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20240321 HOUSE EC LDT FDA 3hr | Otter.ai

20240321 HOUSE EC LDT FDA 3hr

Bruce Quinn2h 55min

Speaker 1

00:25

proposals to update his regulatory framework and the Biden administration's current proposal to regulate laboratory developed tests or L DTS as medical devices. The current oversight structure for our dog diagnostic tests, including laboratory developed tests is split between us foot US Food and Drug Administration and the Centers for Medicare Medicaid Services. In 1976, Congress gave the FDA the explicit authority to regulate the medical device industry. At the time of enactment, the FDA adopted an enforcement discretion policy as a matter of practice over LDTs. Overtime, it became clear to policymakers, industry stakeholders and patient groups that a separate regulatory approach was needed for LDTs to protect the health and well being of patients, as well as create more standardization across the healthcare system, which led to the passage of the 1988 Clinical Laboratory Improvement amendments in establishing the clear clear instruction in the CLIA program. Congress intended to ensure the accuracy and reliability of all laboratory testing in the wake of reports of inaccurate clinical tests. LD T's are viewed as an important as important tools for medical uses from helping to treat cancer to come and public health purposes, like helping law enforcement and healthcare professionals determine which drugs are being trafficked and sold in their communities. lab developed tests also must go through certification requirements under CLIA, in addition to state public health regulators and independent accrediting agencies such as Dr. Carter's organization, the College of American Pathologists, or cap. Despite many known benefits of lab developed tests, the FDA has repeatedly attempted for almost two decades to completely reform how these tests are regulated, in order to give the agency sole discretion and policing power over all diagnostic tests, regardless of whether they are developed and run by the same laboratory or developed to be in to be sold and used elsewhere. Under proposed FDA rule announced in September 2023, the vast majority of LDTs will be regulated as medical devices. This means they would need to go through FDA is existing medical device framework, such as the 510 K clearance process, or pre market approval, labs will not be able to make simple modification to existing diagnostic tests, or even novel tests undermining the flexibility provided to the LDTs. Even more problematic. The proposed rule doesn't include a grandfathering clause that would allow for the continued use of CLIA certified LDTs. without disruption. Commissioner Kaila cited concerns relating to the performance of current LDTs that could potentially lead to unnecessary care or delaying necessary care as a primary reason why the MTA needs this additional policing power. He further states that over 70% of medical conditions rely on LDTs and other senior FDA officials have stated the current approach to disincentives innovation, the current approach disincentivize in innovation as conventional kit manufacturers do adhere to the medical device framework. To be clear, I agree with Commissioner Kaler that our regulatory approach always needs to ensure we're protecting patients while facilitating innovation. However, I remain concerned whether FTAs proposal will protect patients in the most effective way, achieve lower costs or foster greater innovation. However, we cannot overlook the unintended consequences of this were pro rules. Proposed Rule could cause namely, it could lead to greater consolidation among testing providers, reducing access to high quality care for patients living with life threatening diseases, especially in the cell and gene therapy space. Set our healthcare system back on our mission to move closer to toward closer toward personalized medicine and have harmful effects on disadvantaged and rural populations. Also question whether the FDA is going to execute the authorities that it seeks given its experience with an influx of COVID applications. To put all of this into greater context, the American Hospital Association's comment letter, one of nearly 7000, the FDA received on this proposed rule mentioned one of its systems has 1600 lab developed tests, assuming they were pursuing a 510 K clearance, the 2023 user fee rates paid by manufacturers or the FDA for a 510 K. This can mean the system ends up paying upwards of more than 31 million to comply with the FTAs rule. As diagnostic testing becomes more complex, I believe it is essential that Congress worked with the public health community physicians and patient groups to address any current challenges with providing patients with the highest quality diagnostics without stifling innovation. I cannot support the FTAs proposed rule and hope it is withdrawn but do look forward to continue the discussion on possible legislative proposals to address outstanding challenges with L DTS. Thank you and I yield back. The Chair now recognizes the ranking member Ms. Eshoo for five minutes for her opening statement. Thank

Speaker 2

05:27

you, Mr. Chairman. And good morning, colleagues. Good morning. To the witnesses. Thank you for being here. Today we're going to discuss, excuse me, how diagnostic tests are regulated by the FDA, and hear how Congress can improve processes in place. To ensure that tests that patients rely on are safe and effective, Congress passed the medical device amendments to the Food, Drug and Cosmetic Act in 1976. To give the FDA additional authority over medical devices, the FDA has generally not required diagnostic tests to complete pre marketing approval, and instead allows tests to be used in medical settings if they can meet certain requirements. Today, I think we're in a golden era of medical innovation. Diagnostic tests available are increasingly complex, and I identify an array of medical conditions for large patient populations. Diagnostic tests are firmly enmeshed in our healthcare system, and their results influence more than 70% of all medical decisions. tests we may think of as simple can be a big deal, and there should be better processes in place to validate whether tests patients rely on are reliable and effective for detecting COVID cancer or other medical conditions. Certainty is sorely needed. FDA Center for Devices and Radiological Health reviewed 125 requests to grant COVID tests emergency use authorization the EUA and found two thirds of tests had major issues such as inadequate or missing data. 41% of tests with major issues were ultimately denied or declined EUA status or withdrawn from consideration. Another study completed in 2022 of sophisticated technology for analyzing cancer causing genes produce substantially different results. Despite assessing samples of the same DNA. We should ensure test results are accurate, accurate, and do not contribute to worsening health outcomes or higher costs for patients simply put, Americans rely on and they should be safe and effective. And I think that's something we all agree on, which is why I support the FDA is intent to bring certainty to diagnostic tests by requiring lab developed tests LDTs to go through more rigorous review processes. However, I don't believe the FDA proposed rule is the only way to achieve our shared goal and the device 510 K review process is not perfectly tailored for LDTs. Our subcommittee previously considered the valid Act introduced by representatives Wu Shan and to get which establishes a specific framework for regulating diagnostic tests similar to how drugs are approved and monitored for safety or quality issues. The legislation also directs a report on the unique challenges academic medical centers, and hospital based labs face. I believe the FDA is proposed rules should reinvigorate discussions on the legislation and call all stakeholders back to the table to earnestly negotiate the framework. So I look forward a genuine look forward to the testimony today on this rather complex issue. And thank you, Mr. Chairman, and I yield back.

Speaker 1

09:26

Thank you. The gentlelady yields back. I now recognize the chair of the full committee chair Rogers for five minutes for an opening statement.

Speaker 3

09:33

Good morning, everyone. Today this committee will continue our work to ensure America remains the world leader in biomedical innovation. We've previously heard testimony on many examples of regulatory and reimbursement challenges that are stifling innovation and delaying patient access to care. Unfortunately, the FDA is doubling down on this troubling pattern by failing to account for the important role will laboratory testing plays in this country, patients, doctors and caregivers rely on diagnostic test to detect guide treatment decisions and monitor a host of medical conditions and diseases. Some of these tests are made in the form of kits by conventional manufacturers for the use by other entities such as laboratories, health care practitioners or even patients. Other tests known as laboratory developed test or LDTs, are designed, manufactured and used within a single laboratory. While conventional manufacturers certainly serve an important role LDTs fill in the gap for indicators that have a smaller patient population, such as rare diseases, particularly cancers, and certain pediatric conditions where large scale commercial manufacturing and distribution do not make sense. Instead of capitalizing on advancements in precision medicine, and exciting genetic technologies to help patients, the FDA has proposed dramatically increasing the regulatory burden on a subset of diagnostic test, specifically LDTs. These regulations extend far beyond any of the legislative proposals that Congress has considered. Under the proposed rule, laboratories will incur significant costs to come into compliance, new administrative and clerical burdens along with oppressive submission fees will be a substantial drain on our labs limited resources. Take for example, a lab that offers 1000 laboratory developed test by FDA is estimate 50% of existing LDTs will require pre market submissions. That alone translates to hundreds of millions of dollars, not even accounting for ongoing changes in maintenance. Moreover, for a phase out period over four years, this lab will need to submit 250 tests a year or one per working day, something that is likely impossible for the lab to do and for FDA to review in a timely manner. According to a recent survey of over 500 Clinical Laboratory respondents only 3% of the labs believe that they will have the financial resources to pay user fees. For the overwhelming number of labs without the financial resources, they will have to stop performing test, severely limiting access for some of our most vulnerable patient populations, and his preliminary preliminary regulatory impact analysis. The FDA estimates estimates that there's 80,000 LDTs currently on the market, and nearly 8000 New LDTs per year that would be affected by the rule. By comparison, the agency approved a little over 3000 premarket submissions in 2022. As currently written, the rule would take FDA years to simply review the test that already exist on the market. But what does this all really mean? Given that the FDA is already struggling to keep up with innovation, and what it currently regulates? This undertaking would mean fewer diagnostic diagnostics, diagnosis is higher cost and delays in care for patients who can't afford to wait for the FDA to approve a test. They need to finally figure out what is wrong and the path to getting well. Their lives depend on it. I know members of this committee hold a variety of positions on the need for regulating LDTs and the manner in which Congress should do so I would hope that we would all agree that this rule is on the wrong path. I look forward to hearing more from our witnesses about legislative alternatives to this stifling administrative action. Thank you and I yield back. Thank

Speaker 1

13:52

you. The Chair yields back. I now recognize the ranking member of the full committee Mr. Pallone for five minutes for an opening statement.

Speaker 4

13:58

Thank you, Mr. Chairman. New technologies can improve the lives of patients and the products we're discussing today. Laboratory developed tests or LDTs are no exception. But for them to make a difference for patients they must be accurate and reliable. Congress gave the FDA authority over lab developed tests under the medical device amendments in 1976. In 2015, we held the hearing in the Subcommittee on regulation of diagnostic tests, and laboratory operations. Even then, almost a decade ago, we saw the use of the scientific advances also have potential to pose serious risks to patients if they're not accurate. For example, they can lead patients to undergo unnecessary treatment, or delay or forego proper treatment resulting in harm. In the past FDA journal generally applied an enforcement discretion approach for LDTs because most were manufactured in small volumes by local laboratories to meet the needs of local patient populations, or were similar to other well understood standard tests. However many LDTs And now used more widely with large laboratories accepting specimens from across the country and in larger volumes. LDTs have also gotten more complex and they increasingly rely on more advanced technology and software. With advancements in artificial intelligence, it's likely that this trend will continue. The FDA has expressed increasing concern that some LDTs may not produce accurate results or performed as well as tests that are reviewed by the agency or otherwise comply with FDA standards. concerns include issues with COVID-19 diagnostic tests, genetic non invasive prenatal screening tests, and the blood tests manufactured by the infamous biotech company Torontos. And yet, there is no required post marketing reporting for LDTs. So we don't know the full extent of harm. Inaccurate tests can lead to the Centers for Disease Control and Prevention estimates that 70% of medical decisions are made based on laboratory test results. With many of these results coming from LDTs. It's scary to think that these tests do not currently have oversight and are not validated by FDA. New York state's Department of Health has conducted pre market review for 1000s of LDTs. The department's that over half of the LDCs they've received for review could not be approved based on their initial submission due to problems that called into question the reliability of the tests. And we've also seen that some manufacturers buy research grade components that are not intended for clinical purposes. Because these parts are cheaper, it simply does not make sense that tests are treated differently based on where they're made. Now, I continue to believe that we have a responsibility to provide patients with greater certainty over the tools that are used to guide their medical decisions. That's why FDA is action in proposing a rule to regulate LDTs and and their enforcement discretion approach is an important step. It's my hope that this will help eliminate patient's arm from unnecessary treatment, or under treatment from inaccurate LDTs. Not to mention the cost to the overall healthcare system. So I'd like to submit a letter from Dr. Dan Hayes, an expert with more than 40 years of experience as a laboratory clinical investigator, and a medical oncologist and academic breast cancer programs. He noted and now I'm quoting that clinic clinicians and patients depend on the FDA to carefully review the data and render difficult but reliable decisions about whether a drug is safe and effective. He went on to write that FDA should take the same approach towards diagnostics. He continued that quote, a bad tumor biomarker test is as bad as a big drug. And I completely agree. The information that LDTs provide clinicians and patients is of grave consequence. And that's why many major cancer advocacy groups and those in the lab community welcome greater FDA oversight, physicians have years of training in the best interests of their patients in mind. But by not providing oversight of LDTs. We're failing them by not ensuring they can trust the tools that they have to guide their patient counseling and develop effective interventions. So the proposal is, in my opinion, an important step to help ensure that health care decision decisions are made based on test results that providers and patients can reliably trust. I look forward to hearing from our witnesses today to understand how we can level the playing field. So patients and the healthcare providers know that they can trust the FDA process, while keeping up with medical progress. And with that, Mr. Chairman, I yield back. Thank you.

Speaker 1

18:27

Thank you. The gentleman yields back. That concludes opening statements for members. And so I'm introduce all of our witnesses. And then I'll call on you one at a time for five minutes for your opening segment. Those of you who have been testified before there was a green you'll have a green light in front of you for four minutes, and then it'll turn yellow. That means you have a minute and when it turns red, it's time to wrap up. So we appreciate you being here and I will introduce our witnesses. First we have Miss Susan Van Meter. She's the president of the American clinical laboratory Association. We have Mr. Zack Rothstein, Executive Director of Adva medics add mimetics is that though he set correctly

Unknown Speaker

19:05

at the Med dx, thank you, Adam med dx, okay.

Speaker 1

19:07

All right. And then we have Donald. Dr. Donald Karcher is the President of the College of American Pathologists. We have Dr. Jeff Allen, who is the president and CEO of cancer friends of cancer research, and Dr. Dara Eisner, who is the director of Colorado molecular correlates laboratory. So we now will begin begin to your opening statements and Mr. Van Meter you're recognized for five minutes for your opening statement.

Speaker 5

19:41

Chair Rogers, Ranking Member Pallone Subcommittee Chairman Guthrie Vice Chair Busan, Ranking Member Su and members of the committee, thank you for the opportunity to testify today. I'm Susan Van Meter. I'm the president of the American clinical laboratory association or acla. acla is the trade association representing leading laboratories that develop an offer Essential diagnostic testing services to patients and providers acla advocates for the expanded access, improve patient outcomes and advancing the next generation of patient personalized care. Laboratories offering testing services have delivered brown groundbreaking innovations for decades. One example the first test to detect bracha gene mutation which revolutionized breast cancer care was offered by an ACL a member laboratory. Laboratories also frequently are frequently the first to respond to emergencies public health threats play pivotal roles in the development of new drugs and biologics and address unmet patient needs. We are proud of the extraordinary contributions laboratories have made to advance the public health of this country. But today, the FDA is poised to reshape the industry by bypassing Congress and unilaterally imposing medical device regulation. But device regulation is inappropriate when applied to laboratories and raises profound concerns. My written testimony provides a more complete description of our concerns, but let me briefly address three areas patient access, innovation and legal concerns. First, device regulation would result in reduced patient access to critical diagnostic testing services. Laboratory developed testing services would be removed from testing menus, not because they don't yield reliable and accurate results. But because seeking FDA approval can be prohibitively expensive. We are acutely concerned about that patients will lose access to essential testing services, especially those that serve pediatric patients, small patient populations, and patients with rare diseases. Cases where revenue is modest. Excess would also be harmed because FDA would become a bottleneck. Because the proposed rule lacks a grandfathering provision, FDA would receive an avalanche measured in the 10s of 1000s of applications of existing tests, FDA lacks the resources to deal effectively with that surge in workload. Let me give you an example. Last year and acla member obtained the first FDA authorization of a groundbreaking genetic tests that helps identify patients who are at risk of developing cancer, but it took the laboratory over one year and seven figures to prepare the submission. It it took the FDA two and a half years to review and authorize it. During that time, the laboratory performed the test for over 230,000 patients, of which more than 22,000 tested positive for an actionable result had FTAs rule been in place those 22,000 patients and their families would not have learned about their risk of cancer or had their cancer care informed by their genetics. And an exemption for academic medical centers is not the answer to these problems. That type of exemption would exacerbate health disparities by favoring patients who can be treated at an academic medical center, leaving everyone else without access to the care they need. Second, if the FTAs rule is finalized, innovation and diagnostic testing would suffer. Instead of developing the next generation of diagnostics labs would be forced to justify tests that physicians have been using for decades. Given the timelines proposed by FDA laboratories would need to begin this work immediately. And in fact, our members have begun work towards implementation. Innovation would also be harmed because the device framework is wrong for laboratories. Device regulation is rigid and cannot account for the rapid evolution that occurs in diagnostics. The device approval standard and numerous other aspects of device law do not work when applied to professional services. Third, regulating laboratory developed tests services is beyond the agency's jurisdiction. Congress has always been clear FDA regulates medical products, but not healthcare services. Laboratory developed testing services are not products, but professional services that leverage a variety of tools to derive a test result for a patient. Let me end with a commitment over the past several years acla work collaboratively with this committee, as well as with the FDA and other stakeholders, many here today on legislation that could have established a role for the FDA and an appropriate regulatory system designed specifically for diagnostics. acla steadfastly maintains that legislation is the right and only approach for regulatory regulation of laboratory developed testing services. We would be pleased to work with the members of this committee on an appropriate legislative framework. I thank you for this opportunity to testify. And I look forward to your questions.

Speaker 1

24:24

Thank you for your testimony. And also I need to recognize the ranking member asked for a letter to be put in the record we're gonna put to the Documents List and we'll act on it the end of the hearing. So, so Miss duck Mr. Rothstein, you're you're now recognized for five minutes for your opening statement. Good

Speaker 6

24:38

morning. Thank you. Chairman Guthrie, Ranking Member Eshoo, Chair McMorris Rogers, Ranking Member Pallone, and members of the committee for the opportunity to testify. My name is Zack Rothstein. I'm the Executive Director of ABA DX division of ABA med which is the med tech Association. ever met DX members are among the world's most innovative companies they brought to market nationwide and accessible to patients of all backers. rounds, exceptionally sophisticated, groundbreaking and technologically advanced diagnostic products. These companies have developed many of the diagnostic tests that are a cornerstone of the modern healthcare system. Many diagnostic tests that are performed by clinical laboratories are what are referred to as test kits. They are subject to FDA medical device regulations, which generally include premarket review and post market requirements, and which can be used in more than one laboratory. Other diagnostic tests are developed by clinical laboratory as laboratory developed tests are LDTs and are used solely in that laboratory. These clinical laboratories often utilize instruments and other materials made by our members. In most cases, LD T's are used for the same diagnostic purposes as other tests that are FDA regulated. There are currently two federal frameworks applicable to diagnostic tests and to laboratory testing. IVDs, which are subject to FDA regulations promulgated under the Food Drug and Cosmetic Act or the FTCA are often reviewed in the pre market context for both their clinical and analytical validity to provide for a reasonable assurance of the test safety and effectiveness. The FTCA also provides for comprehensive post market oversight of IVDs, including the reporting of adverse events, malfunctions and recalls. In contrast, the Clinical Laboratory Improvement amendments of 1988 are CLIA ensures that laboratories operate and perform tests appropriately, unlike the FTCA. CLIA does not require pre market evaluation of a test accuracy or its clinical validity. Nor does it provide for a comprehensive postmarket oversight mechanism for tests themselves, including LDTs. Indeed, CMS has stated that the CLIA program is separate in scope and purpose from FDA oversight, and that simply updating CLIA is insufficient to ensure the analytical and clinical validity of LDTs being used to inform patient care. While most LDTs have not been subject to FDA regulation as medical devices, there have been notable exceptions, as several dozens of LDTs have applied for and received FDA clearance or approval as devices. The FDA has long played a critical role in ensuring the safety and effectiveness of IVDs under the existing law. But we strongly support comprehensive legislative reform to modernize the diet the device framework, so that it is tailored to provide an appropriate risk based oversight program for all IVDs including test kits LDTs and the instruments upon which they run. The current regulatory framework was established decades ago. And while there have been important targeted improvements, it has remained fundamentally unchanged. Despite dramatic advancements in the field. An updated and modernized framework, reflecting the unique nature of diagnostics is essential to foster continued innovation and ensure patients and providers have confidence and transparency in the tests they use and rely upon. In particular, we appreciate the interest of members of Congress from both sides of the aisle on this issue, and the leadership of representatives who shone into get in developing the valid Act. The approach envisioned in the legislation would serve patients and providers now and well into the future. Today, the testing community is at a crossroads. After more than a decade of efforts to bring clarity to LGBT regulation through other means. FDA initiated rulemaking last October, to clarify that an IV D that meets the statutory definition of a device is a device regardless of who makes the test. The rulemaking comes as the gap and diagnostics oversight continues. And as they grow as they grow and become the test become more varied and complex. In med tech, everything we do comes down to how best to serve patients because all of us have been or will be patients at some point. The vast majority of us do not know where the test that might diagnose or life threatening disease or infection is made. But we should have the confidence that whatever test we use, and wherever it is made that it has met the same standard and is subject to the same oversight as any other test. For high stakes tests such as for cancer diagnosis, or to guide important treatment decisions. We believe that those standards should involve a premarket review of analytical and clinical validity. And for all tests, there should be appropriate controls and post market monitoring. comprehensive reform of the regulatory system would benefit all test developers and most importantly, patients by supporting access to trusted, reliable and cutting edge diagnostics. I'd also like to point out that regulatory certainty is a critical element to encourage a favorable innovation environment for diagnostic tests. A unified oversight program would clarify regulatory expectations and to reduce the ambiguity that currently hampers investment decisions. Thank you for the opportunity to participate in today's hearing, and we look forward to the continued engagement on this issue.

Speaker 1

29:37

Thank you for your testimony. Dr. Carter, you're now recognized for five minutes.

Speaker 7

29:40

Thank you. Chair McMorris Rogers, Chair Guthrie, Ranking Member, Pallone, and Ranking Member Su. Thank you for the opportunity to testify today. The College of American Pathologists appreciates the subcommittee's interest in this important topic. I'm Dr. Donald Carter, president of the CAAP I'm also professor immediate past chair of Pathology at George Washington University. I've been a practicing pathologist for more than 40 years, including eight years in the Army, two years in private practice, and most of my career as an academic pathologist. The CAAP is the world's largest organization of board certified pathologist and the leading provider of Laboratory Accreditation and proficiency testing programs supporting the highest standards of laboratory quality in the US and around the world. The CIP has been constructively engaged for over a decade with Congress and the FDA, on developing a framework to oversee laboratory developed tests LDTs. Our position has always been to put patients and quality first, all LD t should be safe and effective. LDTs are developed and used in a single clinical lab to meet a specific specific clinical need. These tests are developed almost always because there's no FDA approved or cleared test that meets the specific need in question. Most LDTs are developed and used for patients being cared for in the hospital or healthcare network where the lab is located. Although many LDTs represent innovations in patient care, most utilize well established laboratory methods that medium and large sized labs already have experience using. The clinical validity of the majority of LDTs is already well documented in the medical literature before the test is developed. The CA P strongly believes that any LD T regulation must allow innovation to continue and must not to continue and must not introduce overly burdensome or costly requirements for the lab. stifling innovation and burdening labs would lead to many labs having to stop developing LDTs depriving their patients of these life saving tests. This is why we have significant concerns with the proposed rule released by the FDA in October. We believe the proposal as written would reduce the number of highly accurate LDTs available to patients and delay medical innovation and timely patient care. Instead, the FDA should be focused mostly on tests that pose the highest risk to patients. Such a test was developed more than 10 years ago by an academic medical center to detect a form of cancer and resulted in many women receiving false positive results that lead to unnecessary removal of their ovaries and other surgeries. the right balance would have the FDA exercising full regulation of only the highest risk LVTs with sufficient flexibility in their oversight of these and all lower risk LDTs. This would allow clinical labs to continue to develop and run these vitally important tests. This is the LD T framework that Congress should adopt. To that end, the valid EC dealing with LGBT regulation has enjoyed bipartisan and bicameral support. It would establish a reasonable and balanced regulatory framework that would ensure quality testing for patients and minimize the regulatory burden on labs. It focuses FDA as resources mostly on the highest risk LDTs and provides flexibility with lower risk LDTs to preserve quality and patient safety. Further, it places guardrails around LD T regulation to prevent duplicate duplication of existing clear requirements and infringement on the practice of medicine. Fine. Finally, there's been some discussion in Congress to legislatively change CLIA to address LVDT oversight. The CAAP strongly opposes this effort. CLIA, which provides the basis of all clinical lab operations in the US has stood the test of time. We recognize that a periodically needs minor updates to reflect changes in practice and technology. This is currently being done through the regulatory process, opening CLIA legislatively to address this issue, risk creating a parallel structure with the FDA, and severely disrupting the framework under which clinical labs have provided high quality testing for decades. Thank you again for holding this hearing. The CPAP stands ready to work with you to ensure that patients have continued access to accurate, innovative and timely laboratory tests. I look forward to answering your questions.

Speaker 1

34:31

Thank you for your testimony. The Chair now recognizes Dr. Allen for five minutes for your opening statement.

Speaker 8

34:37

Good morning, Chairman Guthrie, Ranking Member Eshoo, and members of the committee. I'm Jeff Allen, President, CEO of friends of cancer research and advocacy organization dedicated to accelerating science and technology from bench to bedside. It's an honor to testify here today and provide the perspective of my organization and on behalf of patients at this as this committee examines how diagnostic tests can serve toward the future of medicine and patient care. The treatment that patients with cancer have access to today are many cases far more effective, but also more complex than their predecessors. It's not unusual for a variety of diagnostic tests to be used by healthcare providers to identify elevated risk, diagnosed certain conditions, inform treatment options, or even measure if a treatment is working. Above all, it's imperative that these tests performance and accuracy be well characterized before their results are used for important treatment decisions. inaccurate or unreliable test can have significant implications on healthcare cost, system burden, and patient outcomes. A report from the National Academies concluded that diagnostic errors including from some molecular test account for 17% of adverse events and hospitals and play a role in 10% of patient deaths. Given the critical role of diagnostic test and patient care, the approach to regulating these tests needs to be realigned, tested, manufactured and sold his diagnostic kits as well as those marketed as companion diagnostics are subject to premarket review by the FDA. This review process ensures that their tests meet stringent standards for safety, efficacy and accuracy before they're made available to the public. Conversely, laboratories that establish and run lab developed tests LDTs are subject to CMS oversight under CLIA. While CLIA provides an important regulation. It focuses more on the standards for laboratory operations, rather than the clinical validity of individual tests. CMS themselves has acknowledged that the agency does not have the expertise to assure that tests work. For patients, consumers and healthcare providers. It's the information provided by the test that's important, not the place that's manufactured. This distinction and oversight creates regulatory landscape where the rigor of test validation and review can vary significantly, potentially impacting the consistency and reliability of results across different testing platforms. This is not uncommon. Our research indicates that there are many tests use every day for which performance and accuracy have not been independently verified. Specifically, we conducted an audit on hundreds of medical records from across the country, and found that nearly 30% of lung cancer patients were evaluated for key biomarkers with versions of LDTs that had not gone through premarket review, despite the availability of an FDA approved test. While it's a positive that there has been increased testing for recommended biomarkers, tests that have not been independently reviewed for accuracy are being used to inform treatment decisions. Without centralized FDA oversight, it's not known how many death tests are even being offered, let alone how they may perform. This is not the reliable path to precision medicine. The reality is some patients may be making major major medical decisions based on potentially discrepant test results. To begin to resolve this, we partnered with 17 leading diagnostic test developers and clinical laboratories to determine and define differences and how each of their tests measure emerging biomarkers using a common set of samples. These pilot projects demonstrated that there is variability across different tests and multiple factors contribute to differences in test results. So as future policies are considered improved transparency of tests performance would help identify and manage potential variability and ensure consistency in the information being utilized by patients and healthcare providers. Over the last several years, the need for modernizing the regulatory requirements for diagnostic tests has been acknowledged. Most recently, the valid Act was introduced with bipartisan support. This proposed legislation would provide the framework for the future by establishing a quality assurance floor for the performance of all tests, while ensuring an open ceiling to foster future innovations and diagnostic testing. In the absence of congressional action, FDA has moved forward with the public process of rulemaking to clarify uniform policies for diagnostic tests. It should be noted that nothing precludes Congress from continuing to work on a legislative approach as FDA continues working on its on its proposed rule. No matter the path forward action to ensure high quality test performance is needed. And progress to that end can no longer be stalled. The future of precision medicine and the health and lives of patients depends on the accuracy of these tests.

Speaker 1

39:26

Thank you for your testimony. The Chair now recognizes Dr. Eisner for five minutes for your opening statement.

Speaker 9

39:35

Good morning chairs. Good morning chairs Rogers and Guthrie ranking members Pallone, and issue and members of the subcommittee. Thank you for the opportunity to testify today. I'm also honored that my representativeness to get is in attendance today and I thank you for everything you've done for medical research. My name is Dr. Dara Eisner. I'm representing the academic Coalition for effective laboratory developed tests. My testimony does not reflect the view With my employer, the coalition represents 325, pathologists and professionals from 100 academic and hospital based laboratories across the US, we oppose the FTAs rule. I am a triple board certified pathologist and the Medical Director of the Colorado molecular correlates Laboratory at the University of Colorado, where we perform testing for patients and oncology, genetics and infectious disease. I am also a cancer patient. As a physician with expertise in laboratory testing, I've trusted my own care to LDTs even when FDA approved choices are available for the same clinical question. Professionally, I find the FDA proposal to be misguided, and I worry for the future of American medicine. Personally, I fear the consequences for me and my family. LDTs are not devices, they are processes performed with expertise. Knowledge of all the steps combined with an understanding of the scientific and clinical data allows for nuanced care that simply cannot come from an assay kit. The use of FTAs device infrastructure is quite simply forcing a square peg into a round hole. There is no substantive evidence of systematic harm arising from LDTs. Just anecdotes, the FDA has vastly underestimated the number of LDTs the rule would create delays to implementation of essential care and a contraction of the laboratory market would be inevitable. This will magnify inequities with disproportionate impact on marginalized, underserved rural, pediatric and rare disease populations. Innovation will be directly hampered owing to cost and unpredictability. These are not hypothetical concerns. The oldest targeted therapy in lung cancer, one of the most effective forms of precision medicine is based on a mutation that was first reported in 2004. Labs started offering LDTs for that mutation, that very same year. The first FDA approved test kit for the mutation came out nine almost nine years later. In that interval, roughly 2 million Americans were diagnosed with lung cancer, which would mean 100,000 patients with the mutation. Cutting edge therapies mean little if patients cannot access the testing that renders them eligible for it. The steady decline of mortality for many cancers can be directly attributed to precision medicine. In 2010, we use PCR based tests to look at one gene in lung cancer. Today, we use next generation sequencing NGS and examined dozens or hundreds of genes at a time. For 20 years, the vast majority of sequencing tests for all cancers have been LDTs. Under the FDA proposal, NGS a transformative technology would likely still not be in place to the detriment of hundreds of 1000s of cancer patients. The coalition's members are not manufacturers, we have years of training, board certifications and experience to provide specialized care for our patients. A regulatory system needs to recognize that the testing environment impacts risk mitigation. A regulatory system should hold everyone to the same standard. But that means working to ensure outcomes are similarly safe and effective. Not that regulations are similarly burdensome. There are other approaches for an outcomes based paradigm. Instead of a one size fits all approach. I'd like to circle back to where I started today. I am a cancer patient. That's a hard truth to hear for anyone, especially someone who has spent her career on cancer diagnostics. In facing it. I never questioned the use of LDTs in my care, not once, not even a little. I know that if the FDA role moves forward, patients will suffer. Ultimately, we all want the same thing to provide the best possible care for all Americans. As a physician, I want to deliver the most up to date testing for my patients. As a patient. I want to know that the next decision in my cancer care is based on science and access to testing is not hampered by counterproductive regulation. For the sake of patients like me, I urge the FDA to withdraw the rule, Congress should endeavor to explore all outcomes and modernize oversight that fosters innovations, and leads to the best patient outcomes. We look forward to partnering with you to advance a sensible path forward. Thank you again for the opportunity to testify, and I look forward to your questions.

Speaker 1

44:58

Thank you for your testimony. Any that concludes all of our witness testimony. And we will now begin the questioning period of the hearing. And I will recognize myself for five minutes for the hearing. And Dr. Eisner, you got it summed up. The issue we're trying to deal with is that you have LD t that was developed within the same year and put out and then nine years for the FDA to approve. And we're always dealing with that we had a witness the other day talking what's a few months and FDA approval is sometimes it's not a few months, but depends on what your diagnosis is, how much a few months matters, you know, it's a lot of times, regulators and nothing this was a professor at Harvard Law was just everything is not theoretical. It's it's real and effects realize, but we want to make sure they're accurate as well make sure they're moving forward. And so and we do things in Congress like Right to Try accelerator approvals to try to get around this this. Try to not get around the tried to get around how long it takes try to make to speed the process up to make it but we want to make sure they're safe and effective as well. And Dr. Carter, I know the College of American Pathologists officers proficiency testing for LDTs. And do you have any data to suggest that le DS perform any better or worse in that proficiency testing.

Speaker 7

46:16

So proficiency testing is a very important part of maintaining the quality of all laboratory testing. We do occasionally have problems with a number of tests that are recognized by proficiency testing, we're oftentimes analyzing data from hundreds, maybe 1000s of laboratories that are doing the same methodologies. So like any other tests, yes, LDTs do occasionally have there are inaccurate, inaccurate results or just submitted by laboratories. That said, we still feel that it is one of the best ways to independently verify the accuracy of results, regardless of whether or not it is an FDA approved or cleared test, or an LT T.

Speaker 1

46:57

Okay, thank you for that. And Miss Van Meter. Do you believe that? So it gets back to the process here. Do you believe that the LD T rule effectively eliminates bottom up innovation in diagnostics? And do you believe this could lead to consolidation within the diagnostic space and cause price increases and limit access to care?

Speaker 5

47:17

I feel strongly that implementation of the rule will have a downward impact on innovation. It will reduce the number of innovative tests that are available to patients and it will extend the amount of time it takes for an innovative test to reach patients. We think about the example I offered of a test that had been approved by New York State assess for analytical and clinical validity and was offered to patients over a period of time, during which they took that test through the FTA a seven figure cost, all told three and a half years to get through the agency. In the meantime, 22,000 patients received an actionable result, those 22,000 patients under an FTA regime such as the proposal puts forward would not have had the benefit of that information. Certainly there could be consolidation under this regulation within the market. I think that's a possibility. I think at the end of the day, the medical device authorities the application to laboratory developed testing services and inappropriate and we'll see a constraint and access and an innovation. It's really not the right approach. And we encourage the committee to look at comprehensive legislation.

Speaker 1

48:29

Okay, thank you. And I will ask this for a couple of witnesses haven't gone forward yet. So Mr. Rothstein and also Dr. Allen, Dr. Eisner if we have a minute and a half. So again, my question, What in the current clear framework most needs modernizing? And do you believe the FDA is proposed rule will help address any challenges posed by the current framework?

Speaker 6

48:51

Thank you for the question. I would defer to my colleagues who are more familiar with the CLIA construct in terms of what needs modernization however, I would say there are two elements that's missing and CLIA compared to what is in the FDA statute, which is premarket review for both clinical and analytical validity, as well as comprehensive post market oversight.

Unknown Speaker

49:10

Thank Dr. L.

Speaker 8

49:13

concern with even mixing the two is that clear was designed to provide oversight for laboratory operations, not individual performance of tests. So I mean, CMS also has noted that they in house do not have the expertise to evaluate these tests properly. So instead of trying to reconstruct that agency's approach, I think it would be more effective to allow it to continue to be able to provide its vital services for laboratory operation, oversight, but then give the FDA the tools that it's needed that are needed to be able to identify potentially underperforming tests in advance before they're even used. Okay,

Unknown Speaker

49:54

thanks, Doctor iser,

Speaker 9

49:56

I think it's important to recognize that CLIA is nearly 36 years old, it was put into place before computers were part of our modern day to day life. So no matter where the ultimate solution to this lies, Clea needs to be updated, no matter how you look at it. I think for us to say that we are we know what that looks like now, and how that would impact a future framework that deals with LDTs. We got to tackle one thing at a time, let's tackle a 36 year old statute that needs updating, and then go from there. Thanks.

Speaker 1

50:30

My time has expired. So I appreciate your answers that I will yield to the I'll yield back and then recognize the ranking member for five minutes for her question.

Speaker 2

50:38

Thank you, Mr. Chairman, and thank you to each one of the witnesses for your testimony. There are a couple of things that I know going into this, and that is that this is the sixth year for Congress to be grappling with the valid act. So we have not acted validly. Alright, so we have to accept that. I do know that Dr. Sharon has expressed to me many times that, you know, that, generally speaking, he he supports the valid act. And I know that the authors of the legislation, have been working with stakeholders, I think, rather consistently over this period of time. I think that the issue of place is is not the issue. And I don't know, I'm not so drawn to, you know, revamping clear. I think it complicates this issue. I don't think that that should be a part of it. But having said all of that, I want to ask each witness so that we have this for the record. Do you prefer the FDA rule or the passage of the valid act? Why don't we start with you? I think you've already expressed it, but let's say it again,

Unknown Speaker

52:17

we think that the valid Act has which

Unknown Speaker

52:19

one good what do you support?

Speaker 5

52:22

We would prefer comprehensive legislation to unilateral FDA and EU support the valid act. We think there are a number of extremely positive attributes of the valid act and committed to working with the community. You're

Speaker 2

52:32

no on one and lukewarm on the other. Is that right?

Speaker 5

52:35

We think legislation, yes or no? Do

Unknown Speaker

52:39

you support the valid act? If you don't, you don't,

Speaker 5

52:41

if we have worked earnestly on it, and we will commit to continuing to do so we think it's the right approach moving forward. Okay.

Unknown Speaker

52:50

We strongly support the ballot Act.

Speaker 7

52:56

The CIP also strongly supports the Valletta act, and we have real problems with the FDA is proposed rule as it's currently written.

Speaker 8

53:05

We also support the valid act and feel that inaction would be the worst outcome.

Speaker 9

53:12

I cannot, I cannot speak for all academic medical centers. But those guys you're here with

Unknown Speaker

53:18

testifying, do you?

Speaker 9

53:21

Those that I represent do not support the valid act, we believe there's room to find middle ground, we do not support that middle ground. The middle ground is to ask the question, what are all of the options? Why do we need to go all the way to 100? out of the gate? What what are the other options? There are other options here? There are options for an outcomes.

Speaker 2

53:48

I'm asking you to state the outcomes you see other other pathways.

Speaker 9

53:55

One, one pathway is to center on proficiency testing. Dr. Carter mentioned, the importance of proficiency testing, a pathway that asks laboratories to undergo proficiency testing prior to launch achieves the endpoint without the burden. There are other options.

Speaker 2

54:12

You know what? What terrifies me having a test relative to cancer, and it comes up positive. But it's not accurate. And I think that that is most troubling to me. That frightens me. And I think that it's a it's a chilling case for for anyone. I do think that that there is a good support solid support for the valid act. And I most frankly, I think that Congress needs to be pursuing that the lack of action by Congress really forced FTAs hand To come up with their proposal. And I think that's a fact of life here. So I think it's fashionable, at least in some quarters to just bash the FDA coming and going. But it's up to Congress to act. And I do think that the answers with some refinements in the valid Act would be an appropriate way to go. So I can ask many questions. I mean, there are only two states in the in the country, New York State and Washington state. They're the only two states to pass laws to regulate el LDTs. The New York experience is a really rather broad one. And, of course, States approved the labs. But there are only two states that do that. So we can't look to a majority of states in their experiences. But it's worth mentioning that two states do have passed laws to regulate the LDTs. I think I'll yield back.

Speaker 1

56:08

Thank you. Gentlelady yields back and The Chair recognizes the chair, chair Rogers for five minutes for questions.

Speaker 3

56:15

Dr. Karcher, a laboratory in my district develops drug tests to detect substances and aid in substance use disorder treatment. This committee has heard house xylazine has been mixed into fentanyl, and made that crisis even worse, as xylazine does not react to overdose reversal medications. Are there any drug tests approved or cleared by FDA that would detect xylazine, the laboratory my district has one already available for health care providers. And it seems like if this rule had been in place, Spokane may not have access to that valuable resource.

Speaker 7

56:53

There is no FDA approved or cleared test that I'm aware of for that substance. And therefore, you're exactly right. If the proposed rule, as published by the FDA in October, were to go into effect as written. That lab in Spokane and frankly anywhere would have a difficult time developing a very important LD T to care for people that are suffering from, from potential contamination with a substance. Thank you. We agree with you. Thank

Speaker 3

57:26

you, Dr. Eisner. In your role as pathologists, how is the expertise you bring to your patients just don't distinguishable from the results of routine commercial test kits?

Speaker 9

57:45

Okay, sorry about that. I'll apologize for stumbling because it's a it's a broad question. And it is something I feel very passionate about. You know, I think an example I can provide for you is that a sample that comes in and has a lot of pre analytic factors that have rendered it highly fragmented, is something that I analyze differently than a sample that came in and is very pristine. And it's because I have the knowledge of the sample. It's because of the data tells me something about the sample. It's because I can look at the patient's situation and say, if I look at the data through the lens of a highly fragmented sample, and I see this versus I assume it's a clean sample, and I see this, how does it all come together? It's really about bringing it all together in a way that you can make everything makes sense. I tell my pathology trainees that being a pathologist is about being an integrative Titian, we really work to bring all of the pieces of data together.

Speaker 3

58:46

Thank you as a follow up, in what circumstances do you rely on your specialized medicine training to best support your patients clinical care?

Speaker 9

58:53

I would argue that there's no situation where I don't. It's every day, every specimen, every piece of data. Thank you.

Speaker 3

59:03

Miss Van Meter. As referenced in your testimony, your organization provided an economic assessment to rebut the criminal preliminary regulatory impact analysis that accompanied the FDA is proposed rule. Could you please summarize your findings and conclusions and how those might have differed from FTAs estimates of cost and benefit?

Speaker 5

59:23

Yeah, thank you for the question. We did analyze the FTAs economic impact analysis of the rule. And in short, we believe that the FDA has dramatically underestimated the cost, while also significantly overestimating the benefit. If I may, I will give you just a couple of facts and figures here. Or I think we can show that there are just fundamental flaws and the logic and that work could have been done to more accurately assess what the impact would be. I'm going to just utilize FTAs own assumptions, let's presume For a moment that they are correct on the number of total LDTs. We believe it's too low. But let's assume it's correct that there are 80,000 laboratory developed testing services that exist. It presumes the FDA does that ltt revenue is about 28 point 6 billion that was a 23 figure. That would roughly mean for each LD T service on average, there generates $350,000 in annual revenue. For tests that would have to go through the PMA or pre market review application, FDA estimates the cost of submission would be 4.3 million, the math simply doesn't work. So given the agency's projections of the number of LD T services that we go through premarket review de novo 510 K pathways, it projects a cost of all submissions of $32 billion. Recall the same analysis of total FTA services revenue is at $28.6 billion. It's not possible to bring all of those tests through the agency. Simply the math doesn't work. Thank you.

Speaker 3

01:01:04

Thank you for those insights. And appreciate everyone being here today as we sort through this issue. With that, I yield back. Thank you, Mr. Chairman. Thank

Speaker 1

01:01:13

you. The Chair yields back and The Chair recognizes the ranking member for the full Committee, Mr. Pallone for five minutes for questions.

Speaker 4

01:01:19

Thank you, Chairman. I wanted to start by expressing my appreciation to all our witnesses for coming here today to talk about this important issue. And I've heard arguments that the FDA is proposed rule will have a negative impact on the LD T market. But I would say that anyone who's concerned about the cost of the FTAs proposed rule on LDTs should also be concerned about the potential costs every day in our healthcare system from unproven tests. The FDA is analysis showed the benefits of the regulations significantly outweigh the costs. So we know the downstream costs for unproven treatments can be staggering. And I think about cancer and other conditions where the costs of having the wrong treatment, or waiting too long to be treated are enormous. Nevermind, the pain is suffering for patients and their families. So I basically had two questions. First is Mr. Rothstein. Do you agree there is potential for significant costs to our healthcare system? If we do not ensure that tests work, regardless of where they're made? We do. Yes. All right. And then let me go to Dr. Allen, what are the consequences for cancer patients who received the wrong treatment or are failed to be treated early on when they need it?

Speaker 8

01:02:41

In some cases, it probably depends on the different scenarios, but there is data that is emerging that if a patient receives the wrong treatment, they may not respond to subsequent treatments. And this is due to the changing mobile modality of treatments and where there has been detrimental effects shown for patients that, you know, for example, receive a targeted therapy, the immunotherapy that they may also be available for, you know, it isn't it's shown to be not quite as effective, let alone potentially just excluding them from something that that would work. And I think that's that's the biggest concern of having tests that are not properly identifying the treatments that have been shown to benefit patients.

Speaker 4

01:03:24

All right. Well, you both answered my questions briefly. So let me go back to since I still have two and a half minutes, let me go back to Mr. Rothstein about the potential for significant costs. You want to if we don't ensure the tests work, you want to talk a little bit more about those costs and what they might mean. Yes,

Speaker 6

01:03:43

thank you, Congressman. So there are really two areas that we think about in terms of how costs of tests that are either inaccurate or inconsistent among different classes could potentially lead to more cost within the healthcare system. The first of course, is to the patients themselves and the actual costs associated with those patients needing to go back for retreatment. undergoing treatments that are otherwise unnecessary, and other similar costs that are actually economic costs incurred by the healthcare system. The other cost is just incent in the sense of how those types of inaccurate tests or variable tests ultimately lead to less confidence in the testing community. And that's something that we are acutely concerned about, in the sense that it is important that patients providers all have confidence in the test that they have received, that they have all undergone similar review similar regulatory oversight. And that there there is a public repository, especially for them to have their information known so that patients and providers can understand the context in which they're using these tests. Okay.

Speaker 4

01:04:52

Look, I will just say I we can discuss what the exact solution should look like. But at this Morning, I just think we can all agree that the status quo was not tenable. And there is a problem that needs to be solved. And I think we have a responsibility to make sure that FDA has the tools it needs to allow patients and health providers to trust the results of these tests. And I understand that these tests are used in many cases is screening. But the fact is that the results of these tests are being used for treatment decisions, regardless of whether whether they're accurate. And that's that's the problem that I see. So thank you all. And with that, I yield back. Mr. Chairman.

Speaker 10

01:05:35

gentleman yields back. I now recognize Dr. Burgess five minutes.

Speaker 11

01:05:38

Thank you, Chairman. centimeter, I've got some questions for you. But before I do that, I would like to insert into the record a list of quotes from 40 pathologists across the country, citing the impact of the rule on the innovation and patient access test, as well as a Wall Street Journal article citing a potential outcome of the FDA regulating LDTs. And I'll ask for those people to be considered for the record. And let me just ask you, Miss Van Meter, and maybe I might ask you, Dr. Reisner. Would you care to respond to the question that was what was just posed by Ranking Member Pallone when he said what is the cost of a test that is in error, but there is also a cost? If a test is not done? Is that correct? There

Speaker 5

01:06:23

is no question about that the cost to patients if access is diminished to test that we use for day to day care it for times when you know we're looking at precision medicine laboratory developed test services are driving precision medicine. Without those tests. Think about the 22,000 patients in the example I offered not that long ago, they and their families would not have had the information they need to make a decision about their cancer or their potential for cancer. So I think that's an enormous factor.

Speaker 11

01:06:54

Thank you and decoration, or would you like to respond to that?

Speaker 9

01:06:58

I agree completely, that the cost analysis is a one sided analysis that only looks at presumed errors and tests and does not evaluate the benefit that is gained by having LDTs in the market with nimbleness and adaptability patients would be on diagnostic odysseys cobbling together a piecemeal of FDA approved tests, as opposed to tests that are put together specifically for indications that are not covered by FDA tests, spoken

Speaker 11

01:07:27

like an integrated tissue, if I may say so. I've got way more questions that I'll have time for. So I'm going to submit a number for the record. And I do ask that, that pay attention to those because they're important. But let me just say this. We've had this hearing a lot of times since the reauthorization in 2007. I was here for that for the FDA reoffer of the of the user fee agreements. There have been numerous times where I have asked Dr. Sharon, what is the problem that you're trying to solve? And frequently he will be unable to tell me the problem that he is trying to solve it look, all of us want access to tests timely. We want the test to be accurate. The but honestly, Dr. Eisner, if you did a test for a biomarker for someone for lung cancer, just taking that single result, would you recommend the patient of a thoracotomy?

Speaker 9

01:08:25

Absolutely not everything is taken in a context. It's taken in totality. And part of what a practitioner like me who's integrated into the medical system can bring to the system is exactly what I referred to earlier this earlier this integrate Titian, this does everything makes sense. Question. Yes.

Speaker 11

01:08:42

And that's, that's so important. We forget that they're, you know, most physicians do not practice the protocol we practice using our clinical judgment are based on our years of training and experience with will always say, so that's what has been particularly irritating to me when we have this discussion. And people say, Well, someone could get an errant test, and then undergo the procedure to remove a body part. And the test was inaccurate, they didn't need it. Well, wait a minute, no doctor does that you get an abnormal tests. Next thing you do is you call up your friend or we radiologist and get imaging or or you do subsequent testing. This is not a it's not a conditioned response. Do you get an abnormal test result and you hit the operating room? I'm going to run out of time, but I'll just have to tell you something. And this is what we forget. Sometimes when we deal with laws, and we do we do pass a lot of legislation. I've passed legislation this committee. One of the things you find is after the law is passed after you go to the signing ceremony and everybody pat themselves on the back. It goes to the agency. And just as we're talking about, we're worried about the FDA promulgating a rule when they violated the Administrative Procedures Act. If we pass the valid act, I get I don't have the current in front of me, but I guarantee you there's going to be language that says, and the Secretary shall are the commissioners shall. And what happens next? An episode of rulemaking? So how can we construct the legislation? So we get the desired result. And we don't leave ourselves open to an invalid interpretation by the agency when the rules are written? Again, I've got several more questions. I think they're all important. I encourage you to look at those and provide answers. Look, I can, again, we've had multiple hearings on this in the last 20 years. I'll bet this is not the last one. So thank you very much. I'll yield back. gentleman

Speaker 10

01:10:43

yields back. recognize Mr. Sarbanes, for five minutes.

Speaker 12

01:10:46

Thanks very much, Mr. Chairman, thank you all for being here. Today, we're going to be hitting the same themes as you can imagine. We certainly know that. Over the last decade, FDA has made known its need and its intent to modernize regulation of of lab developed tests, which is the subject of this hearing. It's a good thing that Biomedical Research and Innovation has also dramatically increased over the last decade, it's yielding more and increasingly complex diagnostic tests that have the potential dramatic potential to improve care and save lives. At the same time, this increase in the existence and use of LDTs has also as we know, presented increased regulatory challenges and increased urgency to ensure that the regulatory approach is keeping pace with this innovation to keep patients safe. And by the way, in my former life actually did work with a lot of these labs as an as an attorney, so I certainly understand the varying perspectives here. Dr. Allen and CDC estimates that LD T's are being used in form approximately 70% of medical decisions these days, that's incredible. Could you just give me a sense kind of walk through the spectrum of the kinds of decisions like categories of decisions that are being made now based on results from diagnostic testing current medicines, just give us a sense of what's at stake here?

Speaker 8

01:12:16

Sure. I'll focus my comments and oncology, although there are countless other therapeutic areas that diagnostic testing plays an equally important role. But in cancer alone, it ranges from the initial diagnosis, which may require a test in order to detect the presence of cancer, it would continue and to characterizing that type of cancer does it harbor certain molecular alterations that render render different treatment options, be the best course of action for that potential patient, it could continue to even monitoring, if the treatment is working, best case scenario it is and that cancer may be alleviated. And diagnostic testing may play an important role in order to monitor the potential or presence of recurrence. So it is really through the gamut of, of its high

Speaker 12

01:13:10

stakes rates very high, very high stakes, millions of patients each year making critical decisions about their health potential treatment plans, as you just said, and more based on these tests. And yet, we know FDA has very little ability to fully understand exactly what tests are out there, how they're being used or marketed and their accuracy. So there's there's a lot of potential risk here. Or existing risk, frankly. And it's something that's worrisome as one wrong test could truly mean the difference between receiving preventative care appropriate treatment or diagnosis. For patients. Dr. Allen, what are the real world implications of inaccurate diagnostic tests? And how important is it that FDA be able to ensure the accuracy of all tests being used in the practice of medicine, maybe just take the second half of that FDA, given what its mission is right, and what we invest in it as the public in terms of our expectations of its overview of the landscape? Why is it so important to make sure that the accuracy of these tests is sound?

Speaker 8

01:14:19

I think just given the magnitude of decisions that are made based on the results of these tests, and the risks associated if an inaccurate result is provided. And this environment continues to get increasingly complicated. What we've seen from our research itself, is that there are multiple different tests that are out there that have a similar intended use. It doesn't mean they necessarily all perform the exact same doesn't mean they're all wrong. It just means that there needs to be a more transparent system to be able to understand how different tests relate to one another, to ensure that when the patients are given the results, no matter which tests they receive, they're able to be correctly interpreted in the right action taken

Speaker 12

01:14:59

right I've long advocated for increasing FTAs oversight of LDTs to ensure this patient safety to give providers the tools they need to best serve their patients. Of course, you know, the finalization of the rule doesn't preclude Congress from continuing to work together to further promote patient and provider confidence in or the safety and efficacy of the diagnostic test. But we know patients deserve to be able to trust the diagnostic results they receive from any test, regardless of where it is May. I mean, just we all know from our own lives, like how much you hang on to this result, it's coming the expectations that are there, and how it can affect you. And so I hope to continue to engage with my colleagues on this critical issue. And, Mr. Chairman, yield back the time. Thanks.

Speaker 10

01:15:57

gentleman yields back, I now recognize myself for five minutes. Certainly I agree with Dr. Burgess, congressional intent is commonly misconstrued. And that's why we need to be very prescriptive. And that's why we're going through this process. Today. For me, it's an exciting day. I've been working on this issue for many years over seven years. I know it's a complicated topic. So I want to express the appreciation to all my congressional colleagues who are participating here today so that we can learn more about this critical issue. I would like to associate myself with the comments of many of my colleagues who have expressed displeasure at the thought of the FDA regulating LDTs as medical devices. For a lot of reasons. One that we've already heard, we'll continue and continue to hear these unique tools should not be evaluated in the same way that the FDA reviews machines, implants, and other kinds of devices. But it's not just that LDTs are ill suited to be a vet to be evaluated as medical devices. The entire category of in vitro diagnostic tests should be differentiated from devices and provided their own less burdensome pathway for review and approval. Congress needs to act. That's the idea behind the valid Act, which Congresswoman to get and I have been working on again, as I mentioned for over seven years. While the valid EQ like the LD T rule assumes that diagnostic regulation is in need of change takes a much different approach. First of all, there is a grandfathering clause invalid, which is really important. And valid creates a new pathway for the FDA approval of in vitro diagnostics, including LDTs. Under a framework test would be categorized as low, medium, or high risk and treated in a manner that is appropriate for each level of risk. For example, low risk tests could bypass FTAs pre market approval process altogether. And even most medium risk tests could obtain a technology certification would allow them to immediately enter the market. Under valid high risk tests, while generally subject to FDA approval, would be exempted. If developed for specific individuals, or small groups of people, this would allow for example, a hospital to offer a highly sensitive tox toxicology test to a toddler presenting with seizures, and altered mental state to accurately identify potential substance substances consumed. The valid act is complex. So I'll spare everyone further details at this time. But I just know that it is a carefully developed, well vetted piece of legislation that needs further work. And that many experts and stakeholders have weighed in on this. In fact, many of our witnesses and their organizations work constructively. In fact, all of our witnesses organizations work constructively with Congress to provide feedback and valid and I'm grateful to them. So I think some of you've already answered this. But would you be willing to continue to work with Congress in this committee to find a good, good place to be on regulation of these tests? Yes, sir. Thank you.

Unknown Speaker

01:18:52

Yes. Thank you.

Speaker 7

01:18:53

Yes, definitely. Excuse me. Yes, definitely.

Unknown Speaker

01:18:56

Absolutely. Thank you.

Unknown Speaker

01:18:58

Absolutely. Thank you. That's,

Speaker 10

01:19:00

that's great. And thank you for all of that. To my colleagues, please don't let the FDA is overreaching over burdensome rule dissuade you from taking action related to diagnostic testing. This is a there's a lot of work here that needs to be done. The future will include more complex testing, including genetic testing has been has been talked about today. This requires a regulatory climate that ensures accuracy and clinical relevance. Patient safety is paramount as a physician. I can't overstate that. Mr. Rothstein. Do you believe that the valid Act actually encourages innovation as compared with the status quo? Or how so and particularly if the rule is

Speaker 6

01:19:49

implemented? Sure. Thank you for the question. So in terms of the current economic environment that the laboratory testing and in vitro diagnostic testing community engages in It's, it's really riddled with regulatory uncertainty. So at an initial level, the valid Act would bring in regulatory confidence in the sense that investors, laboratories, manufacturers would all understand where this issue would finally lie. In addition, we think that the valid Act has a number of provisions in it that are really helpful to bring innovative products to market. These include modernized frameworks, like the technology certification program, that allows for a company to go to fda one time with a technology platform and be able to iterate on top of it in the market without going back to FDA for future tests that utilize that same platform. It also offers better provisions around how device modifications are made in the post market context. So again, not like texture, but something similar, it would allow for test makers to develop new parameters of their tests that allow them to iterate in the market also without potentially going back to the agency. In addition, I would just add one more, and that is the fact that the valid Act includes mitigation measures, that FDA can deem certain types of individuals who make the tests as a mitigation measure to bring that test down to a lower risk classification, which would also help spur innovation and bring more tests to the market.

Speaker 10

01:21:22

Thank you for those answers. And thank you all for your commitment to continue to work with the committee in this really what I see as a critical area that needs to be addressed. With that I yield back. And I recognize Mr. Cardenas for five minutes.

Speaker 13

01:21:35

Thank you, Mr. Chairman. And I'd also like to thank the Ranking Member, and the chair, the committee for holding this important hearing and like to thank the witnesses for being here and providing your expertise and your opinions in full view of the public. As many colleagues have discussed, laboratory developed tests, or LDTs are being used to guide important medical decisions for many Americans. Not only is there a clear public health impact, but LDTs often influence medical decisions and help determine the best course of treatment. Ensuring these tests are adequately regulated and held to the proper standard is vital to functioning a functioning health system. More importantly, patients deserve peace of mind when it comes to the health information and test results that are communicated to them. As diagnostic technology advances, it is our responsibility to make sure we are taking the appropriate steps to maintain quality and accessibility while allowing innovation to continue. Finding the balance between the elements is precisely why I'm looking forward to hearing from our witnesses today. We cannot proceed without first understanding what kind of resources are available to the FDA to appropriately mitigate public health risks and guarantee safety and efficiency. In diagnostic testing. I'm encouraged by the collaborative efforts from my colleagues on both sides of the aisle in recognizing the importance of addressing the regulatory environments of LDTs. Seeing as we agree on the need for access to trusted and reliable diagnostic testing, I like to direct my first questions to Mr. Rothstein. Mr. Ross, thing in your testimony, you mentioned the importance of providing necessary appropriated resources to support the implementation of regulatory frameworks. What are some of the resource constraints you expect FDA to have, if any? And how can Congress ensure implementation is resourced appropriately?

Speaker 6

01:23:37

Thank you for the question. In terms of, I guess, there's two ways we could think about this. One is in terms of the proposed rule itself, and how FDA will implement it, the other is in terms of valid and what valid would require and I think, when we look at things like the valid act, we would expect for Congress to help FDA increase its ability for review capacity of additional products, it would also set up a user fee program and that user fee program is essential to bringing both the industry and the FDA together to ensure that both the product makers and the regulator have kind of clear rules of the road in terms of what that review timeline would look like. And that FDA would be able to meet those timelines. Of course, Congress would also have a say in this after those user fee negotiations are complete. Thank

Speaker 13

01:24:30

you. So I want to discuss how to best ensure patients are getting trusted results. Can you clarify your concerns with leaving the FDA framework as it exists currently?

Speaker 6

01:24:42

So currently, laboratory developed tests that are not subject to FDA regulations don't include a public repository of the data associated with how they operate. CMS has actually testified to this issue before before this committee in the sense that Not only could different LDTs have variability in their results, but also that there's no public mechanism to understand what that variability looks like. And so we think it's important that any comprehensive regulatory reform in this space, include that public repository so that both patients and providers have access to that information are able to understand the decisions they're making with these tests.

Speaker 13

01:25:22

Thank you, as we look to regulate effectively access to innovation should be an important focus. How would you respond to concerns that oversight could prevent or unnecessarily delay the development of LDTs? Well,

Speaker 6

01:25:35

I think as an initial matter, I would say as a nation, we would all be better off in a system that that really puts test makers in a place where they are competing based on quality and innovation, not gaming out a bifurcated regulatory program. The valid Act has a lot of provisions in it to really encourage not just the regulatory certainty that the community needs, but also to encourage the development of cutting edge novel diagnostics, that patients would be able to access through programs such as the technology certification, and through also a clarified mechanism for all tests to follow.

Speaker 13

01:26:14

Thank you. Mr. Allen, can you elaborate on the dangers of not taking a uniform regulatory approach and diagnostic testing for cancer patients in particular?

Speaker 8

01:26:27

I think it begins with uncertainty. You know, we've heard a number of times today, both from those of us at the table, and from members and their statements that everyone is citing estimates of the number of tests that's out there, under their current paradigm, there's no way of knowing the number of tests that are being offered, let alone how they are performing. And I think that that is issue number one. That would be achieved by additional oversight here by bringing all tests into a common construct a level playing field and understand what is being done in the environment and giving FDA the ability to act if warning signs are seen so that they can work with a developer mitigate those challenges and make sure that they're resolved. Thank

Unknown Speaker

01:27:10

you, Mr. Chairman. I yield back.

Speaker 10

01:27:12

gentleman yields back now recognize Mr. Latta five minutes.

Speaker 14

01:27:15

Oh, thank you, Mr. Chairman. And thanks for our witnesses for being with us today. clinical tests play a major role in nearly 70% of all clinical decisions through screening, diagnosing and managing diseases and medical conditions. As innovation advances, we are better able to intervene, intervene and assist with our health infrastructure. Accessibility and accuracy of tests save lives. I'm very concerned about what the Food and Drug Administration's proposed regulation for laboratory developed tests will do. It's out it is an outrageous overreach of the agency's statutory authority. The rule will limit our healthcare professionals ability to tailor and modify LDTs to patients needs. Ms. Van Meter, diagnostic diagnostic tools used in pediatric health are sometimes vastly different than for adults. LDTs allow pediatric focus institutions to serve pediatric patients for the use of age appropriate and needed technical modifications. How will this role impact pediatrics and just by coincidence, this week, I was at a pediatric facility and this came up, and well we in fact be discriminate against discriminating against our children because of this rule.

Speaker 5

01:28:32

Thank you for the question. We are tremendously concerned about pediatric patients, small patient populations, patients with rare diseases. LDTs are the principal source of diagnostic tools that serve these patient populations. I fear that with a one size fits all application of the medical device authorities tremendously inflexible authorities, we are going to see patients lose access to those necessary services. I will give you an example of a tremendous test I'm sure that you heard about in your visit recently, there is a laboratory developed test service that is used on patients in the neonatal intensive unit or smallest patients rapid hold genomic sequencing. This tremendous test allows for the to be determinations of what is ailing the patient and 40 to 50% of cases avoiding a diagnostic odyssey for patients and families. That's a laboratory developed test service, I worry that patients will lose access to those types of services, if in fact this rule is implemented.

Speaker 14

01:29:34

I follow up given the that the proposed rule does not contain any exemptions for low volume or custom or even humanitarian tests. I didn't anticipate your members will adapt when providing care for rare diseases.

Speaker 5

01:29:48

I think that the laboratory community across the country and certainly acla members are already doing the work to determine how to implement this rule. That means calling through test menus to make determinations About for which test can submissions be developed and submitted. And keep in mind, it's within three and a half years, that all high risk test submissions must be submitted to the agency. That's an impossibility that that guy could happen. So in short, I think we will see some tests come off of tests menus. And I worry most about those who serve the small patient populations, for which revenue is modest. Thank

Speaker 14

01:30:24

you. Dr. Eisner, what are the impacts to diseases with a genetic basis that require more specialized and sophisticated tests, this is Gene and cell therapy.

Speaker 9

01:30:38

In order to effectuate gene and cell therapy, a number of tests have to be developed on a per patient basis. And oftentimes, an individual patient needs to have a test developed just for them. It is unclear how a laboratory could establish a paradigm in which they have the ability to move forward with this. If these tests are determined to be high risk, I believe that the technology certification no longer applies. I think that there is a real danger that we will cut off the ability to bring about the most cutting edge of the most innovative testing. An example I can give you is a laboratory at the University of Colorado is working on cell therapy. And they have sought out our approach our assistance in molecular diagnostics to make sure that their product doesn't have any contamination from any of the non patient cells that are needed to generate the product. These are things that we can adapt to on the fly because we know what we're doing.

Speaker 14

01:31:40

Thank you are in my last 37 seconds. Mr. Rothstein. Oh, do you anticipate your member companies allocating their investments into research and development differently if the final rule is published,

Speaker 6

01:31:55

in terms of the current regulatory uncertainty that exists within the environment that we deal with today, the final rule would bring about at least some level of certainty potentially long term, however, litigation is likely to ensue. We would prefer regulatory certainty through valid because that would really allow for investments, decisions, both from the investment community and from members who make art who have r&d dollars to spend to really understand what the future of diagnostics regulation will look like.

Speaker 14

01:32:25

And I'm sure my time has expired. But I assume then when you're looking at pediatric diagnostic tests, and other small specialty markets, I assume you'd say that those would be hard hit then.

Speaker 6

01:32:38

But no patient should lose access to these critical tests. At the end of the day, you know, if if there are concerns in the docket, we would expect FDA to address them in terms of how it implements the final rule. We don't think though, that, you know, any patient, particularly those in a vulnerable population, should have a test that has not gone through the same standards of review as any other patients. And that's why again, we think valid, has a number of provisions in it to really bring those types of tests to vulnerable populations, those with unmet needs, rare diseases, and pediatrics, and a much more equitable fashion. It has that technology certification platform that allows for test to be made more rapidly without going through the FDA review. There is a low volume exception in it as well. Plus, it includes grandfathering, which means all the tests that are on today, and potentially those for the next four or five years after the Act will be implemented could also remain on the market without going through FDA review.

Speaker 14

01:33:37

And I appreciate the indulgence of the chair. Thank you very much and yields

Unknown Speaker

01:33:41

back. recognize Dr. Ruiz.

Speaker 15

01:33:44

Thank you, Mr. Chairman, we must continue to work towards developing new diagnostics and treatments, and we need to ensure adequate protections for patients along the way. Patients must be able to have access to accurate information about their health and providers need to be able to trust that the tests they are prescribing for their patients work and are safe. Many of these tests have the potential to change the way we approach cancer detection such as multi cancer screening tests. These tests have life saving potential. And that's why I'm an original co sponsor of the bipartisan Nancy Garner school Medicare multi Cancer Early Detection screening coverage Act. This bill would require such tests to receive FDA approval before being able to even engage Medicare in the National Coverage Determinations process. So Miss Van Meter, how can we evolve our testing capabilities as we learn more about biomarkers and cancer DNA and ensure patients feel safe and assured of test performance?

Speaker 5

01:34:47

Thank you for the question. I would like to take the opportunity to explain that there is significant regulation and oversight in place right now for library Torre developed testing services that not only includes CLIA, and all acla members are accredited at the highest level to develop high complexity tests. Every acla member is also accredited by CIP the College of American Pathologists, the vast majority go through the risk based assessment program that New York State offers looking at analytical and clinical validity. And the majority of molecular laboratories in this country are within the 28 states that Medicare's modex program assesses for analytical and clinical validity. In short, I would say that patients and providers should have confidence now, in the accuracy of tests, we can see a potential role for the FDA, not through unilateral rulemaking to take the medical device authorities and apply them to laboratory developed test services. They're not medical devices, their professional services. This is an opportunity, I think, to do this right and would encourage the committee to look at comprehensive legislation.

Speaker 15

01:36:00

The FDA is proposed rule lays out several examples of lab developed tests that produce inaccurate results that lead to harmful outcomes for patients. COVID made clear the importance of FDA oversight of these tests. If these tests don't work, we undermine the public health response to such public health emergencies. FDA published an analysis of the first 125 emergency use authorizations requests for COVID-19 LDTs were 82 showed problems. In one case, the approach to test validation was so poor that when read done correctly, there was a 400 fold difference in performance. Multiple laboratories that offered their test did not provide any analytical or clinical validation data and the EUA requests that they submitted after the test were in use. Mr. Rothstein, what are the consequences for patients and the public health response if FDA is not reviewing tests for public health emergencies?

Speaker 6

01:37:02

Thank you, Congressman for the question. Look at the end of the day, if there are not, if we do not have the regulator with expertise to review these products, looking at them ahead of time, we lead to a situation where patients and providers will lose trust in the market. It also again creates regulatory uncertainty in the investment community, which is not good as we want to try to develop tests rapidly and iterate. I would like to point out that during the COVID pandemic, the diagnostics industry really had a tremendous response here ramping up our production, domestically increasing our ability to bring novel tests for COVID-19 to market, in addition, not just for laboratories, but also at the point of care. Those are at clinics and and other types of providers outside of the hospital setting.

Speaker 15

01:37:52

Thank you. Think I have one minute left. Dr. Carter, in your testimony, you discussed a tiered risk based approach. How would creating a tiered risk based approach to FDA approval of LDH protect patients?

Speaker 7

01:38:08

Thank you. Thank you for the question. Thank you very much for the question. So we do advocate a tear based approach we have for 10 years, actually longer than 10 years. We believe that there is a group of high risk test. It's a small subset of laboratory developed tests that are really in need of high level oversight. And we believe the FDA is the appropriate agency to do that, that would protect patients that are receiving those tests. Likewise, we also strongly believe that there should be significant flexibility in the oversight of the West lower risk test so that it would allow those tests to continue to be developed without any restraint, and that patients would have continued to have access to all of those tests, including now, Iris tests with a higher level of competence. Thank you.

Speaker 10

01:39:06

gentleman yields back. I now recognize Mr. Bill raucous five. Thank you.

Speaker 16

01:39:10

Thank you, Mr. Chairman. I appreciate it. As co chair, the rare disease Congressional Caucus has been our priority to improve the development and access to diagnostic testing for the more than 30 million Americans with rare diseases. There's been an incredible amount of innovation in this space, particularly in the field of molecular diagnostics for rare cancers as we move forward towards personalized position precision medicine. For example, Moffitt Cancer Center in my home state of Florida, currently serves over 20,000 patients per year with innovative biomarker testing with Fast, safe and accurate results to improve patient outcomes. Needless to say, I'm highly concerned that the FDA is proposed rule To regulate lab develop tests would reduce patient access to these types of innovations and I appreciate the panel's testimony this morning. Miss Van Meter. There are many challenges in treating rare diseases, including the small patient populations, lack of natural history studies, and LinkedIn diagnostic journeys for most rare patients, while the FDA is LD T rule, add further challenges to conducting clinical trials for potential treatments and cures for rare disease patients. And how should Congress think about the economic and patient impact trade offs of offering LD T services for rare disease under the FDA is proposed framework?

Speaker 5

01:40:48

Thank you for the question. We do indeed think that there will be a downward impact on patient access to testing generally, we are acutely concerned about patient populations, small patient populations, rare diseases, in particular laboratory develop testing services is really the backbone of diagnostics for those patient populations. So we're very concerned with the unilateral approach that FDA is taking in this proposed rule to apply the medical device authorities which are dramatically inflexible and ill suited for diagnostics period to laboratory develop testing services.

Speaker 16

01:41:23

Thank you. Our next question for Mr. Rothstein. Can you share your perspective on the FDA rules impact on rare disease patients? Is there a way Congress could tailor diagnostics regulations to avoid or mitigate these concerns? And do you believe FDA is recent announcement of its intent to down classify most high risk IV ds will provide a less burdensome pathway for most LDTs. Again, for Mr. Roston.

Speaker 6

01:41:56

Thank you for the question. In terms of the proposed rule, again, our position is that no patient should lose access to these important tests, and FDA needs to respond to any comments that are in the docket on this point. We do continue to believe, though that all patients deserve tests that undergo the same regulatory review. And that's why the valid act really provides a much, much more suitable mechanism here, particularly for those with rare diseases and unmet needs. The valid Act includes a technology certification program, which allows for test to be rapidly iterated and brought to market without going to FDA. It provides for modifications to be made once the product is in the market to there's also a low volume exemption, which is included in the valid act at this time, that would allow for tests up to 10,000 to be brought into the market without going to the FDA, under the valid act in terms of the down classification proposal that FDA has issued. That's something that I would have to look into a bit more to provide a more succinct answer for you.

Speaker 16

01:42:59

Today, if you can get back to us, we'd appreciate that. Third question. Dr. Carter, given your organization's perspective accrediting CLI a labs, do you believe the proposed timeline for ending enforcement discretion is realistic for labs to meet in order to prevent gaps in care? Again, for Dr. Carter?

Speaker 7

01:43:22

Thank you for that question. So we do not believe that that laboratories would be able to function and provide the services that are vitally important to patients, if enforcement is ended prematurely, we think that it would take laboratories a much longer period of time to be able to adjust to the changes that are in the rule as written. And therefore, lab, many laboratories would simply give up and stop developing ltt. So we think would really impact access.

Speaker 16

01:43:57

Well, thank you so much, very valuable information, great feedback. And we appreciate it so much. Thank you. I yield back. Mr. Chairman, gentleman

Speaker 10

01:44:05

yields back. I now recognize the gentlelady from Michigan. Mr. Engel five minutes.

Speaker 17

01:44:12

Thank you, Mr. Chairman. As we've heard today, the FDA plays a very important role in regulating ensuring the highest levels of safety to laboratory developed tests or LDTs. As we've been talking about. The new proposed rule aims to provide greater oversight of LDTs to improve their safety and effectiveness. In addition to diagnosing, monitoring and treating diseases. This new rule has implications for the testing and screening of serious diseases such as tuberculosis, that can be transmitted to patients and donor materials used for medical procedures. A lack of oversight and accountability for tissue donation services can lead to devastating consequences for patients and their families. In fact, I am co leading the bipartisan Shandra. I sync a human cell and tissue Product Safety Act to strengthen awareness and accountability of tissue product providers. This legislation comes as a response to the passing of Shandra Sanga, a woman from Michigan, who's actually her sister works for my colleague John Molnar, due to the complications of tuberculosis infection, she fatally contracted TB after receiving a bone graft that was used from an effective donor. Miss Mr. Roston? My understanding is there is not currently an FDA approved test to detect to or closest in donor materials. What impact might the new proposed rule on LDTs have on the testing and screening of tuberculosis in donor materials to prevent infection? Thank

Speaker 6

01:45:52

you for the question. And as as as I've said, no patient should lose access to critical tests as a result of the FDA rule. What I would like to point out, though, is that the current market dynamics are likely what leads to the lack of an FDA approved test to be on the market today, as opposed to innovation within the manufacturing community of IVDs. With a two prong system in terms of how we bring tests to market right now, there are cases even documented in FDA as proposed rule that show once a IV D manufacturer brings a product through the FDA program into the market LDTs are then developed and compete with them. And so right now under the current system, the manufacturers of IV DS have to consider that potential for whether or not they bring a test to market through the agency. That's why comprehensive diagnostics reform would be so important, it would put everybody into the same program into the same system, and patients would continue to receive these products and we would be able to understand how to best allocate our investment resources or r&d dollars to meet the patient needs that exist. So

Speaker 17

01:46:57

Mr. Ostium, from a public health standpoint, why use an equally important for FDA to have oversight are all diagnostic tests, including conventionally manufactured tests, test kits, those developed and used in laboratories and tests used in academic settings?

Speaker 6

01:47:15

Sure, thank you for the question. At this time, LDTs and IVDs continued to become more and more complex, they also continued to be made by various and very different types of entities, more than just those that are represented at this at this table right now. The current framework is very old, to say the least but valid. Well, valid is a much more appropriate approach here to bring these tests to the market because what it would do is offer again a more tailored mechanism for them to come into the fray. However, under the current system, all LDTs right now do not go through pre market review. They also do not have consistent post market review, or analysis or a comprehensive program to capture any adverse events, malfunctions, or recalls that occur.

Speaker 17

01:48:07

Thank you. This question is going to be for Dr. Allen. Some have also raised concerns that prenatal testing has led to false positives that wrongly indicate a fetus has a genetic condition. Also, women who have been tested for breast or ovarian cancer have received false positives, which could impact their decision to receive a mastectomy or hysterectomy are huge medical decision that relies on can rely on inaccurate information. Dr. Allen, can you speak about the inaccurate results from LDTs? How would oversight from the FDA be helpful in lowering such errors?

Speaker 8

01:48:42

I think I think what you've noted here is just the magnitude of the issue that's at hand. And so that that's really the insurance that FDA oversight would provide, and do so before these tests are being utilized in the market. That's an important distinction with with pre market review would ensure the performance of the test before they're being applied. And those results are available to patients. So in these particularly high risk scenarios, the true accuracy of the test is what's very important, not where it's developed. And that's what a level a level policy at FDA would provide.

Speaker 17

01:49:19

Thank you, Mr. Chairman. I'm out of time. So I yield back and we'll be submitting questions for the record.

Unknown Speaker

01:49:24

Gentlelady yields back recognized Dr. Dunn five minutes.

Speaker 18

01:49:27

Thank you very much, Mr. Chairman, for holding this hearing today. The testimony that's been presented is very compelling, and I hope that the administration and the FDA are listening. I'll be clear, I strongly oppose the proposed FDA rule. I appreciate hearing perspectives from industry leaders, practitioners and patients. Sweeping decisions about the regulation of lab developed tests that are utilized by hundreds of 1000s of patients and providers should not be left to FDA bureaucrats, many of whom have never worked in a lab in Our lives. We know the FDA is slow, they move at a glacial pace to approve innovative medicines and devices. And we know that clear provides robust oversight of laboratory operations as outlined in the testimony of Mr. Rossi. I agree with our witnesses today the FDA rule would crush innovation, but unsustainable upward pressure on the cost to labs and set America back on genetic testing, toxicology, testing, and screening. Why in the world, would we subject our innovators to review by an agency that is already bogged down with inefficiencies that deterred innovation? The landscape of lab development test is robust. It's very successful. Today we have a plethora of test that exists to diagnose and screen for rare and common diseases, ensuring that patients and physicians not bureaucrats are in the driver's seat when it comes to delivering care should be our goal. This is particularly important in rural areas like my district with access challenges, smaller labs that develop tests that allow rural patients access complex diagnostics in a timely manner close to home. Imagine if a custom diagnostic test had to pass through the web of the FDA device approval regulations to be available. That diagnostic test would likely be obsolete a true fossil by the time and actually saw the light of day. That is not to mention that the rural facilities my constituents have access to would be crushed under the increased regulations that this would require. And let's not forget that the impact of this rule would have on high performing cancer centers as well, such as the NCI designated Moffitt and University of Miami and Florida UF in Orland, Florida. These centers provide top of the line laboratory developed tests and quality control processes to deliver high quality tailored care to their patient populations and their teams of world renowned experts in faculty members, who interpreted many 1000s of tests every year would be hampered. Dr. Teresa Boyle of Moffat has said that this proposal to change the FDA policy of enforcement for the LDTs will shut down our routine and our innovative molecular testing at Moffitt, such as the philanthropically funded pre screening tests for clinical trial matching. In an era of highly personalized medicine, and strides in rare disease research, inhibiting clinical trial matching is an unacceptable consequence of this rule. Dr. Eisner, thank you so much for sharing our expertise today, both from the physician perspective, but also from the patient perspective. Can you speak to the incentives that would drive workforce decisions? You know, you do wonderful work at your lab in Colorado, the molecular correlates laboratory. There are facilities such as cancer centers and academic medical centers have can't innovate in the lab, I suspect we'll see a stagnation in innovation and consolidation of in the pipeline, you'll see fewer people applying what do you think?

Speaker 9

01:53:23

I agree completely. I think that if I need to stop innovating new lab tests and bringing new lab tests into the lab, in order to retroactively focus on the things we've already done, I will have to completely restructure who we hire, why we hire them. We will have more regulatory staff than we will have technical and r&d staff. And I think that that will bring the pace of the lab to a grinding halt.

Speaker 18

01:53:54

Thank you very much for that Miss Van Meter. Can you elaborate on some of the issues that medical device style regulation might have on toxicology testing? For developers in hospitals, and in the emergency room?

Speaker 5

01:54:07

Yes, thank you for the question. When patients are being treated for substance use disorder on toxicology testing is really essential to drive the right care and also for public policy to ensure that we understand what substances are impacting our communities. So laboratory developed test services are the core testing available for the circumstances. As was pointed out earlier, during the hearing, for example, xylazine. With fentanyl, which is plaguing communities around the country, the only test for those substances is in LD T. And so we think the downward impact on the accessibility of needed testing for toxicology would suffer tremendously under the FDA role.

Speaker 18

01:54:54

Thank you very much, and I thank the chair for this meeting yet. Thank you panel.

Speaker 10

01:54:59

gentleman yields back. I now recognize Miss Kelly, for five minutes.

Speaker 19

01:55:06

Thank you, Mr. Chair and thank Chair Guthrie's Ranking Member Eshoo for holding today's important hearing. The FDA and CMS have issued a joint statement reiterating that modernizing the Clinical Laboratory Improvement Amendment is not the answer to addressing concerns about the accuracy of laboratory diagnostic testing or LDTs. In fact, CMS has repeatedly said and testified before this committee, that it does not have the expertise to assure the tests work. This expertise lies with the FDA, the joint FDA and CMS statement we iterate that CMS is clear program is separate in scope and purpose from FDA oversight and misstatement we're seeing Ms posted on his website. CMS specifically said that they support FDA proposed rule on LDTs. CMS also clearly says that expand and clearer to oversee LDTs would be duplicative of what FDA is already doing and would create more government bureaucracy and inconsistencies that to Alan, what are the deficiencies and CMS is current regulatory structure? And how would FDA regulations address those.

Speaker 8

01:56:15

As you mentioned, they were just set up to be very different. And so to expect a agency that has been directed for decades to oversee laboratory operations, to shift their focus and start focus on focusing on the performance of individual tests, and the analytical and clinical validity of them, is not in their wheelhouse. And so I think it would be a misguided approach to what we are hoping to see achieved through additional oversight, as you said, the expertise and the experience, frankly, lies at the FDA, they have been reviewing similar diagnostic tests for many years. And I have the faith that they have the expertise to continue to do. So.

Speaker 19

01:56:57

Thank you for your response. Mr. Rothstein, it is evident that even among FDA approved diagnostics, women and individuals from marginalized communities are underrepresented in the trials necessary for approval, resulting in these tools being less effective across all populations. The FDA is working to improve this by encouraging diversity and clinical trials. But my concern is that for LDTs, the issues and lack of representation could even be worse than for commercial tests, given the lack of oversight, how can we ensure ensure that laboratory developed tests in use are equally effective and screening for conditions across diverse populations?

Speaker 6

01:57:36

Thank you for this question. It's a very important issue. And in terms of the current status of representation in the population use to validate LDTs, we simply don't know. And that partly comes to the fact that LDTs do not have currently a public repository, we still believe that the valid act or other types of comprehensive regulatory reform would be most appropriate to bring all tests under a single framework. By doing so we would ensure that all the tests that are currently LDTs are also going through the same process at FDA that IVDs do that ensure that the clinical trials represent diverse populations.

Unknown Speaker

01:58:15

Thank you so much for your response. And I yield back.

Speaker 10

01:58:20

Gentlelady yields back. I now recognize Mr. Carter for five minutes. Thank

Speaker 20

01:58:23

you, Mr. Chairman, thank all of you for being here. We appreciate this is extremely important. And I I know that my colleagues have pointed this out that diagnostic tests including laboratory developed tests are play such a critical role in our healthcare system as as a health care professional as a pharmacist, I understand that. And I appreciate that and appreciate what y'all do. It's been estimated that 70% of all health care decisions are influenced by my lab tests. I know I was a consultant pharmacist at nursing homes, and we depended on lab tests quite often to to help us in our decision making on drug therapy. And that was extremely important. The rules that the FDA is proposing could stifle innovation, as we all know, and that's our fear and our concern, and it could hinder patients access to tests Miss vnv Mater, I wanted to ask you, and I don't mean to be redundant. I suspect you've answered this already. But could you elaborate again on the importance of laboratory developed tests and for innovation and diagnostics and medicine?

Speaker 5

01:59:29

Yes, thank you for the question. So laboratory developed tests really are the cutting edge when it comes to leading the foundational work for a personalized medicine. Laboratory developed tests are among the first tests that are developed when we're facing a new pathogen of concern. Among the first EUs for example, for COVID tests were laboratory developed tests and laboratories across the country were able to dramatically augment the nation's testing capacity. So if it's for infectious disease, is it for precision medicine laboratory developed tests are really leading the way on innovation. So we're significant concern that a medical device authority application broadly in this unilateral fashion, without any exceptions is not the right approach. We think a comprehensive legislative approach would be the right direction.

Speaker 20

02:00:16

Okay. I want to ask each of you a yes or no question. You pretty much just answered it. Miss Van Meter. But yes or no? Do you think the current medical device framework is best suited to address regulation of all diagnostic tests, including laboratory developed tests? I do not.

Speaker 6

02:00:32

Know, we believe something similar to the ballot Act would be much preferred.

Speaker 7

02:00:36

We do not. And we also believe that that valid Act would provide the flexibility that we would need for this kind of oversight.

Speaker 8

02:00:44

It's better than the absence of oversight, but would favor the Validate. Right.

Speaker 9

02:00:48

We do not believe the device approach is appropriate.

Speaker 20

02:00:54

Okay. Dr. Carter, let me ask you, do you think that the LD T rule places independent pathologist and large corporations on an equal playing field? And I'll preface that question or add to that question by saying that I was an independent retail pharmacist? So I'm very concerned about independent pathologist as well. And I have quite a few in my district as well.

Speaker 7

02:01:18

Thank you very much for that question. And it's a very pertinent observation. So no, it does not create a level playing field. Local laboratories were very, would be very disadvantaged. If this rule were to go forward as written. We think it's very important that laboratories that are performing LDTs, develop and perform those LDTs for patients in the hospital or the network where that laboratory is located. We're familiar, as a pathologist, I can say we're familiar with those patients, we're in constant communication with their physicians. And that allows us to safely offer those tests so we would be at a disadvantage, and patients would equally be disadvantaged. Right,

Speaker 20

02:02:01

good. Well, thank you for that answer. Dr. Eisner, let me ask you, do you share the same way that I do, and that is that raising the barrier to accessing new cancer diagnostics will be another arrow aimed at cancer patients?

Speaker 9

02:02:15

I absolutely do. And I can speak from personal experience as a patient who accessed LDTs for my own personal patient care. The environment that allowed those tests to exist in the first place is the reason I was able to avoid chemotherapy. That's a really big deal to me. And I think that if we lose the ability for people to bring new and innovative technology, that we're going to be treating everybody in a in a very broad fashion, rather than tailoring the care that we need to tailor. Thank

Speaker 20

02:02:47

you for that. Mr. Rothstein. Let me ask you one last question. As we consider possible legislative approaches to address this issues that have been raised here today, what would be the most important component of of any alternative legislative proposal and what should we avoid?

Speaker 6

02:03:05

Sure. Well, thank you for the question. In terms of what the proposal should look like, we think the valid Act takes it pretty much all of the way there in terms of a single framework that addresses patient needs, provides a single regulator with innovative pre market, and importantly, post market concepts included in terms of avoidance. I would defer to my colleagues on the on the clear side there in terms of what issues they experience will be most problematic.

Speaker 20

02:03:34

Great. Okay. I'll leave it at that. But thank you all. And I yield back. Mr. Chairman,

Speaker 10

02:03:38

gentleman yields. Now recognize Dr. Schrier for five minutes.

Speaker 21

02:03:47

Thank you, Dr. Chairman. And thank you to all the witnesses for coming here to discuss the FDA proposal to regulate lab developed tests. I know all of us here have varying views on how the federal government should regulate LDTs which tests require regulation, how the urgency and the severity of illness should factor into these decisions also how the absence of a good alternative should factor in. To me the heart of this issue is ensuring a balance a balance is struck between ensuring that the tests are trustworthy and accurate, but also maintaining that access to testing. We don't want to allow inaccurate testing to mislead and harm clinicians or patients. We also want to ensure that people have adequate access. And we just heard about a case where having access to a lab develop test guided guided treatment. Dr. Allen My first question is for you. Can you just point to maybe a couple examples of now this testing can save lives but the opposite is true. Whew, as well, it could have missed a guided the way that cancer was treated in this case, could you share some potential harms some of the potential benefits?

Speaker 8

02:05:12

Sure, you know, I think that, you know, the role that diagnostic testing is playing in oncology care, diagnosis, decision making is increasingly complicated, the analytes that are being evaluated in order to determine treatments continue to evolve, and that has, you know, to the benefit of patients that are receiving these tests. And I think their their availability is hand in hand with the their accuracy. And we need to make sure that both are accounted for. And I think it's important to look at it perhaps at a at a local level. It had been mentioned earlier that a number of these tests are regulated by New York State laboratories big and small, have been able to comply with those regulations. And I don't believe that patients and New York state whether they be in urban or rural areas, are, are precluded access to these innovative tests. Given their importance, I think that's something to consider as we look toward federal,

Speaker 21

02:06:14

we also have a state regulation in the state of Washington. I just want to quickly mention there's lots of tests that have different sensitivities and, and specificities like flu tests that we use the strep test, we use even the COVID test, we all had to understand that if you got a negative the first time you check two days later, I just would like to mention that like with these lab develop tests, you can also have that discussion with the patient about how accurate you think this is and how much we can depend on it and kind of the risk involved. I wanted to turn to pediatrics, my specialty. And I want to commend the FDA for taking action to move this effort forward. But I have some concerns about the the lack of consideration of PD, pediatrics, rare diseases, and kids require specialized care. And LDTs plays a critical role because they also may need very urgent care. We just heard from his Van Meter about rapid genetic testing in a sick newborn. I often emphasize the importance of early detection, even with newborn screens, we get a confirmation the day later to make to see what type of a disease they have and how urgently it needs to be treated. So many labs need to do these tests in house. children's hospitals use LD T's when there's no FDA approved alternative, or when they have a test that's just better and faster. Dr. Karcher there doesn't seem to be any specific mention of Pediatrics, children's hospitals. In this proposal, I was wondering how FDA might make some exceptions.

Speaker 7

02:08:07

Thank you so much for that question. Because we very much worry about pediatric patients really being on the losing end, if if this proposal goes forward, as written there there, we clearly need to be able to allow pediatric hospitals who developed a large percentage of LDTs, as you know, well, in your own practice, we need to find a way to have a flexible system that ensures accuracy and validity of the test, but also allows enough flexibility that they don't, they're not prevented from continuing to develop those life saving tests.

Speaker 21

02:08:42

I appreciate that and five seconds, I'll just say that I agree that we need this flexibility and that when we talked with researchers at University of Washington and Seattle Children's, they described lack of flexibility in this role as potentially devastating. Thank you. I yield back.

Speaker 10

02:08:59

Gentlelady yields back. I now recognize Dr. Joyce five minutes.

Speaker 22

02:09:04

Thank you, thanks to the panel for being here today for testifying on an issue that could have dramatic impact on patient care specifically with diagnostic testing. The FDA is decision to clarify laboratory developed tests as medical devices has rightfully raised concerns among pathologist hospitals, including children's hospitals, and others across the industry. I would like to thank both Dr. Sean and representative to get for their work and putting together a comprehensive bill that negates the need for the FTAs regulatory overreach here and settle many of the problems that this new regulation would allow to come to the table. My first question is for you, Mr. Rothstein. Can you elaborate a little bit more on what would happen in this space? If we do not statutorily exempt tests for rare diseases and let's clarify rare disease. Because I think we all recognize that rare diseases have impacts, each described as a rare disease. If there are more than 200,000 cases in America, rare diseases like cystic fibrosis, rare diseases like sickle cell disease, diseases that many of us don't consider to be so rare.

Speaker 6

02:10:18

And thank you for the question. And it's a really critical issue that we address here. And we think that the valid act really provides thoughtful mechanisms to ensure that these tests can come to market quickly and efficiently. The valid Act provides for a couple of platforms that allow for this to occur. One is the technology certification program, where a company would be able to iterate on top of a platform that has already gone through FDA once but does not require further FDA review. There are also low volume exemptions provided in the valid Act, which we think are really important in this context. And lastly, the valid Act includes grandfathering, meaning all the tests that are on the market today, and tests that will come onto the market in a certain period of time, after enactment, think it's currently a five years would also be exempt from going through FDA.

Speaker 22

02:11:09

Dr. Eisner, as a physician also, I've witnessed the evolution of innovation in cancer detecting tests from relatively simple antigen markers for cancers being diagnosed by next generation sequencing. Do you feel that significant innovation would be stifled if we do not address this appropriately with legislation?

Speaker 9

02:11:34

I am confident that innovation will be stifled. And I do not believe that a uniform approach, ie a so called level playing field is the thing that we should be focusing on here, a level playing field assumes we're all playing the same sport, when in fact, we've got different leagues. And the reality is, is that the resources of a hospital based lab are not the same as the resources of a test manufacturer, a hospital based lab does not box their kit up and distribute it to other labs, thereby needing additional stringent controls. A hospital based lab and an academic lab monitors the assay right in front of them. So I think this idea that everybody needs to go through the same process doesn't account for the nuance of the reality of our medical care.

Speaker 22

02:12:22

And I think that nuance has been so clear, as we've seen innovation continue and allow more diagnoses to occur earlier allowing more lives to be saved. Dr. Karcher, the FDA says that they lacked the evidence to quantify the number of LDTs currently on the market, as there is no publicly available source of this data. would such a central site be a value?

Speaker 7

02:12:47

Excellent question. Thank you for that question. Absolutely. And it would be very helpful for us to know the scope of what we're dealing with. I know that their estimate of 80,000, we believe is an underestimate of the actual number of LD T's that are out offered currently today for patients. Would you also would be helpful, would

Speaker 22

02:13:04

your organization or even clearer program be able to collate such information on all available tests

Speaker 7

02:13:11

under the current structure in CLIA that would be difficult to do? I mean, our organization has deemed status from from CMS to do Laboratory Accreditation and ensure clear standards are being met. But that's not one of the mandates. That's part of our Diem status. So we don't really have a mechanism, we could certainly investigate that and we'd be happy to work with you to see if we could find a way to make that calculation.

Speaker 22

02:13:38

Miss Van Meter. You talked briefly about xylazine testing with fentanyl. And as we have seen the opioid crisis continue to rapidly approach so many borders, so many individuals, so many families in the United States. Can you talk about the ability for laboratory developed tests to address the presence of xylazine and in that overlap between xylazine and fentanyl, as so many overdose and substance use patients have to be able to be aware, as do those who address that with them as a present? Yes,

Speaker 5

02:14:11

thank you for the question. It's essential to have laboratory develop testing services in order to discern what are these new and damaging substances that are coming into the country every day? xylazine live fentanyl has been one that has ravaged communities across the country. And it is only through a laboratory developed tests can clinicians and public health officials discern that it's actually in their communities. So really, laboratory developed tests are essential to toxicology testing.

Speaker 22

02:14:38

I thank all of the panel for being present here today for your widespread and wide approach to how we address this from a congressional basis. Mr. Chairman, I yield back.

Speaker 10

02:14:49

gentleman yields back now recognized Miss Harshbarger. Five minutes.

Speaker 23

02:14:54

Thank you, Mr. Chairman. Thank you to the witnesses here today. I'll start with Dr. Karcher. Um, CMS recognizes your organization's Laboratory Accreditation Program to help ensure CLIA compliance. What's the importance of CAP accreditation? And what's generally being caps experience inspecting CLIA labs?

Speaker 7

02:15:16

Yes. So thank you for recognizing that role that the CDP has and we do. We have this we do this work through our Diem status from CMS. We believe that Laboratory Accreditation, obviously ensures at a minimum that laboratories are upholding CLIA standards. We'd like to believe that actually our accreditation goes above CLIA standard so that CAAP accredited laboratories, we believe are the best in the world.

Speaker 23

02:15:44

Okay, very good. And I'll follow up with you again, the FDA proposed rule references third party review programs and helmet caps, checklists be updated and leveraged to reflect the validation that FDA is looking for and in lieu of duplicative oversights, or

Speaker 7

02:16:05

yes, thanks for that question. So, you know, we are in a way, we are an example of a third party reviewer because of our accreditation program. For CLIA. We've learned a lot of lessons in applying that our expert member, pathologist members and other laboratorians, manage, you know, administer our program, inspect the labs update our standards as needed for new technology and practice. So I think an X external review, accreditation or review process, some of the same benefits could very likely be brought to this process as well.

Speaker 23

02:16:41

Okay. Your organization endorsed the valid act, but a lot of your pathologist have diverse views about the act. And how did you come to the decision that you would do that?

Speaker 7

02:16:54

Yeah. So thanks very much for that question. It was a very tough decision for us. And we do support the valid act, we did endorse it. But we endorsed it really at the very end of the process in 2022, because it needed work. And we worked very hard with Congress and the FDA to get it to the point where we could endorse it. You're right, not every one of our members is it feels exactly as we do about the valid act. All of our members do however, care about patience and want the best thing ultimately, for patients how we get there, obviously, there is a difference of opinion. So you're absolutely right, not 100% of our members support that but it was

Speaker 23

02:17:37

gives the FDA more authority, and only as a pharmacy

Speaker 7

02:17:41

does, but we believe the valid actin makes that authority very flexible and allows laboratories to continue to develop these life saving tests.

Speaker 23

02:17:48

Okay, thank you, sir. Miss Van Meter, if the FDA proposed rule is written more to go in to effect what type of testing move out of hospital laboratories into large reference labs? And can you describe any potential challenges with such a development?

Speaker 5

02:18:06

Thank you for the question. So acla member laboratories, our clinical laboratories throughout the country, many of our member laboratories work hand in glove with hospital laboratories, on a day to day basis, I think across the board for laboratories, if this rule does, in fact, go into effect. And to be fair, right, we anticipate that it will and our members are already working to understand how to implement it. I think across the board, clinical laboratories will be taking a hard look at their testing menus. And those menus will shrink as a result of implementation.

Speaker 23

02:18:39

Well, I look at it as national consolidation. Have you feel about that? Would that hasten that toward national consolidation?

Speaker 5

02:18:50

I think there's the potential for some consolidation. And I just come back to thinking about the patient access issue. Yeah. And if we have curtailed menus of testing from laboratories across the country that's not serving patients. Well. Exactly.

Speaker 23

02:19:02

Thank you, ma'am. Dr. Eisner. You know, I've heard worries that FTAs proposal could make it more difficult to treat antibiotic resistant infections and address antimicrobial resistance and currently FDA has no pathway for off label antibiotic test. And at Vanderbilt University Medical Center ICUs roughly 60% of antibiotics prescribed are for off label organisms or off label indications and use of off label antibiotics are made possible by LD T testing for antibiotic susceptibility. How would the loss of such test affect the management of patients including those with compromised immune systems or facing extremely rare infections?

Speaker 9

02:19:48

Thank you for the question. I think that it's quite evident that the FDA rule as proposed would clamp down on LDTs in a way that would bring testing such as antimicrobial resistance testing to a halt, that could leave hospitalized patients without a pathway to exiting their infectious status. It could lead to overtreatment with multiple antibiotics in an attempt to eradicate which can lead to kidney failure, liver failure, etc. I think that it is a huge challenge to understand the global impact of LDTs because it is not just about oncology genetics, it's about infectious disease. It's about rare disease. It's about anatomic pathology, it's about there isn't a field of medicine, where LDTs aren't part of the picture. And I think it is. It is understandable that we are talking a lot about oncology today. I for one, appreciate that perspective. But I think when you look at the larger landscape of laboratory testing LDTs plays such a pivotal role across every specialty. Oh, it does.

Speaker 23

02:20:57

And I know I'm over time, but thank you all for being here. And Antibiotic resistance is a huge issue. And that's something that we need to look at. Thank you, sir. And I yield back.

Speaker 10

02:21:06

Gentlelady yields back. I now recognize Mr. GATT from Colorado for five minutes.

Speaker 24

02:21:12

Thank you so much, Mr. Chairman, and thanks for your partnership and all these years and working on the valid act. I'm here bat and clean up. So I'll do I'll do my best. Ms. Ms. Harshbarger, asked about some of your members, Dr. Carter, who who don't really like the valid act. But I would wager to say they liked the valid act a lot better than the proposed FDA rule. Would that be correct?

Speaker 7

02:21:40

I cannot read their minds. However, I believe you're right. I believe what we're dealing with what we're looking at today, I think many people would look back into the past and say the valid Act would have certainly been much more workable than what we're facing today. Thank

Speaker 24

02:21:55

you. Now. Also, Dr. Carter, you work in an academic setting. Is that right? Yes, ma'am. Now, do you think the valid act or something similar to the valid Act would bring your lab to a grinding halt? Yes or no and work with? I'm sorry? Would you bring your lab to a grinding halt the valid act? No, ma'am, I don't Q. Now, I want to I want to talk for a minute about the valid act, because because it's it's not a one size fits all system. It's a fit for purpose risk based system to oversee lab diagnostics, including LDTs. And, and so it focuses on the high risk tests, which is what we really need to do. So Dr. Allen, I want to ask you, very briefly, in your view, what constitutes a high risk task? And what are the consequences to pay patients have a high risk test if it does not return an accurate result?

Speaker 8

02:22:54

I think those high risk tests include things that are directly utilized in order to inform a treatment decision that that that that result is the definitive factor. And because of that the potential harm that could come with an erroneous test lends to its rest risk level and as you say, requires proper oversights. So

Speaker 24

02:23:16

some people have said there's really no evidence of inaccurate test results. And so therefore, we don't need to regulate these LDTs. Is it Do you know, have examples of how there have been problems with in some of these hybrid situations?

Speaker 8

02:23:33

Yeah. Well, thank you for that question. I think, you know, what we have seen from our own work is that there is variability between different tests, including those that would fall into the high risk categories, because they are diagnostic directly informing the utilization of a drug. One of the challenges of pinpointing whether there is harm that has come from those tests is the lack of oversight that is currently there. The tests that go through FDA, hopefully those challenges of underperformance are mitigated in advance and they never make it to the market. That may not be the same with LD T's. And I don't say that because LD T's are inherently banned. There is just not the same level of oversight before they get used.

Speaker 24

02:24:12

Right. So we just don't know. Correct. Now. I want to ask you, Dr. Carter, can you describe instances where pre market review might be appropriate?

Speaker 7

02:24:25

Yes, thanks for that question. So we believe that there are very high risk test that would benefit from pre market approval and premarket review by the FDA. We, however, believe that the numbers of those very high risk tests are small, and that the valid Act, as you well know, introduces, you know, several mitigating measures that might down risk some of those tests because of the use of well established laboratory methodologies, the ability to do proficiency testing that literature that supports the validity of of let's say the variant that that otherwise high risk task would introduce.

Speaker 24

02:25:09

Is there currently any premarket review federally for LDTs?

Unknown Speaker

02:25:15

There is no, thanks. Now,

Speaker 24

02:25:18

I haven't frankly heard anybody say they support using medical device regulations for LDTs. Today, and and so I'd like to know from I think, Miss Van Meter, is medical device regulation appropriate for in vitro diagnostics in general? Could we improve on it? And is a comprehensive system needed?

Speaker 5

02:25:44

Thank you for the question. I really think that's the heart of the matter here. Yeah. I think that the medical device authorities are wholly inappropriate for diagnostics, and certainly for laboratory developed test services. I think the valid act that you have authored with Mr. Wu Shan is precisely the right type of legislative effort that we create diagnostics specific framework that suits the characteristics of diagnostics, understands the roles of clinical laboratory. So there was really a tremendous opportunity here, not to go with a unilateral approach and superimpose medical device authorities. It's not the right direction for patients and for innovation, but instead to look at a comprehensive approach through legislation that's diagnostics specific, and I commend you for that. Thank you.

Speaker 24

02:26:27

I just have one more question, Mr. Chairman, if I can, and that is to humans, Mr. Rossi, does clear ensure clinical value validation.

Speaker 6

02:26:38

There is no premarket review by a CLIA inspector for clinical or analytical validity. Thank

Speaker 24

02:26:45

you, Mr. Chairman. I'm sure we'll have many more questions. And we'll submit them to the panel. But I just want to thank all of you, in particular, my constituent for coming today to testify. Appreciate it. I yield back

Speaker 10

02:26:57

Gentlelady yields. I'm gonna take a short period of personal privilege as being in the Chair and thank Congresswoman to get for working closely with me for many years on trying to address the issues that I think have been well outlined today in this hearing. now recognize Mr. Crenshaw for five minutes.

Speaker 25

02:27:17

Thank you, Mr. Chair, thank you for holding this hearing on an important subject that could impact our economy to the tune of billions of dollars. And I just want to start as every policymaker should with trying to identify the problem, before we take a hammer to a regulatory regime and to our industries. What problem are we trying to solve? So I hear conflicting testimony on that? So maybe we'll start with you, Dr. Alan, what is the problem? We're trying to solve our Do we just we really have these laboratory testing facilities just just running amok hurting patients constantly to so it's so bad that we have to do we have to make such a drastic change? I

Speaker 8

02:28:02

hope we're not in that scenario. I don't think running amok would be the proper characterization of that. But definitive fact is, in most instances, we don't know. So the number one issue that I think we're trying to solve is awareness. The number two issue that we're trying to solve is the ability to act if a problem is identified. Is there an expert entity that has reviewed those challenges and helped mitigate them and fix them? And number three, I think is trying to avoid errors before they happen. Yeah.

Speaker 25

02:28:36

I agree with that. But I didn't hear a glaring problem in any of that, you know, I think there's room for scalpel approach to some of these, Dr. Eisen, or you've had a somewhat different opinion on this, can you? I

Speaker 9

02:28:48

do, indeed, have a different opinion on this. And I will cite for you this paper from Jama oncology, which showed that LDTs and FDA approved assays had equivalent performance for tests that dictate cancer therapy for melanoma, colorectal cancer and lung cancer, I think we have vastly lost sight of the fact that the magnitude of the problem is a very narrow, constrained concern. And, frankly, as somebody who focuses on biology, I can say that when I see that there are areas that laboratories struggle to find the same answer, it's because we are not yet fully studied up. We don't understand the biology of what's happening. It's not because the test is wrong. It's because of the biology is so complex. We haven't gotten there yet. I think there is ample data from decades of proficiency testing data provided by my colleague was organization at CAAP that demonstrates that laboratories perform at an exceptionally high level. This idea that there is no post market review, I think does not account for the fact that there is proficiency testing and laboratory ins are encouraged. credibly committed to monitoring their assays longitudinally, yeah. And

Speaker 25

02:30:04

look, but not having dealt with this problem in depth before like some of my colleagues have. And walking into this, it does not appear to me that there is a major problem that requires a very extreme solution. And if there was a major problem that should be the loop deliberated by a body like this one, where we do hearings, and we have debates, and then it has to go through the Senate, God knows what happens in the Senate, and then actually signed into law by the President, we have a process for this, we, when we make national law, we have a we have a very arduous process to do so because it affects so many people. And that's a good thing. What is not a good thing is when unaccountable bureaucrats just decide things and try to do it through regulation. This is happening way too often. And in this case, the FDA now believes that lab developed tests should just go under the same pathway as medical devices. Why? I'm not sure what the explanation is for that. But it's obviously overreach, and overreach with pretty severe consequences. Those consequences have been laid out by our by our witnesses, multiple times. I think it's, I think it's worth noting just some of them. The FDA shows that they'd have to approve between 40,160 1000 diagnostic tests currently on the market, between nearly 4015 1000 new lab diagnostic tests per year. That's That's an enormous increase. And just having, you know, personal experience watching, watching pretty simple medical devices tried to go through that pathway and it taking years because they don't even have the right personnel and the right expertise to even assess those medical devices. I can't imagine how they're going to assess complex lab tests, which involve, I mean, a number of people a number of processes, a number of different chemical reactions. I mean, I can't imagine how they're going to do it. So I can't imagine how this stuff is going to actually get get approved. And then we're left with nothing, we're left with no tests. I mean, we can question the validity of a test. But we can be sure that if you have no test, you're not going to get any result. Good or bad. And that's a real problem. And we have to be careful about that. Just just as, as, as legislators as regulators, we can't have safety at any cost. We have to have, we have to understand that there are trade offs in these things. It's worth mentioning the third party review program, because that's part of the FTAs. claim is that, you know, they're going to they're going to ease the burden of this excessive amount of new applications through the third party review program. But but that only reviews 3000 applications or submissions a year. So just do the math. It's just it's just never going to work. With Rothstein. Given the current program, is it realistic for FDA to estimate that at least, that I really go over that font? Geez, I was really on a

Unknown Speaker

02:33:25

roll. And as time has expired, I yield back. All right, Mr. Griffith, five minutes.

Speaker 26

02:33:32

Thank you very much. I apologize to the witnesses and to the other members of the committee that I've been upstairs chairing an oversight and investigation subcommittee hearing, so I was not able to be with you all. I will probably try to go back and watch some of the testimony at a later time. Miss Van Meter. To your knowledge, will any allergy testing be hindered by the proposed FDA diagnostic lab ruined? Let me explain. Previously, some of my allergist, I'm a patient have indicated that the FDA has said that, Oh, they've got to have a big lab in order to work on their serums that they do for shots for allergies, which 10s of 1000s if not millions of Americans take on a regular basis without any problems. So do you see any problems with where we're going here? No,

Speaker 5

02:34:21

thank you for the question. I can't unfortunately speak specifically to allergy assays. But I can say as a general matter, I'm very concerned about the broad availability of all tests that Americans rely on today if the rule moves forward. And

Speaker 26

02:34:37

that would be my concern, too. I agree that I didn't see anything that said anything about allergies, but when I look at the big picture, it looks like to me that could be either next or considered a subgroup of what's going on anyway. All right Karcher, the current Center for Tobacco Products within the FDA got all kinds of issues. Do you think I think that if we go forward with what they've recommended for the FDA to regulate labs, is that going to keep them from being able to get to other work, like working on some of these tobacco product issues that they haven't been able to get to? Is it going to keep them from getting their work done?

Speaker 7

02:35:18

Thanks for the question. I certainly cannot comment about the FTAs ability to deal with tobacco products. We do know, however, if the rule goes forward, as written, it will, for sure inhibit laboratories. And we've all heard today how it would overwhelm parts of the FDA.

Speaker 26

02:35:36

It's going to overwhelm the FDA. So it's going to affect all aspects and and in oversight, we've had real concerns about how many inspectors they have, not only in foreign lands, but even in the United States getting to facilities that make our medicines or our baby formula. And so I'm not sure we want to add extra things to their list. Would you agree with that?

Unknown Speaker

02:36:00

I would agree with that statement.

Speaker 26

02:36:01

And with that said, Mr. Chairman, I will yield any time that you might wish to year.

Speaker 10

02:36:05

Thank you for yielding. I just have a follow up question I was someone asked question about Anna my antimicrobial resistant efforts, which is a long standing issue we've been trying to address and Mr. Rothstein under that, under that, how do you how would you see a framework like valid handle new anti microbial resistance tests that might come available?

Speaker 6

02:36:30

Thank you for the question. And this is a topic that's actually very well suited for the technology certification program contemplated and valid right now anti microbial testing, which is so important for our nation, but for patients and for ensuring that we have antibiotics available. For the long term requires for each test of whether it's a bacteria or a fungus, each of those tests has to go through FDA one at a time. Under the technology certification program in valid a manufacturer or a laboratory could develop a platform in which FDA looks at once, and then any subsequent bacteria, fungus or other type of micro organism that needs to be detected, could go through that platform without going to FDA as long as the parameters are met within the agreement between FDA and the industry. And it would make the process for antimicrobial resistance products to come to market in an extremely efficient mechanism matter. Thank

Unknown Speaker

02:37:31

you for the answer. And I'll yield back Mr. Griffith.

Speaker 26

02:37:33

And I would just say thank you, Mr. Chairman. I'm sorry, I missed that discussion. I understand Miss Hershberger broke that up. And I'm a big, big fan of phage therapy. But so I'm sorry, I missed that part of the discussion. We'll have to go back and and watch that. And I yield my time back. gentleman

Speaker 10

02:37:46

yields back. recognize Dr. Miller Meeks five minutes.

Speaker 27

02:37:51

Thank you, Mr. Chairman, and I thank the witnesses for testifying. Before the subcommittee today, I was in another hearing in Cannon, so I apologize for not being here for all of your testimony and all of the questions. Dr. Eisner, your testimony describes ways in which you and your patients rely on the results of customized lab developed tests LDTs? How would the impacts of the proposed rule be experienced across different areas of medicine, such as for oncology versus more generalized health practices?

Speaker 9

02:38:22

Thank you very much for the question. I think this is a very rubber hits road question. And I think, again, I will point to this Jama oncology paper from 2018. And I think one of the critical things to recognize from this paper is that even among labs that used FDA approved test kits, a substantial fraction of them modified them. And that is the reality of medical practice is that the constraints that come with an FDA approved test are not necessarily seen in day to day practice, you some you sometimes have to color outside the lines to be able to get the test for your patient. And the ability to color outside the lines, I think will be completely hampered.

Speaker 27

02:39:06

Given the increasing reliance and clinical practice on sophisticated instrumentation, such as AI or software used in conjunction with genetic testing, how does your lab establish safeguards?

Speaker 9

02:39:18

I think that's an excellent question. I am personally able to avoid that at the moment as we do not use AI and most of my colleagues that I have pulled on this also do not use AI at their academic medical centers. I do think one of the big concerns is that to be able to be able to focus on those concerns about security, about patient privacy concerns, we need resources. And if we are devoting all of our resources to an FDA review process, there will be nothing left to focus on the other important issues.

Speaker 27

02:39:49

Thank you, Dr. Allen, you and your organization have been engaged on the LD T issue for years. Do you feel there are differences between the standard of validation for test kits and laboratory developed tests that warrant tailored regulatory approaches.

Speaker 8

02:40:07

Yes, I do think there are differences in the in the current requirements that are required for lab develop tests versus in vitro diagnostic kits. And hopefully, that's something that we can resolve through these discussions today. I think we need to focus more on the results that the tests are providing, as opposed to the place that they're, that they're being developed by.

Speaker 27

02:40:31

And some stakeholders have observed that the technology certification provision in the valid act is particularly well suited to regulate AI and software products. Do you agree?

Speaker 8

02:40:43

Yes, I think it is one component of that. I think there are a lot of complexities. And I know this committee has done a lot of work around the role of AI in healthcare. But I do think it's also well suited for things that we've been involved in around looking at how different tests compare to one another. This is particularly true for complex diagnostic tests currently, because there are so many different alterations that are incorporated into those measures, to try and understand how each of those different measures contribute to the end result is important for consistency and testing. I think we'll see the same thing for AI based testing as well.

Speaker 27

02:41:16

Thank you. And hopefully this will be a very short answer question. If this particular rule was in place during COVID, we already saw the challenges with the CDC and the FDA, getting testing approved even though the University of Washington had a task. So would this have created more difficulty in getting testing out to the public in a rapid manner if this rule was in place? Any of you?

Speaker 6

02:41:44

Thank you for the question. I don't believe so. Because tests during that are put out into the market during public health emergencies currently are required to obtain any UI. And this rule does not address that issue. So

Speaker 27

02:41:57

you don't think that they would utilize the current rule that they would transfer it I'm always concerned about government overreach. We follow we continue to face a pernicious opioid substance use disorder crisis in this country beyond opioids, new deadly synthetics are constantly changing, and must be tracked so that doctors and other caregivers can best understand how to care for those struggling with substance use disorders. And even as a state senator and Director of Public Health, we had to deal with this issue in Iowa. Miss Van Meter, can you talk about the role that LDTs serve in testing for such substances? And how shifting to the medical device authorities would impact patient access?

Speaker 5

02:42:34

Yes, thank you for the question. Laboratory developed test services are absolutely essential and central to toxicology testing, to ensuring that public health understands what new substances are in communities that patients can be cared for who are going through substance use disorder treatment.

Unknown Speaker

02:42:52

Thank you much, very much. And I yield back Gentlelady

Speaker 10

02:42:55

yields back, recognized, recognized Miss Mr. Over Nulty from California five minutes.

Speaker 28

02:43:01

Thank you, Mr. Chairman. This Van Meter, I'd like to start with a question for you. I really enjoyed reading the ACA LA's response to the FDA proposed rule. And in particular, you had a section in that response in which you highlighted your belief that the FDA is methodology for evaluating laboratory developed tests was deeply flawed. Can you give us a couple of examples of cases in the FDA? The FDA is rulemaking that where you think the data was cherry picked?

Speaker 5

02:43:34

Thank you for the question. Yes. So the FDA offers a de minimis number of examples of LDTs it suggests are problematic. We have enormous respect for the FDA and worked hand in glove with the agency, not only through COVID and Mbox. But certainly in discussions on the valid act. And we want to continue to do that. But we're very concerned about the prejudicial language that the agency uses to describe laboratory developed test services, and the handful of examples of problematic LDTs that it offers. Frankly, most of those are not based in scientific literature. In fact, some are taken from media reports. So I worry very much about that. Within its analysis, it relies on a single flawed since debunked academic article to suggest that there is a significant proportion of problematic LDTs. So again, I would offer simply, there is a dearth of evidence to suggest there's a systemic problem.

Speaker 28

02:44:30

And did the FDA respond to your comments?

Unknown Speaker

02:44:35

Not at this point.

Speaker 28

02:44:38

Dr. Allen, I enjoyed your testimony, I thought you did a great job of highlighting the two ideas that we're talking about that are in fundamental tension. The one is that as you say, we need the FDA to ensure the accuracy and the efficacy of these tests. And we have an obligation to our constituents to make sure that we're enforcing them under these rules for their safety, but as other people have testified, we're also very concerned that increased FDA involvement in LDTs is going to lead to much longer times to market, higher costs, and less affordability and less availability of the tests. So, you know, these are the two ideas that are in tension here. I'm wondering if agencies like organizations like yours could provide a solution to this, because what has happened in other sectors of the consumer space is that organizations step in and provide analysis of efficacy and an accuracy. And people patients and their physicians can use that as a guidepost in deciding which LDTs to order. And then as that will lead to market competition. And as Mr. Rothstein testified, competition between different LDTs to make sure that there are so policing going on to make sure that they're providing accuracy and a good value for the patient dollar. So do you think that that's a viable solution?

Speaker 8

02:46:05

I hope that it's part of the solution. I don't think that in itself, it will be sufficient. But I do think that there are opportunities here and I recognize that there is certainly the presence of competition in the market for these types of tests. But in order to achieve the goals that I think most of us have had outlined today, there also needs to be collaboration. And, you know, some of the issues that have been raised around rare testing, in the concerns around that I do think there has to be a new approach where we're perhaps different laboratories can do things like leverage common samples in order to make sure that the appropriate validity testing is able to move forward. So it has to it has to come with a mix. And I fully appreciate the concerns that that additional regulation could come with burdens, and we don't want to see that result in a hindrance to access. But, you know, my my colleagues here that are working at extremely high performing expert laboratories, I think many of their tests probably can achieve the validation standards that are that may be requested of them. So I think that as we move forward, you know, and I thank the doctor Bishan and Mr. gap for their work, you know, that a flexible approach that the valid acts will enable all of these different approaches to be part of the mix.

Speaker 28

02:47:23

Well, thank you. I appreciate your perspective. And thanks to all our witnesses, I found it a fascinating hearing. I yield back.

Speaker 10

02:47:28

gentleman yields back that can. That concludes member questioning. I'd like to thank all the witnesses for their time. First of all, I know it's a big time commitment. And for their testimony and the answers to the questions proposed by members. I ask unanimous consent to insert into the record the documents included on the staff hearing documents list. Without objection, that will be the order. I remind members that they have 10 business days to submit questions for the record, and I asked the witnesses to respond to the questions promptly. Members should submit their questions by the close of business April 4 2024. Without objection, the subcommittee is now adjourned.

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