Briana E. Mittleman, Stanford Law School, JD 2023

As the pandemic escalated, in August 2020, the Trump administration Health and Human Services (HHS) directed the Food and Drug Administration (FDA) to stop requesting premarket approval for clinical laboratory tests, including those designed to detect Covid-19.[1] As some applauded the decision because test producers no longer needed Emergency Use Authorization (EUA) to develop and administer Covid-19 tests, others worried about the potential consequences of inaccurate tests.[2] The Biden Administration withdrew the Trump policy in fall 2021, returning discretionary authority to the FDA to require premarket review for laboratory developed tests.[3] In support of the decision, Dr. Jeff Shure, director of the FDA’s Center for Devices and Radiological Health, stated, “[b]y focusing our review on these types of tests, and helping to ensure that available tests have appropriate oversight, we can better respond to the pandemic as the nation’s testing needs continue to evolve.”[4]

The government grapples with the tradeoffs between safe deployment of accurate tests and the goal to allow rapid development of flexible new technology in deciding FDA’s regulatory oversight far beyond Covid-19 testing. Between 2010 and 2017, the FDA itself reconsidered its policies for laboratory developed test regulation. In 2017, the agency announced it would not finalize new guidelines, but invited Congress to address the issues.[5]

VALID act addresses issues with in vitro diagnostic and laboratory developed test regulation

The FDA’s previous attempt to modify regulations and the executive office disagreement on Covid19 test policy likely contributed to the eventual congressional action. The Verifying Accurate Leading-edge IVCT Development (VALID) Act, originally introduced in 2020[6] and reintroduced in 2021,[7] introduced a revamp of the FDA regulatory framework for in vitro diagnostics and laboratory developed tests.

The House Energy and Commerce committee introduced the Verifying Accurate Leading-edge IVCT Development Act (VALID Act) of 2021 on June, 24, 2021 as H.R. 4128.[8] On the same day, the Senate Health, Education, Labor, and Pensions Committee (HELP) introduced an identical version of the bill as S.2209.[9] The bill introduces a new product category called in vitro clinical tests (IVCT) and creates a new regulatory pathway called technology certification.

IVCTs as a product regulatory category

The bill defines a new regulatory category for diagnostic testing[10], called in vitro clinical tests (IVCT) that would encompass both IVDs and LDTs. The act defines IVCTs as:

“(A) means a test intended by its developer (as defined in section 587) to be used in collection, prepare, analysis, or in vitro clinical examination of specimens taken or derived from the human body for the purpose of – (i) identifying or diagnosing a disease or condition; (ii) providing information for diagnosing, screening, measuring, detecting, predicting, prognosing, analyzing, or monitoring a disease or condition, including by making a determination of an individual’s state of health; or (iii) selecting, monitoring, or informing therapy or treatment for a disease or condition; and (B) may include – (i) a test protocol or laboratory test protocol; (ii) an instrument (as defined in section 597(11); (iii) a specimen receptacle; (iv) software …” (internal quotation removed, exceptions excluded)[11]

By creating the new category, VALID addresses FDA, stakeholder, and congressional concerns that LDTs have increased in complexity to that closer to IVDs but lack federal oversight.[12] The need or level of review needed for approval will depend on ICVT risk categories. High-risk ICVTs would require preapproval review.

High-risk ICVTs:

“present[] unreasonable risk for serious or irreversible harm or death to a patient or patients, or would otherwise cause serious harm to the public health; or otherwise likely to result in the absence, significant delay, or discontinuation of life-supporting or life-sustaining medical treatment; and (ii) shall account for the degree to which the technology for the intended use of an in vitro clinical test or tests is well-characterized and the criteria for performance of the test or tests are well-established for the intended use, the clinical circumstances under which the in vitro clinical test is used, and the available of other tests (such as confirmatory or adjunctive tests)”[13]

Review pathways for high-risk tests will include assessments of both analytical and clinical validity for their intended use.[14]

In comparison, low-risk diagnostics could come to market after an agency listing. Low-risk ICVT either present minimum or no harm to users or are high risk with mitigating factors described in the legislation.[15] Under VALID, the Secretary must maintain a list of low-risk categories.

Tests falling into neither category may be categorized as moderate risk. These ICVTs may require “special premarket review”, meaning the manufacturer will not need to submit raw data to the FDA as the do for high risk tests.[16]

Technology Certification as a New Review Model

VALID also introduces a new a regulatory pathway called Technology Certification (tech cert, §578D) to account for adaptability of ICVT technology. With a tech cert for a representative technology, a manufacture could market multiple tests as long as they are in the scope of the original approval.[17] To obtain a tech cert, the FDA will review both analytical and clinical validity.[18] Figure 1, originally published by the Health and Human Services, summarizes the review pathway under VALID 2021.[19]

Once or if VALID is signed into law, the novel VALID frameworks would not take effect for 4 years.[20] Any tests already on the market when the law takes effect will be grandfathered into the current regulation.[21] Thus, currently approved IVDs and LDTs will not have to apply for approval as an ICVT.

Congressional Passage for VALID is uncertain

Despite bipartisan and bicameral support for VALID, Congressional action to reauthorize the FDA User Fee Agreement legislation has complicated the fate of the VALID Act of 2021.[22] June 8, 2022, the House passed the Food and Drug Amendments of 2022 to reauthorize the FDA user fees program through 2027.[23] On May 26, 2022 the Senate introduced their version of a bill to reauthorize the user fees program, Food and Drug Administration Safety and Landmark Advancements Act of 2022 (FDASLA Act of 2022).[24] Among the differences between the House and Senate versions of the reauthorization act, FDASLA includes a version of VALID (VALID Act of 2022).

In a turn of events, in response to partisan divide over additional attachments to FDASLA in committee, one of the VALID Act of 2021’s original sponsors and ranking member of HELP, Richard Burr, introduced a clean version of bill on July 13, 2022.[25] In addition to stripping out other additional provisions, the Senate user fee reauthorization no longer includes VALID.[26] Congress passed the clean version of the FDA reauthorization bill on September 30^th, 2022.[27] VALID is not the only FDA policy reform that got left out of the final bill, the clean version also removed modernization of cosmetic regulation, listing requirements for dietary supplements, clinical trial diversity improvement reforms, reforms to accelerated approval and responses to the infant formula crisis.[28] Experts, including practicing attorneys in the space, expect renewed legislative pressure for VALID and these other policy reforms in the near future.[29]

 

[1] Jacqueline Howard, Trump administration says FDA will no longer require premarket review of certain lab tests, including some Covid-19 tests, CNN, Aug. 21, 2020, https://www.cnn.com/2020/08/21/health/covid-lab-developed-tests-fda-hhs-bn/index.html.

[2] See id. This is the tradeoff that will underline this entire paper. We care about getting tests to the public as soon as possible but we also want to ensure safety and accuracy.

[3] Jacqueline Howard, HHS withdraws Trump administration policy that limited FDA review of certain Covid-19 tests, CNN, Nov. 15, 2021, https://www.cnn.com/2021/11/15/health/covid-lab-tests-hhs-withdraws-policy-bn/index.html.

[4] FDA News Release, FDA, Coronavirus (COVID-19) Update: FDA Updates Test Policies to Help to Ensure Accuracy and Reliability of Tests and Increase Access to At-Home Tests (Nov. 15, 2021), https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-updates-test-policies-help-ensure-accuracy-and-reliability-tests-and.

[5] William McConagha & Amanda H. Chan, FDA Oversight of Laboratory-Developed Tests Continues To Evolve, Skadden, Arps, Slate, Meagher & Flop LLP (Sep. 20, 2020), https://www.skadden.com/insights/publications/2020/09/quarterly-insights/fda-oversight-of-laboratory-developed-tests.

[6] See Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2020, H.R. 6102, 116th Cong. (2020).

[7] See Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2021, H.R. 4128, 117^th Cong. (2021).

[8] Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2021, H.R. 4128, 117th Cong. (2021)

[9] Verifying Accurate Leading-edge IVCT Development (VALID) Act of 2021, S. 2209, 117th Cong. (2021); Citations in this memo refer to the House bill but the Senate bill contains identical language.

[10] Currently diagnostic tests fall into two categories IVDs and LDTs. IVDs are “those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body.” 21 C.F.R. § 809.3(a) (2013). The FDA requires premarket approval of varying types for IVDs based on risk-based classes. LDTs are “a class of in vitro diagnostics that are manufactured, including being developed and validated, and offered, within a single laboratory.” Federal Register 75 (June 17, 2010): 34,463. FDA exercise “enforcement discretion” over LDTs so premarket approval is not necessary.

[11] H.R. 4128, 117th Cong. §3 (2021).

[12] See The Role of Laboratory-Developed Diagnostic Tests in the In Vitro Diagnostics Market, The Pew Charitable Trust (Oct. 22, 2021), https://www.pewtrusts.org/en/research-and-analysis/reports/2021/10/the-role-of-lab-developed-tests-in-the-in-vitro-diagnostics-market.

[13] Id.

[14] See H.R. 4128, 117th Cong. §587 (2021).

[15] Mitigation factors “(B) include[] as appropriate, applicable requirements regarding labeling, conformance to performance standards or guidance, performance testing, submission of clinical data, advertising, website posting of information, clinical studies, postmarket surveillance, use compression studies, training, and availability of confirmatory laboratory or clinical findings.” H.R. 4128, 117th Cong. §3 (2021).

[16] U.S. Dept. Health & Hum. Serv., Department of Health and Human Services, Technical Assistance on VALID Act of 2021 (2021).

[17]See H.R. 4128, 117th Cong. §587 (2021); Diagnostics Reform Heats Back Up with Introduction of the Verifying Accurate Leading-edge IVCT Development Act of 2021, Akin Gump Strauss Hauer & Feld LLP, (Jun. 24, 2021), https://www.akingump.com/en/news-insights/diagnostics-reform-heats-back-up-with-introduction-of-the-verifying-accurate-leading-edge-ivct-development-act-of-2021.html.

[18] H.R. 4128, 117th Cong. §587D (2021). (“(A) in accordance with subsection E(2)(D), there is a showing of reasonable assurance of analytical validity for all eligible in vitro clinical tests within the proposed scope of the technology certification, as evidenced by the procedures for analytical validation; (B) in accordance with subsection(2)(E), there is a showing of reasonable assurance of clinical validity for eligible in vitro clinical tests within the proposed scope of the technology certification, as evidenced by the clinical program, including procedures for clinical validation”)

[19] See U.S. Dept. Health & Hum. Serv., Department of Health and Human Services, Technical Assistance on VALID Act of 2021 (2021).

[20] H.R. 4128, 117th Cong. §5 (2021).

[21] H.R. 4128, 117th Cong. §587A (2021).

[22] In 1992, the first FDA User Fee Act (Prescription Drug User Fee Act (PDUFA)) was enacted. The law gave the FDA authorization to collect various user fees from companies when they submit drug applications. The law has been reauthorized every 5 years and in subsequent iterations the legislation has been updated to include User fee schemes for Medical Decvices (MDUFA), Biosimilars (BsUFA) and Generic Drugs (GDUFA). The User Fee reauthorizations allow Congress, the agency, patients, industry, and other stakeholders to negotiate fees and performance goals. The current authorization expires on September 30th 2022 and has historically been considered “must pass” legislation. See It’s UFA Time Again: Reauthorization of the FDA User Fee Acts Takes Center Stage in Congress, Akin Gump Strauss Hauer & Feld LLP, (Feb. 3, 2022),https://www.akingump.com/en/news-insights/its-ufa-time-again-reauthorization-of-the-fda-user-fee-acts-takes-center-stage-in-congress.html.

[23] H.R. 7667, 117th Cong. (2022)

[24] FDASLA Act of 2022,  S. 4348, 117th Cong. (2022) (Version Reported to Senate on 5/26/2022)

[25] FDASLA Act of 2022, S. 4348, 117th Cong. (2022) (Version Reported to Senate on 7/13/2022); Senator Burr Introduces Clean Reauthorization of FDA User Fee Programs, Richard Burr U.S, Senator for North Carolina, (July 14, 2022), https://www.burr.senate.gov/2022/7/senator-burr-introduces-clean-reauthorization-of-fda-user-fee-programs.

[26] See id.

[27] Congress Enacts Clean Reauthorization of FDA User Fees, Leaving Uncertain Future for Important Policy Reforms, Ropes & Gray, (September 30, 2022), https://www.ropesgray.com/en/newsroom/alerts/2022/september/congress-enacts-clean-reauthorization-of-fda-user-fees-leaving-uncertain-future#:~:text=the%209th%20Circuit.-,Congress%20Enacts%20Clean%20Reauthorization%20of%20FDA%20User%20Fees%2C%20Leaving,Future%20for%20Important%20Policy%20Reforms&text=On%20September%2030%2C%202022%2C%20Congress,end%20of%20the%20fiscal%20year.

[28] See id.

[29] See id.