I. INTRODUCTION
COVID-19Footnote 1 emerged in December 2019 and quickly spread across the world, becoming a pandemic unlike any experienced in the last one hundred years. To date, there have been over 163 million cases and 3.3 million deaths globally.Footnote 2 The coronavirus pandemic (referred to here on out as “the pandemic”) hit the United States particularly hard, accounting for over thirty-two million cases and over half a million deaths.Footnote 3 The pandemic will have lasting impact for years, maybe even decades, to come in both unknown and clear ways.Footnote 4 Much of the government response has fallen onto the U.S. Food and Drug Administration (“FDA”) to address widespread shortages of necessary medical supplies and the need for new products.Footnote 5 Specifically, the FDA is responsible for the availability, safety, and efficacy of medical devices such as face masks, respirators, ventilators, diagnostic tests, and serology tests.Footnote 6 The FDA’s regulatory decisions made over the course of the pandemic to address these needs, their consequences, and their criticisms echo the general call for heightened oversight over medical devices. How medical device regulation during the pandemic will impact medical device oversight generally is yet to be seen. The relaxed and fix-it-later nature of COVID-19 medical device emergency regulations, however, has clearly impacted the effectiveness of the COVID-19 response and reflects the continuous problems with medical device regulation as a whole.
This Note seeks to explore the initial COVID-19 response regarding medical devices, the state of medical device regulation generally, and the implications going forward. Part II will provide background on the pandemic and the need for medical devices. Part III will set the foundation for further discussion by explaining the law behind medical device regulation, the FDA’s responsibilities, and the public health emergency response. The section will first describe medical device regulation under ordinary circumstances, including its problems, before describing the Emergency Use Authorization (“EUA”), the FDA’s main tool in addressing public health emergencies. Part IV will examine the agency’s response to the pandemic by focusing on four types of medical devices: face masks and respirators, ventilators, diagnostic and laboratory developed tests (“LDTs”), and serological “antibody” tests. FDA action and EUA outcomes for each of these medical devices have met both successes and failures. While some decisions remain on course, the FDA has rolled back various other measures in reaction to harsh criticism and public health safety risks.
After reviewing the state of medical device regulation and the impact (so far) of COVID-19 EUAs, Part V will discuss the benefits, necessities, and inherent flaws concerning use of the EUA in pandemics. Comparing EUA utilization during the Zika virus crisis and the EUA utilization during the pandemic will emphasize the importance of review in the EUA process. Part VI will discuss the potential implications of COVID-19 device regulation on the medical device regulatory landscape generally and vice versa. First, the section will discuss how the rules and advisories for laboratory developed tests are evolving and whether certain decisions made during the pandemic may continue to be applied after the crisis. The potential impact of the VALID Act, a bill introduced in Congress in early 2020 seeking to increase LDT regulation, will be discussed. Second, the section will draw comparisons between the controversial 510(k) clearance process and the FDA’s emergency response to highlight the need for heightened regulatory oversight of medical devices as a whole. Additionally, this Note will make recommendations to provide adequate and appropriate controls on medical device risks without sacrificing efficiency in the approval process, both generally and during a public health emergency. Ultimately, this Note will conclude that legislation like the VALID Act and reform emphasizing premarket and postmarket review offer the best path forward.
II. THE PANDEMIC AND MEDICAL DEVICES
Even before the pandemic struck the world, medical devices in the United States were already subject to much less stringent requirements than many other FDA-regulated products.Footnote 7 The most stringent regulatory process for medical devices, premarket approval (“PMA”), requires only one clinical trial, while new drugs typically require at least two randomized controlled trials.Footnote 8 Less than ten percent of medical devices, however, are even subject to PMA.Footnote 9 The 510(k) process allows most medical devices to sidestep these required trials entirely,Footnote 10 while other devices are exempt from even the 510(k) process.Footnote 11 Experts argue there is a “very low bar” to gain medical device regulatory approval in general.Footnote 12 A 2010 survey of medical device manufacturers revealed that only sixteen percent believed the FDA’s medical device approval process to be very good or excellent.Footnote 13 Another investigation found that the FDA received more than 1.7 million injury reports and 83,000 death reports related to medical devices in just a ten-year period,Footnote 14 further underlining the importance of properly evaluating medical devices.
For these reasons and more to be discussed later on, medical device regulation has been criticized in the medical, scientific, and industry communities for its relaxed regulatory approach.Footnote 15 Failures in device efficacy and safety can cause significant harm, up to and including death, and cost both money and resources.Footnote 16 Patients, the medical community, and other users of medical devices rely on FDA approval for guidance and protection from these industry failures. The significance of this reliance is amplified in the current worldwide pandemic.
The pandemic presents challenges to the FDA, the medical community, and the world in general. As the infection situation worsened and the impact of the pandemic became clearer in 2020, government action proved to be necessary.Footnote 17 Diagnostic tests for COVID-19 had yet to be developed, and existing devices such as respirators, face masks, and ventilators were quickly becoming crucial supplies in high demand.Footnote 18 On January 31, 2020, Secretary of the Department of Health and Human Services (“DHHS”) Alex Azar determined that a public health emergency exists in the United States regarding the novel coronavirus, pursuant to section 319 of the Public Health Service Act.Footnote 19 On February 4, 2020, the Secretary declared that the public health emergency has created circumstances which permitted the authorization of the emergency use of in vitro diagnostics for detection and diagnosis of COVID-19.Footnote 20 To explain the importance of this government action, Stephen Hahn, the FDA’s Commissioner of Food and Drugs, notes that, “medical devices, particularly diagnostic tests, are the first line of defense against an emerging outbreak.”Footnote 21
With little time to prepare, the COVID-19 pandemic required an adaptable government response to address testing and contact tracing, medical equipment supply, and other domains.Footnote 22 Shortages of personal protective equipment (“PPE”), critical supplies and materials, ventilators, and testing supplies immediately challenged hospitals in March and continue to do so.Footnote 23 In order to curb the spread of COVID-19 effectively, experts called for the expansion of testing.Footnote 24 As the Centers for Disease Control (“CDC”) and public health laboratories lack the capacity to process testing on such a mass scale, major clinical diagnostic companies had to develop and manufacture testing kits to test effectively.Footnote 25 To meet this need, the FDA turned to its emergency procedures, including EUAs.Footnote 26
As of September 18, 2020, the FDA had authorized 516 medical device EUAs during the pandemic, almost ten times the number authorized in all prior national emergencies.Footnote 27 By November 2020, there existed 289 EUAs for COVID-19 tests, including both tests for active SARS-CoV-2 infection and antibodies from prior infection.Footnote 28 Over the course of the pandemic up to September 2020, the FDA received over 1734 pre-EUAs and 3040 EUA applications.Footnote 29 While these EUAs have helped ensure availability of and access to devices necessary to combat the pandemic, the expedited approval of some of these tools has been met with controversy and backlash for allowing devices on the market that simply do not work. During such a grand scale public health emergency, failures in efficacy, safety, and accuracy can jeopardize individuals, health care workers, the public health, and the government response as a whole.
Ideally, every moderate to high-risk medical device would be subject to a high standard of review requiring clinical trials and other scientific evidence supporting the efficacy of the device. In reality, this level of review is unattainable during public health emergencies that require timely action. EUAs and FDA enforcement discretion in times of crisis lower the review standard or waive review altogether. The question then becomes not whether EUA devices are effective, safe, and accurate when no clinical trials have been performed, but whether these devices are effective, safe, and accurate when no review has been conducted at all. Recent emergency decisions reflect regulators’ lack of concern for medical device review as a whole, despite the FDA’s obligation to protect the public health and the potential and significant consequences of unsafe, ineffective, or inaccurate devices.
The FDA decisions regarding EUAs for four products essential to the pandemic response—face masks and facepiece respirators, ventilators, diagnostic tests, and serological tests—demonstrate the need to prioritize speed in a pandemic, but also the consequences of prioritizing speed over safety. To understand the implications of these emergency decisions on the medical device regulatory landscape as a whole, medical device regulation must be examined in non-emergent times and then compared with emergency regulatory authority.
III. MEDICAL DEVICE REGULATION UNDER THE FDCA
The FDAFootnote 30 is responsible for regulating medical devices as well as drugs, food, cosmetics, tobacco products, and radiation-emitting devices.Footnote 31 In total, the agency oversees about twenty-five percent of all U.S. consumer spending.Footnote 32 The FDA’s mission statement has three pronouncements particularly relevant to this Note:
The [FDA] is responsible for protecting the public health by ensuring the safety, efficacy, and security of … medical devices… FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their public health. FDA … [fosters] development of medical products to respond to deliberate and naturally emerging public health threats.Footnote 33
The overriding purpose of the FDA is to protect the public from unsafe, ineffective, and deceptively labeled products.Footnote 34 The agency’s obligations to the general public, scientific and medical communities, and government are even more pronounced during the pandemic and response.Footnote 35 Despite the need for timely action in public health emergencies, the FDA’s priorities should ultimately remain the safety, efficacy, and security in its medical device decisions and guidance. The FDA has systems in place to accomplish this purpose.
A. Regulating Under Ordinary Circumstances
The Medical Device Amendments of 1976 (“MDA”) authorized the FDA to regulate medical devices.Footnote 36 The MDA defines medical device as “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is … intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.”Footnote 37 Ventilators, for example, are “machines” for the purpose of this definition while “in vitro reagents” include both diagnostic and serology tests for COVID-19. The MDA created a range of standards, or classes, for medical devices regulation, dependent on the amount of oversight necessary to ensure safety and efficacy.Footnote 38
Medical devices are categorized into three classes, with Class I subject to the least regulatory oversight and Class III to the most.Footnote 39 Class I devicesFootnote 40 come with minimal risks and, as such, are typically only subject to general controls.Footnote 41 Class II devices are subject to special controls because they require more oversight to ensure safety and efficacy.Footnote 42 Most Class II devices are subject to the 510(k) clearance process, requiring a finding from the FDA that a device is “substantially equivalent” to another device legally in U.S. commercial distribution.Footnote 43 For such a finding, the device must have the same intended use as the predicate device and either the same technological characteristics or different technological characteristics that do not raise questions about safety and effectiveness.Footnote 44 If a device is found to be “not substantially equivalent” to a predicate device, or if the developer determines there is no substantially equivalent predicate device on the market, the developer may submit a de novo request to reclassify the device as Class I or II.Footnote 45 De novo classification is a risk-based process for low to moderate risk devices.Footnote 46 The classification is intended to provide a pathway for novel medical devices of which general and special controls alone can provide reasonable assurance of safety and effectiveness, avoiding the extensive PMA process.Footnote 47
Class III devices are subject to the more stringent PMA review process because they either pose a significant risk to safety, support or sustain human life, or prevent impairment of human health.Footnote 48 New devices not found to be substantially equivalent to other legally marketed devices are also considered Class III devices subject to PMA, unless reclassified under the de novo pathway.Footnote 49 There are only three limited situations in which a Class III device will not be subject to PMA.Footnote 50 PMA is based on a determination that sufficient scientific evidence standing on its own exists to assure that the device is safe and effective for its intended use.Footnote 51 Valid scientific evidence may include controlled studies, objective clinical trials, well-documented case histories, and reports of significant experience.Footnote 52 Importantly, PMA typically requires at least one clinical investigation.Footnote 53 Clinical studies in support of PMA are subject to investigational device exemption (“IDE”) regulations and must be approved by an Institutional Review Board (“IRB”).Footnote 54 Upon achieving PMA, a device may still be subject to post-approval requirements such as conducting postmarket surveillance studies and reporting clinical studies using the device.Footnote 55 The PMA process is, obviously, much more stringent than the 510(k) clearance process. These safeguards are based in evidence and go above the various general controlsFootnote 56 applied to all medical devices to better ensure safety and reliability where the stakes are higher.
1. 510(k) Approval: Innovation Over Review
As will be discussed later on, the 510(k) program controversy offers a point of comparison and reflection for FDA emergency response.Footnote 57 Currently, the 510(k) clearance offers an avenue for many medical device manufacturers to sidestep the PMA process and its requirements, thereby evading review and the need to present scientific evidence showing safety and efficacy.Footnote 58 The FDA reports that fewer than ten percent of medical devices are subject to PMA,Footnote 59 while other sources report the number may be as low as one percent,Footnote 60 thanks to the availability of the 510(k) clearance process. The medical device industry harbors a widespread belief that devices do not require the same level of safety and efficacy evidence as drugs in order to be approved and used.Footnote 61 Yet the vast number of approved 510(k) clearances, which often lack scientific evidence and review and come with potential for risks, carry significant implications for the public’s health. Between 2003 and 2009, for example, eight and a half percent of devices cleared under a 510(k) were subject to recall within six years.Footnote 62 During this time, recalls were much more likely to affect life sustaining Class III devices with significant patient risks.Footnote 63
Advocates in the scientific and medical community argue the bar for device regulatory approval is too low.Footnote 64 Substantial equivalence is often a relatively easy standard to meet, as 510(k) applications are rarely denied.Footnote 65 Further, the standard on its own is not designed to evaluate safety or efficacy. The Institute of Medicine (“IOM”) published a report on the 510(k) clearance process that concluded “the 510(k) clearance process is not intended to evaluate the safety and effectiveness of medical devices” because the substantial equivalence standard cannot replace a premarket evaluation.Footnote 66 Substantial equivalence does not guarantee that a device poses only the same risks as an older predicate, and the logic of the standard only works in cases where the device is a clone of a currently marketed predicate.Footnote 67 Further, even where the device is a clone, “[s]ubstantial equivalence determinations provide little protection to the public … . If the earlier device poses a severe risk or is ineffective, then the latter device may also be risky or ineffective.”Footnote 68 The IOM report questioned how the 510(k) process is serving either industry or patients,Footnote 69 and it seems to fail to meet its own goals of ensuring safety and efficacy while promoting innovation. The report’s primary criticism was that the 510(k) clearance process does not involve any kind of evaluation, premarket or postmarket.Footnote 70 The report ultimately recommends the design of a completely new regulatory framework for Class II devices involving additional studies and delaying approval for competitive devices.Footnote 71 One recommendation suggests developing a modified and risk-based de novo process for evaluating the safety and effectiveness of Class II devices.Footnote 72
In response, the FDA announced changes to modernize the 510(k) clearance process.Footnote 73 No Class III device was cleared through the 510(k) process in 2018.Footnote 74 While these actions have had some positive effects, they ultimately fall short of the IOM’s recommendations for a new regulatory program to eliminate the logical inconsistencies within the substantial equivalence standard.Footnote 75 There are also FDA efforts to update the de novo classification process to reduce 510(k) applications and phase out predicates older than ten years,Footnote 76 but the results of these efforts are yet to be seen.
A. Emergency Use Authorizations
Despite the efficiencies of the 510(k) clearance process and the theoretical assurances of the more rigorous PMA process, in public health emergencies the FDA must look for a speedier approach to address medical device needs and shortages. Following the World Trade Center attacks on September 11, 2001, Congress recognized a clear need for FDA emergency authorities.Footnote 77 The Project Bioshield Act of 2004Footnote 78 first introduced the EUA procedure into section 564 of the FDCA.Footnote 79
The Secretaries of DHHS, Defense, or Homeland Security each have authority to determine that an emergency or significant potential for emergency exists involving a chemical, biological, radiological, and/or nuclear (“CBRN”) agent.Footnote 80 After this determination, the Secretary of DHHS may make an EUA declaration, declaring that circumstances exist justifying authorization for emergency use.Footnote 81 Only then will the FDA have authority to issue an EUA for an unapproved medical product, and only if certain criteria are present.Footnote 82
An EUA comes with statutory authorization conditions as well as additional conditions the FDA will impose if deemed necessary. The EUA must ensure that both health care providers administering and patients receiving the product are informed about the circumstances of the product’s EUA and the risks.Footnote 83 As with medical devices generally, manufacturers of an unapproved product under an EUA must monitor the product and report adverse events,Footnote 84 as well as maintain records accessible by the FDA.Footnote 85 An EUA may also impose additional conditions relating to distribution, administration, and advertising,Footnote 86 or waive or limit compliance with other medical device regulations.Footnote 87 For example, while EUA products are generally expected to comply with CGMPs, a specific EUA may waive CGMP requirements on a case-by-case basis.Footnote 88 Prescription requirements may also be waived based on the circumstances of the emergency.Footnote 89
An EUA will specify the effective date and generally remain in effect for the duration of the EUA declaration under which it was issued.Footnote 90 The FDA can revoke an EUA earlier, however, if the criteria for issuance are no longer met or as appropriate to protect the public health and safety.Footnote 91 The FDA should periodically review the circumstances of an EUA, including those that might warrant revocation, and regularly assess the progress made on approval, licensure, or clearance of the EUA product.Footnote 92 Significant adverse inspectional findings at the manufacturing site, reports of adverse events linked to the EUA product, product failure, product ineffectiveness, material changes in the risk/benefit assessment, approval status changes, or a request from the manufacturer may all warrant EUA revocation.Footnote 93
In the case of diagnostic tests, an EUA may indicate whether the test is categorized so that it may be performed at a point-of-care setting, such as through testing kits, or only in a laboratory certified for high complexity testing.Footnote 94 Along with additional conditions for testing EUAs, the Clinical Laboratory Improvement Amendments (“CLIA”)Footnote 95 govern COVID-19 diagnostic and serology testing in laboratory settings. CLIA certification requirements help to ensure that test results are reliable and accurate,Footnote 96 primarily done by assessing an LDT’s analytical validity, or whether the test performs as intended, after the laboratory has already started testing.Footnote 97 CLIA plays an especially important role in respect to LDTs, to be discussed later on.Footnote 98 Whether the FDA has authority to require premarket review of LDTs, or EUAs for LDTs developed at CLIA-compliant high complexity laboratories, is unclear.Footnote 99 This Note discusses EUAs, as well as both successes and revocations, for four types of medical devices needed in the pandemic response.
1. The PREP and CARES Acts
The Public Readiness and Emergency Preparedness (“PREP”) Act and the Coronavirus Aid, Relief, and Economic Security (“CARES”) Act are other laws outside the FDCA relevant to medical devices during the pandemic.Footnote 100 The PREP Act authorizes the DHHS Secretary to issue a declaration providing immunity from liability, except for willful misconduct, for claims of loss involving medical countermeasures used in public health emergencies.Footnote 101 DHHS Secretary Alex Azar has issued several PREP Act declarations to provide liability immunity for medical countermeasures responding to COVID-19.Footnote 102 Additionally, the CARES Act established a new category of covered countermeasures eligible for liability immunity during the pandemic.Footnote 103 The PREP Act declaration gives liability immunity to any antiviral, drug, biologic, diagnostic, respiratory device, other device, or vaccine used to treat, diagnose, cure, prevent, or mitigate COVID-19 or the transmission of SARS-CoV-2.Footnote 104 These benefits are especially important for commercial manufacturers and distributors who may need incentive to develop needed medical devices during the pandemic.Footnote 105
IV. FDA RESPONSE TO THE COVID-19 PANDEMIC AND EMERGENCY USE AUTHORIZATIONS
The FDA has granted EUAs and issued various guidance documents throughout its pandemic response with varying levels of success. FDA decisions regarding EUAs for four medical devices—face masks and facepiece respirators, ventilators, diagnostic tests, and serological tests—demonstrate these varying outcomes. They reflect the FDA’s hands-off approach in regulating essential devices despite the public’s heightened reliance on such devices in a large-scale crisis. These circumstances ultimately emphasize the dangers of lessening premarket review standards and the importance of postmarket surveillance, while highlighting a need for consistency. Notably, these shortcomings are not completely rooted in emergency circumstances, as the identifiable issues echo the weaknesses in medical device regulation as a whole.
A. Face Masks and Respirators
PPE have been subject to sporadic shortages since the beginning of the pandemic, putting health care workers and patients at risk.Footnote 106 Face masks, face shields, and respirators are generally regulated as Class II medical devices, though face masks used by the general public are unclassified to allow for “enforcement discretion” during the pandemic.Footnote 107 The FDA has issued numerous EUAs for filtering facepiece respirators used by health care providers, including those approved by the National Institute for Occupational Safety and Health (“NIOSH”),Footnote 108 imported disposable filtering facepiece respirators (“FFRs”) from certain jurisdictions,Footnote 109 and disposable FFRs manufactured in China.Footnote 110 The FDA has also issued an EUA for face masks for general public use, though these face masks are not intended for PPE use by health care providers.Footnote 111
Under FDA guidance, face masks used for a medical purpose, but not intended to provide liquid barrier protection, and surgical masks intended to provide liquid barrier protection are not required to submit a 510(k) premarket notification where the face mask does not create an undue risk.Footnote 112 Manufacturers must make their own safety determinations, including whether their mask meets fluid testing requirements, without submission of data.Footnote 113 Given the importance of masks for preventing the spread of COVID-19, one can argue that any mask without review creates an undue risk. For the most part, and despite large discretion given to manufacturers, these actions have succeeded in increasing the supply and availability of face masks for health providers and the general public.Footnote 114
These decisions produced some drawbacks, however. Originally, the FDA issued an April 2, 2020 guidance allowing distribution and use of certain respirators not FDA-cleared or authorized under another EUA.Footnote 115 In just one month between the April guidance and the subsequent May 2020 guidance, certain respirators underperformed and concerns over efficacy grew.Footnote 116 CDC testing revealed many respirators and protective face masks unreviewed by the FDA, particularly those subject to different international standards but also those measured by U.S. standards, had filtration efficacy as low as eleven percent.Footnote 117 The CDC also found a high prevalence of counterfeit products, meaning that some products had labels from legitimate manufacturers despite not being produced by those manufacturers.Footnote 118 The CDC has no way of verifying neither the authenticity nor the identity of counterfeit masks and respirators—a situation that proves to be especially concerning because some counterfeit products show poor filtration results.Footnote 119 The FDA discontinued its policy, recognizing the need for greater oversight of respirators to protect public health.Footnote 120 The FDA now recommends only using respirators that are FDA cleared or authorized under an EUA, though other respirators can still be used as face masks by the general public.Footnote 121
As the FDA seeks a balance between availability and efficacy during the pandemic, the reversal of this respirator policy exemplifies regulatory rollback due to safety concerns after no review was initially conducted. The CDC testing also mirrored the benefits of postmarket surveillance by providing the FDA an opportunity to correct itself before too much harm was done. Though the direct consequences of this lack of regulation are unclear, they have potential to be significant. These events also show that not all medical device developers can be trusted to conform to established standards. As such, issues with counterfeits and differing international standards demand further device review.
B. Ventilators
Ventilators and other life-saving medical devices for treating COVID-19 patients became scarce as the number of COVID-19 cases and hospitalizations rose quickly in March 2020.Footnote 122 In April, the United States had an estimated 60,000 to 160,000 ventilators, including those with only partial functionality.Footnote 123 At the time, the United States was expected to need several hundred thousand to care for COVID-19 patients; the country simply did not have enough ventilators to meet this estimated need.Footnote 124 Today, the FDA maintains a public and up-to-date list of devices in shortage, with three types of ventilators still in shortage since August 14, 2020.Footnote 125 Notably, as COVID-19 treatment has developed and the medical community turns to other options for breathing management, the need for ventilators has dropped.Footnote 126 In fact, the problem at the end of 2020 no longer seemed to be a shortage of ventilators but rather of critical care doctors with training to operate them.Footnote 127
In response to initial supply concerns, the FDA issued an umbrella EUA for ventilators, ventilator tubing connectors, and ventilator accessories that meet safety, performance, and labeling criteria.Footnote 128 Generally, most ventilators are Class II devices requiring 510(k) clearance on a showing of substantial equivalence to another device on the market.Footnote 129 High-frequency ventilators are designated as Class III and require even more review.Footnote 130 The EUA waived CGMPs and quality system requirements, reducing the quality controls for safety and efficacy, though the ventilators must still conform with authorization conditions outlined in the FDCA.Footnote 131
FDA guidance also encourages manufacturers with capability in other sectors to make ventilators and ventilator accessories under the umbrella EUA process.Footnote 132 Companies including General Motors, Ford, Dyson, Rolls-Royce, and Tesla shifted some of their manufacturing facilities to produce ventilators.Footnote 133 Despite the high stakes involved with ventilators as life sustaining devices, this FDA response is one successful example of EUA utilization that has yet to be met with negative consequences and rollback. Ventilators produced under EUAs have been successful and function properly. This success is partially because ventilators are not new devices created for the pandemic response, nor do they need to be adapted to address COVID-19 specifically.Footnote 134 In reality, most ventilators are likely “substantially equivalent” to ventilators on the market before the pandemic.Footnote 135 The FDA’s emergency review decisions and other similar standards should not be judged solely by their successes, however, and the inherent problems in low review standards will be discussed further.Footnote 136 Most significantly, the success of the ventilator EUAs can also be attributed to the umbrella EUA’s safety, performance, and labeling criteria because these requirements ensured premarket review.
C. Diagnostic Testing
Diagnostic testing for active COVID-19 is an essential part of the pandemic response.Footnote 137 For any return to a “new normal” and a safe lessening of restrictions, grand scale and regular testing is needed to contain and reduce community spread.Footnote 138 So far, the United States has been unable to meet testing demands, in large part due to supply shortages.Footnote 139 The Inspector General’s report to DHHS regarding hospitals’ pandemic response stated that hospitals saw their “most significant challenges centered on testing.”Footnote 140 “Severe shortages of testing supplies and extended waits for test results limited hospitals’ ability to monitor the health of patients and staff.”Footnote 141 The inability to meet testing demands further exacerbated other challenges, including bed availability, staffing shortages, patient care, and reducing community spread.Footnote 142 The importance of testing is—at least in the public health community—uncontested, and the FDA has sought to increase testing speed and availability by issuing EUAs to new products.Footnote 143
The FDA’s initial approach to the EUA process was, however, largely a failure with epic consequences during the early stages of its pandemic response.Footnote 144 The FDA issued its first diagnostic test EUA to the CDC on February 4, 2020.Footnote 145 The test took an extraordinarily fast seven days to develop, and was rolled out to testing facilities in all fifty states.Footnote 146 Unfortunately, scientists and lab technicians soon discovered the testing kits were faulty and produced untrustworthy results.Footnote 147 Many labs discovered their own solutions to make the tests work, but could not continue testing with the changes because the FDA required an EUA for COVID-19 LDTs.Footnote 148 The CDC took twenty-one days to approve a method to make the tests work; critical time to respond to the pandemic was lost and false results threatened public health.Footnote 149 Responding to criticism over the stringent EUA process from laboratories and commercial developers, the FDA authorized laboratories certified by CLIA to perform high complexity tests to develop and use their own COVID-19 diagnostic tests, followed by FDA notification and an EUA submission within fifteen days.Footnote 150 Given the massive consequences of the botched U.S. testing launch, the first COVID-19 diagnostic test EUA was considered a failure prior to its multiple amendments.Footnote 151
The CDC and FDA prioritized speed over accuracy and safety in the EUA process for testing,Footnote 152 raising questions about how safe accelerated review can be. Tests with consistently reliable results are crucial to the pandemic response and individual treatment decisions. As FDA Commissioner Stephen Hahn noted, “[f]alse diagnostic test results can lead to significant adverse public health consequences—not only serious implications for individual patient care but also serious implications for the analyses of disease progression and for public health decision-making.”Footnote 153 Lab technicians, many working in CLIA labs certified to perform high complexity testing, figured out the issue with the CDC tests and a solution long before the CDC or FDA but were unable to take action because the FDA required an EUA for COVID-19 LDTs .Footnote 154 If users could detect the problem so quickly, why did the EUA validation process not catch it before the test was approved and distributed? Since this rocky start, the FDA has issued EUAs for two major categories of diagnostic tests, including polymerase chain reaction (“PCR”) tests,Footnote 155 also known as molecular tests, and antigen diagnostic tests.Footnote 156 The FDA has issued 224 individual EUAs for molecular tests and seven for antigen tests,Footnote 157 as well as an umbrella EUA for molecular LDTs.
1. Laboratory Developed Tests
On March 31, 2020, the FDA issued an umbrella EUA for molecular LDTs for SARS-CoV-2 performed by laboratories certified under CLIA to perform high complexity tests, following its previous February 29, 2020 guidance.Footnote 158 Testing under this EUA is limited to the single CLIA laboratory that developed the test.Footnote 159 To be eligible, the LDT must be subject to an EUA request using either the CLIA EUA Template provided by the FDA or equivalent data.Footnote 160 FDA guidance provides that CLIA laboratories may begin testing while preparing their EUA request as long as the LDT has been validated and the laboratory has notified the FDA of the validation.Footnote 161 LDTs whose EUA request demonstrates their eligibility will be added to Appendix A list of authorized LDTs; so far, thirty-four LDTs are authorized under Appendix A.Footnote 162 While the FDA guidance is technically non-binding, there is a “practical binding effect” creating widespread compliance.Footnote 163
On August 19, 2020, DHHS announced that the FDA will no longer require premarket review of LDTs.Footnote 164 The notice clarified that while laboratories that develop and use LDTs may voluntarily seek FDA approval or an EUA, they are not required to do so.Footnote 165 Those that do not seek premarket review, however, will not be eligible for liability protections under the PREP Act.Footnote 166 The laboratories remain subject to CLIA regulation, and those with active EUAs are unaffected by the new policy.Footnote 167 The lack of required review for a medical device with such a dire impact is questionable, possibly echoing the early testing failure of the CDC and FDA’s teamwork. Proponents of the decision, however, argue that the FDA’s assertion that it could require EUAs for COVID-19 LDTs in its original guidance led to that initial testing delay.
Seven weeks later on October 7, 2020, the FDA announced it “is declining to review EUA requests for LDTs at this time.”Footnote 168 While concerning for safety reasons as described above and throughout this Note, this announcement is also particularly worrisome for LDT developers seeking the benefits of an official EUA or approval. Though the FDA has called into question the validity of current guidance, thereby implying revised guidance will be issued soon, whether the same benefits afforded LDTs authorized under an EUA will also extend to future LDTs that can no longer seek an EUA is unclear. For example, the CARES Act amended the Families First Coronavirus Response Act (“FFCRA”) to require that insurers cover certain COVID-19 tests authorized under EUAs without any cost-sharing requirements or prior authorization.Footnote 169 Another benefit for devices authorized under an EUA concerns liability immunity under the PREP Act.Footnote 170 Further, clinicians and other consumers often rely on FDA approvals to choose medical products, including COVID-19 tests, hurting both business for future LDTs and individuals far from laboratories with EUA approved LDTs.Footnote 171 On November 16, 2020, DHHS Assistant Secretary for Health and White House coronavirus testing czar Brett Giroir sought to reverse the decision and directed the FDA to review EUA applications for COVID-19 LDTs in a timely manner.Footnote 172 To date, the FDA has updated its website to reflect the reversal, though it is unclear whether the FDA has caught up with what is likely a backlog of requests.Footnote 173
The FDA has also given flexibility to state LDT authorizations. Beginning with a request from the New York Department of Health to authorize certain state laboratories to begin patient COVID-19 testing, the FDA stated on March 12, 2020 it would not object to this practice.Footnote 174 The next day, President Trump issued a “Memorandum on Expanding State-Approved Diagnostic Tests” and instructed the DHHS Secretary to facilitate state requests to authorize laboratories within the state to develop and perform COVID-19 tests.Footnote 175 The FDA’s official guidance on COVID-19 testing policies allows states to take responsibility for tests developed and performed by laboratories in their states.Footnote 176 A state may also authorize high complexity CLIA-certified laboratories to perform COVID-19 testing under its own authority and processes.Footnote 177 The laboratory need not notify the FDA if following this approval route, but rather must only adhere to the state procedures.Footnote 178 The FDA will not review state processes, but expects states to have a validation process.Footnote 179 The lack of FDA review of even the state’s own authorization processes raises concerns over proper review and oversight.Footnote 180 Nine states and territories have opted to authorize COVID-19 testing under their own policies and procedures.Footnote 181
2. Testing Accuracy and Risks
So far, no major issues have arisen involving the functioning of diagnostic tests and LDTs such as the problems presented with the initial CDC test EUA. The FDA has not revoked any EUAs for diagnostic tests, including the CDC’s.Footnote 182 Concerns still remain over testing accuracy, however.Footnote 183 The FDA holds out a minimum eighty percent sensitivity standard for diagnostic tests. Given the potential consequences of a test producing false negatives twenty percent of the time, this minimum standard is set too low.Footnote 184 Rapid tests, a new focus for test developers and the FDA, are, generally, less accurate than the “gold standard” reverse transcription PCR (“RT-PCR”) tests.Footnote 185 For example, the first antigen tests to receive EUAs demonstrated sensitivity ranging from 84% to 97.6%, but were often unable to detect antigen levels collected after five to seven days from symptom onset.Footnote 186 While the post-test probability of infection despite a negative test result can vary depending on an individual’s circumstances, including recent exposure, early symptoms, and community spread, tests with higher sensitivity can provide more confidence that a false negative has not occurred.Footnote 187 At the quality of current testing, one working study suggests that up to fifty-four percent of COVID-19 positive patients may have an initial false negative test result.Footnote 188 Diagnostic testing can only help open the country safely “if the tests are highly sensitive and validated under realistic conditions against a clinically meaningful reference standard.”Footnote 189 Steven Woloshin et al. suggest that ninety-five percent sensitivity is a better standard, despite inherent imperfections, because the high sensitivity level can guard against false negatives when coupled with lower pre-test probability—achieved by proper social distancing measures.Footnote 190 Many tests on the market report sensitivity of ninety-five percent or higher, so this standard is hardly unattainable.
We depend on the FDA for gatekeeping to ensure high quality results to safeguard our safety in this pandemic. While highly sensitive tests should not be discarded for failing to reach perfection, tests with lower sensitivity pose a risk to people who rely on the test’s results. The FDA recognizes that “[p]atients, as well as their physicians, depend on FDA to assure the tests they use to make medical decisions are accurate, reliable, and clinically meaningful.”Footnote 191 The risk is not only to the individuals receiving coronavirus test results, but to their communities who may be exposed by their reliance on a false negative. Tests that eventually prove to be ineffective after emergency authorization pose an even greater risk to the public.Footnote 192 This failure was precisely the issue with initial antibody tests.
D. Serological “Antibody” Tests
The FDA has issued EUAs for serological tests, “which can help identify individuals who have developed an adaptive immune response to the virus, indicating recent or prior infection, by detecting antibodies to SARS-CoV-2 in human blood specimens.”Footnote 193 Fifty-eight serological tests, also known as antibody tests, have been issued EUAs.Footnote 194 Serological tests cannot be used to diagnose active COVID-19 infection, however.Footnote 195 The FDA notes these tests are an important tool to help understand a population’s exposure to COVID-19 because people who have recovered from exposure to COVID-19 will likely have antibodies to SARS-CoV-2 in their blood.Footnote 196 Serological tests may provide information on disease prevalence and the frequency of asymptomatic infection as well as identify potential convalescent plasma donors.Footnote 197 The tests may be especially useful in settings where resources are limited, such as in health care and developing countries, because they have a quick turnaround time, cost relatively little, and have the capacity to be produced on a massive scale.Footnote 198
Serological tests come with limitations, however. Studies show that serological tests often do not provide the accuracy needed to produce reliable enough results for a targeted public health response.Footnote 199 Even the FDA recognizes that “all tests can provide at least some false results” and urges individuals to perform a serology test at least twice to produce reliable results.Footnote 200 Some experts emphasize a great need for high quality clinical studies to evaluate serological tests given their potential benefits.Footnote 201 Despite studies warning against early use of serological tests, especially for point-of-care testing, the FDA recently granted its first point-of-care antibody test EUA.Footnote 202
On March 16, 2020, the FDA published guidance that allowed serology tests to be marketed with only FDA notification and certain labeling requirements, but without the submission of an EUA or evidence of accuracy.Footnote 203 The move was intended to expand the number and variety of diagnostic tests and encourage development of serology tests.Footnote 204 In addition to this policy, the FDA issued an umbrella EUA for commercial serological tests that are evaluated by the National Institutes of Health’s (“NIH”) National Cancer Institute (“NIC”).Footnote 205 As a result, commercial serology tests on the market were fairly inaccurate and inappropriately promoted,Footnote 206 with numerous manufacturers marketing fraudulent tests and making fraudulent claims.Footnote 207 This put the public at risk because, as the FDA recognized in its statement on the original March 16, 2020 policy, “[i]naccurate diagnoses during a pandemic can impair prevention efforts and delay appropriate treatment for sick patients.”Footnote 208 Officials and experts grew weary of faulty serological testing, especially concerned over the use serological tests to issue immunity passports or certificates or make point-of-care diagnoses.Footnote 209
The House Committee on Oversight and Reform investigated serology tests and found that the FDA’s inability to validate the accuracy of antibody tests already on the market and failure to review any rapid antibody test kits before they went on the market allowed manufacturers to make fraudulent claims about test efficacy.Footnote 210 The report lambasted the FDA’s handling of serological tests, stating, “[the] FDA has failed to police the coronavirus serological antibody test market, has taken no public enforcement action against any company, and has not conveyed any clear policy on serological tests.”Footnote 211 In a briefing on the role of serological testing in response to the pandemic, medical experts called the FDA’s March 16, 2020 policy “a colossal failure.”Footnote 212
After the Committee urged Commissioner Stephen Hahn to update the FDA’s policies and guidance on serological testing,Footnote 213 the FDA reversed course and put stricter rules in place for the tests.Footnote 214 The new policy instructs commercial serological test manufacturers to notify the FDA of validation before distributing the tests and then submit an EUA request within ten business days.Footnote 215 The policy also sets forth performance threshold recommendations for specificity and sensitivity.Footnote 216 CLIA-certified laboratories can still develop serology tests in accordance with the notification and labeling requirements originally prescribed in the March 16, 2020 policy.Footnote 217 The FDA also began publicly posting test performance data from NIH’s NIC validation studies.Footnote 218
The umbrella EUA for serological tests evaluated by the NIH’s NIC continued, despite the fact that no tests met the criteria for authorization, until its revocation on July 21, 2020.Footnote 219 The FDA determined that revocation was necessary to protect the public health and safety,Footnote 220 given continued issues with inaccurate testing despite the updates on policy. The FDA preferred to issue individual EUAs for serological tests instead to allow broader scopes of authorization, unique conditions to address individual tests, and a more streamlined EUA amendment process.Footnote 221 While the FDA has granted forty-six individual EUAs for serological tests, it has also revoked two EUAs for tests that later proved ineffective.Footnote 222 The FDA found revocation necessary to protect the public health because of the risks accompanying false test results.Footnote 223 Further, published serology test performance data show some tests still have a high probability of producing false positive results,Footnote 224 particularly dangerous for those who misunderstand what the presence of antibodies can mean in terms of immunity. These rollbacks leave us questioning the validity of the medical device and testing EUA process for responding effectively to public health emergencies.
The FDA is well aware of the potential consequences of allowing a serological test on the market without proven efficacy. For example, the FDA regularly updates a “‘removed’ test list” for serological tests with significant performance problems, or those that do not submit an EUA request within ten days of marketing.Footnote 225 The FDA recommends that laboratories and health care providers stop using the tests on the list and remove remaining stock.Footnote 226 Most importantly, the FDA also recommends health care providers evaluate whether prior test results may have been incorrect, and whether the patient should be retested with an FDA-authorized test.Footnote 227 This recommendation, while certainly necessary, shows that the FDA recognizes its own regulatory failings in ensuring testing accuracy, and the possible consequences for patient care and public health.
The FDA prioritized the quick development and availability of serological tests over ensuring accuracy, efficacy, and safety. Similarly, the first EUA for the CDC’s diagnostic test prioritized speed over accuracy, a move which some have argued resulted in the fast and unmitigated initial spread of COVID-19 throughout the United States. There must be a better balance between the need for timely access to such tests and control measures to protect the public. While the FDA has sought to find this balance, the relaxed and fix-it-later nature of COVID-19 test regulations echoes the persistent problems with medical device regulation as a whole.
V. COSTS AND BENEFITS OF EMERGENCY USE AUTHORIZATIONS IN CRISES
While this Note highlights many of the FDA’s mistakes in its handling of medical devices during the pandemic, it also seeks to recognize the FDA’s successes. The creation of the EUA has given the FDA a crucial tool for responding to large-scale public health emergencies. For one, medical device EUAs allow the FDA and manufacturers to more quickly rollout essential countermeasure products. Medical device EUAs also ensure that desperately needed products not yet in existence before the crisis can be developed without the burden of various time-consuming and resource-intensive regulatory barriers. FDA requirements for investigational products are difficult to meet in emergency scenarios requiring mass distribution, and EUAs can allow for emergency uses that would otherwise violate the FDCA.Footnote 228 The PREP Act also provides important liability protections for EUA devices to remove risk for developers, thus incentivizing production.Footnote 229
Prioritizing speed and efficiency comes with some costs, however, as evidenced by the various EUA revocations over the course of the pandemic.Footnote 230 Medical devices under an EUA are held to a “may be effective” standard, providing “for a lower level of evidence than the ‘effectiveness’ standard that FDA uses for product approvals.”Footnote 231 Essentially, there is an inherent tradeoff between effectiveness and emergency response in EUA review. As discussed, this tradeoff can have drastic consequences during large-scale public health emergencies.Footnote 232 In the case of testing for contagious diseases, the potential risks that should be considered are not only those that are physical and directly related to the patient, but also those that affect the patient’s surrounding community.Footnote 233 Further, EUAs are often subject to little or no review to satisfy this “may be effective” standard, heightening safety risks and failing to ensure reliability.
The FDA has some discretion to waive and limit requirements for EUA medical devices, but the best response requires a balance between speed, effectiveness, and safety. The FDA should balance its major goal of protecting the public from unsafe and ineffective productsFootnote 234 with emergency preparedness, rather than forgoing one in favor of the other.
Ultimately, the FDA’s failings in its use of the EUA during the pandemic reflect many of the problems with medical device regulation generally, such as the 510(k) approval process. For example, the FDA’s EUA successes reflect an emphasis on review with an effective standard while its failures are rooted in lack of review. The EUA has proven to be a strong tool in the recent past when used with sufficient review mechanisms, such as during the Zika virus crisis.
A. The Zika Virus and Testing Emergency Use Authorizations
While EUAs have been issued in the past to address crises including the Ebola virus, H1N1 virus, the Middle East Respiratory Syndrome Coronavirus, and anthrax attacks,Footnote 235 the Zika virus response in particular shows how useful testing EUAs can be. Detection assay and diagnostic testing EUAs were one of the major factors that “triggered an international decline in the incidence of Zika.”Footnote 236 The FDA required and reviewed performance data before issuing an EUA for the first diagnostic Zika test in 2016,Footnote 237 presumably conducting more review than for the CDC’s COVID-19 diagnostic test EUA; that test was both developed and authorized under an EUA in just seven days.Footnote 238 Comparably, another CDC test for Zika, dengue, and chikungunya, took three months to develop before applying for an EUA.Footnote 239 Several EUAs for other Zika diagnostic tests followed and none experienced functioning issues or inaccuracies anywhere near the level of the initial COVID-19 diagnostic test EUAs.Footnote 240 Despite the potential for false positives, these tests were fairly successful in mitigating the impact of Zika in the United States.Footnote 241 Had the FDA given the same care towards its review of the CDC’s initial COVID-19 test, the test’s problems may have been identified before distribution and a massive failure could have been avoided despite the EUA ultimately being delayed.
Recently, LDTs for Zika have become more prevalent.Footnote 242 The FDA is requesting more information for review and urges that LDTs not be used for clinical diagnoses without FDA approval, reasoning that “it is essential that in vitro diagnostic tests for Zika virus provide accurate and reliable results.”Footnote 243 This level of attention to LDTs is in stark contrast to the FDA’s push to drop review of COVID-19 LDTs completely, including the (recently reversed) decision to decline to review voluntary EUA submissions.Footnote 244 Given the “relatively greater speed, stealth, and ease of the coronavirus’s spread,”Footnote 245 accurate and reliable diagnostic testing is even more crucial to the public health than in the case of the Zika virus. The differences in LDT EUA policies also reflect the longstanding and continuing debate over LDT regulation, highlighting the need for reform and clarification.
VI. IMPLICATIONS AFTER CRISIS AND RECOMMENDATIONS
Issues with the FDA’s medical device emergency response seem to generally mirror the criticisms of two regulatory areas: LDT regulation and 510(k) approval. While the COVID-19 LDT regulatory inconsistencies are the same obstacles faced by the FDA in non-emergent times, comparisons between the EUA process and the 510(k) program are more abstract. The nature of the 510(k) program emphasizes innovation and cutting corners in initial review, an attitude clearly articulated by the FDA in a few different instances throughout its emergency medical device decisions and guidance. The lack of premarket review in favor of innovation is not exclusive to the 510(k) and EUA programs, but also remains a core argument in the LDT regulation debate. Reform is needed to increase premarket and postmarket review generally, and legislation seeking to do so already exists for LDTs.
A. Laboratory Developed Tests Advisory Beyond COVID-19 Testing
LDTs historically have not been subject to premarket review and other FDA requirements, and are regulated almost entirely by CMS under CLIA.Footnote 246 LDTs were once simple lab tests of limited availability but have now evolved and proliferated significantly due to advances in technology.Footnote 247 “Some LDTs are now more complex, have a nation-wide reach and present higher risk.”Footnote 248 Several high-risk LDTs have demonstrated significant issues including claims unsupported by evidence, erroneous results, and data falsification.Footnote 249 There has thus been a push in recent years for more FDA involvement in LDT oversight.
The problem here is that there is no explicit grant of authority to the FDA to regulate LDTs.Footnote 250 The FDA regulates products, and LDTs have generally been regarded as services.Footnote 251 LDTs also technically fit the FDA’s definition of medical devices, however, because they consist of “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article … intended for use in the diagnosis of disease or other conditions.”Footnote 252 An LDT is a type of “in vitro diagnostic test” as included in the definition of medical device.Footnote 253 The FDA asserts that it has always retained authority to regulate LDTs despite its enforcement discretion general practice and policy.Footnote 254
For the past decade, the FDA has sought to enhance its regulatory oversight of LDTs.Footnote 255 The FDA developed draft guidance in 2014 but opted not to issue a final guidance in favor of awaiting a legislative solution.Footnote 256 Various actions, including the call for Zika test LDTs to submit an EUA request for review, have continued to blur the precise limitations on the FDA’s current authority over LDTs.Footnote 257 For example, DHHS’s announcement that it will no longer require premarket review of LDTs seemed to recognize the limited nature of the FDA’s authority to regulate LDTs and clarify CLIA’s almost exclusive role.Footnote 258 DHHS clarified that LDTs may still voluntarily apply for an EUA, which can offer substantial benefits during public health emergencies, further confusing the FDA’s authority to conduct premarket review of LDTs.Footnote 259 The confusion was only intensified by the FDA’s decision, and then reversal, to stop reviewing EUA requests for LDTs.Footnote 260
The reality that the FDA may not have authority to require EUAs for LDTs, along with the fact that FDA guidance is non-binding, could jeopardize the FDA’s influence over LDTs in emergency times if an LDT developer were to challenge it.Footnote 261 Further, the lack of clear statutory margins for the FDA’s authority may have contributed to the major delay in testing development seen in February upon the distribution of the CDC’s failed initial COVID-19 diagnostic test.Footnote 262 Given the significant problems that can arise from faulty LDTs,Footnote 263 the FDA would want to establish controls in a time of crisis. Accurate, reliable, and timely testing is more essential during public health emergencies than any other time. But there must also be a balance between increasing the availability of testing—or just developing a test, for that matter—and ensuring that tests produce reliable results. Ultimately, the FDA’s assertion of emergency authorities over LDTs, lacking full statutory support, failed to find this balance.
1. The VALID Act as a Potential Solution
The pandemic response highlights the desperate need for legislative reform concerning LDTs. Two opposing bills were introduced early on in the pandemic to address this need: The Verifying Accurate Leading-edge IVCT Development Act of 2020 (“the VALID Act”)Footnote 264 and the Verified Innovative Testing in American Laboratories Act of 2020 (“the VITAL Act”).Footnote 265 The VALID Act is a bipartisan effort to grant FDA authority to regulate LDTs through a risk-based framework that categorizes LDTs as high risk or low risk.Footnote 266 The VITAL Act, on the other hand, would clarify CLIA’s sole authority over LDTs and exclude the FDA from LDT oversight even during public health emergencies.Footnote 267 The VITAL Act accomplishes little more than ensuring that FDA guidance never seeks to require anything of LDT developers again, as CLIA already regulates LDTs. It also seeks to alleviate concerns that a new LDT framework could disrupt innovation and limit patient access by placing undue regulatory burden on laboratories.Footnote 268 But the VITAL Act does nothing to address the regulatory inconsistencies between LDTs and other diagnostic tests or concerns over testing accuracy.
The VALID Act, on the other hand, seeks to solve the current regulatory problems with LDTs. For example, the FDA has argued that CLIA only addresses analytical validity while ignoring clinical validity,Footnote 269 and cites to examples of public health harms when LDTs were later found to be clinically invalid.Footnote 270 The VALID Act would apply a standard of review considering both analytical and clinical validity.Footnote 271 The Act attempts to align LDT regulation with existing medical device regulations while also diverging in discrete ways to adapt to the idiosyncrasies of LDTs.Footnote 272 While not perfect,Footnote 273 the VALID Act proposes a workable framework to guide the FDA in shaping its new regulations and guidance documents with substantial opportunity for industry input. A more nuanced approach considering the policies that have performed well for low-risk and traditional tests could provide the needed modifications to satisfy both regulators and industry, especially smaller labs.Footnote 274 Perhaps most importantly, however, the VALID Act seeks to fix the regulatory inconsistencies between LDTs and other diagnostic tests by regulating LDTs in a clear, standardized manner.
Enacting the VALID Act would also statutorily and clearly establish the FDA’s authority to regulate LDTs through EUAs, a notion emerging in 2020 guidance documents but questioned by some scholars.Footnote 275 “The proposed VALID Act would solidify the FDA’s authority to regulate clinical laboratories, granting powers that the FDA asserted without a clear statutory basis in COVID-19 EUA guidance documents.”Footnote 276 While some voice concern that granting the FDA power over LDTs in emergency situations will only cause further testing delays like that seen in February,Footnote 277 the EUA exceptions echo the edited FDA guidance released after the initial failures and the umbrella EUA for LDTs. The umbrella EUA served to expedite the availability of LDTs while also controlling for potential validity concerns and providing emergency liability protection to developers.Footnote 278 The guidance worked well, and over thirty-seven LDTs sought the benefits of an EUA despite the FDA’s questionable authority to require an EUA submission.Footnote 279
An adaptive legislative response is needed to address issues with LDTs both in emergency situations and generally, and the VALID Act presents a viable working framework. The Act would settle a longstanding debate overdue for a solution. Though the Act has some flaws and needs modification, the legislative process, as well as the regulatory process if enacted, provides opportunity for substantial editing. The bill should be reintroduced in the coming congressional session with modifications taking into account the parts of LDT regulation over the past decades that have worked well. Conforming parts of LDT regulation with the risk-based approach to medical device regulation can bring about positive changes, as the pandemic medical device response has highlighted the need for a more risk-based framework for both EUAs and medical devices generally.
B. Emergency Use Authorizations and 510(k) Approval: Parallels and Need for Reform
The deficiencies in the pandemic medical device response have reflected that the FDA should not sacrifice review in the name of speed and efficiency. Regulatory rollbacks after EUA devices proved ineffective, including the debacles with serology testingFootnote 280 and respirator policies,Footnote 281 particularly emphasized the need for scientific and risk-based review of medical devices in all circumstances. The call for an updated medical device review process with a more scientific, risk-based approach is far from new.Footnote 282 Comparisons between the controversial 510(k) approval process and EUAs can provide points for criticism, lessons on regulatory considerations, and recommendations for updates. Both processes involve a low standard of review, if any review at all, are subject to recalls or revocations, and have been met with wide criticism for prioritizing speed over safety.
At the heart of the matter, both the 510(k) process and EUAs are subject to a low standard of review, and the FDA emergency response often excuses review entirely. 510(k) review is subject to the logically flawed substantial equivalence standard, which does not evaluate safety, effectiveness, or the risks of the predicate device.Footnote 283 EUA review is subject to a “‘may be effective’ standard,” a term adopted by the FDA that admits the standard’s failure to fully evaluate effectiveness.Footnote 284 Neither standard is intended to evaluate the safety or effectiveness of medical devices. While the EUA standard at least considers the known and potential risks and benefits, in practice, however, evaluators have seemingly failed to recognize the full weight of some pandemic risks and often excused EUA review completely.Footnote 285 And though many devices subject to these standards end up being safe and effective, these successes cannot be a measure of the standards’ validity when they are meant to guard against faulty devices. Those failures are what ultimately underscore the standards’ flaws.
For example, the EUAs for ventilators were largely successful, possibly owing to the fact that ventilators are not novel devices nor need modifications.Footnote 286 The guidance allowing the distribution of respirators that were not FDA-approved or authorized under an EUA and its subsequent failures,Footnote 287 however, demonstrated how even devices that do not seem particularly novel or modified can be ineffective and should not be released to the market without review. Ineffective respirators and face masks also pose higher risks during a pandemic, warranting review in order to protect the public health.Footnote 288 The FDA’s emergency response is intended to include a risk-benefit analysis, even under its low “‘may be effective’ standard,”Footnote 289 but the FDA circumvented EUA review in many cases despite the high risks demanding the existence of high benefits to meet the standard. Just as the 510(k) process conducts no risk-benefit analysis, the FDA’s pandemic response often sidesteps this review. Ultimately, both the 510(k) program and EUA process, even with its risk-benefit analysis, subject medical devices to a fairly low standard that can in no way ensure reliability.
As a result, devices under both processes are often subject to recalls and revocations.Footnote 290 The recalls of 510(k) cleared devices are too numerous to estimate, though one study found that between 400 to 500 FDA recalls of 510(k) devices occurred annually from 2003 to 2009.Footnote 291 The presence of ineffective medical devices on the market poses potential safety risks that can jeopardize public health. For example, faulty and untested hip replacements with high failure rates drastically reduce quality of life, and malfunctioning infusion pumps can lead to serious injury and death.Footnote 292 The safety risks posed by medical devices during the pandemic are sometimes less direct, as is the case with testing. Though an inaccurate COVID-19 test does not physically harm the patient, “false results not only can negatively impact the individual patient but also can have broad public health impact.”Footnote 293 Other medical devices used in the pandemic can have more direct consequences, such as a malfunctioning ventilator or surgical mask.Footnote 294 The many 510(k) recalls, EUA revocations, and emergency policy reversals recognize the potential, and sometimes realized, safety risks in allowing a device on the market without proper review.
The FDA’s main responsibility is to protect public health by ensuring the safety, efficacy, and security of medical devices.Footnote 295 Yet both the 510(k) and EUA programs seem to prioritize speed and efficiency. The 510(k) pathway is meant to encourage innovation and competition by allowing devices to enter the market more easily and with fewer burdens than a full review process.Footnote 296 Its popularity and widespread use over the years have often led to the prioritization of the “fast-track” process over ensuring medical devices as safe and effective. The scientific and medical communities, industry, and the general public are now less confident in medical device regulation.Footnote 297 The EUA program and other FDA emergency authorities likewise seek to speed market entry and encourage medical device developers to contribute to an emergency response by lessening regulatory burdens.
Encouraging innovation and emergency preparedness should not come at the expense of ensuring safety and efficacy, however. There was no available COVID-19 test when the pandemic first hit the United States, and the rush to develop and distribute the CDC’s test led to the FDA skipping essential review. The FDA prioritized quick distribution over ensuring accuracy and reconsidering its LDT guidance, ultimately causing a disastrous delay to the U.S. pandemic response.Footnote 298 Innovation and emergency response should be priorities for the FDA, but only after safety and effectiveness. The 510(k) and EUA processes need reform to find a balance between timely authorization and control measures.
1. Evidentiary, Risk-Based, and Adaptive Review as a Starting Point for Reform
Given the similarities between the criticisms of the 510(k) and the EUA, the recommendations called for by multiple groups over the past decade to overhaul the 510(k) process can be adapted and applied to EUA review and emergency policies. Similarly, lessons from the pandemic echo concerns for medical device regulation in general. Premarket and postmarket review are essential to an effective regulatory scheme, especially in public health emergencies. Reform for medical device regulation and EUA policies should focus on evidentiary and risk-based review, allowing for adaptation where emergency circumstances require it.
The substantial equivalence standard should be replaced with risk-based and evidentiary premarket review, and the FDA should require some practical evidence in its risk-benefit analysis before enacting all emergency guidance. IOM and other groups recommend overhauling the current 510(k) process in favor of a new regulatory framework that emphasizes evidentiary review and a risk-based approach.Footnote 299 IOM specifically focuses on the potential benefits of a modified de novo process, using a risk-based approach to assess practical evidence of safety and efficacy without the high evidentiary burdens of the PMA process.Footnote 300 EUAs are already subject to a risk-based approach, yet the FDA often requires no evidence or skips the review process entirely. As with LDTs, premarket validation of testing and other medical devices is necessary for a consistent regulatory approach. A standard that takes into account the potential risks of a device and the underlying circumstances is appropriate for EUA assessment to allow for an adaptive emergency response. Simply requiring some type of evidentiary review of devices before market should be the bare minimum, including in emergency situations.
The IOM also recommends implementing a more comprehensive strategy for postmarket surveillance, a particularly weak area of 510(k) regulation.Footnote 301 Postmarket surveillance allows regulators to better manage a device’s risk-benefit ratio over time and provides a control for correcting mistaken determinations on safety and efficacy.Footnote 302 Postmarket surveillance can be an especially important tool in managing and evaluating EUAs, and device developers are already required to report adverse events and maintain accessible records.Footnote 303 The FDA can use these reporting requirements to continuously assess low-risk devices that are granted an EUA under little evidentiary proof of efficacy and safety because they are ultimately needed for the emergency response. Postmarket review could be particularly appropriate in a circumstance where a new device is granted an EUA on a limited scale in order to collect information on its efficacy, similar in concept to the investigational device exemption. There may also be cases where an adaptive approach is needed, such as that of the testing guidance allowing LDTs with validation data to enter the market without submitting an EUA request for fifteen days. Of course, postmarket surveillance should not replace the initial premarket reviewFootnote 304 but rather serve as a supplement to balance the competing interests in speed and well-supported review in emergency situations.
The major takeaway in these recommendations is that FDA emergency response needs a more hands-on approach than was utilized in the first months of the pandemic. Particularly, the decisions to allow respirators and serology tests on the market without EUA review or postmarket surveillance showed the consequences of failing to conduct both premarket and postmarket review.Footnote 305 The hands-off approach to these devices is reminiscent of the 510(k)’s low standard for premarket review and weak postmarket surveillance mechanisms. Implementing recommendations to improve premarket and postmarket review, along with legislation to confer regulatory authority over LDTs, could provide consistency in the regulatory response to the next public health emergency. Most importantly, these recommendations seek to correct the witnessed imbalance between rapid response and ensuring safety and effectiveness.
VII. Conclusion
The pandemic tested the United States and the FDA in unprecedented ways, and reflection on the initial response is due. “While law is an essential tool of public health … . it should be subject to ongoing revision and reform, based on careful assessment, post disaster, of its application to given events.”Footnote 306 The pandemic response highlighted the shortcomings of medical device regulation, and this will certainly not be the last pandemic or public health emergency where the FDA will have to balance the need for timely availability with necessary control measures for safety, efficacy, and accuracy.Footnote 307 The FDA has sought to find this balance in its medical device emergencies policies, but many of its initial decisions failed to do so and rather reflected an attitude prioritizing innovation and speed, an attitude prevalent in current medical device regulation.
It would not be off base to say that the failings of some of the FDA’s policies and use of EUAs are unsurprising given the FDA’s relaxed approach to, and the lack of industry confidence in, medical device regulation. The 510(k) process and the debate surrounding LDT regulation are major controversies attributing to poor outcomes, confusion, and general lack of confidence. The policies involving four types of medical devices demonstrated how the initial emergency medical device response suffered from the same problems seen in the 510(k) and LDT regulatory landscapes. Though these policies were speedily reversed and replaced with working solutions, the consequences for the overall spread of COVID-19 are serious.Footnote 308
Recognizing how the relaxed and fix-it-later nature of the FDA’s initial pandemic policies is exemplified in both the attitude of the 510(k) program and the push for LDT oversight, and allows us to identify the overriding concerns and develop starting points for reform. The FDA is not inherently wrong in wanting to foster development and speed innovation,Footnote 309 but these priorities must ultimately be balanced with safety and efficacy controls. As such, medical device regulation reform must focus on balancing the competing interests in innovation, speed, and flexibility with safety, effectiveness, and accuracy. Introduction of legislation, such as the VALID Act, is one immediate action, while further development of a more evidentiary and risk-based approach to premarket and postmarket review will require more diligence over time. These reforms could prevent negative outcomes and reinvigorate confidence in medical devices.
