Affidavit: Healthcare and the Law - Could COVID-19 Data Help Medical Device Manufacturers Accelerate the FDA Approval Process?

Contributors: Frederick Ball and Erin Duffy
To learn more about Frederick and Erin, click here.

Medical device shortages and shortcomings during the COVID-19 pandemic have led the Food and Drug Administration (FDA) to grant Emergency Use Authorization (EUA) to many medical devices manufacturers. Were it not for these EUAs, these manufacturers would be unable to market their devices, as their FDA applications would still be pending. Once the present “emergency” ends, these EUAs will expire, and manufacturers will again be unable to market their devices for the indications cleared under the EUA.

Still, the real-world evidence (RWE) gained about these devices while marketed under the EUA need not be lost with the passing of the pandemic. Once the pandemic ends, manufacturers should be able to use the data collected to support their pending applications for market clearance and for new indications for already-cleared devices.

When a manufacturer wishes to market a new medical device or market an already-cleared device with modifications or for new uses, it must obtain pre-market clearance, either through a Premarket Approval Application (PMA), a De Novo Classification Request, or a 510(k) submission.  In each case the applicant must show the device is safe and effective for the proposed indications for use.  For example, a 510(k)  must demonstrate a device is safe and effective by showing it is substantially equivalent to an already-cleared device. See id. §§ 807.92(a), 807.100(b). “[S]ubstantial equivalence” means the new device (1) has the same intended use as the predicate device and (2) either has the same technological characteristics as the predicate device or has enough data showing it is as safe and effective as the predicate device and does not raise different questions of safety and effectiveness than the predicate device. See id. § 807.100(b).

For devices found not to be substantially equivalent, or found to be substantially equivalent to a Class III (i.e., high-risk) device, manufacturers must seek a De Novo Classification or file a PMA.   Both the De Novo and PMA process have more stringent requirements than the 510(k) process.

EUA creates a fourth pathway.  During certain emergencies, as declared by the Secretary of Defense, Health and Human Services, or Homeland Security, the FDA may authorize the use of an unapproved medical device if that device is intended for use during such an emergency. See 21 U.S.C. §§ 360bbb-3(a)(1), (b)(1) (2017). The FDA may do so only if the following factors are satisfied: (1) the agent causing the emergency can cause a serious disease or condition, (2) the available scientific evidence shows the device may be effective in treating the disease or condition, (3) the known and potential benefits of the device outweigh its known and potential risks, and (4) no adequate, approved alternatives are available. See id. § 360bbb-3(c).

The data requirements for factors 2 and 3 are not particularly difficult to satisfy; whereas the 510(k), De Novo, and PMA processes require evidence of “effectiveness,” EUA designation only requires evidence that a device “may be effective.” FDA, Emergency Use Authorization of Medical Products and Related Authorities: Guidance for Industry and Other Stakeholders, 8 (2017). Given the lower bar, the FDA will consider most forms of scientific evidence when making an EUA determination, from device performance data to patient experiences. See id. at 8, 14-15. EUA applications should describe the device, its intended uses, its safety and effectiveness and its risks and benefits. See id. at 11-15. As mentioned above, EUAs usually expire upon termination of the relevant emergency declaration. See 21 U.S.C. § 360bbb-3(f) (2019).

Because EUA devices typically lack extensive clinical trial data, EUAs often rely on RWE — evidence of a medical device’s risks and benefits obtained from a source other than traditional clinical trials. See 21 U.S.C. § 355g(b) (2017). While traditional clinical trials typically occur in specialized, controlled research settings with specific populations and intensive data monitoring and auditing, RWE instead comes from analyzing real-world data (RWD). See FDA, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff, 24 (2017). RWD are data that concern patient health status or healthcare delivery and are collected routinely during the provision of healthcare; sources include electronic health records, claims and billing data, and disease registries. See id. at 4. Since RWE come from RWD, RWE sources can span the spectrum from observational studies within an existing dataset to large simple trials. See id. at 4, 8.

RWD must be relevant and reliable for FDA to consider the resulting RWE in deciding whether to grant EUA. See id. at 9, 12. RWD are relevant if they contain sufficient detail to capture the device’s uses, the outcomes of interest and the questions of interest, and are interpretable using informed scientific judgment. See id. at 13. Whether RWD are reliable depends on how they were collected and whether adequate processes were in place to assure data quality. See id. at 15.

The FDA expects to use RWE in EUA determinations, and has done so recently, given that traditional clinical trial data are often unavailable for such devices. See FDA, Emergency Use Authorization, 13 (2017). Examples of RWE considered in granting EUAs in the COVID-19 emergency include: bench performance tests used to approve the Airway Dome for HCPs; data extrapolated from the “reported clinical experience” used to approve the Impella RP system manufactured by ABIOMED; and ECG and echocardiogram datasets from electronic health records used to approve the ECG Low Ejection Fraction Tool (ELEFT), a software intended to be used by healthcare professionals to provide an assessment of Left Ventricular Ejection Fraction (LVEF) for use as a diagnostic aid to screen for potential cardiac complications associated with Coronavirus Disease 2019 (COVID-19) or underlying cardiac conditions that may affect clinical management of COVID-19. See IkonX, Inc., FDA Emergency Use Authorization Letter, 2 (July 24, 2020); Abdiomed, Inc., FDA Emergency Use Authorization Letter, 2 (May 29, 2020); Eko Devices, Inc., FDA Emergency Use Authorization Letter, 2 (May 11, 2020).

When the COVID-19 EUAs expire, device manufacturers should be able to use the RWE in their EUA applications and the RWE generated by their EUA use to support their pending applications for both marketing clearance and additional indications for already-cleared products.

Manufacturers could simply utilize FDA’s existing supplementation processes to provide newly acquired RWE. For example, PMA applicants may amend pending applications and must periodically update them with new data “that may reasonably affect an evaluation of the safety or effectiveness of the device.” 21 C.F.R. §§ 814.20, 814.37 (2019).  With pending De Novo Requests or 510(k)s, we suggest that applicants approach the FDA with a proposal of how best to incorporate RWD and RWE generated during EUA use.

To be sure, supplementing an application with additional data requiring review may not accelerate the process. Still, more data indicating a device is safe and effective should make it more likely for the FDA to conclude the device is safe and effective (or not, as the RWE may suggest) and enable the FDA to draw its conclusion faster. Therefore, manufacturers should be able, and encouraged, to support their device applications using all of the available RWE once the devices’ EUAs expire.


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