Laboratory Developed Tests (LDTs)

Laboratory Developed Tests (LDTs) / en Sat, 26 Apr 2025 01:22:28 -0500 Tue, 01 Apr 25 15:51:17 -0500 Court strikes down FDA rule on regulating lab-developed tests /news/headline/2025-04-01-court-strikes-down-fda-rule-regulating-lab-developed-tests The U.S. District Court for the Eastern District of Texas March 31 <a href="https://www.amp.org/AMP/assets/File/advocacy/FDA%20Final%20Rule/LDT%20FINAL%20JUDGMENT%20033125.pdf?pass=18" target="_blank">ruled</a> that the Food and Drug Administration does not have the authority to regulate laboratory-developed tests.The FDA <a href="/news/headline/2024-04-29-fda-issues-final-rule-applying-medical-device-rules-laboratory-developed-tests" target="_blank">last April</a>&nbsp;issued a final rule that would have phased out its general enforcement discretion approach for most lab-developed tests over four years. The phase-out deadlines set in the final rule are no longer in effect.The AHA previously expressed concerns about the proposed rule and <a href="/lettercomment/2023-12-01-aha-letter-fda-laboratory-developed-tests-ldts-proposed-rule" target="_blank">urged</a>&nbsp;the FDA not to apply the rule to hospital and health system lab-developed tests.“This ruling ensures that hospital-based labs are able to continue to develop innovative and high-quality tests that provide physicians with important clinical information to help diagnose and treat patients,” said Jason Kleinman, AHA director of federal relations. “The LDT final rule would have stifled medical innovation and dramatically increased regulatory burden and costs for both hospitals and the federal government.” Tue, 01 Apr 2025 15:51:17 -0500 Laboratory Developed Tests (LDTs) Early Disease Detection: 3 Tech Trends to Watch /aha-center-health-innovation-market-scan/2025-02-11-early-disease-detection-3-tech-trends-watch <div class="container"><div class="row"><div class="col-md-8"><img src="/sites/default/files/inline-images/Early-Disease-Detection-3-Tech-Trends-to-Watch.png" data-entity-uuid="bec1f837-1fe4-4d47-a813-bd1185da4364" data-entity-type="file" alt="Early Disease Detection: 3 Tech Trends to Watch. A transparent head with a brain showing electric activity; a scan of an eye; a view inside a pair of kidneys." width="100%" height="100%">Using artificial intelligence (AI) to aid in disease detection has been going on for some time now. However, recent investment trends in AI startups indicate these applications may soon be deployed earlier in clinical workflows.One trend CB Insights analysts are watching is how AI is helping patients engage with health systems before the diagnostic process begins and to flag diseases earlier. The consultancy, which uses data, machine learning and algorithms to track startups, private companies and investment trends, highlights this and a couple other important AI developments to watch in its report <a href="https://www.cbinsights.com/research/briefing/webinar-tech-trends-2025/" target="_blank" title="CB Insights: Tech Trends to Watch in 2025">Tech Trends to Watch in 2025</a>.<h2>1 | Keep an Eye on Symptom Trackers</h2>Devices like <a href="https://ubiehealth.com/" target="_blank" title="ubiehealth.com homepage">Ubie</a>, a free AI-enabled symptom tracker app, are gaining traction, notes Ellen Knapp, CB Insights senior intelligence analyst, in a <a href="https://www.cbinsights.com/research/briefing/webinar-tech-trends-2025/recording/" target="_blank" title="CE Insights: Tech Trends to Watch in 2025 webinar recording">webinar</a> about the tech trends findings. The app, developed in Japan, allows consumers to ask questions on their smartphones about symptoms they are experiencing and to indicate the location of symptoms on an anatomical diagram.The program is trained on medical data and uses conversational AI to respond to patients’ questions and input. The app is targeted toward the large number of people who otherwise might ignore symptoms that can lead to worse outcomes or become more serious without medical intervention, creating greater strain on the health care system, Knapp says.Symptom tracker software usually is connected to infrastructure that can link patients to a local doctor or care center. Investors are paying more attention to this sector, Knapp explains, noting that there was a flurry of equity investment rounds in 2024, including an investment by Google Ventures in Ubie.<h2>2 | Early Disease Detection Becomes More Affordable and Scalable</h2>AI also is enabling earlier disease detection — sometimes before symptoms appear, Knapp says. AI-enabled testing/screening device solutions are helping disease management become more proactive across specialties to detect Alzheimer’s disease, heart disease, depression, cancer, liver disease and more.“One trend we’ve got our eye on is retinal scanning. Companies like <a href="https://www.retispec.com/" target="_blank" title="RetiSpec homepage">RetiSpec</a> and <a href="https://mediwhale.com/" target="_blank" title="Mediwhale homepage">Mediwhale</a> are using quick standard eye scans to detect cardiovascular, kidney and eye diseases as well as signs of neurodegeneration,” Knapp says in the webinar.In the case of neurodegenerative diseases like Alzheimer’s, early detection is critical because now there are more therapeutics that can slow disease progression, even though there are none yet that can reverse loss of brain function. Early detection will become increasingly important as the nation’s 65-and-older population increases.<h2>3 | Identifying At-risk Individuals</h2>AI algorithms also are being used to analyze health data and identify high-risk patients proactively without direct testing. This has led to a number of startups focusing on identifying at-risk patients before symptoms appear and patients at higher risk of serious diseases – before those diseases become life-threatening.Organizations like Mayo Clinic, Amazon Web Services (AWS) and Bayer have invested in some of these companies. Mayo Clinic and Commure, a General Catalyst portfolio company, in 2021 led the Series A funding for <a href="https://lucemhealth.com/" target="_blank" title="Lucem Health homepage">Lucem Health</a>, which enables providers to mine health data sources to proactively identify high-risk patients without direct testing.AWS, meanwhile, selected <a href="https://www.closedloop.ai/" target="_blank" title="ClosedLoop homepage">ClosedLoop</a>, which created a data science platform to drive improved clinical performance, for its Healthcare Accelerator for Health Equity. And Bayer has formed a digital health partnership with <a href="https://www.carenostics.com/" target="_blank" title="CareNostics homepage">CareNostics</a>, which develops AI solutions targeted toward identifying earlier opportunities for clinical interventions with chronic disease patients.Although many of these startups are in their early stages, the problems they are trying to solve highlight the fact that AI excels in analyzing large datasets, making it well-suited toward identifying at-risk populations. And with some of the huge players in health care investing in this sector, the field bears watching, Knapp says.“The field is large, but it’s not going away,” she says.</div><div class="col-md-4"><a href="/center" title="Visit the AHA Center for Health Innovation landing page."><img src="/sites/default/files/inline-images/logo-aha-innovation-center-color-sm.jpg" data-entity-uuid="7ade6b12-de98-4d0b-965f-a7c99d9463c5" alt="AHA Center for Health Innovation logo" width="721" height="130" data-entity- type="file" class="align-center"></a><a href="/center/form/innovation-subscription"><img src="/sites/default/files/2019-04/Market_Scan_Call_Out_360x300.png" data-entity-uuid data-entity-type alt width="360" height="300"></a></div></div></div>.field_featured_image { position: absolute; overflow: hidden; clip: rect(0 0 0 0); height: 1px; width: 1px; margin: -1px; padding: 0; border: 0; } .featured-image{ position: absolute; overflow: hidden; clip: rect(0 0 0 0); height: 1px; width: 1px; margin: -1px; padding: 0; border: 0; } h2 { color: #9d2235; } Tue, 11 Feb 2025 06:51:50 -0600 Laboratory Developed Tests (LDTs) FDA Issues Final Rule to Regulate Laboratory Developed Tests as Medical Devices <div class="container"><div class="row"><div class="col-md-8">The Food and Drug Administration (FDA) on April 29 issued a&nbsp;<a href="https://public-inspection.federalregister.gov/2024-08935.pdf">final rule</a>&nbsp;that will phase out, over four years, its general enforcement discretion approach for in vitro diagnostic tests (IVDs), which include laboratory developed tests (LDTs). 1,2 In finalizing its policies, the agency cites concern that some of these tests may not provide accurate results or perform as well as FDA-approved IVDs. In comments to the proposed rule, the AHA had <a href="/lettercomment/2023-12-01-aha-letter-fda-laboratory-developed-tests-ldts-proposed-rule">urged</a> the FDA not to apply the medical device regulations to hospital and health system LDTs. Due to the AHA’s and other stakeholder comments, the FDA decided to exercise targeted enforcement discretion for certain categories of LDTs. The final rule will be published in the Federal Register May 6.&nbsp; &nbsp;<div class="panel module-typeC"><div class="panel-heading"><h2>KEY HIGHLIGHTS</h2>FDA, in the final rule:<ul><li>Amends FDA regulations to make explicit that IVDs, including LDTs, are devices under the Federal Food, Drug, and Cosmetic (FD&amp;C) Act.</li><li>Phases out, over four years, its general enforcement discretion approach for in vitro diagnostic tests (IVDs), which include LDTs.</li><li>Requires, after the four-year phase-out, all IVD makers to meet the same applicable device requirements, except where FDA has decided to apply targeted enforcement discretion.</li><li>Exercises targeted enforcement discretion for certain categories of LDTs. Among these are: (1) LDTs developed and performed by a laboratory integrated within a health care system to meet an unmet need of patients receiving care within the same health care system, (2) LDTs that were first marketed prior to April 29, the date of issuance of the final rule, and (3) LDTs approved by the New York State Department of Health’s (NYS) Clinical Laboratory Evaluation Program (CLEP).</li><li>Seeks comments on two draft guidance documents that describe its current thinking for use of the rule’s enforcement discretion policy during an infectious disease outbreak or public health emergency.</li></ul></div></div><h2>AHA TAKE</h2>We appreciate that the FDA has recognized the unique value and safety of laboratory tests developed by hospitals and health systems for direct use in patient care. The enforcement discretion provided in this final rule is of particular importance. We also welcome the agency’s acknowledgment of the gaps in FDA-authorized commercially available tests in meeting certain patient needs, such as for rare diseases or conditions. The FDA’s decision to apply limited enforcement discretion for currently marketed LDTs rightly recognizes that applying the full scope of its device regulations to these tests would likely prompt many hospital laboratories, particularly small ones, to stop offering safe and effective tests upon which patients and their communities rely.However, we remain concerned that many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork, especially as certain FDA device requirements are phased in over the next four years. As a result, this will cause a substantial reduction in patient access to innovative and targeted diagnostic tests. We will continue to evaluate the rule closely and work with the FDA.<h2>WHAT YOU CAN DO</h2><ul><li>Share this advisory with your senior management team, clinical leadership team and clinical laboratory leadership. Ask them to examine the impact of the final rule on your laboratory operations, particularly as it relates to any LDTs your hospital or health system has developed and uses in clinical care.</li><li>Consider providing comments by July 5 on the FDA’s <a href="https://www.fda.gov/news-events/press-announcements/fda-takes-action-aimed-helping-ensure-safety-and-effectiveness-laboratory-developed-tests" target="_blank" title="FDA's draft guidance">draft guidance</a>.</li></ul><h2>SUMMARY OF KEY HIGHLIGHTS</h2><h3>Background</h3>Many hospitals and health care systems develop and use LDTs, particularly larger hospitals and academic medical centers. They include everything from routine tests such as blood counts to more complex molecular and genetic tests related to cancer, heart disease, and rare and infectious diseases. LDTs provide timely patient access to accurate and high-quality testing for many conditions for which no commercial test exists or where an existing FDA-approved IVD does not meet current clinical needs. They also provide physicians with important clinical information to diagnose and treat patients and are critical in the practice of all areas of medicine. These tests are developed at the request of, and in close collaboration with, clinical caregivers and are typically only used in the context of patient care within the hospital or the health system.To date, the FDA has generally exercised its enforcement discretion and has not enforced applicable device regulations with respect to LDTs. However, due to changes in the complexity and use of LDTs over time and the associated increased risks to patients, the agency stated that it no longer believes broad enforcement discretion is appropriate.&nbsp;View the detailed advisory below.&nbsp; __________1 IVDs are diagnostic test systems that are performed on samples taken from the human body for the purpose of detecting diseases or other conditions, monitoring a person’s overall health, identifying patients who are likely to benefit from specific therapies, or otherwise helping to diagnose, cure, mitigate, treat or prevent disease. Some IVDs are manufactured by conventional manufacturers for used by other entities such as laboratories or health care providers. Other IVDs are manufactured by laboratories for use by the same or other laboratories.&nbsp; 2 FDA defines an LDT as an IVD that is intended for clinical use and that is designed, manufactured, and used within a single laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and meets the regulatory requirements under CLIA to perform high complexity testing.</div><div class="col-md-4"><a href="/system/files/media/file/2024/05/fda-issues-final-rule-to-regulate-laboratory-developed-tests-as-medical-devices-advisory-2-3-24_0.pdf" target="_blank"><img src="/sites/default/files/2024-05/cover-fda-issues-final-rule-to-regulate-laboratory-developed-tests-as-medical-devices-advisory-2-3-2.png" data-entity-uuid data-entity-type="file" alt=" Cover Regulatory Advisory: FDA Issues Final Rule to Regulate Laboratory Developed Tests as Medical Devices" width="NaN" height="NaN">&nbsp;</a></div></div></div> Fri, 03 May 2024 11:21:37 -0500 Laboratory Developed Tests (LDTs) FDA issues final rule applying medical device rules to laboratory developed tests /news/headline/2024-04-29-fda-issues-final-rule-applying-medical-device-rules-laboratory-developed-tests The Food and Drug Administration April 29 issued a <a href="https://public-inspection.federalregister.gov/2024-08935.pdf">final rule</a> that would phase out its general enforcement discretion approach for most laboratory developed tests over four years, citing concern that some of the tests may not provide accurate results or perform as well as FDA-approved in vitro diagnostic products. The final rule amends FDA regulations to make explicit that IVD products, which include laboratory developed tests, are devices under the Federal Food, Drug, and Cosmetic Act. After the four years, the agency would require all IVD makers to meet the same applicable device requirements, except where FDA has decided to apply enforcement discretion for certain device rules, such as those for premarket requirements and quality systems. The rule takes effect 60 days after publication in the May 6 Federal Register.&nbsp; AHA had <a href="/2024-04-01-aha-responds-fdas-proposed-regulation-diagnostic-tests">urged</a> the FDA not to apply the proposed rule to hospital and health system laboratory developed tests. In the final rule, FDA said it intends to exercise limited enforcement discretion for certain categories of IVDs, including LDTs developed and performed by a laboratory integrated within a health care system to meet an unmet need of patients receiving care within the same health care system, currently marketed LDTs that were first marketed prior to the date of issuance of the final rule, and LDTs approved by the New York State’s Clinical Laboratory Evaluation Program. In addition, the agency released <a href="https://www.fda.gov/news-events/press-announcements/fda-takes-action-aimed-helping-ensure-safety-and-effectiveness-laboratory-developed-tests">draft guidance</a> on the rule’s enforcement discretion policy during an infectious disease outbreak or public health emergency.&nbsp; "We appreciate that the FDA has recognized the unique value and safety of laboratory tests developed by hospitals and health systems for direct use in patient care," said Stacey Hughes, AHA executive vice president. "The enforcement discretion in this final rule is of particular importance. We also welcome the agency’s attention to the gaps in FDA-authorized commercially available tests in meeting certain patient needs, such as for rare diseases or conditions. The FDA’s decision to apply limited enforcement discretion for currently marketed laboratory-developed tests rightly recognized that applying the full scope of its device regulations to these tests would likely prompt many hospital laboratories, particularly small ones, to stop offering safe and effective tests upon which patients and their communities rely."However, we remain concerned that many vital tests developed in hospitals and health systems may be subjected to unnecessary and costly paperwork, especially as certain FDA device requirements are phased in over the next four years. As a result, this will cause a substantial reduction in patient access to innovative and targeted diagnostic tests. We will continue to evaluate the rule closely and work with the FDA."AHA members will receive a Special Bulletin with additional information about the final rule.&nbsp; Mon, 29 Apr 2024 15:58:02 -0500 Laboratory Developed Tests (LDTs) AHA to Congress: FDA proposed rule for laboratory developed tests overreaches /news/headline/2024-04-01-aha-congress-fda-proposed-rule-laboratory-developed-tests-overreaches The Food and Drug Administration’s proposal to regulate laboratory developed tests would undermine innovation and reduce access to effective and appropriate care for patients, AHA April 1 told the Senate Health, Education, Labor &amp; Pensions Committee Ranking Member.“While we support the need for additional oversight of the development and use of some LDTs and in-vitro diagnostics (IVDs) offered as LDTs, the FDA’s proposal to apply its device regulations to hospital and health system LDTs is misguided,” AHA said in a <a href="/2024-04-01-aha-responds-fdas-proposed-regulation-diagnostic-tests">letter</a> to Ranking Member Bill Cassidy, M.D., responding to his request for information on the proposed rule. “These tests are not devices — they are diagnostic tools developed and used for essential patient care. Regulating LDTs under the FDA’s device regulatory framework could cause patients to lose access to many critical tests and stifle innovative advances in hospital and health system laboratory medicine.” Mon, 01 Apr 2024 15:01:00 -0500 Laboratory Developed Tests (LDTs) AHA to Congress: FDA proposal to regulate laboratory developed tests overreaches /news/headline/2024-03-21-aha-congress-fda-proposal-regulate-laboratory-developed-tests-overreaches The Food and Drug Administration’s proposal to regulate laboratory developed tests would undermine innovation and reduce access to effective and appropriate care for patients, AHA March 21 told the House Energy and Commerce Subcommittee on Health.“While we support the need for additional oversight of the development and use of some LDTs and in-vitro diagnostics offered as LDTs, the FDA’s proposal to apply its device regulations to hospital and health system LDTs is misguided,” AHA said in a <a href="/testimony/2024-03-21-aha-house-statement-evaluating-approaches-diagnostic-test-regulation-and-impact-fdas-proposed-rule">statement</a> submitted for a hearing on the proposed rule. “These tests are not devices — they are diagnostic tools developed and used for essential patient care. Regulating LDTs under the FDA’s device regulatory framework could cause patients to lose access to many critical tests and stifle innovative advances in hospital and health system laboratory medicine.” &nbsp; Thu, 21 Mar 2024 16:03:00 -0500 Laboratory Developed Tests (LDTs) AHA Statement on "Evaluating Approaches to Diagnostic Test Regulation and the Impact of FDA’s Proposed Rule." /testimony/2024-03-21-aha-house-statement-evaluating-approaches-diagnostic-test-regulation-and-impact-fdas-proposed-rule Statementof the�� Associationfor theCommittee on Energy and CommerceSubcommittee on Healthof theU.S. House of Representatives"Evaluating Approaches to Diagnostic Test Regulation andthe Impact of FDA’s Proposed Rule."March 21, 2024On behalf of our nearly 5,000 member hospitals, health systems and other health care organizations, our clinician partners — including more than 270,000 affiliated physicians, 2 million nurses and other caregivers — and the 43,000 health care leaders who belong to our professional membership groups, the �� Association (AHA) appreciates the opportunity to comment on the impact of the Food and Drug Administration’s (FDA) proposed regulation of diagnostic tests.Many hospitals and health care systems develop and use laboratory developed tests (LDTs), particularly larger hospitals and academic medical centers. These tests are developed, validated and performed in-house by individual laboratories — they are not commercially distributed. They range from routine tests like blood counts to more complex molecular and genetic tests for cancer, heart disease, and rare and infectious diseases. LDTs provide timely patient access to accurate and high-quality testing for many conditions where a commercial test does not exist or does not meet current clinical needs. They provide physicians with important clinical information to diagnose and treat patients and are essential to the practice of medicine.The AHA is concerned that the FDA has overreached in its proposal to regulate LDTs as medical devices. We urge Congress to exempt hospitals and health systems from being included in this FDA device framework or help ensure that regulatory oversight of LDTs is modernized in a manner that both supports medical innovation and ensures that these clinical laboratory tests remain accessible, safe and effective.While we support the need for additional oversight of the development and use of some LDTs and in-vitro diagnostics (IVDs) offered as LDTs, the FDA’s proposal to apply its device regulations to hospital and health system LDTs is misguided. These tests are not devices — they are diagnostic tools developed and used for essential patient care. Regulating LDTs under the FDA’s device regulatory framework could cause patients to lose access to many critical tests and stifle innovative advances in hospital and health system laboratory medicine.Hospital and health system LDTs benefit from the many factors that distinguish them from companies that distribute commercially marketed IVDs. These include the integration of laboratory test development and use into the continuum of patient care, the many patient safeguards that laboratories are already subject to, and the FDA’s existing ability to investigate and remove any LDT or IVD from the market regardless of the entity that develops it. The AHA has urged the FDA to continue to apply its enforcement discretion to hospital and health system LDTs and defer regulation of these tests mainly to the Centers for Medicare &amp; Medicaid Services’ strict Clinical Laboratory Improvement Amendments (CLIA) oversight, the College of American Pathologists accreditation and state law.Enforcement discretion is particularly important for low- and moderate-risk LDTs, including modifications to FDA-approved IVDs. Modifications improve the performance of approved diagnostic tests on certain patient populations, address problems or issues with FDA-approved devices, and allow the latest research and clinical knowledge to be rapidly incorporated. They are intended to improve testing accuracy and safety. If the laboratory is following the CLIA regulations and is subject to the factors described above, low- and moderate-risk tests, including modifications to commercially marketed IVDs, should be exempt from FDA regulatory oversight.The AHA also supports continued FDA enforcement discretion for LDTs that are subject to established laboratory evaluation programs, such as that developed by New York State. Many hospital and health system laboratories participate in these evaluation programs for their rigorous validity and quality reviews and even the FDA has accredited the New York State program as a third-party reviewer on behalf of the agency for the premarket clearance process.As highlighted in greater detail in our <a href="/lettercomment/2023-12-01-aha-letter-fda-laboratory-developed-tests-ldts-proposed-rule" target="_blank" title="AHA comment letter to FDA.">comment letter</a> to the FDA, we are concerned that this rule — if finalized as proposed — could significantly increase hospital burden and costs and decrease the ability to provide the most effective and appropriate care to patients.<h2>CONCLUSION</h2>Thank you for the opportunity to provide feedback on the FDA’s proposed regulation of diagnostic tests. We look forward to working with Congress on this important issue. Thu, 21 Mar 2024 08:35:40 -0500 Laboratory Developed Tests (LDTs) AHA comments on FDA proposed rule for laboratory developed tests /news/headline/2023-12-01-aha-comments-fda-proposed-rule-laboratory-developed-tests AHA Dec. 1&nbsp;<a href="/lettercomment/2023-12-01-aha-letter-fda-laboratory-developed-tests-ldts-proposed-rule" target="_blank">urged</a> the Food and Drug Administration not to apply its device regulations to hospital and health system laboratory developed tests. Commenting on a proposed rule that would phase out FDA’s general enforcement discretion approach for most laboratory developed tests, the association said the proposed rule is too broad, does not contain sufficient detail, can potentially increase hospital burden and costs significantly, stifle innovation and decrease hospitals’ ability to provide effective and appropriate care to patients. AHA urged the agency to continue to apply its enforcement discretion to hospital and health system LDTs and defer regulation of the tests mainly to the Centers for Medicare &amp; Medicaid Services' Clinical Laboratory Improvement Amendments program, the College of American Pathologists accreditation and state law, as it currently does. "These tests are not devices; rather, they are diagnostic tools developed and used in the context of patient care," AHA wrote. "As such, regulating them using the device regulatory framework would have an unquestionably negative impact on patients’ access to essential testing. It would also disrupt medical innovation in a field demonstrating tremendous benefits to patients and providers." Fri, 01 Dec 2023 13:59:40 -0600 Laboratory Developed Tests (LDTs) AHA Letter to the FDA on Laboratory Developed Tests (LDTs) Proposed Rule /lettercomment/2023-12-01-aha-letter-fda-laboratory-developed-tests-ldts-proposed-rule <div class="container"><div class="row"><div class="col-md-8">December 1, 2023The Honorable Robert M. Califf, M.D. Commissioner U.S. Food and Drug Administration 10903 New Hampshire Ave. Silver Spring, MD 20993Re: Docket No. FDA-2023-N-2177: Medical Devices: Laboratory Developed Tests Proposed Rule (Vol. 88, No. 190), October 3, 2023.Dear Commissioner Califf:On behalf of our nearly 5,000 member hospitals, health systems and other health care organizations, and our clinician partners — including more than 270,000 affiliated physicians, 2 million nurses and other caregivers — and the 43,000 health care leaders who belong to our professional membership groups, the �� Association (AHA) appreciates the opportunity to comment on the Food and Drug Administration’s (FDA’s) Laboratory Developed Tests (LDTs) proposed rule.Many hospitals and health care systems develop and use LDTs, particularly larger hospitals, including academic medical centers. LDTs are diagnostic tests that are not commercially distributed to other laboratories but, instead, are developed, validated and performed in-house by individual laboratories. They range from routine tests such as blood counts to more complex molecular and genetic tests for cancer, heart disease, and rare and infectious diseases. LDTs are critical in providing timely patient access to accurate and high-quality testing for many conditions for which no commercial tests exist or where an existing test does not meet current clinical needs. They also provide physicians with important clinical information to diagnose and treat patients and are essential to the practice of all areas of medicine. Indeed, these tests are typically developed at the request of, and in close collaboration with, clinical caregivers.The AHA commends the FDA for its work on LDTs and in vitro diagnostics products (IVDs) offered as LDTs, along with the agency’s commitment to protecting the public’s health. We agree that there is a need for additional oversight of the development and use of some LDTs and IVDs offered as LDTs. However, we strongly believe that the FDA should not apply its device regulations to hospital and health system LDTs. These tests are not devices; rather, they are diagnostic tools developed and used in the context of patient care. As such, regulating them using the device regulatory framework would have an unquestionably negative impact on patients’ access to essential testing. It would also disrupt medical innovation in a field demonstrating tremendous benefits to patients and providers. Instead, AHA urges the FDA to continue to apply its enforcement discretion to hospital and health system LDTs and defer regulation of these laboratory tests mainly to the Centers for Medicare &amp; Medicaid Services (CMS) strict Clinical Laboratory Improvement Amendments (CLIA) oversight, the College of American Pathologists (CAP) accreditation and state law, as it currently does.Enforcement discretion is particularly important for low- and moderate-risk LDTs, including for modifications to FDA-approved IVDs, and for laboratories subject to established laboratory evaluations programs, such as that developed by New York state. Moreover, in recent years, Congress has worked with laboratory stakeholders, including hospitals and health systems, to develop legislative approaches that build on existing, rigorous regulatory oversight for hospital-based testing. The FDA may wish to consider some additional flexibilities taken from these efforts for incorporation into their final rule.Despite the agency’s decision not to extend the comment period as we and many other stakeholders requested, we have consulted with our hospital and health system members to assess the proposed rule’s potential impact on the critically important work hospitals do to ensure safe, effective and accessible diagnostic testing for their patients. In short, continued enforcement discretion is necessary because the proposed rule is far too broad, does not contain sufficient detail, and, as written, has the potential to significantly increase hospital burden and costs, stifle innovation, and ultimately decrease hospitals’ ability to provide the most effective and appropriate care to patients.For example, if implemented as proposed, many hospitals would be unable to bear the significant costs associated with complying with the FDA’s unfamiliar device regulatory framework and exorbitant user fees. Efforts to comply would cause confusion and delays that would prevent hospital and health system laboratories from continuing to develop cutting-edge LDTs in response to immediate clinical-care needs. This could dramatically slow down advances in laboratory medicine, leading to patients’ loss of access to many critical tests.<h2>Additional Detail Is Needed</h2>The FDA provides minimal detail on the proposed regulatory changes in this rule. The agency merely makes explicit that IVDs, including those “manufactured” by laboratories, would be considered devices under the Federal Food, Drug, and Cosmetic Act (FD&amp;C Act), and therefore would be subject to the full scope of the FD&amp;C medical device regulations after a proposed four-year phase out of the FDA’s enforcement discretion.<a href="#fn1">1</a> The rule does not include any relevant or specific information about how the FDA’s medical device regulations would apply to LDTs. Indeed, the FDA itself has acknowledged it would need to publish a series of guidance documents to clarify its enforcement approach after the final rule is issued. Thus, it is currently impossible for hospital and health system laboratories to fully assess how each part of the device regulations would apply to their LDTs. This uncertainty is problematic; it further underscores the need for continued enforcement discretion, most particularly in certain areas, such as for low- and moderate risk tests.Our specific comments and recommendations follow.<h2>Broad Scope of the Rule</h2>Differentiating Hospital and Health System Clinical Laboratories from IVD Manufacturers. Hospital and health system-based clinical laboratories have several distinctive characteristics that distinguish them from other types of commercial laboratories and IVD manufacturers that develop and market IVDs and IVDs offered as LDTs. These factors are a large part of the reason why the FDA for many years applied enforcement discretion to the development and use of LDTs in hospitals and health systems.Specifically, hospital and health system laboratories that develop LDTs:<ul><li>Are typically integral components of teaching hospitals and/or academic institutions which provide direct patient medical care.</li><li>Have a primary role in providing testing and interpretation for the benefit of the patients and clinicians in affiliated hospitals or health systems as a part of larger clinical treatment decision-making processes for patients of these institutions.</li><li>Have been certified to conduct high-complexity tests by the CMS through the CLIA program.</li><li>Are subject to comprehensive oversight and regulation by other federal, state and private regulatory bodies, such as: CMS’ enforcement of the Medicare Conditions of Participation (COP); state agencies’ licensing and oversight of the function of these facilities; and respected laboratory accreditation organizations, such as CAP and The Joint Commission’s (TJC) provisions of stringent laboratory and other oversight. In fact, CAP addresses LDTs in five separate checklists as part of its accreditation process.<a href="#fn2">2</a></li></ul>Moreover, unlike commercial companies that develop IVDs and IVDs offered as LDTs, hospital and health system LDTs are typically developed at the request of, and in close collaboration with, clinical caregivers for use within the context of comprehensive patient care within a hospital or health system. That is, the testing is conducted for hospital inpatients and outpatients and provides physicians with important clinical information to diagnose and treat patients in all areas of medicine.Given that hospitals and health systems integrate laboratory test development and use into the continuum of patient care, the many other safeguards for patients to which such laboratories are already subject, and the FDA’s existing ability to investigate and remove any IVD or LDT from the market regardless of the entity that develops it, the AHA strongly recommends that the FDA not prioritize for oversight these clinical laboratories and their LDTs. Rather, we recommend that the FDA continue to use its general enforcement discretion for hospital- and health system-developed LDTs and that they be exempt from the proposed regulatory changes.We further recommend that, for health systems with multiple locations, this enforcement discretion be applied at the health system level so that LDTs developed by one health system laboratory would be permitted to be used for the care of patients located in another health system location without having to forfeit their enforcement discretion. This is particularly critical for certain specialties where care is regionalized, such as pediatric specialty care, where the patient would only have access to such testing if the LDT developed by one health system clinical laboratory can be performed at another system location. This is especially true for children on Medicaid with medically complex conditions, like cancer or other rare diseases. This approach enables children to receive follow-up and continuing care from local providers, allowing them to stay in their homes, communities and schools, reducing stress and burden on their families and overall well-being.Instead, the AHA recommends that the FDA apply its regulatory oversight only to commercial manufacturers and for-profit laboratories developing, selling and distributing IVD test kits and IVDs offered as LDTs, all of which, unlike hospital and health system LDTs, are developed outside of the physician-patient context. The IVDs and IVDs offered as LDTs sold by such manufacturers do not have the mitigating factors described above and, as a result, often have a history of serious issues and deficiencies that may cause patient harm and danger to the public’s health. An example is the widely reported issue with prenatal genetic tests developed by commercial IVD companies.<a href="#fn3">3</a> Other examples include IVDs offered as LDTs by commercial manufacturers for detecting autism<a href="#fn4">4</a>, detecting genetic variants for breast cancer<a href="#fn5">5</a> and for predicting response to certain medications.<a href="#fn6">6</a><h3>Modifications to FDA-approved Tests</h3>Under current FDA device regulations, certain types of changes or modifications to FDA-approved or -cleared devices require a premarket approval (PMA) supplement, a new 510(k) or other submission to the FDA. Under the proposed rule, such modifications to IVDs and LDTs, which are very common and necessary practices undertaken by hospitals and health system laboratories, would also become subject to these device regulations.For hospital and health system purposes, modifications may improve the performance of approved diagnostic tests on certain patient populations, address problems or issues with the FDA-approved devices and allow the latest research and clinical knowledge to be rapidly incorporated. They are intended to improve testing accuracy and safety. For example, changes could be made to scoring systems or to add specimen types that are dictated by medical guidelines or regulations (e.g., National Comprehensive Cancer Network, American Society of Clinical Oncology or CAP). They could be made to modify sample locations or types, which is particularly important in pediatric specialty care. For example, in cases of perinatal transmission, testing for C. trachomatis and N. gonorrhoeae polymerase chain reaction using the commonly available Cepheid platform is not FDA-approved for use in swabs of eye, rectum or throat mucosal membranes, but modifications resulting in LDTs permit this non-invasive testing of newborns. Such modified LDTs are regulated by CLIA and must undergo validation prior to their use for patients.To require a hospital or health system laboratory to prepare burdensome and costly submissions to the FDA, such as a PMA supplement or a new 510(k) for all these modifications is not practicable. It would be too onerous and would serve as a disincentive for laboratories that otherwise would make such changes to improve the capabilities of FDA-approved tests. This would harm patient access to the most advanced diagnostics. As such, low- and moderate-risk modifications to commercially marketed IVDs certainly should be exempted from FDA regulatory oversight, as long as the laboratory is in compliance with the CLIA regulations and is subject to the mitigating factors described above.<h3>Leveraging Established Laboratory Evaluation Programs</h3>The AHA appreciates that the FDA requested comments on whether the agency should leverage established laboratory evaluation programs when considering which tests to subject to its device regulations. Indeed, many hospital and health system laboratories participate in validity and quality review programs, such as those directed by the New York State Department of Health’s (NYS-DOH’s) Wadsworth Center. The value of such programs is clear and yet another reason that the FDA should continue to use its general enforcement discretion for hospital- and health system-developed LDTs, including for those approved by programs such as the Wadsworth Center’s Clinical Laboratory Evaluation Program (CLEP). In New York state, LDTs are already subject to review and approval by the Wadsworth Center and its CLEP, under which the state surveys New York laboratories in lieu of CMS, given the quality of the Wadsworth Center’s standards and survey process. The Wadsworth Center’s CLEP has been reviewing LDTs since 1991. It also reviews and approves not only LDTs developed by laboratories in New York state, but also those developed in laboratories across the country and the world.In the proposed rule, the FDA asks about the specific characteristics of and activities within this program that would justify an enforcement discretion approach. The CLEP’s first step of review is for a committee of subject matter experts to assign each LDT to a risk category that determines the subsequent technical review process. This process allows certain low-risk tests to be approved without technical review. It also allows Wadsworth to prioritize reviews for higher-risk tests and has enabled laboratories to begin offering lower-risk tests more quickly. The only LDTs that do not go through the committee are those submitted by laboratories that lack approval to offer that category of testing, because these tests are automatically designated high-risk.The risk criteria include the laboratory’s experience with the test method, the importance of the test in diagnosis/prognosis/treatment and the impact of an inaccurate test result on the patient. LDTs identified as low-risk or that fall under an exemption are not subject to technical review and are approved at the time of risk assignment. In contrast, high-risk LDTs are subject to technical review and the laboratory cannot offer the test until fully approved. Moderate-risk LDTs are subject to technical review, but they are conditionally approved and can be offered by the laboratory during the technical review process. Tests used only for clinical trials are not reviewed for analytical and clinical validity.Last, but certainly not least, the Wadsworth Center’s procedures for reviewing LDTs are considered to be of such high quality and so rigorous that the FDA itself has accredited the Wadsworth Center as a third-party reviewer on behalf of the agency for the premarket clearance process.<h2>High Burden and Cost</h2>Applying the FDA’s device regulations to LDTs, even with a four-year phase out of the current enforcement discretion, would pose nearly unsurmountable burdens and costs on both the FDA and hospital and health system laboratories. The unfortunate outcome likely would be the decline in the rate of clinical innovation, which would negatively impact the U.S.’ ability to keep our health care system at the forefront of discovery, provide quality care to patients, and respond quickly to emerging public health risks. This is yet another reason we urge FDA to continue to use enforcement discretion, particularly for the areas we have highlighted, for LDTs developed by hospitals and health systems.<h3>Increased Burden on the FDA and Hospitals</h3>Subjecting all hospital and health system LDTs to the FDA’s device regulations would result in a tremendous surge in the number of applications submitted to the FDA. This is because under these regulations, nearly all LDTs would require a PMA, a 510(k), or other application to the FDA. One large health system noted that they have at least 1,600 existing LDTs; under the proposed rule, they would need to submit 1,600 applications for approval in the first year of the phase-in. Another large hospital has developed over 150 new LDTs in the areas of microbiology, chemistry, molecular pathology, transplant medicine and digital pathology over just the last two years, for each of which during the first year of the phase-out they would have to submit applications. These figures are from one single health system and one additional hospital out of AHA’s nearly 5,000 member hospitals. Because a substantial number of these hospitals likely develop LDTs, such a change would quickly result in overwhelming burdens on the FDA, hospitals and health systems.Even under the current scope of the FDA’s oversight, the agency does not have a strong track record for timely processing of submissions for PMAs, 510Ks and emergency use authorizations (EUAs). For example, for Class 2 devices, the FDA is required to respond to complete 510(k) submissions with a notice indicating a complete application and acceptance for review within 60 days of receipt. However, according to a Qualio report<a href="#fn7">7</a>, currently the average length of time for clearance under the traditional 510(k) pathway is almost three times as long — nearly six months. For Class 3 devices using the PMA pathway, the average approval time is over four times as long — over eight months. Several hospitals laboratory leaders with whom we consulted said that during the COVID-19 pandemic they submitted EUA applications to the FDA and are still awaiting a final response from the FDA — over two years later. The novelty of the FDA review process for hospitals and health systems means that the processing timeframe for these applications would likely be even longer.Looking at the figures another way, according to a recent report from Emergo<a href="#fn8">8</a>, in 2022 the FDA received approximately 18,800 submissions. Yet, under the proposed rule, additional submissions likely would be in the tens of thousands. We are concerned that the FDA is not prepared to process this volume of applications in a reasonable timeframe.For hospitals and health systems that have hundreds, or even thousands of LDTs that would need to go through this process, this poses not only a delay for approving already existing LDTs but would also drastically slow down medical innovation for new LDTs and for modifications to currently marketed IVDs/LDTs.<h3>Increased Costs to Hospitals</h3>Hospitals and health systems continue to face significant financial challenges as sustained increases in the costs required to care for patients have been met with woefully inadequate increases in reimbursement. In fact, between 2019 and 2022, hospitals’ expenses increased 17.5%, while Medicare reimbursement for inpatient care only increased 7.5%. This reality, in part, created an environment where in the first quarter of 2023 the highest number of bond defaults among hospitals occurred in over a decade. While hospitals have seen a meager stabilization of their operating margins in 2023 relative to historic lows in 2022, with median operating margins hovering around 1%, many hospitals continue to operate in the red. Moreover, workforce shortages coupled with upward wage pressures continue to create new and challenging workforce dynamics for hospitals and health systems. These changes are particularly problematic because labor on average accounts for about half of a hospital’s budget. Collectively, these indicators signal uncertainty to hospital operations and financing in the future.At a time when hospitals and health systems are facing persistent financial headwinds, we are very concerned about the impact of the FDA’s proposal to impose its costly and largely redundant regulatory framework on hospitals, particularly in terms of compliance with the proposed rule. Such compliance would impose tremendous additional costs on hospitals and health systems, including the additional staff time and outside expertise needed to understand, complete and manage FDA applications for both existing and new LDTs, as well as the exorbitant FDA user-fee costs<a href="#fn9">9</a> that would be required for nearly every LDT.Hospitals and health systems, unlike traditional device manufacturers, are largely inexperienced in working through the FDA’s regulatory processes. As a result, they do not have internal FDA regulatory mechanisms in place to complete all the steps necessary to gain approval in a timely and accurate manner. Thus, they would have to retain experienced consultants and outside counsels to prepare, submit and manage their applications. These new costs would rapidly escalate for the hundreds or thousands of applications that hospitals and health systems would have to submit to the FDA in the first year of the phase-in alone.The FDA’s user fees would also rapidly escalate with the number of applications filed. For instance, in 2023, the FDA charges $6,493 to register a facility. In 2023, the FDA charges $19,870 for one 510(k) application, $441,547 for one De Novo application<a href="#fn10">10</a> and $132,464 for one PMA. Although there are reduced rates for “small businesses,” the fact that hospitals would need to submit many applications, both for their existing LDTs as well as new and modified LDTs, would rapidly escalate these costs. For example, in the health system example we mentioned above, even if all of the health system’s 1,600 applications were 510(k) applications, they would be required to pay a staggering $31,798,493 throughout the approval process. Even if this health system was able to qualify as a “small business,” the amount would still be almost $8 million — a substantial amount. Hospitals and health systems simply will not be able to absorb these costs. Indeed, several hospital leaders told us that these fees would lead to tough choices about which LDTs they could continue to offer and restrictions on how they can adapt their diagnostic testing to care for patients.Imposing these additional costs and burdens is untenable and would ultimately lead to institutional decisions that would limit the types and number of LDTs offered by the institution, leading to a substantial reduction in patient access to innovative and targeted diagnostic tests.<h3>1976-Type LDT</h3>The FDA proposes to continue to apply its general enforcement discretion to 1976-Type-LDTs. The rule describes such tests as having characteristics such as: use of manual techniques (without automation) performed by laboratory personnel with specialized expertise; use of components legally marketed for clinical use; and design, manufacture, and use within a single CLIA-certified laboratory that meets the requirements under CLIA for high complexity testing. However, additional information is needed on which LDTs would fall into this category. Hospitals have many tests that could be considered 1976-Type-LDTs; given the importance of this possible grandfathering, we recommend that the final rule include much greater detail, including more specific definition of terms such as “automation” and “specialized expertise,” as well as and specific examples of such LDTs.We appreciate your consideration of these issues. Please contact me if you have questions or feel free to have a member of your team contact Roslyne Schulman, AHA’s director for policy, at <a href="mailto:rschulman@aha.org?subject=RE: AHA Letter to the FDA on Laboratory Developed Tests (LDTs) Proposed Rule">rschulman@aha.org</a>.Sincerely,/s/Stacey Hughes Executive Vice President<hr><ol><li id="fn1">By adding to § 809.3 Definitions “(a) * * * These products are devices as defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the act) and may also be biological products subject to section 351 of the Public Health Service Act, including when the manufacturer of these products is a laboratory.”</li><li id="fn2">The biannual CAP accreditation inspection process includes LDT validation requirements in five checklists. These include the “all common” checklist, which all labs must go through, and the checklists for molecular pathology, microbiology, anatomic pathology and cytogenetics.</li><li id="fn3"><a href="https://www.nytimes.com/2022/01/01/upshot/pregnancy-birth-genetic-testing.html" target="_blank">https://www.nytimes.com/2022/01/01/upshot/pregnancy-birth-genetic-testing.html</a></li><li id="fn4"><a href="https://www.spectrumnews.org/news/blood-test-autism-not-fast-experts-say/" target="_blank">https://www.spectrumnews.org/news/blood-test-autism-not-fast-experts-say/</a></li><li id="fn5">U.S. FDA, "Letter to deCODEme Complete Scan," <a href="https://www.fda.gov/media/79216/download" target="_blank">https://www.fda.gov/media/79216/download</a></li><li id="fn6">U.S. FDA, "Letter to 23andMe Personal Genome Service," <a href="http://web.archive.org/web/20191214010336/https:/www.fda.gov/media/79205/download" target="_blank">http://web.archive.org/web/20191214010336/https:/www.fda.gov/media/79205/download</a>.</li><li id="fn7"><a href="https://www.qualio.com/blog/fda-medical-device-approval-process" target="_blank">https://www.qualio.com/blog/fda-medical-device-approval-process</a></li><li id="fn8"><a href="https://www.emergobyul.com/news/us-fda-annual-report-nearly-6000-medical-device-authorizations-2022#:~:text=In%202022%2C%20FDA%20authorized%3A,3%2C229%20510(k)s" target="_blank">https://www.emergobyul.com/news/us-fda-annual-report-nearly-6000-medical-device-authorizations-2022#:~:text=In%202022%2C%20FDA%20authorized%3A,3%2C229%20510(k)s</a></li><li id="fn9"><a href="https://www.registrarcorp.com/blog/fda-announces-new-medical-device-user-fees-for-fy-2023/" target="_blank">https://www.registrarcorp.com/blog/fda-announces-new-medical-device-user-fees-for-fy-2023/</a></li><li id="fn10">The De Novo request provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device.</li></ol></div><div class="col-md-4"><div class="external-link spacer"><a class="btn btn-wide btn-primary" href="/system/files/media/file/2023/12/AHA-Letter-to-the-FDA-on-Laboratory-Developed-Tests-LDTs-Proposed-Rule.pdf" target="_blank" title="Click here to download the AHA Letter to the FDA on Laboratory Developed Tests (LDTs) Proposed Rule PDF.">Download the Letter PDF</a></div><a href="/system/files/media/file/2023/12/AHA-Letter-to-the-FDA-on-Laboratory-Developed-Tests-LDTs-Proposed-Rule.pdf" target="_blank" title="Click here to download the AHA Letter to the FDA on Laboratory Developed Tests (LDTs) Proposed Rule PDF."><img src="/sites/default/files/inline-images/Page-1-AHA-Letter-to-the-FDA-on-Laboratory-Developed-Tests-LDTs-Proposed-Rule.png" data-entity-uuid="e59058bd-f8e4-465c-8c92-09d0dbd8022c" data-entity-type="file" alt="AHA Letter to the FDA on Laboratory Developed Tests (LDTs) Proposed Rule page 1." width="692" height="900"></a></div></div></div> Fri, 01 Dec 2023 09:05:28 -0600 Laboratory Developed Tests (LDTs)