. It is
just ironic that as we are proceeding with the Cures
Initiative, and trying to remove some of the barriers, we are
trying to facilitate the faster Cures, the promise of the 21st
Century, that this morning we are having a hearing on what I
consider to be a potential new roadblock or bottleneck on that
path to Cures.
I have been to every Cures event here in D.C., I have been
to several around the country. Repeatedly, we hear the
potential for genomic medicine to help us understand illness,
quickly diagnose it, and target treatment. This has been
embraced in a bipartisan manner, and I strongly believe in that
potential. Here is an example. A few months ago, the Centers
for Disease Control briefed my office on an emerging global
threat in the form of a virus. They had sequenced the virus,
provided information to researchers, and even knew where in the
particular country's jungle the virus had originated. It was
impressive, to say the least.
Here is another one. Back in 2009, H1N1, and many of us
remember, that subtype of the influenza A virus spread very
rapidly. During the first week of the outbreak, 16 laboratories
had laboratory-developed tests that could identify H1N1 from
other H1 viruses. Most were available within 24 hours. The
speed helped inform public health reactions. The FDA had no
approved commercial kit, however, if they had, under this
proposed framework which we are discussing this morning, if
they had had a test, even if it was much older and inferior,
these laboratory-developed tests would have been blocked from
doctors and public health officials.
The Food and Drug Administration regulation of tests like
these will be burdensome, and will slow the ability of clinical
laboratories to develop tests that can allow us to respond to
public health crises when they occur. This is also duplicative.
Congress established a regulatory framework applicable to labs
and laboratory testing, known as the Clinical Laboratory
Improvement Acts of 1988, or CLIA. I am concerned that
additional review of certain tests may be warranted, but
previously I did introduce legislation to meet patient needs
and ensure tests are accurate, reliable, and clinically valid
by making improvements to CLIA, not replacing it. I authored
Section 1143 of the Food and Drug's Safety Innovation Act so we
would be able to discuss how patients, the practice of
medicine, innovation and the economy could be harmed if the FDA
tried to fit laboratory-developed tests into a misaligned
definition of a medical device.
I fundamentally believe that the FDA has no statutory
authority to regulate laboratory-developed tests. For FDA to
have jurisdiction, it must have a traditional device and be
commercially distributed among the states. LDTs do not fall
under either category. Professional medical services are
currently not regulated by the FDA, and I do not believe they
should be.
In addition to these significant jurisdictional issues, the
process the Food and Drug Administration is considering is of
great concern. Even the courts determined that the FDA
authority over laboratory-developed tests, the Agency would
need to amend its current regulations through rulemaking. The
Food, Drug, and Cosmetic Act, the Administrative Procedures Act
of the Supreme Court all require disseminating rules to modify
current regulation, or to create legally-enforceable
regulations. Instead, the Agency continues on with its
jurisdictional power grab by attacking innovation, threatening
professional practice, and risking jobs in order to claim
authority over everything they see. They are doing this even at
the expense of allowing the core mission of the FDA to suffer
as a consequence. I can't think of a worse result: denying
patients and doctors innovative tests, while redirecting
resources that could be used to approve the next miracle drug
or device.
Mr. Chairman, I would ask unanimous consent to insert into
the record a statement by the American Medical Association on
the topic of this hearing this morning.
Mr. Pitts. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Burgess. And further, Mr. Chairman, I would also like
to submit into the record a copy of a bill, Senate Bill 796,
introduced March 23 of 2007, by Senator Obama and Senator Burr,
and this was the personalized medicine for all Americans by
expanding, accelerating genomics research and initiatives, and
one of the key parts of this legislation was to create within
CLIA a specialty area for molecular medicine and genetics and
clinical tests, instead of supplanting CLIA with the FDA, this
proposal would have actually modernized CLIA in an approach
that I think would be much more useful. So I will submit a copy
of this legislation for the record also.
I appreciate the indulgence, and I am going to yield back.
Mr. Pitts. Without objection, so ordered. \1\
---------------------------------------------------------------------------
\1\ The information has been retained in committee files and is
also available at http://docs.house.gov/meetings/IF/IF14/20140909/
102625/HHRG-113-IF14-20140909-SD009.pdf.
---------------------------------------------------------------------------
Mr. Pitts. All Members' opening statements will be made a
part of the record.
We have two panels today. On our first panel, we have Dr.
Jeff Shuren, Director, Center for Devices and Radiological
Health, U.S. Food and Drug Administration. Thank you very much,
Dr. Shuren, for coming today. You will have 5 minutes to
summarize, and your written testimony will be made a part of
the record. So at this point, Dr. Shuren, you are recognized
for 5 minutes for an opening statement.
STATEMENT OF JEFFREY SHUREN, M.D., J.D., DIRECTOR, CENTER FOR
DEVICES AND RADIOLOGICAL HEALTH, FOOD AND DRUG ADMINISTRATION
Dr. Shuren. Mr. Chairman and Members of the subcommittee,
thank you for the opportunity to testify today.
FDA's risk-based proposal for oversight of laboratory-
developed tests, or LDTs, is intended to ensure that patients
and their health care providers make major medical decisions
based upon accurate, reliable, and clinically-meaningful test
results, while encouraging development and access to new tests.
It would focus on those LDTs that pose the greatest risk to
patients if the results are not accurate.
FDA historically exercised enforcement discretion over
LDTs, namely, we opted not to enforce requirements LDT makers
were subject to, because back in 1976, LDTs were limited in
number, relatively simple tests, and typically were used to
diagnose rare diseases and uncommon conditions. LDTs offered
today, however, are often very different from those 40 years
ago. These tests have increased in both complexity and
availability, and many are now used to diagnose common diseases
and conditions. Increasingly, patients and their health care
providers are relying on the results of LDTs to make major
medical decisions. This evolution in complexity and volume has
significantly increased patient risk of harm from higher-risked
LDTs, and in some cases, there were already FDA-proved tests
available; tests proven to be safe and effective. So using an
LDT may put patients at unnecessary and avoidable risks.
These risks are not theoretical. There are cases of faulty
LDTs for cancer, infectious diseases, heart disease, and other
conditions leading to the wrong diagnosis, sometimes resulting
in the wrong treatment, or the failure to treat when an
effective therapy is available, and resulting in unnecessary
costs to our health care system and American taxpayers.
Numerous stakeholders believe the current system of uneven
oversight is having a negative impact on innovation.
Conventional device manufacturers may go through the premarket
review process and obtain clearance or approval for an IVD kit,
only to be faced with immediate competition from labs
manufacturing and marketing similar tests which did not obtain
premarket review or meet other requirements to assure their
tests are accurate and reliable. This has created disincentives
for them to invest in developing innovative tests, and creating
more U.S. jobs. But we have also heard from some academic
medical labs that they make tests to address unmet needs,
because there are no FDA-approved tests. We understand the
value of and the need for these types of tests. Therefore,
after listening to the perspectives from a broad range of
stakeholders, we opted not to propose the same level of
oversight for all the LDTs, nor to create a completely level
playing field between tests developed by labs and those made by
conventional manufacturers. Instead, we would continue to
exercise enforcement discretion for many LDTs, including those
that are low risk, LDTs for rare diseases, LDTs for unmet needs
where no FDA clear or approved test exists for that specific
intended use if made by a health care facility responsible for
the care of the patient. FDA would also focus on high and
moderate risk LDTs, and phase-in premarket review requirements
for this subset over 9 years using a public process that
includes expert advisory panels, as even recommended by the lab
community. This flexible approach would balance the importance
of accurate test results, with the need to facilitate
innovation and prevent disruption of access to diagnostics. The
more narrowly tailored and balanced oversight approach that we
would propose for LDTs is also critical to the success of
personalized medicine. Getting the right treatment to the right
patients depends upon having accurate and reliable tests to
identify who are, in fact, the right patients, and who should
not receive a treatment that can cause them harm but provide no
benefit. LDTs that steer patients to the wrong treatments
unnecessarily hurt patients, while jeopardizing the advancement
of personalized medicine altogether.
We seek to facilitate innovation and test development, and
we seek to assure that tests are safe and effective. The issue
should not be do we regulate, but rather how we should regulate
to best achieve both of these important objectives, the dual
objectives that are at the core of the FDA's statutory mission:
to protect and promote public health. Patients deserve no less,
and our health care system can afford no less. That is the
dialogue we need to have with laboratories, conventional device
industry, as well as patients, providers, and other members of
our medical device community.
So thank you for the opportunity to testify today, and I
will take any questions that you may have.
[The prepared statement of Dr. Shuren follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The chair thanks the gentleman.
And we will now go to questioning. I will begin the
questioning, and recognize myself 5 minutes for that purpose.
Dr. Shuren, issuing this guidance document would constitute
a significant change to almost four decades of Agency policy.
It goes well beyond a set of recommendations or a description
of current Agency thinking. How would implementing this new
regulatory framework via guidance comply with the
Administrative Procedures Act?
Dr. Shuren. So we have in place what we call an enforcement
discretion policy. Labs are currently subject to the
requirements of the Food, Drug, and Cosmetic Act. We have, as a
matter of policy, opted not to enforce compliance. Those kinds
of general policy statements where we are not imposing a new
requirement, that requirement is there but we are enforcing it,
we are not interpreting legal norms, are not subject to
Administrative Procedures Act to rulemaking.
Mr. Pitts. Understanding this approach would be a departure
from existing practice, and have a substantial impact on
regulated industry. Is the FDA not required to proceed with
notice and comment rulemaking?
Dr. Shuren. No. Under the Administrative Procedures Act,
this change in enforcement discretion policy is not subject to
those requirements.
Mr. Pitts. If a company or any other individual or entity
invest in the research and development of an innovative
diagnostic test and it is approved or cleared by FDA, I feel as
though labs should not be able to simply copy the technology
and market their own version the next day. This is particularly
relevant if the test was reviewed as a companion diagnostic in
concert with a drug. How frequently does this situation occur,
and what can we do to address it?
Dr. Shuren. Well, our understanding is it does happen
commonly. It has particularly occurred with some of our
companion diagnostics. So one example is Roche made a drug for
treating metastatic melanoma, and it only worked in a subset of
patients so they had a diagnostic test to identify which
patients should get the drug and which shouldn't. The day they
go on the market, there are 9 other labs who say we make the
same test; in fact, some of them said they make a better test.
But the only clinical study, all that data, Roche had it. They
are the ones who had the drug, they did the study. So those
labs made these claims, they are saying that, in fact, they
have a better test, but there was no data there to actually
show it. Those are kind of the risks, and even Roche has said
this has created disincentives for them to create new drugs for
personalized medicine and have companion diagnostics.
Mr. Pitts. While I do have some concerns about the process
by which FDA is proposing this new regulatory approach, patient
groups have questioned whether there are gaps in the current
system that are jeopardizing patients' safety. If that is the
case, we must work together to address them, and in your
testimony, you cite several examples where FDA is aware of
faulty or unproven LDTs. Can you provide the committee with
detailed descriptions of each of the instances of harm you
referenced, and any other adverse event or anecdotal data FDA
has compiled that forms the basis for proposing this new
regulatory framework?
Dr. Shuren. Yes, we can provide you with more details. I
will say too, one of the challenges here is that there is no
requirement for reporting adverse events or related
malfunctions, so you don't have a surveillance system in place
to even identify problems. Many of these have been found
because researchers looked at the data, the reports in
scientific articles, whistleblowers have come forward, or
sometimes the labs have come to us. We have seen the data, and,
in fact, we were able to see, you know what, the data isn't
good, this test doesn't work. And that is just the tip of the
iceberg, because we don't have a system in place to actually
identify problems.
One of the things we are proposing is having that system in
place so we know when problems arise. This isn't bureaucratic,
it is actually good medicine, so that if problems are there, we
want to make sure they get fixed, and we are aware of it.
Mr. Pitts. You state on the one hand that all high-risk
tests should be reviewed by the FDA, regardless of whether they
are developed in a lab or manufactured as a kit. That may very
well be necessary. You go on, however, to discuss that the
Agency will continue to exercise enforcement discretion with
respect to tests that do not have an FDA-approved equivalent.
Are these consistent positions?
Dr. Shuren. So we are trying to strike a balance between
assuring that there is availability of tests in cases where
there aren't tests, but to have some protections in place, some
mitigations for the risks that occur in those settings where
you may not have a properly validated test that we have been
able to see to assure it is safe and effective. On the same
token, if you do now have an FDA-approved test on the market
and you have another test for the same intended use, then we
should be reviewing it or go ahead and use the test that has
been proven to be safe and effective. That is the balance that
we tried to strike, and our focus still is on those higher-risk
devices, because the low-risk devices we have said we are
exercising enforcement discretion towards, regardless. All we
ask is, tell us what they are, and if there is a problem,
report it, but other requirements you do not need to comply
with.
Mr. Pitts. My time has expired. I have a few follow-up
questions on--with that question, but I will submit them to you
in writing.
The Chair recognizes the Ranking Member, Mr. Pallone, 5
minutes for questions.
Mr. Pallone. Thank you, Chairman Pitts.
Dr. Shuren, I want to start out with some basic questions
about FDA's role with respect to LDTs. I know you described
this in your testimony but I would just like to hear more.
Some have questioned whether FDA has the authority to
regulate LDTs in the first place. Specifically, they say that
LDTs are not medical devices at all, instead, they assert LDTs
are services that are offered in one place, making them more
akin to a form of practice of medicine than to an article that
can be sold in state commerce.
So, first, can you respond to this claim? Why does FDA
believe the Agency has the authority to regulate LDTs?
Dr. Shuren. Well, LDTs are in vitro diagnostics. They are
reagents, instruments or systems that are intended to be used
to diagnose a disease or other condition. And essentially, at
its core you have a process, you have instructions for use for
how you prepare a specimen from the body, like blood, and then
how you go ahead and examine and analyze it to identify a
particular substance in there that then is linked to the
diagnosis of a disease. And when you make that test, those
various components, the reagents, the instruments, the device
developer may not make those. They may assemble them together,
put them out, or they may tell you what their instructions for
use, their process, which components to use. Labs do the same
thing; they develop this process which, by the way, is IP, they
get patents on a lot of these, and then they put together those
reagents or those instruments and assemble that device. And
that is, in fact, a device, and they have that in commercial
distribution. They are out there marketing those tests.
The law doesn't distinguish between who makes the test, it
is just if you make the test, if you make the device.
Mr. Pallone. All right.
Dr. Shuren. And as for regulating, even CMS has recognized
that LDTs are IVDs, they are subject to FDA oversight. Even
labs have come in for approval. I have to tell you one lab,
very vocal opponent, and they have orally and in writing
publicly stated they don't make IVDs, they make services, but I
have here their submission to the FDA in-house right now where
they say here is our test, it is an in vitro diagnostic test.
They describe the method, the process they made, and then they
identify the various components that they don't make but they
form part of the test.
Mr. Pallone. OK. Well, let me follow up a little bit about,
you know, how traditional device manufacturers differ from
clinical labs with respect to LDTs.
The ACLA claims they are two totally different entities
because manufacturers make and sell kits, while labs design,
validate, perform, and interpret tests and furnish the results
to physicians. And one question ACLA raises in its testimony is
how to define where the manufacture ends and the performance
begins.
So, again, I would like to know your response to that.
Specifically, what is the implication, significance and
relevance of that question for FDA regulatory purposes?
Dr. Shuren. Yes, so we define who is a manufacturer that
sits in our regulations, and essentially it is a person who
manufactures, prepares, propagates, compounds, assembles, or
processes a device by chemical, physical, or biological or
other procedure. They make the test, they design the test, they
develop the test. That is the manufacturer. When they perform
the test, they are acting as more of a traditional lab. And a
lab can do both, and some only do the testing, some develop the
test and they perform the test.
Mr. Pallone. All right, and then lastly, there has been a
lot of concern about whether a stronger FDA regulatory stance
with respect to LDTs might hinder the innovation that has been
flourishing in this area. And that is obviously something we
have to be concerned about.
Presumably, all sides would agree that there should be
enough oversight of tests to ensure that they are accurate and
clinically relevant, but the oversight should not be so
burdensome as to prevent or unnecessarily delay the development
of important new tests or the improvement of existing tests.
The difficulty, of course, is in achieving that balance. Our
second panel will have witnesses who believe your guidance
appears to achieve that balance, and other witnesses who
believe FDA is inherently the wrong agency to even attempt to
achieve that balance.
So I would like to get your response to some of the
criticism that is being leveled at your whole approach. How do
you respond to claims that FDA's involvement will hinder
innovation?
Dr. Shuren. Well, our intent is try to strike the right
balance. We have proposed a risk-based framework in which we
continue to exercise enforcement discretion for a subset of
LDTs to try to make them available, but by the same token, try
to assure in other cases that we do have that proper validation
that those tests are safe and effective. And the point for
putting all of this out is, let us have that dialogue. If what
we are proposing doesn't hit the mark right, then let us talk
about what is the best way to hit that mark. Whatever we come
up with, we are not going to satisfy everyone, I will tell you
that. Whatever we get at the end of the day, someone is not
going to be happy because there are so many different
perspectives, but we are going to try to hit it the best as we
can. And the real solution is we need the parties at the table,
we need the lab community to come in and talk to us, to
hopefully move away from, you don't have oversight for us, we
don't want to talk, rather say, OK, we get it, let us figure
out how to make this work. Let us hit that right balance on
innovation and safety and effectiveness, the right balance on
protect public health and promote public health.
Mr. Pallone. All right. I thank you for your response. And
I just think it is clear, we need to have the FDA overseeing
these tests.
Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the Vice Chairman of the Subcommittee, Dr.
Burgess, 5 minutes for questions.
Mr. Burgess. Thanks, Mr. Chairman. Dr. Shuren, good to see
you again. I am happy to hear you talk about a spirit of
openness and cooperation. I just find it curious that my
discussion with my own office staff and committee staff, there
was no outreach by the FDA to talk about this prior to issuing
the letter that you did at the end of July, triggering the
guidance that you are putting forward. So I hope that perhaps
you have just signaled a change in tone. I hope there is the
willingness to indeed work with many of us who are concerned
about this, and clearly the concern exists, you knew that
because of the language that was in the FDA reauthorization
bill, and again, I just find it curious you would not have had
any discussion with committee staff prior to issuing that
notice about guidance.
Let me just underscore something that the chairman asked
you. Will you provide our committee with all internal FDA
assessments of the harm that has been completed or were the
bases for the Agency's concern in this proposed framework?
Dr. Shuren. Well, we were asked if we could provide details
on those cases, and we will provide the details as requested.
Mr. Burgess. But all internal documents that you have
received at the FDA that formed the basis of this decision, may
we look forward to you sharing those with us in this new spirit
of openness that you just proclaimed?
Dr. Shuren. So let me go back and talk with people. When
you say all documents, if I have draft documents, we usually
try to move forward to things that are final and the completed
information. So we want to get you everything that is right,
and we will go ahead and do that.
Mr. Burgess. Well, specifically, we are looking at how many
of these tests are performed daily, what is the extent of the
harm, have there been similar problems with FDA approved and
cleared kits, and then lastly and perhaps most importantly, do
you believe physicians are not concerned about patient harm?
Dr. Shuren. Right.
Mr. Burgess. So those would be the specifics that we would
be asking for.
Now, we have had these discussions before, and I firmly
believe the FDA lacks statutory authority to regulate medical
practice. Laboratory-developed tests are a service and not
commercialized devices.
Do you have or did you rely on any legal opinion or memo
from FDA counsel, and if so, can you produce that legal
guidance for us?
Dr. Shuren. We did get guidance from legal counsel, and I
will go back to them to see what materials we have or areable
to provide.
Mr. Burgess. It is critical that, again, that information
be shared with us.
So let me ask you a question. In 30 days, we had asked for
a notification 60 days prior to undergoing the guidance. So you
notified us at the end of July, so what is going to happen in
about 30 days, will the FDA be releasing guidance, draft
guidance, or regulation based on this framework?
Dr. Shuren. Our intent is to release draft guidance, to
have a public process to get input on that, to have a dialogue
that includes not only an open public docket, public meetings,
opportunities to discuss in-person with us. We want to have an
open dialogue moving forward, and that is the process. Very----
Mr. Burgess. You----
Dr. Shuren [continuing]. Public, very collaborative.
Mr. Burgess. So the FDA is proposing to modify a regulation
through a guidance document. Regulation the FDA specifically
indicated it would not regulate laboratory-developed tests, so
where is the legal authority for this decision?
Dr. Shuren. Actually, we have been consistent for years
that we do regulate LDTs. If you have statements that say that
we don't have authority over LDTs, that would be helpful to
see. We have always said we have authority. We haven't enforced
requirements. That is a matter, that is decision on the part of
the Agency, that is enforcement discretion, and that is what we
have done. We are not changing a particular regulation, we are
not imposing a requirement that isn't already imposed upon the
labs, but simply we have not been enforcing.
Mr. Burgess. Well, forgive me, but enforcement discretion
does not give me a warm fuzzy feeling, and it is not just with
this Administration, it was with the previous Administration as
well. We are all familiar with the statement, ``I am from the
government, I am here to help.'' We are not going to bother you
because we have enforcement discretion, so we won't bother you
up until the day that we do. Most people find that as a very
nebulous framework in which to work, and a very difficult
framework in which to plan, plan for the future and plan for
expenses.
So how will this all work? Guidance should not, and the
courts have determined does not, have the enforcement power of
regulation, so how does the FDA intend to bring this framework
upon the world and have it function without clear authority
from Congress, and without providing the normal regulatory
framework?
Mr. Shuren. Well, again, there is authority under the
statute and that authority is there and it is applied now. We
haven't enforced it. And while this discussion isn't new, we
have been talking about enforcing those requirements in LDT as
the existing requirement since the 1990s. We have been called
upon by the Department of Energy. We had two Secretary Advisory
Committees, Secretary of HHS, saying that we should be
exercising our authority over LDTs. The Institute of Medicine
came back to say that. In 2007, we issued draft guidance
withdrawing enforcement discretion for a subset of LDTs, but
the lab community came back and said please don't do this
piecemeal because that is not predictability for us. Please
instead put in place an overarching framework. Seven years
later, 7 years later, that is what we are doing, 4 years after
we had a public meeting in 2010 to do this. This is no sudden
change; this is years. The question shouldn't be where did this
come from, the question should be, FDA, what the heck took you
so long?
Mr. Burgess. Mr. Chairman, I have additional questions
which I will submit for responses in writing, and look forward
to the speedy responses, and yield back.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the gentleman from Georgia, Mr. Barrow, for
questions. No questions? Who is next? The chair recognizes the
gentleman from Virginia, Mr. Griffith, 5 minutes for questions.
Mr. Griffith. Thank you very much, Mr. Chairman.
I am going to follow up a little bit, although maybe a
little different than what Dr. Burgess was going after. And I
understand some of the concerns, but the Supreme Court has held
that an agency has a right to change its policy so long as it
supplies a reasoned analysis for that change. An agency,
however, may not change its policies in a way that simply
disregards rules that are still on the books. FDA's current
regulations specifically exempt clinical labs from medical
device registration and listing requirements.21 C.F.R.
807.65(i).
In an attempt to avoid directly conflicting with this
regulatory exemption, the proposed guidance documents claim not
to require a clinical laboratory to register and list their
tests, but to create a new notification option where labs could
notify the FDA of the types of LDTs they develop. If, however,
a lab does not submit a notification, it will then be subject
to registration and listing requirements, along with the
related fees.
Now, it doesn't seem like there is a whole lot of choice in
there. So, Dr. Shuren, where in the statute does FDA claim the
authority to establish such a notification process?
Dr. Shuren. So the labs are currently subject to
registration and listing. Our interests for many of these is to
know which are the LDTs out there so we can use that
information to then determine the risk classification for them.
We have offered as an option for not complying to provide the
notification. I will tell you the reason we did it. If you
notify and you don't do, instead, registrational listing, you
are not subject to the device tax. That is what we did, plain
and simple.
Mr. Griffith. Because there is a lot of pressure regarding
the medical device tax?
Dr. Shuren. No. We, in looking at this, said, you know
what, for a lot of these too, if we are not going to then
subsequently actively regulate them, because they are going to
be under enforcement discretion, we weren't going to trigger
all the other things that come with that. And that is what we
tried to do, we were trying to give labs a break.
Mr. Griffith. If a lab fails to submit a notification and
is therefore subject to registration listing, how would this
not directly conflict with the FDA's current regulations?
Dr. Shuren. I am not aware that there is a conflict with
current regulations.
Mr. Griffith. You know, you indicated earlier, and I
thought this was kind of interesting based on some of the
things I have read, that it is not a question of, and I am
paraphrasing a little bit, but it is not a question of do we,
but how we regulate, and yet by doing guidance, you are not
going through the normal administrative process active
procedures, and there is a lot of concern that folks won't be
able to get their input put into the Agency.
So if it is a question of do we--not do we, but how do we
regulate, shouldn't you be going through the APA?
Dr. Shuren. No. So, again, this is a general policy
statement. These requirements already apply. They are supposed
to be complying with it. We are not enforcing those
requirements as a matter of policy. Making those changes, the
Administrative Procedures Act does not impose rulemaking on
those kinds of policies.
However, you raised the point about input, because notice
and comment is about do I have the opportunity to provide
input. In rulemaking, notice and comment is, yes, you can
submit comments on the rule. In our guidance document, you will
be able to submit comments on the guidance document. We will be
holding a public meeting. We will have opportunities in other
venues to talk about this. There will be lots of opportunity
for public discussion, for people to get their viewpoints on
the record or off the record. That is what we will do so we can
have a fully informed decision. And we want to hear from
people, so we ultimately hit this right.
I do want to get back to you on that particular regulation.
The regulation pertains to labs who are using an FDA-approved
test, not to labs when they are making an FDA test. When they
are making the test, they then become a manufacturer. It
triggers all the requirements. That is what the regulation is
about.
Mr. Griffith. I think there is some disagreement on that,
and it clearly is not what is stated in the regulation. It just
says clinical laboratories are exempt under Part 807 as well,
but anyway.
With that being said, Mr. Chairman, unless somebody else
would like my time, I will--well, Dr. Burgess, I yield to Dr.
Burgess.
Mr. Burgess. Does the gentleman yield for the last few
seconds?
Mr. Griffith. You got it.
Mr. Burgess. Let me just ask you a question, Dr. Shuren, as
far as the scalability. I mean do you have the personnel, the
resources? We are constantly confronted during the Cures
Initiative discussions that the FDA is kind of behind in its
information architecture. Do you have the personnel and the
scalability to take on this vast new regime that you are
proposing?
Dr. Shuren. One of the reasons we proposed the long phase-
in was in part so that labs could have the time to get used to
the framework. The second is taking into account our resources
so that we are not imposing these day one. The phase-in on
premarket review is over 9 years, so that we are able to then
identify based upon risk, calling in in segments these
particular tests those who would be subject to review, and then
there are a number that will still be under enforcement
discretion, but those that would be----
Mr. Burgess. Will you collect user fees from those labs?
Dr. Shuren. For which ones?
Mr. Burgess. For the labs that you are now regulating under
guidance.
Dr. Shuren. So for the ones who come in in premarket
review, we actually have the authority to waive fees, and one
of the reasons was put into MDUFA III when we did this with the
device industry was specifically for that purpose, that if we
withdrew enforcement discretion on labs during MDUFA III, we
would have the ability not to enforce user fees, but then the
labs should be at the table for those discussions. Now, we
invited them to the table for MDUFA III, they declined to come,
but we would hope if we are moving forward then they would come
to the table in MDUFA IV and then let us talk about that, but
for right now, we have the ability to waive fees. Again, none
of this starts until we are out with final guidance. We still
have to get the proposed guidance out, go through the public
process, then final guidance, and then the first round for
submissions doesn't start until a year after that for premarket
review.
Mr. Burgess. I yield back to the gentleman.
Mr. Griffith. And, Mr. Chairman, I would also ask--Dr.
Burgess previously asked the question about legal memorandums,
and if we could have both in-house and outside counsel
memorandums if they exist. And I yield back.
Mr. Pitts. The chair thanks the gentleman.
I now recognize the gentleman from Texas, Mr. Green, 5
minutes for questions.
Mr. Green. Thank you, Mr. Chairman. Again, welcome.
I understand the number of FDA cleared or approved tests
represents a small fraction of the tests relative to the number
of LDTs. Do we know how many LDTs are actually out there?
Dr. Shuren. We don't have an absolute number on those, in
part because there is no system on notification where you put
them in a database. We have estimates of what we think are out
there.
Mr. Green. OK. Given the number of LDTs that are now the
subject of premarket review under this proposed framework, how
will FDA implement this proposal and will additional resources
be needed?
Dr. Shuren. So, again, the phase-in was an attempt to try
to fold this in with the current resources that we already
have, and, again, during this time, tests remained under
enforcement discretion. So if it turned out, as we get a better
lay of the landscape of what is out there, if we need more time
on implementation or for review, we can do that, it is not
going to put that lab to have to take that test off the market.
And if it turns out there is a need for additional resources,
that is the kind of conversation we have as a part of user fee
reauthorization.
Mr. Green. I have heard that----
Dr. Shuren. And then there were discussions about
legislation previously, and I do know when CMS looked at that
bill, they thought that the cost for that would be about $50 to
$100 million to implement, starting with $20 million at the
outset to create a duplicative bureaucracy. And that isn't the
best way of investing dollars or spending dollars, to simply
rogue government and have duplicative oversight, and a costly
one. So here we have experts already, we are leveraging them to
do their kind of work they do every single day and they have
been doing for decades, and now let us fold this in with the
resources we have and if we need to address more, we will have
those conversations----
Mr. Green. OK.
Dr. Shuren [continuing]. And user fee discussions.
Mr. Green. OK. I have heard the proposed framework would
actually put the FDA in the business of regulating the practice
of medicine, since LDTs is a service rather than medical
device. How does FDA respond to this assertion and at what
point is LDT a medical device,when does its use,
interpretation, application, and modification become a service
provided by a pathologist or physician on behalf of a patient?
What is the breaking point?
Dr. Shuren. Well, again, if they are making the test, all
right, and that can be as a manufacturer assembling the test,
they have developed the process and they put it together then
with reagents and instruments, and now they are out there
marketing it, they have made a test. When they are running the
test, they are performing the test, then they are acting as a
laboratory, then providing a service. That is subject to
oversight under CLIA. The FDA framework is complementary to
assure the safety and effectiveness of the tests that they use,
whether that is made by someone else or they make it themselves
in the laboratory.
Mr. Green. OK. Under the framework, will professionals
working in CLIA-regulated labs be treated as both device
manufacturers and users?
Dr. Shuren. So if they are making tests, then we would
treat them as a manufacturer, keeping in mind that for a
variety of categories of LDTs, we are still exercising
enforcement discretion. So even though they make a test, like a
test for an unmet need, we are saying to them tell us what it
is, report problems, but otherwise you don't have to come in
for premarket review, you don't have to put in place quality
systems, the kinds of controls to assure that when you make a
test, you make a high-quality test.
Mr. Green. But they are actually manufacturing it and using
it, so does this framework create a duplicate system,
regulatory oversight between CLIA and FDA?
Dr. Shuren. No. We view these as complimentary. CMS views
them as complimentary. In fact, even when CLIA was passed in
1988, the then-administrator of what was the Health Care
Finance Administration, former name for CMS, Bill Roper even
said CLIA is complimentary to what FDA does. But we really need
both. If labs are in the business of acting as manufacturers
and making tests, then there is complimentary of FDA oversight
to assure the tests are safe and effective, and there is CLIA
oversight to assure that the services that are performed by the
laboratory are done at high quality, that the people are
appropriately trained.
Mr. Green. Well, the history of our committee, we sometimes
have trouble for two agencies actually trying to cooperate
together, and sometimes it takes statute to do it, but looking
at the future of medicine, the importance of innovation and
effective diagnosis are impossible to overestimate, and looking
forward to working with the FDA, the committee and the
stakeholders to see that the regulatory framework ensures
patient safety while unleashing the potential for LDTs and
diagnostics in general. So, discretion is important and the
partnership between the two agencies is really important
because we don't want to stop the success that we are seeing in
that individual health care.
Thank you, Mr. Chairman. I yield back.
Mr. Pitts. The chair thanks the gentleman.
I now recognize the gentleman from Illinois, Mr. Shimkus, 5
minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman. It is great to be
here. Dr. Shuren, welcome.
Just on a side, over the break, we had a 21st Century Cures
panel hearing in the State Capitol of Springfield. It just went
phenomenal. I think there is a lot of excitement on both sides
and in the health care communities, and I hope we can keep
moving forward, and I know this isn't really specifically about
that, but there is a new era coming in health care delivery and
the like, and I just wanted to report back that that was a very
productive hearing we had, Mr. Chairman.
So, Dr. Shuren, again, welcome. Under the practice of
laboratory medicine, CLIA requires disclosure of known
information relevant to use of a test by a certified laboratory
to a treating physician, without regard to, and I quote,
``labeling claims.'' This proactive approach to dissemination
of information by a clinical laboratory may be in consistent
with the restriction on dissemination of information by a
medical device manufacturer under FDA regulation.
How would FDA manage conflicting requirements governing
consultations with physicians about patient test results?
Dr. Shuren. So we don't view that as in conflict because
the labs can have those kind of communications. That does not
run afoul of the Food, Drug, and Cosmetic Act.
The issue becomes if they are out there promoting, they are
marketing I have this test that I can perform, and if they are
marketing it in a case where they should have come in for
review, they need to come in for review, but they can have
those discussions with treating physician--treating physician
can ask them to run a test in an off-label fashion. That is
fine, that is not inconsistent with our program.
Mr. Shimkus. What types of diagnostic or patient treatment
claims would be permissible, and what kinds of evidence would
be required by the FDA?
Dr. Shuren. Yes, so in terms of permissible, one would be
permissible without coming to the FDA, and we have mentioned,
well, first of all, the low-risk tests you don't come in
anyway, and we have said we are exercising enforcement
discretion for a number of the requirements. For rare diseases,
we are continuing to exercise enforcement discretions. You
don't come into us, where otherwise a conventional manufacturer
would have to come into us. And even if there is an approved
test for a rare disease, we are still saying you don't have to
come into us.
If you are making a test where there is no FDA-approved or
cleared test, you can go ahead and do that until the point
where there is an FDA-approved test. Now, we have a mitigation
in place which is a lab and a health care facility where you
are treating that patient, or within that health care system,
because you have a shared accountability for both testing the
patient and treating the patient. That is the mitigation we
have put in place because here, we don't have that independent
validation the test is actually safe and effective, and that is
a balance we have tried to put in. But then in other cases
where, for example, we have an FDA-approved test, if you want
to continue to market as such a test, you would come in the
door, much like the other manufacturer, to show you are safe
and effective, because at that point, we have a test we know
which works. That is in the best interests of patients to use
it. If you have one that is good, or you think you have one
better, then provide the data to show you are better because
you may not be, and if you are not, that hurts patients because
doctors and patients can go, it is a better test, I will use
that one, in fact, it may not be.
Mr. Shimkus. Great. On the medical device quality system
regulation requirements would apply upon filling of a premarket
submission with the Agency, but the draft guidance does not
adequately tell clinical laboratories how to comply. As one
example, what constitutes a malfunction of a finished device if
the test is an LDT?
Dr. Shuren. So a malfunction is where the test does not
meet its performance specification, or it doesn't perform as
intended. That is a malfunction, and that has applied for IVDs,
and we have information about that.
Now, I will say in terms of the application of quality
systems, we have been working with the Clinical and Laboratory
Standards Institute on developing education modules about how
quality systems would apply to laboratories, and to get that
out there for better training for the labs so they have
information, they have people who will have training programs
with them, we will get feedback on that. If people feel they
need more information, we will work with the lab community on
what they need to be successful, but we will have more
information that is out there.
Mr. Shimkus. I thank you for your time.
And Chairman, I yield back.
Mr. Pitts. The chair thanks the gentleman.
I now recognize the gentlelady, Ms. Schakowsky, 5 minutes
for questions.
Ms. Schakowsky. Thank you, Mr. Chairman. And I apologize,
Dr. Shuren, that I just arrived from another meeting, but I did
want to ask you an important question.
CMS, obviously, could not be here today to participate in
this hearing, and I think it is unfortunate because much has
been made of the role that CMS plays in overseeing LDTs under
the authority provided by the Clinical Laboratory Improvement
Amendment. To be sure, CMS plays a critical role in regulating
laboratory practice in this country, but I think we need to be
clear about the limitations of that role as well.
So I have a document that I obtained from the CMS Web site.
It is entitled CLIA Overview, and it contains CMS's responses
to several frequently asked questions, and I would like, Mr.
Chairman, unanimous consent to enter this document into the
record.
Mr. Pitts. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Ms. Schakowsky. So let me refer to a couple of excerpts
that appear to explain the difference between the roles that
CMS and FDA play with respect to LDTs.
First, this document states, ``when a laboratory develops a
a test system such as an LDT in-house without receiving FDA
clearance or approval, CLIA prohibits the release of any test
results prior to the laboratory establishing certain
performance characteristics relating to analytic validity for
the use of that test system in the laboratory's own
environment. This analytic validation is limited, however, to
the specific conditions, staff equipment, and patient
population of the particular laboratory. So the findings of
these laboratory-specific analytic validation are not
meaningful outside of the laboratory that did the analysis.
Furthermore, the laboratory's analytic validation of LDTs is
reviewed during its routine biannual survey after the
laboratory has already started testing.'' And it goes on to
describe the FDA's role. In contrast, the FDA's review of
analytic validity is done prior to the marketing of the test
system and, therefore, prior to the use of the test system on
patient specimens in the clinical diagnosis/treatment context.
Moreover, FDA's premarket clearance and approval process assess
the analytic validity of the test system in greater depth and
scope. The FDA's processes also assess clinical validity.
According to this document, CMS does not assess clinical
validity. So let me ask you this. Here is the question. Can you
please describe the difference between CMS's review of analytic
validity and the FDA's review of clinical validity?
Dr. Shuren. So for analytical validity, we dive into the
data to make sure that, in fact, you have demonstrated there is
analytical validity. And just so folks know, what you are doing
there, it is the accuracy of measuring something in a human
specimen. So let us say measuring protein in the blood. So we
do a deep dive into that to make sure, in fact, that validation
was accurate.
In CLIA, it is a much lighter look. In some cases, it is a
checklist to make sure you have it, or maybe a sampling of the
analytical validity that has been done, not of all the tests.
Ms. Schakowsky. But----
Dr. Shuren. And clinical validity is then the association
of what you measure in the body with a disease, so that you, in
fact, are making a diagnosis. This protein, if we find one of
these markers, means you have this disease. CLIA doesn't have
that. We have that to make sure then when you do the test, and
people are doing a test to make a diagnosis, that, in fact, it
is accurate in making that diagnosis. And the Web site for CMS
also says as a result--and this is talking just about
analytical validity, as a result, FDA review may uncover errors
in test design or other problems with a test system. Errors
that will not be found under the CLIA system. Again, they are
complementary.
Ms. Schakowsky. So I just have a couple of--so how do you
plan to coordinate then with CMS to make sure that we are
getting the best data?
Dr. Shuren. Yes, so we already work with CMS. We have a
very close relationship. We are part of the CLIA program. When
they talk about, to make an LDT you have to be in a high
complexity lab, we make those determinations too regarding
complexity. We make the determination on a waiver for
complexity if they want to do some of these lower-risk tests.
And in developing this framework, we have been in discussions
with CMS. When we look at quality systems, we are in
discussions with them too because there is a little bit of
overlap----
Ms. Schakowsky. Yes.
Dr. Shuren [continuing]. And our plan is not to duplicate
those requirements, it is to just go with the pieces that are
complementary. What we are doing with CLSI is also to focus on
the parts that are different, not to sort of talk about the
things that you may already be covering on CLIA, and then we
don't need to touch that. In fact, we have proposed--we would
propose to have the option for a third party review model for
both moderate risk tests and for inspections, for audits. And
we know some of the CLIA auditors are interested in being
accredited by FDA to do those reviews, and to actually, when
they are in the lab, to go look at it for CLIA to be able to do
the additional look for FDA to try to minimize any disruption
with the labs, and to work with those entities that they are
already accustomed to working with.
Ms. Schakowsky. Thank you for that clarification.
Appreciate it.
Mr. Pitts. The Chair thanks the gentlelady.
I now recognize the gentlelady from North Carolina, Mrs.
Ellmers, 5 minutes for questions.
Mrs. Ellmers. Thank you, Mr. Chairman, and thank you, Dr.
Shuren, for being with us today.
I just want to go back and clarify some of the responses
that you have given to some of the questions, because as this
is going along, I am getting a little confused as to what the
whole process is and why we are approaching this, or why the
FDA has taken this approach.
One, I want to go back to the user fees and the medical
device tax. Now, my understanding is, from what you have said,
that the FDA has no intention of putting a tax on these lab
tests, is that correct?
Dr. Shuren. Well, and just to clarify, we don't handle the
medical device tax. We have nothing to do with it.
Mrs. Ellmers. But----
Dr. Shuren. The trigger is registration and listing of that
device then triggers----
Mrs. Ellmers. OK, so----
Dr. Shuren [continuing]. The device tax.
Mrs. Ellmers [continuing]. The part that the FDA would play
does not intend, can you definitively give us an answer today
that this will not be an item that will be taxed for the
American people?
Dr. Shuren. So some of the tests and labs would be taxed if
they are making a test that then has to come in for premarket
review. If they opt for doing that, at that point then they
would move over to register and list with us, because we have
requirements--it is the registration and listing that then is
the trigger for some of the other requirements.
Mrs. Ellmers. So then this is open-ended? So this is--these
tests can be taxed?
Dr. Shuren. If they are the tests that have to come in for
FDA----
Mrs. Ellmers. And they are not presently being taxed?
Dr. Shuren. They are not presently being taxed.
Mrs. Ellmers. But they can in the future.
Dr. Shuren. They can in the future.
Mrs. Ellmers. OK, that is a good clarification right there.
Now, we talked a little bit about user fees as well between
some of the labs that are being regulated. Can you just--and
there again, I would just like to have you go back and discuss
what you have already said, but I just need clarification.
Dr. Shuren. Certainly. If our framework were to be
implemented during the course of MDUFA III, we would not impose
any user fees. We would waive those user fees. We have the
authority to do that.
Mrs. Ellmers. Now, you have the authority----
Dr. Shuren. Right.
Mrs. Ellmers [continuing]. But you can't say definitively
today that that is not going to happen, correct? I mean----
Dr. Shuren. That----
Mrs. Ellmers [continuing]. That could be changed at any
moment. The FDA could decide tomorrow that now we are going to
institute user fees.
Dr. Shuren. If the framework in place--yes, if people
change their mind, but that is actually why we had expanded the
waiver provision. It was intentionally put in. Now, for MDUFA
IV, we would like to have the labs at the table to have that
discussion, like we invited them for MDUFA III, come to the
table in MDUFA IV and then talk about----
Mrs. Ellmers. Yes.
Dr. Shuren [continuing]. User fees. Should they apply, what
should they look like, that is the discussion to have, just as
we have with other device developers.
Mrs. Ellmers. I want to go back again to where the origin
of all this came from. My understanding is you have stated in
your testimony and in discussion that FDA has always had this
ability to put this forward, but has not in the past and now
has determined to do so, is that correct?
Dr. Shuren. Yes, we have the authority over LDTs, and
subject to those requirements, we haven't enforced it.
Mrs. Ellmers. Where did that come from, what statute, and
when did it become part of the ability for the FDA to institute
this? Can you go back, give us a date, a time, a rule?
Dr. Shuren. So 1976, the law was changed to give us
oversight on in vitro diagnostics. It is agnostic as to who
makes it. That is the FDA law. It doesn't distinguish between
who makes the test, it is if you make the in vitro diagnostic,
that is where we have the authority. When CLIA was passed in
1988, which, remember, was an amendment to a 1967 law that put
in all the licensing structure, that didn't change. Nothing
that was changed in the law, there is nothing there on the
legislative history, that authority for FDA simply persisted.
Mrs. Ellmers. OK, now, what has changed now----
Dr. Shuren. And even recognized by CMS when the law was
passed.
Mrs. Ellmers. And what has changed now that has caused the
FDA to now look at this as something that needs to be
implemented?
Dr. Shuren. Yes, and keep in mind we have been looking at
this for years. We have had these discussions starting in the
1990s, and even started taking steps in 2007 with the draft
guidance to withdraw enforcement discretion for a subset of
LDTs, and again, we heard from the lab community, don't do it
piecemeal, do an overarching framework. Why we have done this
is because the tests have changed. Years ago, these were very
simple tests. They tended to be rare conditions, they were used
locally. There were really within a facility and a treating
physician, and you have the laboratory. Today, we have
increasingly more complex and sophisticated tests, higher-risk
tests, being used for common diseases, being used nationally,
increasingly doctors and patients relying on the results of
that test, and then examples of faulty LDTs. That has been the
push, and the push doesn't just come from us, it is from
outside bodies.
Mrs. Ellmers. Can you cite for the committee or provide--I
realize you probably can't do that right--at this very moment,
can you give the committee those tests that have shown
inaccuracies that you feel that the FDA needs to address this
issue as tests have been innovated, and obviously you are
seeing something that is indicating that we need to implement
more regulation, and I would just like for you, if you could,
to provide for the committee what those tests are that you feel
are being--or are coming up with inaccurate results.
Dr. Shuren. Yes, we will do that.
Mrs. Ellmers. Thank you. Thank you.
And I apologize, Mr. Chairman, I went over on my time, but,
yes, if you could provide the committee with that, that would
be wonderful. Thank you.
Mr. Pitts. The chair thanks the gentlelady.
I now recognize the gentleman from Florida, Mr. Bilirakis,
5 minutes for questions.
Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it
very much.
During the August recess, I held two 21st Century Cures
Roundtables in my district, and I heard from patients and some
of their problems. I also heard from providers and some of
their problems. There were two themes that came up: outdated
payment policies and also the barriers to innovation. I am glad
that we are holding this hearing today because the specific
issue of FDA regulations of labs develop tests was one of these
issues that came up. We had a company talk about their concerns
that the FDA's regulations could slow innovation.
At the end of the day, we want safety, of course, but we
also want to keep innovation products to get to the market. If
we don't, then the patients, in my opinion, will suffer.
Dr. Shuren, I have a couple of questions. Has FDA done a
thorough economic analysis that considers the direct cost to
laboratories and taxpayers if FDA goes through with their
guidance?
Dr. Shuren. So we don't have a formal economic analysis. On
the other hand, we also hear from labs who say, well, when we
make tests, we validate them. CLIA says they are supposed to be
validating those tests when they make them or they modify them.
And so if that is the case and they have that data, the cost
should be a lot less to be able to then provide that to us.
Mr. Bilirakis. Thank you. Under the Regulatory Flexibility
Act, the RFA, federal agencies are required to assess the
impact of their regulations on small businesses. The analysis
should include such things as how many small businesses there
are, the projected reporting, recordkeeping and other
compliance requirements of the proposed rules, any significant
alternatives to the rule that would accomplish the statutory
objectives while minimizing the impact on small entities, and
it requires agencies to ensure that small businesses have the
opportunity to participate in the rulemaking process. However,
if FDA goes forward with guidance and not formal rulemaking, it
undermines laws that protect due process, such as the RFA or
the Administrative Procedures Act.
Will the FDA go through with the traditional process of
rulemaking?
Dr. Shuren. No, because this is a policy of enforcement
discretion. The requirements are already there. They are
subject to the requirements. We are not imposing that. We have,
as a matter of policy, decided not to enforce them. We are now
changing that policy and enforcing requirements in certain
cases. Those general policy statements under the Administrative
Procedures Act are not subject to rulemaking, and actually have
significant impact if they are for our ability to do so.
However, as part of the process with guidance, there is a
public process for small businesses and others to weigh in, not
only on the docket and written comments with public meeting, we
will have meetings that are occurring in other venues and other
discussions. Some groups have already been in talking with us
about the framework, and we will have that dialogue. What we
hope is that people will come and talk to us, that the lab
community will be in the door and have those conversations.
Some have. We would like to see the full community come in the
door, not talk about we provide services, these aren't IVDs,
don't regulate us, but rather come and say, OK, we get it, but
let us figure out how to do this right because we think labs
developing tests is a good thing. We are not here to stop that,
we are here to try to have that balance between the development
of new tests, but also tests that work, making sure it is safe
and effective, because there is no value to doctors and
patients if the test doesn't work. That hurts people and that
is a cost on our health care system.
Mr. Bilirakis. How many labs would suddenly fall under the
FDA authority under the proposed guidance?
Dr. Shuren. In part, we will see that with notification. We
are estimating that that number--we know for the labs who can
make LDTs, who are allowed to, according to CMS that number is
6,000, but not all of them make LDTs. That number is much
smaller. And we think a number of these LDTs are also subject
to the continued enforcement discretion. So for some of these
labs that are making tests that, again, they are not coming in
the door for us.
Mr. Bilirakis. I believe this was mentioned earlier, but I
will ask the question again. I have heard concerns that some of
the guidance that FDA issues may be duplicative or
contradictory with the requirements under CLIA. Will FDA ensure
that its guidance will harmonize with the current regulations
required under CLIA?
Dr. Shuren. Yes, and in developing our framework and other
materials, we have been coordinating with CMS. Our goal is not
to be duplicative.
Mr. Bilirakis. Thank you very much.
I yield back, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman.
And now recognizes the ranking member of the full
committee, the gentleman from California, Mr. Waxman, 5 minutes
for questions.
Mr. Waxman. Well, thank you very much, Mr. Chairman.
Dr. Shuren, one of the themes of the 21st Century Cures
Initiative has been that advances in molecular medicine and
information technology will enable the use of smaller, more
efficient clinical trials and faster development of new cures.
For those improvements to be realized, we will need to rely on
increasingly sophisticated tests that can both accurately
analyze the genetic and molecular properties of diseases as
expressed in individuals, and recommend treatment regimens
based on those analyses. Thus, these sophisticated tests appear
to be central to what the 21st Century Cures Initiatives is all
about.
Could you describe for us the kind of genomic and other
sophisticated tests that are in existence or under development
that are aimed at helping to guide clinical decisions, and can
you tell us what role they play or hope to play in developing
and improving treatments, and can you explain what FDA's role
is or will be in their development and use?
Dr. Shuren. OK. So increasingly, we are seeing tests to
identify those patients who would benefit from particular
therapies and those who would not, so that you are not giving a
treatment and exposing that person to side-effects when they
are not going to get a benefit in return. And we see this a lot
in cancer, we are seeing it in some other fields as well.
Getting the right treatment to the right patient depends
upon having accurate and reliable test results. If they are
not, that is where mistakes happen, and that is what has
happened with people who didn't get treatment who should. So
tests that were there for breast cancer had high false
negatives, so people were being told the treatment that is
available, you are not a candidate for, when, in fact, they
would have been a candidate. We heard earlier about Oversure
where one of the treatments is having surgery because if you
have ovarian cancer, have it taken out. And you had examples
where a woman didn't have cancer, had the surgery, woman who
had cancer told not, didn't have the treatment when they should
have had treatment at that point. And we see it even in heart
disease. So there is a case of a test for risk of heart
disease, and then the use of statins--responsive to statins.
Well, it turns out--we wound up seeing the data on this, and
there was a subsequent study that showed these markers didn't
actually predict it. The test was not valid, didn't do it, but
at the time when that data was there, over 150,000 people got
tested. We estimate the cost may be over $2 billion. Even Eric
Topol, who many of you were talking about with personalized
medicine and some of the work there, he actually talked about
that this was a great example. Going forward, this story should
serve as a valuable reminder of the potential pitfalls present
in prematurely adopting a genomic test without sufficient
evidence.
Mr. Waxman. Well, on the next panel, Mr. Mertz, from the
American Clinical Lab Association, will testify that if there
were problems with LDTs, we would have more publicity about
them. He cites a 2008 statement by the Advisory Committee on
Genetics, Health and Society that there have been few
documented cases in which patients experienced harm because of
errors in a CLIA-regulated genetic test.
Do you agree with that, would doctors and patients
necessarily know if tests weren't giving good advice for
clinical decisions? Your testimony mentions some of these, but
please describe any examples of the risks or harms of LDTs that
have led FDA to change its enforcement policy in this area.
Dr. Shuren. Yes. So doctors and patients wouldn't know. I
mean you order a test, you don't know it is FDA approved or it
is not FDA approved. That is the state of affairs. And so you
don't know if you have those guarantees or not. That is the way
things are today. And of course you are relying on those test
results then for making a decision on how to care for the
patient.
Mr. Waxman. Well, CLIA regulates the labs. If CLIA
regulates the labs, should we rest assured that the tests from
that lab will be accurate?
Dr. Shuren. No. CLIA's purpose is not to assure the tests
are safe and effective. CMS recognizes that too and has noted
distinctions between what FDA does and what CMS does. They are
complimentary systems, and in going forward, we need to make
sure we are coordinated and we avoid any duplication, but they
are complimentary systems. And the Secretary's Advisory
Committee did note, yes, there were a few reports of problems
because there isn't a system there for identifying those
problems. That is one of the things that we would put in place,
but that same committee, that same Advisory Council, also said
the absence of evidence doesn't mean that there is an absence
of a problem. And, in fact, they came back and said we
recommend the FDA begin enforcing requirements for LDTs. That
was their conclusion.
Mr. Waxman. So even though we know it is a decent lab, they
live up with the good standards, we don't know if the result of
the test is going to be accurate in helping the patients or
not?
Dr. Shuren. Right. We have for----
Mr. Waxman. May even do them harm.
Dr. Shuren. Right, and we had for H1N1, so when that came
out, by the way, the original samples came from China. Only the
CDC had them. And then when the emergency was declared, CDC had
developed a test and we gave them an EUA within days. Then they
made the samples available to other labs. The labs who
developed things beforehand had no access to the H1N1 samples,
and then they came in the door. Now, we cleared--we gave EUA
authority to some of the labs----
Mr. Waxman. EUA is----
Dr. Shuren [continuing]. But some of them----
Mr. Waxman. EUA is?
Dr. Shuren. I am sorry, emergency use authorization, in the
setting of that pandemic. But some of the labs, their data and
from pretty prestigious academic institutions, their tests were
problematic. And we saw the data, that is how we know, and then
they weren't out there on the market. That is what FDA does,
but again, we are trying to strike that right balance in
innovation, access, and safety and effectiveness.
Mr. Waxman. Thank you.
Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman.
And now recognizes the vice chairman of the full committee,
the gentlelady from Tennessee, Mrs. Blackburn, 5 minutes for
questions.
Mrs. Blackburn. Thank you, Mr. Chairman. And I appreciate
the emphasis that we have on 21st Century Cures, and the
opportunity for all of us to visit with you, Dr. Shuren, and we
thank you for your time and for being willing to come over here
and talk with us and answer the questions. I think that we are
all interested in solving access issues for our constituents,
and part of that being preserving access to affordable health
care for all Americans. And right now the cost of health care
seems to be going through the roof, and we hear about it every
day.
Let us go back and talk a little bit about the guidance
document. I know Mrs. Ellmers and Mr. Bilirakis have both
touched on is with you, and when you are looking at the
guidance document and the LDT issue, you know that there could
be numerous requirements that could be put in place from your
guidance document. We know that you all contend that guidance
documents are not binding on the industry.
Now, when we are out there talking with some of our
innovators, and talking with those that are trying to work
through the process with you all, what we hear is, well, they
might not do something, but they could, and the uncertainty
that exists in that. So how do you, as we talk about answering
the questions for constituents, how do you reconcile that
difference, you might not but you could, and the guidance
documents aren't binding? So how do you reconcile that?
Dr. Shuren. So just to flip around in this case, here we
are talking about the requirements to comply with the Food,
Drug, and Cosmetic Act are already in place for the labs. We
have chosen not to enforce those requirements. We haven't taken
action for the people who aren't meeting it, for the most part,
but that is the change that we are making. So unlike in other
cases where we are imposing a requirement, we are
reinterpreting that requirement under the law, we are not doing
that here, we are simply withdrawing enforcement discretion,
saying here are the requirements, they are already on the
books, there are regulations about them, some cases there are
guidances, and you would meet that just like you would as a
conventional manufacturer, but we maintain enforcement
discretion still in some cases where we say these particular
requirements, as outlined here, you don't have to comply with,
we will not enforce those.
Mrs. Blackburn. Yes, and I appreciate that and I
appreciated your comments about the medical device tax, and you
and I have talked about the Software Act and the medical apps
that are there, but I just want to highlight with you again
that sometimes that discretion, that uncertainty is very
difficult for many that are innovating in that space because
they know you might not do something, you probably won't do
something right now, but it doesn't state what you are going to
do if you change your mind. And as they look at federal
agencies, you all included, mission creep is something that
is--that they are concerned about, and also lack of economic
analysis. So I would just--I would highlight that to you.
Let me go back to something Mr. Griffith raised earlier. In
addition to Section 807.65(i) of the federal regulations which
specifically list clinical labs as a class of entity that is
exempt from establishment, registration, and device listing,
the preamble to these final regulations implementing the
registration requirement unequivocally emphasizes this point in
stating the commissioner believes that full-service labs and
similar establishments are exempted from registration. Were you
aware of these regulatory provisions currently on the books?
Dr. Shuren. Yes, so this provision pertains to labs when
they are using tests. It does not pertain to when they are
manufacturing----
Mrs. Blackburn. OK.
Dr. Shuren [continuing]. Tests. That is the distinction.
And I am also sympathetic, I understand the predictability when
people say, well, if you put a policy in place, and here people
are saying when you exercise enforcement discretion, what
about, you could take it away tomorrow. This should be a poster
child about our taking away enforcement discretion. We have
been at it for years. I was a very young man when this started
back in the 1990s. I now have gray hair. So it does not happen
overnight. In some respects, I hate to say it, I wish it would.
I would probably not have the gray hair.
Mrs. Blackburn. Well, I think we all end up having gray
hair. It is one of the blessings that comes our way from being
able to solve problems and work through issues that affect all
Americans, and we look for a good resolution to those, and I
hope that you are going to commit to work with us on the
software component, the medical apps and keeping these free of
the medical device tax. We have got a lot of people that are
looking to expand access, and that is a good way to do it.
I yield back.
Mr. Pitts. The chair thanks the gentlelady.
Now the chair recognizes the gentlelady from California,
Ms. Eshoo, 5 minutes for questions.
Ms. Eshoo. Thank you, Mr. Chairman. I appreciate the
legislative courtesy. While no longer a member of this
subcommittee, the committee rules do allow members of the full
committee to participate, and I appreciate it.
I have a statement that I would like to submit for the
record, and ask unanimous consent to do so.
Mr. Pitts. I am sorry, I didn't hear you.
Ms. Eshoo. Yes, I just ask----
Mr. Pitts. I am trying to get those----
Ms. Eshoo. You mean you weren't paying----
Mr. Pitts [continuing]. Klieg lights turned off.
Ms. Eshoo. You weren't paying attention to me, Mr.
Chairman. No, I just asked unanimous consent to produce a
statement into the record today.
Mr. Pitts. Without objection----
Ms. Eshoo. Thank you very much.
Mr. Pitts [continuing]. So ordered.
[The prepared statement of Ms. Eshoo follows:]
Prepared statement of Hon. Anna G. Eshoo
Mr. Chairman, thank you for holding this hearing today to
examine the regulation of laboratory developed tests (LDTs). I
appreciate the opportunity to learn more about this issue and
to hear from the FDA and from stakeholders about how the
agency's proposed changes will affect patients, doctors, and
health care innovation.
The FDA's primary mission is to ensure that drugs and
devices are safe and effective. Diagnostics are a critical part
of our health care ecosystem, helping doctors target what's
wrong with a patient so that they can be treated with the
utmost precision, focusing on the necessary therapies while
reducing unnecessary interventions.
While the FDA regulates some diagnostics, many are never
reviewed by the agency. This is because our bifurcated
regulation of diagnostics means that the FDA regulates
diagnostics developed as ``kits'' while CMS regulates LDTs
under the Clinical Laboratory Improvements Act (CLIA). The FDA
has the authority to regulate LDTs but until now, has exercised
regulatory discretion in allowing these tests to be regulated
solely by CLIA.
As diagnostics become more complex and lead to greater
clinical decision making, it's important that they receive
increased scrutiny to protect patient safety. FDA's proposal to
fundamentally change the regulatory paradigm for LDTs can lead
us in the right direction, but the new regulations must be
implemented in a way that furthers innovation and the
development of personalized medicine.
Ms. Eshoo. Dr. Shuren, it is good to see you, as always.
I think the benefit of sitting here and listening to all
the questions and your responses is the following. When I go to
either Stanford University or the Palo Alto Medical Foundation,
part of all of these exams, and if there need to be further
examination of things, are tests. I want my tests to be
accurate. I want my tests to be accurate, and I think every
single one of us do too. And I think that we are at a juncture
today where we should be celebrating something, and that is
that there has been so much innovation that has moved forward
relative to diagnostics, they are far more sophisticated, we
have a broader and greater capacity to make determinations
relative to diseases that were at one time a death sentence and
today can be manageable if, in fact, there is a correct
diagnosis. And so these tests are really central in all of our
lives, and I think that, speaking for myself, the older I get,
I can't wait for the results of the tests to come back to know
that everything is all right, but we depend on accuracy. And I
think that the FDA, in terms of its role, a key role is to
ensure safety and efficacy of drugs and devices.
This is really more of discussion of how this is going to
work. I know that there is a question that has been raised
about whether the Agency has the authority. It seems to me that
you do. My concern is that this be done in a very smooth and
fair way because if in moving through this process, I want to
ask you why it is 9 years. I mean a lot of things can happen in
9 years. I mean can't you do something in a shorter period of
time so that the stakeholders have predictability and know what
the rules of the game are going to be? That is one of my
questions. I know that this was stuck at OMB for a long time,
and I am very curious to know what all of a sudden loosened
this up, so that OMB changed its mind. What was it that
concerned them that held it up for so long, and what is it that
put them in a better mood and gave you the hand signal to move
on? And what would you say to the stakeholders, because I have
listened to many of them, I don't have the answer, but I have
listened to many of them about the effects of the proposed
changes and what is burdensome, what isn't, what would you say
to them about innovation not being damaged as we move forward
to protect the efficacy and the safety that I spoke to both as
a member representing 700,000 people and as a patient, as an
individual?
Dr. Shuren. So phase-in for 9 years, we picked that number
for a couple of reasons. One, we wanted to give labs time to
better understand what requirements were, we wanted to have a
process to also classify----
Ms. Eshoo. But may I----
Dr. Shuren [continuing]. The tests----
Ms. Eshoo. I just want to interject something. If it is
going to take 9 years to understand something, I don't think
that sends the right signal, honestly, because it--then it must
be so enormously complex that it is going to take almost a
decade for people to figure out, so it doesn't seem like it is
a source of comfort to me. Now, maybe it is the flipside. Maybe
that is a comfortable zone for people, that they want to take
it very, very, very slowly, but if your assumption is that it
is going to take 9 years for people to understand something,
that, to me, suggests some kind of complexity that is deep and
broad.
Dr. Shuren. Yes, and if people are looking for faster, that
is a conversation to have. It is a risk-based phase-in, so the
highest risk ones we bring in first. There are a lot of tests
out there that the risk classification hasn't been determined
yet, so we need time for the public process and expert panels
to look at that when we get notification of tests, and then we
want to fold this in with the resources we have so we are able
to manage reviews in a way that doesn't overtax the system that
we have. So that is how we came up with the 9 years.
Ms. Eshoo. Yes.
Dr. Shuren. As to OMB, what I can say is a higher authority
weighed in and we are moving authority. It sounds like Hebrew
National Hot Dogs.
Ms. Eshoo. Higher--it does. I was going to say it sounds
like an ad. Yes.
Dr. Shuren. Yes.
Ms. Eshoo. Yes.
Dr. Shuren. And then in terms of, with innovation, one
thing I will say is innovation isn't just something new----
Ms. Eshoo. Yes.
Dr. Shuren [continuing]. It is also valuable----
Ms. Eshoo. Yes.
Dr. Shuren [continuing]. To patients. If you have an
innovative test, doesn't matter if it is new, it has to be safe
and effective otherwise we are not doing service by patients,
and then it isn't real innovation.
Ms. Eshoo. Yes.
Dr. Shuren. Newness for the sake of newness isn't good, and
spending our health care dollars just because it is new but it
may not work is a fool's errand.
Ms. Eshoo. Yes.
Dr. Shuren. So how do we strike that balance on
innovation----
Ms. Eshoo. Yes.
Dr. Shuren [continuing]. And safety and effectiveness. That
is the dialogue we are trying to have. We put something out, at
least now people can react to it and have a much more
structured conversation.
Ms. Eshoo. Thank you, Dr. Shuren.
Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentlelady.
That completes the round of questioning. We have one
follow-up per side. Dr. Burgess, you are recognized 5 minutes
for follow-up.
Mr. Burgess. Mr. Chairman, I just really, really like to
know the higher authority at OMB, because you and I talked
about this at the end of July when you called me and said, OK,
I am exercising the 60-day requirement, and my question went to
the economic impact and the questions such as Ms. Eshoo asked
at OMB. These are valid questions and, to the best of my
knowledge, you have not answered those. You didn't answer it in
July, you haven't answered it today, so what was the deal at
OMB with assessing the economic impact, or, in fact, are we
proceeding on this where we really have no earthly idea as to
the economic impact?
Dr. Shuren. Well, so two different things. I guess the
question originally was the holdup at OMB, the holdup wasn't
overdoing an economic analysis on this. They had----
Mr. Burgess. Is that not part of OMB's job to look at the
economic impact of changes made by the agencies----
Dr. Shuren. They----
Mr. Burgess [continuing]. Just as a general rule?
Dr. Shuren. They do that in rulemaking for certain rules
when they review those.
Mr. Burgess. Is that why we avoided rulemaking in this
instance?
Dr. Shuren. No, because this is enforcement policy and we
do that with guidance. We have done that historically with
guidance. There is nothing different here, and, in fact, as I
mentioned, we came out with guidance in--7 years ago----
Mr. Burgess. OK, well----
Dr. Shuren [continuing]. In 2007.
Mr. Burgess. But back to the question of the economic
impact.
Dr. Shuren. Yes.
Mr. Burgess. Do we, as we sit here today, do we have any
idea as to the economic impact of this guidance that you are
proposing?
Dr. Shuren. I do not have hard numbers to share with you.
And in part, some of this if you want to look at it is when we
have the lay of the land for those labs that would have to come
in the door and be subject. Part of it too is what will the
final framework be. This is starting a dialogue so we can have
that discussion about what the final policy will look like. And
then lastly, as I mentioned before, labs are supposed to
validate their tests. They are supposed to do the studies. As
people said, hey, it is expensive to do studies. They are
supposed to do that. So if they have done it, the cost to them
is, in certain cases they would be sending it to us so we can
review that.
Mr. Burgess. Thank you, Mr. Chairman. I will yield back.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the gentleman, Mr. Pallone, 5 minutes for
follow-up.
Mr. Pallone. Thank you, Mr. Chairman.
The ACLA claims that once a manufacturer gets a test
approved, it never improves it because of fear of needing new
approval. And they give the example of an HIV Western Blot Kit
not having significant improvement since first one was approved
in the '80s, and the first kit to be approved by FDA was 2
years after the first LDT test was used without FDA approval.
And ACLA also gives the example of a lab making improvements to
an FDA-approved test kit, and says that the approach under the
guidance of requiring labs to seek FDA approval for such
activities is unreasonable, and encroachment on the practice of
medicine and a disincentive that will limit patient access to
cutting-edge diagnostics.
So I just wanted to know how would you respond to that
claim?
Dr. Shuren. Well, so test developers do improve their
tests, and I turn to the people representing that community to
maybe address that on the next panel, but yes, they do come
back and they do improve their tests. In the setting where
there wasn't a test available, one of the things we have in our
framework is an LDT for an unmet need where there is no
approved or cleared test to allow then labs in certain
circumstances to have that test, have it out there and not go
through FDA review, but then when a company comes in and they
make the test for the same intended use, now we have an FDA-
approved test, we have seen the data, we know it is safe and
effective, that is the time for the other lab to say I either
want to bring in my test and share the data, or I will use the
FDA-approved test. And then if they want to improve a test or
they want to make a better test, then have the data to support
it because we have seen where you make a claim it is better but
is it really a better test, because you are telling doctors it
is a better test, so use my test because it is better than the
one the FDA approved. Well, how do doctors know that? That is
what we are here for, to try to make those assurances if you
are truly making it better. And we have seen sometimes you
claim a test is better, you add other markers on, but it turns
out you haven't shown those markers actually better inform the
diagnosis. But you should do that.
Mr. Pallone. All right, thanks. I think we need to achieve
the right balance, but I appreciate it.
Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman.
That concludes the questions of the committee at this time.
We will have follow-up questions for you that we will send. We
ask you please respond promptly. And thank you for your
patience and responsiveness this morning.
This concludes the first panel. We will take a 3-minute
recess as the staff sets up the second panel.
[Recess.]
Mr. Pitts. The subcommittee will reconvene. We will ask
everyone to please take their seats, and ask the witnesses to
please take their seat at the table. Please take your seats. I
would like unanimous consent to submit the following for
today's hearing record: Comments of the Small Biotechnology
Business Coalition; a statement from the Association for
Molecular Pathology; a letter from Randy Scott, Chairman, CEO
of InVitae Corporation in San Francisco; and a letter from the
American Association of Bioanalysts, the AAB, and the National
Independent Laboratory Association, NILA, representing
independent community and regional clinical laboratories.
Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. On our second panel today we welcome each of
you, and I will introduce the panel in the order of their
presentations. First, Mr. Andrew Fish, Executive Director,
AdvaMed Diagnostics; then Dr. Kathleen Behrens Wilsey, Co-
Founder of Coalition for 21st Century Medicine; Mr. Alan Mertz,
President, American Clinical Laboratory Association; Dr.
Christopher Newton-Cheh, Assistant Professor of Medicine,
Harvard Medical School, and Cardiologist, Massachusetts General
Hospital, testifying on behalf of the American Heart
Association; and finally, Dr. Charles Sawyers, Immediate-Past
President, American Association for Cancer Research.
Thank you all for coming. Your written testimony will be
made a part of the record. You will be each given 5 minutes to
summarize your testimony.
And, Mr. Fish, we will start with you. You are recognized
for 5 minutes.
STATEMENTS OF ANDREW FISH, EXECUTIVE DIRECTOR, ADVAMED
DIAGNOSTICS; KATHLEEN BEHRENS WILSEY, PH.D., CO-FOUNDER,
COALITION FOR 21ST CENTURY MEDICINE; ALAN MERTZ, PRESIDENT,
AMERICAN CLINICAL LABORATORY ASSOCIATION; CHRISTOPHER NEWTON-
CHEH, M.D., ASSISTANT PROFESSOR OF MEDICINE, HARVARD MEDICAL
SCHOOL, CARDIOLOGIST, MASSACHUSETTS GENERAL HOSPITAL; AND
CHARLES SAWYERS, M.D., IMMEDIATE-PAST PRESIDENT, AMERICAN
ASSOCIATION FOR CANCER RESEARCH
STATEMENT OF ANDREW FISH
Mr. Fish. Thank you, Chairman Pitts, Ranking member
Pallone, and Members of the subcommittee, for the invitation to
testify at today's hearing. My name is Andrew Fish, and I am
the Executive Director of AdvaMed Dx, the trade association
representing the leading manufacturers of medical diagnostic
tests. I have submitted a longer statement for the record, and
will summarize key points for you this morning.
AdvaMed Dx member companies develop FDA-cleared diagnostic
tests for use in a wide range of health care settings, not only
in clinical laboratories, but also in numerous point-of-care
environments, including emergency rooms, doctors' offices,
clinics, and even in the home.
Whether developing a rapid molecular test for flu or TB, an
implantable blood glucose monitor that interfaces with a
smartphone, advanced genetic tests designed to guide use of
specific cancer drugs, or the first FDA-approved platform for
high-speed gene sequencing, diagnostic manufacturers are proud
to wear the mantle of innovation in this critical area of
health care.
AdvaMed and AdvaMed Dx have been pleased to work closely
with the Energy and Commerce Committee on many issues related
to FDA regulation of medical devices and diagnostics, and
appreciates the committee's continued leadership.
The questions before the committee today are whether and
how laboratory-developed tests or LDTs should be regulated to
assure their safety and effectiveness. Three essential points
support our conclusion that FDA should regulate LDTs under a
risk-based approach. First, LDTs are diagnostic tests, and all
diagnostics present the same patient risks, regardless of
whether they are developed by a manufacturer or a laboratory.
Second, the LDT market has changed dramatically in recent years
to encompass even the most advanced, complex, and high-risk
tests, and under our current oversight paradigm, LDTs are not
reviewed for safety and effectiveness, when the same tests made
by a manufacturer are subject to FDA clearance or approval.
Third, existing statute and FDA regulation already encompass
LDTs, and FDA's decision to enforce those regulations with
respect to LDTs is an appropriate policy decision by the only
agency with the authority, expertise, and infrastructure
necessary to assure the safety and effectiveness of
diagnostics.
We have spoken earlier in this hearing about CMS's
authorities over laboratories under CLIA. CMS itself as the
agency that implements CLIA has made it clear that CLIA does
not duplicate FDA regulation. FDA regulation encompasses
numerous elements that were never intended to be covered by
CLIA, including premarket review and assurance of clinical
validity. It makes no sense to create a new set of authorities
at CMS when FDA has a well-developed regulatory system and
infrastructure that already encompasses LDTs.
For years, stakeholders have recognized the inadequacy of
current oversight of LDTs, and have called for FDA to enforce
existing regulations that apply to LDTs, just as they do to all
other diagnostics. I submitted a document noting comments from
a variety of stakeholders supporting FDA action on LDTs, and
ask that it be included in the record.
The current diagnostics oversight paradigm results in a
tremendous public health gap, and highly disparate treatment of
tests that are the same from the perspective of patient risk
and safety, simply on the basis of whether they are developed
by a manufacturer or a laboratory. This is bad public policy,
provides an opportunity to use tests in a clinical setting that
have insufficient clinical data, and stifles investment in
high-quality products that are assured safe and effective for
patients.
We see these challenges arise, for example, when, shortly
following an FDA approval of a pharmaceutical, along with its
companion diagnostic, laboratories advertise that they can
perform an LDT version of that diagnostic test.
It is important to note that the threshold question of
whether LDTs should be regulated by FDA turns first and
foremost on patient safety. From this perspective, we believe
that FDA oversight of LDTs is necessary. While FDA regulation
is not without challenges for our industry, we have worked
constructively with the Agency on various improvements to its
regulation of diagnostics, and are pleased with significant
progress, including increased use exemptions and a new triage
program to speed reviews. We look forward to continuing to work
with this committee on ways to help improve FDA oversight.
The risk-based approach to LDT regulation that FDA has set
forth addresses current gaps in LDT oversight by focusing
Agency resources on tests that pose the highest risk to
patients. At the same time, FDA appropriately recognizes the
important role that LDTs can play in providing care to patients
in the medical institution setting, and explicitly preserves
the ability of laboratories in those settings to continue
innovating in the area of LDTs. AdvaMed Dx commends FDA for
moving forward to address the patient safety gaps that
currently exist in LDT oversight, and supports the key elements
of the oversight framework that FDA recently announced.
Again, thank you for the opportunity to speak to this
important issue at today's hearing.
[The prepared statement of Mr. Fish follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman.
I now recognize Dr. Behrens Wilsey 5 minutes for an opening
statement.
STATEMENT OF KATHLEEN BEHRENS WILSEY, Ph.D.
Ms. Behrens Wilsey. Good morning, Chairman Pitts, Ranking
Member Pallone, and Members of the subcommittee. I am Dr. Kathy
Behrens Wilsey, Co-Founder of the Coalition for 21st Century
Medicine. On behalf of the Coalition, thank you for convening
today's important hearing to address this critical issue in
health care innovation, and for inviting the Coalition to
testify.
Today, we live in a world in which a woman with breast
cancer can confidently and reliably reject toxic and
potentially life-threatening chemotherapy because testing has
confirmed she will not benefit from such treatment. Without
such testing, she would only experience harmful side-effects
from a treatment protocol that has been, until very recently,
both standard and routine care. With diagnostic test
information, she has more certainty that conventional treatment
would neither improve the quality of, nor prolong her life.
This woman benefits from significant progress in new advanced
diagnostics. Most importantly, this progress has substantially
improved patient outcomes without diminishing safety, though
occurring in the midst of formidable regulatory uncertainty.
I am here today because, despite some well-known examples
like the women who now have far greater certainty about their
treatment pathway, investment in advanced diagnostics suffers
from great uncertainty; uncertainty about evidence development
and reimbursement. The overall return is lower for diagnostics
than for pharmaceuticals, so while the challenges may appear to
be the same, this lower return has resulted in attracting fewer
investors and less capital.
Investment in and development of advanced diagnostics has
declined in recent years as a direct result of 8 years of
regulatory uncertainty. The lack of a clear path for innovation
in vitro diagnostics under the current FDA regulations has been
evident as FDA proposes and withdraws different proposals, each
time rolling back its historic flexible regulatory approach.
Prolonging the current regulatory limbo, or worse, implementing
an incomplete or overly burdensome regulatory framework, will
accelerate the shift to venture capital investment out of
advanced diagnostics and into more predictable endeavors.
And so we find ourselves at a crossroads. The overwhelming
success of the human genome project and its medical and
scientific advances are closer than ever to accelerating what
this committee calls 21st Century Cures: early, rapid and
comprehensive diagnosis, followed by individualized targeted
treatments against serious and life-threatening diseases, and
yet the proposed regulation of laboratory-developed tests
control progress and fight against cancer, cardiovascular
disease, deadly infectious diseases, and countless rare
diseases and disorders that can be more effectively and
efficiently combated through advanced diagnostics.
The framework put forth by the FDA is no doubt an
improvement over the initial draft guidance published in 2006.
Yet, in the interest of extending our impressive progress in
the development of new advanced diagnostics to help patients,
and at the same time avoiding additional barriers to
innovation, the Coalition recommends the FDA provide detailed
substantive guidance on many outstanding issues before its
proposed framework is finalized--a framework that starts a
clock for compliance among affected laboratories. Specifically,
the FDA must, among other things, identify the device within
the LDT service, harmonize FDA and CLIA quality systems
regulations, which have different and, in certain areas,
incompatible purposes, provide clear guidance on requirements
for obtaining labeling that is useful for clinicians and
patients, and accommodate medical communications between
laboratories and treating physicians under an FDA regulatory
framework that imposes substantial limitations on proactive
communications by medical product manufacturers. We also need a
flexible regulatory system which enables the rapid translation
of scientific and clinical evidence that so powerfully enables
timely access to the newest generation of tests. Additionally,
clear and meaningful labeling is critical for physicians and
patients, otherwise public and private payers resist providing
coverage and patients do not get tested. It literally takes
years for payers to approve coverage and payment for advanced
diagnostics, and they are not likely to pay if the FDA-approved
label suggests that the test cannot be used in a clinically
meaningful way. Given the FDA's recent framework, we caution
the subcommittee about the potential number of tests that might
be subject to premarket review.
Finally, we have concerns that the FDA underestimates the
challenges associated with translating regulatory processes
developed to oversee diagnostic products that are designed for
both broad distribution and use, in contrast to services
performed by individual labs. Most venture capitalists
appreciate that there are significant differences between the
two that could substantially risk the successful implementation
of the FDA's plans.
We applaud the subcommittee for exercising its oversight
function by holding this hearing, and encourage Congress to
continue to work with the FDA throughout the public comment
process. We also encourage the subcommittee to consider
legislation where necessary, to fill gaps in the regulatory
framework, and address potential inconsistencies and
duplication across regulatory authorities to ensure that the
balance between advancing the public health and facilitated
American innovation is maintained.
Thank you.
[The prepared statement of Ms. Behrens Wilsey follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentlelady.
I now recognize Mr. Mertz 5 minutes for opening statement.
STATEMENT OF ALAN MERTZ
Mr. Mertz. Thank you, Chairman Pitts and Ranking Member
Pallone, for the opportunity to testify today. I am Alan Mertz,
President, American Clinical Laboratory Association, ACLA, and
we represent the Nation's leading providers of clinical
laboratory services.
I also want to begin by applauding Chairman Upton and
Representative DeGette for launching the 21st Century Cures
Initiative.
Through the innovations in clinical laboratories, we are
diagnosing diseases earlier and more precisely for diabetes,
cancer, and infectious and rare diseases. With these powerful
new diagnostic tools, patients have access to more targeted and
effective therapies sooner, which inevitably increases the
quality of care, saves lives and lowers cost.
America is the leader in this diagnostic medicine
revolution, and recent advancements in genetic and genomic
tests have created over 116,000 jobs, and $16.5 billion in
annual economic output. A reasonable and flexible framework is
essential to preserving this vital leadership role that we have
in the United States.
ACLA is greatly concerned by the FDA's notice of intent to
issue guidance that would completely alter how clinical
laboratory tests will be made available to patients. We do not
believe that the FDA has the statutory authority to regulate
laboratory services, and even if they did, we do not believe
that it is appropriate to create a whole new regulatory process
through guidance documents.
The laboratory industry is already extensively regulated
under an interlocking framework of federal laws, state laws,
and peer review-deemed authorities. As has been discussed
today, the primary federal law governing labs is CLIA, which
creates stringent requirements governing the operation of
clinical labs and their personnel to ensure the safe and
accurate function of labs and testing services they provide.
Further, peer review authorities add additional expertise in
reviewing both the operation of the lab, and the analytical and
clinical validity of the tests. Operating under this
comprehensive yet flexible LDT oversight framework, the field
of laboratory medicine has produced some of the most
spectacular advances in diagnostics.
In short, LDTs have become ubiquitous in clinical patient
care. They range from the most common tests that many of us
will be familiar with, like pap smears, to the most advanced
molecular and genetic tests in cancer and heart disease.
Importantly, the vast majority of new genetic and molecular
tests are LDTs, and most FDA-approved and cleared kits are
based upon tests originally offered as LDTs. Although the FDA
claims that it has no interest in duplicating CLIA's oversight
requirements, the FDA notification that came out does not
address how they avoid such duplication. There has not been any
discussion of how any additional regulation by the FDA would
interact with the regulation already under CLIA. There are many
areas of commonality and overlap, specifically as it pertains
to validation, inspections, quality system regulation, and yet
the FDA has not clarified how it propose the two regulatory
authorities working in such a way as to not overburden the lab
industry, and slow the development of and access to these vital
diagnostic tools. Frankly, we are deeply concerned that the
documents released failed to take into account the fundamental
differences between a device manufacturer and a clinical
laboratory. Unlike a device manufacturer, a clinical laboratory
is an integrated operation consisting of highly trained and
certified personnel who design, validate, perform, and
interpret laboratory tests. Defining exactly what the device is
that FDA seeks to regulate, or where the manufacture of the
test ends and the performance of the test begins, has yet to be
explained.
Lastly, I need to emphasize the enormous scale of the
increase in regulatory oversight. According to FDA's framework,
the Agency will not define high risk or identify how many tests
will require premarket approval for several years. The
potential workload for the FDA is staggering. There are over
11,000 highly complex laboratories that perform laboratory-
developed tests, and the total volume of LDTs numbers at least
in the tens of thousands, and our own surveys of our members
indicate it may be over 100,000 laboratory-developed tests. In
comparison, last year the FDA approved only 23 premarket
applications for diagnostic tests.
In conclusion, the ACLA shares the goals of everyone here
in ensuring patient access to accurate, reliable, and
meaningful tests. We have long supported modernizing the
regulatory requirements under CLIA to keep pace with changing
technology. We are confident that this can be accomplished
without duplicative regulation, oversight, and cost, while
maintaining our status as a global leader in diagnostic
innovation. We look forward to continuing to work with this
committee, with Congress, the FDA, CMS, and other stakeholders
on policies that encourage innovation, ensure safety, and
maintain patient access to these diagnostic services.
And with that, I thank you and look forward to your
questions.
[The prepared statement of Mr. Mertz follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman.
I now recognizes Dr. Newton-Cheh 5 minutes for an opening
statement.
STATEMENT CHRISTOPHER NEWTON-CHEH, M.D.
Dr. Newton-Cheh. The Chairman Pitts, Ranking Member
Pallone, and Members of the subcommittee, thank you for giving
me the opportunity to testify before you today. My name is
Christopher Newton-Cheh, I am a cardiologist at Massachusetts
General Hospital, specializing in heart failure and cardiac
transplantation, and an Assistant Professor of Medicine at
Harvard Medical School. I am also a cardiovascular geneticist,
investigating the root causes of cardiovascular disease, the
leading cause of morbidity and mortality worldwide.
Today, I speak to you not only as a clinician and
researcher, but also as a volunteer for the American Heart
Association, a nonprofit organization dedicated to building
healthier lives, free of cardiovascular disease and stroke. I
am concerned about the lack of enforcement of regulation on
laboratory-developed tests.
The potential for personalized medicine to improve health
and improve the practice of medicine is great. Biomedical
research continues to build on the sequencing of the human
genome to better understand the genetic component of disease,
notably in the discovery of new genetic markers associated with
disease risk, as well as drug advocacy and toxicity.
As we continue to develop a greater understanding of the
genetics of human disease, we will move away from one-size-
fits-all medicine, to more targeted and effective prevention,
treatments and even cures. However, it is imperative that these
tests are scientifically credible.
Over the past few years, a greater number of LDTs have come
onto the market without FDA review that purport to inform
individuals of their risk for cardiovascular disease, and which
medicines and dosages will be most effective or ineffective in
treating their disease. Expert consensus guidelines summarize
research evidence, but there is no regulatory mechanism
enforced that attempts to compare such evidence to claims made
in marketing these tests. The current CLIA-approval process
ensures only the analytical validity or accurate measurement,
but fails to address clinical validity; whether a test result
is clinically important to a patient's health decision-making.
In the absence of such an independent examination, health
care professionals, patients, and payers have no assurance of
the value and limits of each test. The genetics of some
relatively rare cardiovascular conditions caused by single
mutations, like long QT syndrome and hypertrophic
cardiomyopathy, has been well characterized, and LDTs have been
critical components of medical care, family screening, and
development of therapeutics for such diseases. However, we are
in the early stages of understanding how each person's risk for
common disease is influenced by their DNA. An individual's risk
of heart attack, heart failure, or atrial fibrillation is a
complex interaction of their genetics, their behavior, and
their environment.
A 2006 investigative study by the GAO observed the genetic
testing companies they investigated ``mislead consumers by
making predictions that are medically unproven and so ambiguous
that they do not provide meaningful information to consumers.''
And the FTC issued a statement warning the public to be ``wary
of claims about the benefits these products supposedly offer.''
The public is not equipped to do this on its own.
Despite the remarkably rapid progress that has been made in
our understanding of the genetics of cardiovascular disease in
recent years, it is not yet possible to assess a person's DNA
to evaluate their risk for most common diseases with sufficient
accuracy on which to base treatment decisions. It is clear that
some genetic tests lack scientific credibility. Allowing these
tests to continue to be marketed without rigorous oversight
increases the risk of undermining public and health care
provider confidence in the utility of employing genetic tools
to improve health care. There are differences between a test
kit shipped out to laboratories and an LDT that is performed in
a single laboratory. However, regardless of how and where the
test is performed, the interests of health care providers and
patients remain the same. They need to have the same degree of
confidence that it is a high quality test, where the claims of
its validity are substantiated by science, and its application
to improve patient health established.
I have had patients come to me with genetic tests that
suggest slightly increased risks of atrial fibrillation or
heart attack, but they are confused because their regular
physicians do not know how to interpret results. They ask me
whether they should take aspirin, cholesterol-lowering statins,
or blood thinners. These are medications with risks and
benefits that must be carefully matched to individual patient
risks. Statins have been well established to lower risk of
heart attack, and people with coronary disease are at high risk
of it. A currently marketed genetic test purports to determine
whether they are likely not to respond to a statin, or to have
higher risk of heart attack. The small studies that initially
supported this claim have been completely debunked by much
larger studies, but the marketing continues. Not taking a
statin because a patient or their doctor believes falsely that
they will not respond could contribute to a potentially fatal
outcome. This cannot continue. The AHA applauds the FDA for its
decision to reconsider its enforcement discretion with regard
to the regulation of LDTs. This is the right thing to do for
patients.
Thank you very much. I will be happy to answer any
questions you may have.
[The prepared statement of Dr. Newton-Cheh follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman.
I now recognize Dr. Sawyers 5 minutes for opening
statement.
STATEMENT OF CHARLES SAWYERS, M.D.
Dr. Sawyers. Good morning, Mr. Chairman and distinguished
Members of the subcommittee. My name is Dr. Charles Sawyers. I
am an oncologist and a cancer researcher, and the chair of a
cancer research department at Memorial Sloan Kettering Cancer
Center in New York. I am also the immediate Past-President of
the American Association for Cancer Research, or ACR, which is
the world's oldest and largest cancer research organization,
with over 35,000 members, representing basic translational,
clinical researchers, health care professionals, patients, and
advocates in the U.S. and abroad, and I am honored to appear
before you today.
I want to begin by reminding us what a remarkable time it
is in cancer research and with the development of many new
cancer drugs. This all dovetails from our investment as a
country in 1971 to defeat cancer through the National Cancer
Act. Now, more than 4 decades later, this commitment is finally
paying off. By my last count, over 45 new lifesaving cancer
drugs were approved just in the last 10 years, including one
just last Friday.
So I want to point out three things that came together to
make this slope of increase in cancer drug development happen
so quickly over the last 10 years. First, we finally understand
the cause of cancer. Cancer is a disease of mutant genes, and
by knowing the names of those genes and how they cause cancer,
we can discover new drugs that kill cancer cells by attacking
them at their roots. The second is the human genome project. By
knowing the names of all the genes in our DNA, we have been
able to catalog over the last several years all the ones that
are mutated in cancer. This knowledge teaches us that cancer is
not just 10 or 20 different diseases called lung, colon, breast
and prostate cancer, but hundreds of diseases defined by the
mutant genes that cause them. This also empowers us to develop
the drugs to treat each cancer more effectively. And the third
is technology. Just 5 years ago, DNA sequencing was so
specialized that it could only be carried out in research
settings, using highly curated tumor specimens, but today, this
technology is routinely deployed in many of the major cancer
centers throughout our country, and tomorrow, this technology
will become a routine part of workup of all cancer patients.
I know this from firsthand experience. Fifteen years ago, I
co-led the first clinical trial of a drug called Gleevec that
is a highly effective drug for a form of blood cancer known as
chronic myeloid leukemia, or CML. All patients with CML have a
very specific gene mutation, and prior to Gleevec, had a life
expectancy of just a few years, but now CML patients live for
decades simply by taking this pill once a day that targets the
cancer cells without the side-effects of chemotherapy or
radiation. In fact, many of the patients I treated on the first
clinical trial back in 1999 are alive and well today. And
similar stories can be told for melanoma, lung cancer, colon
cancer, and sarcoma and so on, and medical historians will look
back and call this the golden age of cancer therapy.
So why am I here today to talk about LDTs? Well, it is
obvious, because diagnostics are critical to the success of
this targeted cancer therapy. Indeed, as we have heard from
many of the speakers today, the mantra of personalized medicine
is the right drug for the right patient. And the FDA recognizes
this and approves these new targeted cancer therapies in
conjunction with the so-called companion diagnostic which we
have heard about, which undergoes a rigorous validation
process, just like the drug. Therefore, a safe, reliable, and
effective diagnostic test is as important as a safe, reliable,
and effective drug.
Now, the problem is urgent because gene sequencing will
soon become a routine part of cancer care. Hundreds of
thousands, if not millions, of patients are going to be
impacted by this technology in the coming years, and I think we
all agree that physicians and patients must be able to trust
the claims made by the developers of these tests, especially
when they are used to determine the treatment regimen for a
cancer patient. Too much is at stake to compromise on the
regulatory standards that govern them.
And gene sequencing technology is evolving very rapidly,
one of the most innovative industries I have seen, and we are
just at the tip of the iceberg of what may be possible. I think
we will soon be able to detect cancer mutations in a single
drop of blood. Many innovative companies are entering the field
and are looking for clarity from the FDA on how to
commercialize these and related technologies. Just as with drug
approvals, a clearly-defined regulatory process will lead to
greater innovation and investment.
For all these reasons, ACR, which I represent, as well as
my own experience in the cancer research field, I applaud the
FDA for proposing a classification of LDTs based on the risks
posed by the test to the patient. Having a single strict
regulatory approval standard will reassure the American public
that the tests used in a high-risk health care setting are
safe, accurate, and effective, and will encourage the private
sector to invest in this promising area of medicine.
I want to close by submitting for the record the ACR's
policy statement on the regulation of diagnostics entitled,
reliable and effective diagnostics are keys to accelerating
personalized cancer medicine and transforming cancer care.
Thank you.
[The prepared statement of Dr. Sawyers follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman.
Thanks to all the witnesses for your opening statements.
I have a unanimous consent request. Submit for the record a
letter dated September 8 from the Combination Products
Coalition. Without objection, that will be entered into the
record.
[The information appears at the conclusion of the record.]
Mr. Pitts. I will begin the questioning, and recognize
myself 5 minutes for that purpose.
Mr. Fish, we will start with you. I have heard companies
and past witnesses remark that regulatory uncertainty and a
lack of incentives in the diagnostics space have contributed to
innovative products sitting on companies' shelves. Do you
believe this guidance document would address these issues or
create more regulatory uncertainty?
Mr. Fish. Mr. Chairman, we believe that this proposed
framework by the FDA would help reduce the current uncertainty
in diagnostics by ensuring similar review for tests that
present a similar level of risk, and make it clearer for both
laboratories and manufacturers alike what the path forward is
to provide the clinical diagnostics to patients. So in our
view, we believe this would help address the stifling of
innovation we see under the current system.
Mr. Pitts. Mr. Mertz, you state in your testimony that
enhancing CLIA may be the way to go. CMS, the agency that
implements CLIA, recently stated, ``CLIA does not address the
clinical validity of any test, that is the accuracy with which
the test identifies measures or predicts the presence or
absence of a clinical condition or predisposition in a patient.
On the other hand, FDA does.'' CMS has clearly indicated that
it does not want, nor could it handle, additional testing
responsibilities authority in this area. Why are you still
proposing it?
Mr. Mertz. Thank you. And we have known over the years that
CLIA has taken the position that they do not regulate clinical
validity. We actually believe under their statutory authority
that they could, and the regulations on CLIA actually touch on
that. They are required the clinical accuracy of the test, the
performance of the tests are regulated. However, because there
is this perceived gap that they do not regulate clinical
validity, we have been very supportive for many years for
modernizing CLIA, for strengthening CLIA so that it would
specifically require CLIA to look at the clinical validity of
all new laboratory-developed tests. We were supportive of
Congressman Burgess' bill, the Modernizing CLIA Act, which
would specifically have an approval process for all new
laboratory-developed tests, not just a few that the FDA will be
able to look at, but they would review the clinical validity of
all new laboratory-developed tests.
In addition, I would touch on the resource issue that has
been talked about today. The FDA is supported by--20 to 30
percent of their funding is from the user fee. They only
approved 23 tests. CLIA actually is funded 100 percent by a lab
user fee, and a GAO report from a couple of years back
indicated that they had $70 million in carryover money they
hadn't spent. They have a lot of resources there that they
could use. The other thing is they--CLIA would not have to--FDA
is proposing to duplicate all of the things underlying looking
at clinical validity. They will have new inspections, new
registration, licensing, labeling, all these things will be
done a second time. You could very surgically, with CLIA, go
in, add that clinical validity requirement, have adverse
reporting, and it would be fully funded by the laboratory
industry with the funds that we provide in the user fee. So we
think that would actually be a much more effective way to
guarantee the safety of these tests, and establish the clinical
validity of them.
Mr. Pitts. Thank you.
I have a couple of questions for each of you. So regardless
of whether you agree or disagree with the substance of the
guidance, do you believe it would be a significant shift in
longstanding Agency policy and a departure from existing
practice for the regulated industry?
Mr. Fish, we will start with you. Just go down the line.
Mr. Fish. So we concur with FDA's assessment that this
framework would represent a change in practice by the Agency,
but not a change in regulation. Since the FDA is essentially
not proposing to change any current regulation that applies to
diagnostics, but simply to extend its enforcement of those
regulations to laboratory test developers. So we share that
opinion with FDA.
Mr. Pitts. OK, and you can answer yes or no if you would
like. Do you believe, Dr. Behrens Wilsey, that it would be a
significant shift in longstanding Agency policy, and a
departure from existing practice for the regulated industry?
Ms. Behrens Wilsey. The Coalition does think it would be a
significant shift and change in long-term policy, but that is
the reason why we believe many of these questions need to be
answered in advance to finalizing guidance.
Mr. Pitts. Mr. Mertz?
Ms. Behrens Wilsey. And we think if that were the case,
that it would go to resolving a lot of the issues.
Mr. Pitts. Mr. Mertz?
Mr. Mertz. We do think it would be a completely substantial
shift in what they have regulated. From the time that the
device amendments were enacted in 1976 until the early '90s,
they never said anything about regulating laboratory-developed
tests, even while CLIA was being enacted in '88. There was no
mention in Congress, in FDA. They asserted absolutely no
authority over laboratory-developed tests for 16 years after
the Device Act, and there were many, many hundreds of LDTs
being created at that time. So we think this is a significant
shift in their policy.
Mr. Pitts. Dr. Newton-Cheh?
Dr. Newton-Cheh. Yes. This would be an important and
significant shift in the practice of the FDA, exercising
enforcement discretion, and it is welcome.
Mr. Pitts. Dr. Sawyers?
Dr. Sawyers. I would take a slightly different take. I
don't think it is a shift in the sense that companion
diagnostics have been a standard part of the approval of
targeted cancer drugs now for about 8 to 10 years. I think the
shift, of course, is expanding that to LDTs that are measuring
the same thing, but not subject to the same regulation.
Mr. Pitts. All right, and then the second question, we can
go in the reverse order. Dr. Sawyers, do you believe FDA should
establish a new framework of this nature by guidance or
regulation?
Dr. Sawyers. I think guidance would be the start to get it
right, as Dr. Shuren pointed out, through dialogue, and then I
think it should move to regulation.
Mr. Pitts. Dr. Newton-Cheh?
Dr. Newton-Cheh. I think the FDA's use of guidance is
consistent with its past practices and its open to public
comment seems acceptable.
Mr. Pitts. Mr. Mertz?
Mr. Mertz. Well, we question and challenge their statutory
authority to even do guidance or regulation in this area.
However, if they were to proceed, it definitely should be done
through notice and comment rulemaking.
Mr. Pitts. Dr. Behrens Wilsey?
Ms. Behrens Wilsey. I am not an attorney and so I am not
going to comment on FDA's authority, but I will say that the
Coalition believes that guidance could be an effective tool if
used properly and exercised properly.
Mr. Pitts. Mr. Fish?
Mr. Fish. As FDA has noted, it is not proposing to change
existing regulation, but simply to enforce it with respect to
LDTs, and we concur with that assessment.
Mr. Pitts. Thank you.
The Chair recognizes Mr. Green 5 minutes for questions.
Mr. Green. Thank you, Mr. Chairman, and thank our witnesses
for being here.
We have heard a great deal about the boom of innovation in
LDTs since Congress enacted the Medical Device Amendments in
1976. Over the last 4 decades, like many areas in medical
innovation, the products used in patient care have
significantly grown and evolved. When there are revolutionary
advancements in health products, a new oversight framework
tailored to the specific type of device or product may be
warranted. Patient safety cuts both ways, ensuring a product is
safe and effective, and also ensuring fostering innovation so
clinical care improves over time. Since 1976, LDTs have evolved
from being limited in number and relatively simple tasks
primarily used to diagnose rare diseases and conditions. Today,
they have increased in number, complexity, and accessibility.
I understand that nearly all FDA-approved and FDA-cleared
test kits began as LDTs. Some of the innovation we have seen in
LDTs base from labs developing new tests or modifying existing
tests to meet patient needs. Yet, as the complexity and
accessibility of highly sophisticated tests have grown, there
is a need to promote continued innovation, while recognizing
the risk of LDTs posed to patients is much greater than in the
past.
Mr. Fish, we have heard concerns that FDA oversight will
stifle innovation for tests that are for rare diseases, and
will slow patient access to new tests. Can you provide a
response to these concerns, and how the FDA proposes to address
this?
Mr. Fish. Well, I think we recognize that any regulation
comes with a burden, and we think the appropriate question is
not whether or not there is a burden associated with
regulation, but whether there is a rationale for that
regulation and whether the burden is commensurate with a public
health issue. And our feeling is that FDA is seeking to
achieve, and largely is achieving through this framework, a
balance between additional enforcement of regulation with
respect to LDTs, and continued enforcement discretion. FDA has
pointed out, I think pretty clearly in its framework, that with
respect to a number of different categories of LDTs and
settings in which LDTs are both developed and used, that it
will continue to exercise enforcement discretion, thereby
allowing LDT innovation to continue to flourish and serve
patients in those settings.
Mr. Green. OK. Mr. Mertz, I understand that once a test kit
is FDA approved and enters the market, the laboratories may
modify the kits, which is in many cases expanded uses that even
improve tests.
Can you speak to this, and how does the FDA proposal impact
this practice?
Mr. Mertz. Yes, thank you. And this is one of the areas we
are very concerned about because, as has been pointed out, most
of the LDTs, 1,000 or so new LDTs a year, most of them are
created because there is no FDA-approved kit, and the patient
needs the test and there is no kit. For many others, most of
the rest if there is a kit that was originally LDT, now it is
an approved kit by the FDA, but it actually needs modifications
in order to have it keep up with technology. And interestingly,
the one example that Dr. Shuren said earlier was sort of a copy
of a kit that was being used. He was actually referring to the
BRAF test for melanoma patients, and he said the labs claim it
was better. Well, in fact, if you look at the testimony by the
AMA, in fact, the FDA-approved kit turns out that, because it
was frozen in time, you have an approval process and that
technology is frozen in time, that test cannot distinguish
between two different mutations for melanoma, and the AMA
pointed out the clinicians, they actually must know that the
specific mutation, and really to detect the right mutation and
to have the right treatment, they have to use the LDT
modification of the BRAF test.
We see many, many other cases of this where the original
HIV test back in 1987, which was approved still has not been
updated. It is the LDT that has served for 25, 30 years now
because that technology was frozen in time. So really the FDA-
approved kit actually never was the standard of care. And this
is actually what most LDTs are either unmet need or they have
actually made some change that is absolutely essential to
clinicians in treating a patient.
Mr. Green. Do you believe that there should be premarket
review of LDTs to ensure their safety and effectiveness?
Mr. Mertz. Well, first of all, actually what the FDA is
proposing is--in the case of high-risk LDTs is not premarket
approval.
Mr. Green. I know, but would you go as far as----
Mr. Mertz. OK, but in terms of our position--thank you.
First of all, as I said before, we believe that the clinical
validity of the test should be established. That is generally
done within the lab, through the reviews of the crediting
organizations, but to make it absolutely clear that it is, we
supported legislation that would add that requirement under
CLIA to require all new laboratory-developed tests, all 800 or
1,000 a year there are, to go through an approval process at
CLIA to establish the clinical validity. So yes we do, but we
think that would be a much better way than doing it than
duplicating CLIA again under FDA, and putting a much more
burdensome process that will make it really, really untenable
for most tests to go through that process.
Mr. Green. Thank you.
Mr. Chairman, I have one more question, if I could ask?
Mr. Pitts. Go ahead. Proceed.
Mr. Green. Mr. Fish, some of your fellow panelists have
raised questions about whether the FDA has the authority to
regulate LDTs, suggesting that LDTs are more akin to services
provided by physicians than devices. I would like to ask your
views. We heard today, Congress amended the Federal Food, Drug,
and Cosmetic Act in 1976 to give the FDA authority over in
vitro diagnostics, IVTs. Can you describe what the differences
are, if any, between FDA-regulated IVTs and so-called
laboratory-developed tests, and how do you respond to the claim
that LDTs are not subject to FDA jurisdiction?
Mr. Fish. Well, first of all, as you note, the statute
clearly refers to medical devices as including in vitro
diagnostic products, which are the equipment and materials used
to produce in a test. Our view is that LDTs are the same as
diagnostics produced by a manufacturer. The question of whether
or not LDTs are solely services I think obscures the fact that
when a laboratory performs a test, there is still a test at the
heart of what it performs, analogous to a doctor's office or a
medical center providing chemotherapy. There is a service
provided in the application of chemotherapy for a patient, but
there is still a drug at the center of what is being performed
as a service. So our view is that LDTs, from a practical
standpoint, still constitute a regulated article under the
Medical Device Amendments, and FDA has made that case and we
concur with it.
Mr. Green. Thank you, Mr. Chairman, for your courtesy.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the Vice Chairman, Dr. Burgess, 5 minutes
for questions.
Mr. Burgess. Thank you, Mr. Chairman, and I do thank all of
our witnesses for being here today. It is an important topic
that we do need to discuss.
Dr. Behrens Wilsey, let me just ask you a question about
something that could affect, say, the off-label use of a
diagnostic. If you have a manufacturer-distributed test, the
laboratory can use the test off-label in the practice of
laboratory medicine, and that is not going to upset the FDA.
But with a laboratory-developed test, if the FDA considers the
laboratory to be a manufacturer, and considers the LDT service
to be a device subject to the FDA's labeling rules, this could
raise concerns that the laboratory is promoting off-label use.
From your perspective as an investor in laboratories
performing laboratory-developed tests, how would this risk
impact your decision to invest in a particular company?
Ms. Behrens Wilsey. Thank you. I appreciate this question.
This is a concern that the Coalition raised several years
ago, and has discussed with the Food and Drug Administration,
and the question that came up a little bit earlier today, and
we greatly appreciate Dr. Shuren's assurance that this issue
would be resolved reasonably. However, what I would say, the
longstanding practice of labs consulting with physicians about
patient management based on the results of the test is actually
a requirement under CLIA. And at the same time, if labs become
manufacturers under FDA regulations, depending upon the label
and the physician use of the information, the lab consultation
could be considered off-label promotion. And what we believe
needs to occur is we need to wrestle down specifically what
precisely would constitute a consultation, and what would
precisely constitute off-label promotion, or else there is no
question that, as an investor, that would chill investment in
this area. That would be of great concern to investors.
Mr. Burgess. Let me ask you a question. Mr. Mertz, I think,
referenced the disparity between the number of tests and the
number of approvals. From the investment perspective, I am not
a lawyer, I am not an investor, I am a physician, I simply live
downstream from all of this, but from the investor perspective,
what does that do when you are looking at whether or not to put
money into one of these products, the vast number that are
available, the few that have been approved through the FDA, if
there is a furtherance of the FDA's reach into this area, what
is that likely to do?
Mr. Mertz. So----
Mr. Burgess. Dr. Behrens Wilsey.
Ms. Behrens Wilsey. I apologize.
Mr. Burgess. Yes.
Ms. Behrens Wilsey. I----
Mr. Burgess. From the investor's perspective, this
discrepancy between number of tests coming around and the
number of approvals, if the FDA's grasp is indeed increased,
what does that do to the viability from the investor community?
Ms. Behrens Wilsey. We are very concerned about the number
of tests. I was running out of time in my oral comments so that
I didn't cite the same numbers that were provided by ACLA.
Having said that, we are very concerned. What would concern
me as an investor is that you would create a very long line and
a very protracted period of time in which these tests would
have to go through the regulatory process. That absolutely
would diminish interest in investing in this area.
Mr. Burgess. And some of the financial return from a
laboratory-developed test is de minimis when you compare it to
a blockbuster pharmaceutical, is that not correct?
Ms. Behrens Wilsey. Absolutely. I made the point earlier
that the two most important issues affecting investors in
financing companies that develop these types of tests are
regulation and reimbursement. And the quantity of evidence and
the time in which you are required to develop that evidence so
that you can provide it for the purposes of an FDA approval
substantially lengthen the period in which you might generate
some sort of a return. Actually, it substantially generates the
period in which you have any hope of even getting reimbursed.
So that is a great concern, and one of the reasons why this
area does not have the same number of investors as the
pharmaceutical area.
Mr. Burgess. Mr. Mertz, I appreciate your comments about
the legislation introduced in the last Congress. I haven't
planned to reintroduce it yet, just with that caveat, but when
President Obama was Senator Obama and he introduced the bill
that I put into the record this morning, the concept was the
harmonization between CLIA and the FDA. Do you think that the
bloom is off that rose, has that hour now passed and we are
into a different realm where that is no longer possible?
Mr. Mertz. No, and just interestingly, I was at ACLA when
Senator Obama introduced that, and it was in reaction, in part,
to what the FDA was proposing on an earlier iteration of this
guidance, the IVDMIA. They were going to regulate some of the
LDTs, and it was in reaction to that and a much more measured
approach which would rely on CLIA. But I don't think it is too
late to do this with CLIA. As we heard earlier, it is going to
take the FDA 9 years to recreate all of this regulation within
their realm. So, no, I think--and they could ramp up much more
quickly at CLIA because they have the foundation.
If I could, Congressman, quickly on the investment issue.
Of the many hundreds of new LDTs a year, some of them are
created by small startups, they are investor-funded, but
hundreds and hundreds of them are created by academic medical
laboratories. There is a letter that the--that you have and the
committee has from 23 of the most esteemed medical institutions
in the country, the Harvards and Stanfords and all of them, and
they are very concerned. They said FDA regulation of LDTs would
stifle innovation and be contrary to public health. So they are
not really funded by investment capital. The Mayo Clinic, which
is one of our members, they create over 100 new laboratory-
developed tests a year, and they are worried that they are not
going to be able to innovate. It is not even an investment
capital issue.
Mr. Burgess. OK, thank you, Mr. Chairman. I yield back.
Mr. Pitts. The Chair thanks the gentleman, and now
recognize the ranking member of the full committee, Mr. Waxman,
5 minutes for questions.
Mr. Waxman. Thank you, Mr. Chairman.
I don't hear anybody on the panel argue that there
shouldn't be a very careful scrutiny of these tests. It seems
like the question is who should do it; CLIA or the FDA, and I
don't think CLIA has the kind of expertise that we see at FDA.
Dr. Sawyers, you note in your testimony that we have been
able to shift from classifying cancers by their site of origin
in the body, to classifying them by their molecular subtype. I
think this exemplifies the kinds of advances we need to
capitalize on to further develop into targeted therapies for
personalized medicine, and to speed new treatments to patients.
However, we also see what was described in a 2011 New York
Times article as a mini gold rush of companies trying to market
tests based on the new techniques, at a time when the good
science has not caught up with the financial push.
Mr. Chairman, Mr. Chairman, I would like to insert into the
record that article from the New York Times dated July 7, 2011.
Mr. Pitts. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Waxman. Thank you.
Dr. Sawyers, as you note in your testimony, the success of
a targeted therapy is inextricably linked to the successful
development of its companion diagnostic test. You also note
that implementation of FDA's risk-based framework would balance
the need for encouraging innovative medical product development
with the need for ensuring patient safety.
Could you describe some of the harms you see from exempting
lab-developed versions of these tests from FDA oversight, and
some of the benefits you see from having them subject to FDA
oversight? And as part of your answer, could you address
whether you think FDA oversight will unnecessarily limit
patient access to the best new tests?
Dr. Sawyers. OK, well, I think that the benefit of having
more oversight would be more confidence in what I will just
call the me too tests that develop shortly after the approval
of a companion diagnostic. The details of what the regulatory
requirement for approval of those second generation tests is an
important detail. It can't be such a high bar that it impairs
or harms second followers from joining in, but I see that this
next generation cancer drugs develop in a similar way because
there is a clear set of guidelines and developers know what
they need to do.
I also want to make a point about the ability to compare
test results across different centers and across even the
world. A point I made was that cancer is now subdividing into
hundreds of diseases, and so one medical center running an LDT
in that clinical lab can't easily compare the results from
other labs. So a more uniform sort of trust in the sensitivity
and specificity of tests would accelerate the post-approval
understanding of what patients are most likely to benefit from
what drugs.
In terms of harm, the examples have been given earlier of
tests that didn't hold up to the light of day later on in
subsequent publications, as made by my colleague in cardiology
in his oral statement.
Mr. Waxman. Well, Dr. Newton-Cheh, do you want to comment
on the question I asked or what Dr. Sawyers had to say?
Dr. Newton-Cheh. Yes, I think--I mean by way of example,
the American public has by and large supported FDA's regulation
of pharmaceuticals. They would not support rolling back to 19th
Century Wild West where snake oil is indistinguishable from
safe and effective therapies, and I think by the same token,
they would not accept continuing unregulated LDTs in the 21st
Century. I think to draw the----
Mr. Waxman. Why should FDA regulate it as opposed to CMS?
Dr. Newton-Cheh. I think that is what FDA does. I mean FDA
has structures in place with expert advisory committees, and
consultation with stakeholders evaluating clinical claims,
evaluating the literature. That is the business that they have
been in, so I see testing as another component of clinical
validity. I think CLIA historically has been focused on the
laboratory structures, the certifications, the personnel, and
the precision of the measurement of some biologic entity, but
not necessarily the interpretation or application to medical
therapy.
But if I could also draw a distinction between oncology
where tissue is obtained, a molecular specificity is observed,
and a therapy is targeted to that molecule. Well, that is a
greater degree of precision than exists for cardiovascular
disease. The two big killers are cancer and cardiovascular
disease. Cardiovascular disease does not have such a precisely
defined molecular understanding, and so there is, I think, a
potentially greater harm for misapplying the inferences that
are gained in oncology, where it has really been revolutionary,
and I would say in cardiovascular disease it is about 10 years
behind, and much of the claims that are currently out there for
genetic testing to predict response to therapies are just
unsupported.
Mr. Waxman. Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the gentleman from Florida, Mr. Bilirakis,
5 minutes for questions.
Mr. Bilirakis. Yes, I guess it is working, OK.
Mr. Mertz, some here are saying that the FDA's intervention
over laboratories is necessary to ``level the playing field.''
However, your testimony lays out that laboratories are already
regulated by CMS, and have been for decades, and that the FDA's
actions may duplicate regulations rather than streamline then.
Can you talk about the overlapping regulations and the problems
that they could create?
Mr. Mertz. Yes. Thank you, and I appreciate the question.
And some of those who make that argument that it is
unregulated, it is actually a bit of a myth because maybe I can
just describe it best in an example. One of my academic
institutions, it is a big hospital and a lab, and they told me
that the lab is actually--they consider it probably the most
regulated part of the entire hospital, and others in the
hospital look at the lab as being quite highly regulated.
The other point I want to make is that a manufacturer and a
laboratory service are very different, and I think a good
example of that that people understand is that a laboratory-
developed test is not a product, it is not an article, it is
not a machine. Most pap smears historically are laboratory-
developed tests, and this is where a specimen is taken from the
patient, a slide is prepared, a cytologist looks at the slide
to detect cancer. If it is positive, it will be reviewed by a
pathologist. Then they make a determination, give it to the OB/
GYN, and that is a laboratory-developed test, and it could be
considered--there is some risk involved if that diagnosis is
wrong. I don't think many people would consider that procedure
and that knowledge, and all of the physician involvement I just
described, as a physical product that is sold commercially by a
manufacturer. So that is not a manufactured product, it is a
process. So that is regulated as that. So we are regulated,
they are regulated. We are fundamentally different. If you look
at the regulations under CLIA, labs, they do, they regulate
them as labs. The personnel, the procedures, the specimen
collection, the accuracy of the test, which is very important.
You look at manufacturers, it is more about quality systems and
the manufacturing process. It is a very different process. But
adding a whole second layer or a third regulation to
laboratories is not leveling the playing field, it is making
two different playing fields. It would make it very difficult
to innovate, very expensive to innovate, and I would point out
to others here that have brought up cases that--the KRAS test
for colorectal cancer, there was--there has been--there was no
test for 10 years for colorectal cancer until KRAS came along.
The BRC for leukemia, that was a laboratory-developed test
originally. A lot of them were laboratory-developed tests. So
we are sort of playing on an entirely different field. We are
regulated, and by adding another layer of regulation on top of
labs is only going to stifle innovation.
And finally, there are ways if clinical validity, we agree
it needs to be addressed, you could add that to CLIA without
duplicating the rest of the playing field.
Mr. Bilirakis. Very good.
Thank you, Mr. Chairman, I appreciate it. I yield back.
Thank you, sir, for your testimony.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the vice chair of the full committee, Mrs.
Blackburn, 5 minutes for questions.
Mrs. Blackburn. Thank you, Mr. Chairman, and I thank each
of you for being here, and I thank you for your patience. We
appreciate that you are willing to come in and talk with us.
We are focused on 21st Century Cures on medical innovation,
and as I said earlier with Dr. Shuren, how do we preserve
access to affordable health care for all Americans, because
right now, the price is going up, the networks are narrowing,
and it is becoming more difficult for so many individuals in so
many parts of the country to get that access they want.
Mr. Fish, I want to come to you and stay pretty much with
where Mr. Bilirakis is. Looking at how the diagnostics are
approved the same as the medical devices, and I have heard from
a lot of your AdvaMed Dx members, and they feel like this
should be approached differently, that the test should be
approved and the diagnostics should be treated differently than
medical devices. So do you support your members' position in
that they should be handled differently?
Mr. Fish. AdvaMed Dx's position currently is that we are
comfortable with FDA's current regulation of diagnostics. I
think one of the issues that has been recognized is that the
diagnostics are different than other medical devices, and FDA I
think has recognized that in terms of the kind of data and
information that it requires to be provided to approve those
diagnostics as safe and effective, but we are currently
comfortable with the existing regulatory system. I would say,
furthermore, we thank the committee for its 21st Century Cures
Initiative, and as we always have in the past, if the committee
is interested in exploring further any ideas around FDA's
ongoing or changing regulation of diagnostics, we would be very
pleased to work with the committee on that.
Mrs. Blackburn. Great, thank you.
Dr. Behrens Wilsey, I want to come to you. I appreciated
your comments in your testimony so much. Let me ask you this.
You heard Dr. Shuren, and if you were providing guidance to the
FDA as to how they were going to approach their regulation,
trying to get some regulatory certainty into the process, if
you were to talk to them about reining in some of the mission
creep that exists there, and also the LDTs, if you were talking
to them about the LDTs and how that has impacted health care
costs, what would you say to them?
Ms. Behrens Wilsey. We would like to encourage greater
dialogue, as I mentioned earlier, before finalization of the
guidance, in part, because there has been such a long period of
time in which there has been enforcement discretion, because
this would encourage more dramatic changes in this area, and
because this area is really not just exciting technologically,
but the potential applications now of the use of these
technologies, not just by good actors but all actors, are
becoming increasingly clearer and very important for the
patient. So what we would really like to see, and what we would
encourage by the FDA, is to work through greater levels of some
of the details that would lay out in advance of any
finalization of guidance, some of the very specific questions,
many of which have been raised today in our discussion, so that
there is a lot less that is assumed by how the FDA will
approach answering those concerns and those questions after
guidance is finalized, because at that point in time, the clock
starts ticking. At that point in time, companies' investors,
everyone begins to risk the progress and the opportunity for
these types of technologies, so that the lack of certainty and
the judgments that would occur after that are far less clear
than what we think could occur between now and finalization of
guidance.
Mrs. Blackburn. OK, thank you.
I yield back, Mr. Chairman.
Mr. Pitts. The chair thanks the gentlelady.
That concludes this first round. We will go to one follow-
up per side.
Dr. Burgess, you are recognized 5 minutes for a follow-up.
Mr. Burgess. Thank you, Mr. Chairman.
Dr. Behrens Wilsey, just before we leave that concept of
guidance and guidance versus regulation, you heard Dr. Shuren's
response to my question, are we going with guidance because
regulation actually triggers a response from the Office of
Management and Budget as to the financial impact. So I guess
this is part of the problem. Why are we here talking about a
regulatory guidance that apparently has been in the making
since either 1976 or 2006, it is hard to follow, if the onus is
so severe, why not proceed through a regulatory pathway,
through that more established pathway, and let us do the
economic analysis that I think, certainly from the investment
community, I think you would welcome that, would you not?
Ms. Behrens Wilsey. Independent of rulemaking versus the
guidance process, I would say that you could accomplish the
same goal through both mechanisms. One important distinction
being, of course, in rulemaking, the Food and Drug
Administration has to respond to certain questions. On the
question and the issue in the matter, I should say, of
economics, I think that is an important question for everyone,
whether FDA generates the numbers or collaborates with others
in generating those numbers, those are still very important
considerations. In fact, we have discussed whether we could put
our hands on numbers that could be helpful through this
process. So I would say independent of the process, we would
encourage assessment on the economics.
Mr. Burgess. But the economic assessment may be
circumvented by the fact that it is done through guidance
rather than through regulation. That was my point----
Ms. Behrens Wilsey. I understand that.
Mr. Burgess [continuing]. In the earlier question.
Ms. Behrens Wilsey. The distinction that I am making is
that if FDA works through a reasonable process, in our opinion,
they could perhaps not precisely end up in the same position as
everyone would like them to through rulemaking, but we could
certainly come much closer to that. Economics being one of the
considerations.
Mr. Burgess. Well, unfortunately, they may have given
themselves some enforcement discretion on their own purpose.
Mr. Mertz, let me just ask you a question. It has come up
several times on the issue of scalability at the FDA, and
this----
Mr. Mertz. I am sorry?
Mr. Burgess. Scalability----
Mr. Mertz. Yes.
Mr. Burgess. We are talking about a very broad expansion
into an area that is large and growing, and I think I heard you
voice a concern are they actually ready to do this, and I have
that concern and I asked Dr. Shuren and he assured me that they
would, but realistically, as part of the Cures Initiative we
have heard from people saying, look, one of the big problems
with the FDA is their information architecture is so archaic,
they have stuff that is written on paper records that should be
digitized and in the digital age. So, again, I would ask you,
because it obviously impacts your association a great deal, do
you think the FDA is ready for the scale of this undertaking?
Mr. Mertz. No, and as we pointed out, and by the way, Dr.
Shuren said we weren't part of the MDUFA III negotiations, in
fact, we were one of the stakeholders, so we became very
familiar with the process and how much funding they had.
As I mentioned, there are 11,000 complex labs, not 6,000.
There are probably tens of thousands of laboratory-developed
tests. We know that they only were able to look at 23 clear
FDA-approved tests last year. Just the initial highest-risk
tests they are talking about, we had heard some reports that
they may look at 100 highest-risk tests within the first year
or so. That would be a a fivefold increase in the number of
PMAs they would be doing in the first year. They have said
there is no user fee, so they would have no additional money to
do a fivefold increase in the number of PMAs. So we are
concerned it would not only slow down innovation with LDTs, it
could very well slow down the innovation in the FDA, the
regular manufactured kits, so we are very concerned about that.
We agree completely that the rulemaking would flush out the
economic impact because until they define what high risk is,
they won't know how many LDTs they are going to have to look
at. Until you know how many LDTs you are going to look at, you
have no idea what the burden is on industry or the FDA. So I
think requiring them to do the economic impact would really
force them to say what they are going to regulate and how many
LDTs there are, and then it will expose the impact it will have
on the laboratory industry and the FDA.
Mr. Burgess. Thank you, Mr. Chairman, and I will yield
back.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the ranking member of the committee, Mr.
Waxman, 5 minutes for a follow-up.
Mr. Waxman. Well, thank you very much, Mr. Chairman.
Dr. Sawyers, Mr. Mertz has testified if there were problems
with LDTs, we would have more publicity about them. Do you
agree with that? Would doctors and patients necessarily know if
tests were not giving good advice for clinical decisions?
Dr. Sawyers. Yes, I would disagree. I think it is possible
because physicians are so busy and don't know whether the tests
they have ordered is an LDT or an FDA-approved cleared test,
that they may not know, and if there is no requirement for
reporting back, how would we know?So----
Mr. Waxman. Yes.
Dr. Sawyers [continuing]. I think it is an unknown.
Mr. Waxman. And, Dr. Newton-Cheh, how do you respond? Same
question.
Dr. Newton-Cheh. It is completely opaque. I think the
current environment for the practice of health care is
increasingly complex, and I think physicians, patients, payers,
they are all critical stakeholders here, I think they really
rely on having independent evaluation of the claims that are
associated with diagnostic tests.
Mr. Waxman. Thanks.
Mr. Fish, I would like to ask you a couple of quick
questions. One often cited critique of FDA's proposal to
oversee LDTs is that CMS, under its CLIA authority, should
regulate these tests, not FDA. How do you respond to this, and
do you think that CMS regulatory authority for LDTs should be
the sole regulatory authority?
Mr. Fish. I think it is important to distinguish between
what an ethical and competent laboratory currently probably
does, as opposed to what CLIA actually requires, and as Dr.
Shuren pointed out, what CLIA currently requires is vastly
different than what FDA requires. CLIA requires that
laboratories follow good processes and practices to ensure that
their personnel are proficient, and that they have processes in
place that ensure the good practices when they perform their
tests, but FDA, on the other hand, requires a number of aspects
of laboratory testing that are not present in CLIA, including
premarket review and approval of tests, it requires that there
be a demonstration not only of analytical validity but also
clinical validity, in other words, is it meaningful to
diagnosis, they require adverse event reporting and quality
systems regulation, and all of these aspects are missing from
what CMS does. And given the questions around what agency is
prepared to regulate LDTs, I think the answer is no agency is
conceivably as ready as FDA, and they--that is the appropriate
agency to carry this out.
Mr. Waxman. Yes. Let me ask you about this claim about
increased regulatory oversight stifling innovation. How do you
respond to this claim? I know some members of your trade
association, AdvaMed Dx, have had the experience of having
obtained FDA approval for their LDT, only to find that the next
day a laboratory launches a copy of that LDT without undergoing
FDA review at all. Please describe your views on the impact
that this situation can have on innovation.
Mr. Fish. I would first point out that as a core matter,
regardless of how this situation gets reconciled, the current
uncertainty in having two very different paths to market for
the same test is something that shouldn't stand as a matter of
public policy, and it has ripple effects from a number of
different standpoints. It has a ripple effect from the
standpoint of investor certainty that we talked about, it has
an impact on the competition that you just raised of LDTs
coming out that purport to be the same as an FDA-cleared test,
it has implications for clinician and patient transparency as
well. So, again, regardless of the decision that is ultimately
made, perhaps by Congress as well, this is just a situation
that currently can't stand.
As far as innovation goes, FDA made a very important point
when it said that it would not enforce regulations with regard
to LDTs that are developed and used in the academic medical
setting. Mr. Mertz referenced this letter that was sent by a
number of leading academic medical institutions. Shortly
thereafter, FDA came out with its framework and explicitly said
we are not worried about the tests that are being performed in
those settings, we are concerned about stand-alone, independent
laboratories developing tests that are outside the context of
patient care. And that is the test where FDA is concerned. So I
think they acknowledged that innovation could continue on LDTs
in the academic medical setting.
Mr. Waxman. FDA appears to be looking at prioritizing those
tests with the greatest amount of potential harm to patients,
and exempting a lot of other LDTs that might not be as serious.
Do you think that is a reasonable way to prioritize the cases,
or do you think there ought to be a rulemaking, every LDT ought
to be subject to every test and every evaluation?
Mr. Fish. Well, I would first say, regarding rulemaking, if
FDA were to proceed here by rulemaking instead of by guidance,
there would be nothing new to say, it would simply say and you
too, because the regulations already exist. So it is not clear
that there would be any rule to put forth. And FDA, I think, is
taking exactly the right approach. We have called for years for
all diagnostics to be regulated under a risk-based approach to
ensure that the burdens of regulation are commensurate with the
risks presented by those tests.
Mr. Waxman. Yes.
Dr. Behrens Wilsey, I thought your last few statements have
been very wise. It seems to me what you are saying is you want
to see what FDA is going to do, you are afraid it could stifle
innovation, but you think, handled the appropriate way, it
might not stifle innovation at all, is that a correct
statement?
Ms. Behrens Wilsey. Yes. I think even the improvements that
we have seen in the proposed guidance----
Mr. Waxman. Yes.
Ms. Behrens Wilsey [continuing]. Between 2006 and today, we
have already seen some improvements, and we certainly heard
from Dr. Shuren earlier, willingness to hear more, so I think--
--
Mr. Waxman. Yes.
Ms. Behrens Wilsey [continuing]. If we proceeded down a
path that allowed greater transparency, allowed the opportunity
and the time for all parties to discuss the issues, and
actually give some specific answers to some of the questions
that have been raised, I think we would find ourselves in a
very good position.
Mr. Waxman. Yes.
Well, Mr. Chairman, I want to commend you on this hearing.
I think just having this open hearing and getting different
views and hearing concerns can help FDA, can help everybody
make sure that the right thing is done, because we don't want
to stifle innovation, we do want these LDTs to continue, but we
don't--and you certainly wouldn't want investors to put money
into something that could end up doing nothing, and might even
harm people. So let us hope that this process will continue at
FDA and we will get a good result.
Thank you. Yield back my time.
Mr. Pitts. The Chair thanks the gentleman.
And on that note, that concludes the questioning at this
time. Members will have follow-up questions. We will send them
to you. We ask that you please respond promptly. I remind
Members that they have 10 business days to submit questions for
the record, and they should submit their questions by the close
of business on Tuesday, September 23.
Very important, informative hearing. Thank you very much.
Without objection, the subcommittee is adjourned.
[Whereupon, at 12:25 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
Prepared statement of Hon. Fred Upton
Today marks the seventh Health Subcommittee hearing
Chairman Pitts has convened as part of the bipartisan 21st
Century Cures initiative. I would like to thank him again for
his tireless work on this effort, including the exceptional
roundtable he hosted in Lancaster, Pennsylvania, in late August
that I had the pleasure to attend along with Ranking Member
Pallone and Dr. Burgess.
Over August and the early part of September, members from
both sides of aisle held roundtables across the country to
solicit feedback on accelerating cures and treatments for
patients. This really has been a collaborative effort, and we
need everyone to continue providing us with specific ideas--
none too big, none too small--about how we can make a
significant reduction in the time and costs associated with the
discovery, development, and delivery of safe and innovative new
treatments and cures for patients who need them.
Personalized medicine has really been a recurring theme
throughout this entire discussion. According to the
Personalized Medicine Coalition, ``While the potential benefits
of personalized [medicine] are straightforward-knowing what
works, knowing why it works, knowing whom it works for, and
applying that knowledge to address patient needs-the
intervening variables that determine the pace of personalized
medicine's development and adoption are far more complex. Among
those variables are the laws and regulations that govern
personalized medicine products and services used in clinical
practice.''
Today's hearing is an important opportunity to hear from a
variety of stakeholders about just that. Particularly since the
mapping of the human genome, diagnostics provide researchers
and clinicians with valuable tools to match the right patients
with the right course of therapy. We must ensure that our laws
and regulations keep pace so that innovation in this space
continues and patients benefit from accurate and reliable
tests.
On July 31, 2014, FDA notified the committee that the
agency intends to issue draft guidance to implement a new risk-
based framework governing the review and oversight of
laboratory developed tests. FDA has indicated for several years
that it planned on taking this step. Because it will have such
a substantial impact on how these products and services are
currently being used in practice, we required the agency notify
the committee before moving forward This provision in the Food
and Drug Administration Safety and Innovation Act was not an
endorsement of such an approach but recognition of the fact
that a number of legal, procedural, and substantive questions
about FDA's role in this complex policy area remained
outstanding.
I thank Dr. Shuren and our other witnesses for their
testimony about whether the agency has adequately addressed
these issues and what role Congress can play in making sure
that personalized medicine continues to flourish.
----------
Prepared statement of Hon. Henry A. Waxman
In 1976, Congress first passed a law making it clear that
FDA should ensure that diagnostic tests were safe and
effective. At that time, FDA decided that tests developed and
used by clinical laboratories, so called ``laboratory developed
tests'' or ``LDTs,'' did not warrant oversight. They generally
were made in small quantities and were used by local labs. FDA
opted to conserve its scarce resources by refraining from
enforcing applicable medical device requirements against
laboratories making LDTs. That was a policy that made a lot of
sense at the time.
Today, things are quite different. As we move closer to
achieving a new system of personalized medicine, practitioners
are increasingly using LDTs to help make critical treatment
decisions. Choices about which chemotherapies or medicines to
administer-or in some cases, to withhold treatment altogether-
are being made every day on the basis of LDTs.
Additionally, LDTs are no longer made in small local labs
and used by physicians and pathologists working in a single
institution responsible for a local patient population. FDA's
enforcement discretion policy has become untenable as LDTs are
increasingly manufactured by large, national laboratory
corporations, contain sophisticated technologies and complex
algorithms, and are distributed and used throughout the
country.
I applaud the agency for finally taking formal action to
change its LDT policy by issuing the notification of its
impending guidance. It is a step that was long overdue.
One of the primary reasons this step is overdue is that
there is currently a regulatory void surrounding these tests.
The Centers for Medicare and Medicaid Services (CMS) oversees
the laboratories that conduct testing, through the Clinical
Laboratory Improvement Amendments (CLIA). But CMS does not
evaluate whether the tests are clinically reliable. In other
words, under FDA's enforcement discretion policy, no one is
looking at LDTs to assess whether they accurately identify,
measure, or predict the presence or absence of a disease or
condition in a patient.
In today's world of highly sophisticated tests, that is a
situation no American patient should tolerate. When a newly
pregnant woman is given complex genetic tests to determine
whether her unborn child is genetically predisposed to a
serious disease or condition, she expects that the tests have
been found to be accurate. Yet many of these tests are being
marketed without any oversight from our scientific experts at
FDA.
FDA is still in the early stages of its regulatory process,
but from what I can tell, FDA is striking a reasonable balance.
FDA is not proposing to oversee every LDT on the market. On the
contrary, the agency is seeking to regulate only those LDTs
that pose risks for patients if the tests are not clinically
valid. And FDA is providing plenty of time and notice for
companies marketing these tests to comply with any new
requirements, most of which will be gradually phased in over
the course of the next 10 years.
I hope today's hearing will allow our witnesses to exchange
ideas about ways the draft guidance might be improved,
including areas in which more detail could help answer
questions about how FDA intends to oversee these tests and
allay any concerns that have arisen. If useful suggestions are
provided, I encourage FDA to consider them and take them into
account as appropriate.
But concerns about whether FDA is the appropriate
regulatory body to oversee these tests in the first place are
not well-founded. I strongly disagree with those who would
assert that FDA lacks jurisdiction over LDTs and that CMS alone
should regulate them under its CLIA authority. These tests are
a type of ``in vitro diagnostics,'' that is, tests performed
outside the body, for example on specimens taken from the body.
In 1976, Congress amended the law to provide FDA with explicit
authority to regulate in vitro diagnostics. Congress did not
differentiate FDA's authority over such diagnostic tests based
on what kind of entity makes them.
What is most important is the need for FDA involvement. CMS
has stated that FDA is the agency with expertise in evaluating
the clinical validity of these tests. CMS evaluates whether a
particular test finds what it is supposed to find and whether
labs conduct the test appropriately. But it does not evaluate
whether what the test finds is clinically meaningful.
It makes no sense to suggest that CMS should somehow take
on FDA's role over LDTs, while the FDA continues to oversee
other medical devices. This would result in a staggering amount
of bureaucratic duplication. That is not a wise approach for
patients or taxpayers.
LDTs offer great promise to improve human health. But we
need to ensure that the public is protected against unsafe or
ineffective LDTs.
And that is why we should support FDA's proposal to take a
more assertive regulatory stance over these tests.I look
forward to hearing more from our witnesses on this today.
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