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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 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

(II) 

COMMITTEE ON ENERGY AND COMMERCE 

FRED UPTON, Michigan 

Chairman 

RALPH M. HALL, Texas 

JOE BARTON, Texas 

Chairman Emeritus 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOSEPH R. PITTS, Pennsylvania 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

Vice Chairman 

PHIL GINGREY, Georgia 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

CORY GARDNER, Colorado 

MIKE POMPEO, Kansas 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILL JOHNSON, Missouri 

BILLY LONG, Missouri 

RENEE L. ELLMERS, North Carolina 

HENRY A. WAXMAN, California 

Ranking Member 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

FRANK PALLONE, JR., New Jersey 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

JERRY MCNERNEY, California 

BRUCE L. BRALEY, Iowa 

PETER WELCH, Vermont 

BEN RAY LUJAN, New Mexico 

PAUL TONKO, New York 

JOHN A. YARMUTH, Kentucky 

(III) 

SUBCOMMITTEE ON HEALTH

JOSEPH R. PITTS, Pennsylvania 

Chairman 

MICHAEL C. BURGESS, Texas 

Vice Chairman 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

RENEE L. ELLMERS, North Carolina 

JOE BARTON, Texas 

FRED UPTON, Michigan (ex officio) 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

JOHN D. DINGELL, Michigan 

ELIOT L. ENGEL, New York 

LOIS CAPPS, California 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

GENE GREEN, Texas 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

HENRY A. WAXMAN, California (ex officio) 

(V) 

C O N T E N T S 

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. 

(1) 

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. 

2 

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. 

3 

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 labsincluding 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 

4 

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. 

5 

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 labVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00011 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
6 

1The 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. 

oratory-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

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. 

7 

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 

8 

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:] 

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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 

21 

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. 

22 

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. 

23 

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? 

24 

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 reVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00030 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
25 

quirement 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 

26 

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 

27 

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? 

28 

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 

29 

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. 

30 

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 

31 

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 

32 

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. 

33 

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. 

34 

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. 

35 

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 

36 

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? 

37 

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 comVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00043 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
38 

plimentary 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 

39 

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 

40 

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. 

41 

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 

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stand 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? 

43 

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 followup. 

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 

44 

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. 

45 

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 highspeed 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 deVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00051 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
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cision 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:] 

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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 

67 

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 FDAapproved 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:] 

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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 FDAapproved 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, 

84 

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:] 

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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. 

109 

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:] 

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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 canVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00122 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
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cer 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:] 

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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 inspecVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00133 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
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tions, 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. 

129 

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 whethVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00135 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
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er 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 

131 

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. 

132 

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 reaVerDate Nov 24 2008 12:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00138 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-171 CHRIS
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sons 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. 

134 

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 

135 

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 

136 

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 

137 

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 

138 

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 

139 

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 

140 

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 FDAcleared 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—— 

141 

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 

142 

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. 

143 

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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