New FDA guidance aims to relax standards to boost device availability

Four new FDA guidance documents aim to make certain devices used to treat or detect COVID-19 more readily available. The changes will allow companies to market their devices more easily without needing to seek approval or clearance for certain changes.

 
To contact the author of this analysis, please email Laura DiAngelo.
To contact the editor of this analysis, please email Alec Gaffney.

Executive IQ Brief

  • How Things Work Now: Medical devices are typically subject to regulatory review by the FDA before they are allowed to be sold. These requirements apply to new devices as well as devices to which a significant change has been made. Changes can include things like new materials, a change to the manufacturing process, or the addition of new technologies.
  • What’s New: In the last week, the FDA has issued four guidance documents expanding regulatory flexibility to several medical device types in response to the COVID-19 pandemic. These include Extracorporeal Membrane Oxygenation (ECMO) and Cardiopulmonary Bypass devices, Ophthalmic Assessment and Monitoring devices, infusion pumps and their accessories, and electronic thermometers.
  • Impact: The policies are intended to both increase the supply of devices used to respond to the pandemic as well as promote the safety of health care providers by allowing for new technology that reduces the need for a provider to be in the same room as a patient with COVID-19. However, the FDA’s policies and regulatory burden may not be the most significant hold up in medical device supplies.
  • What’s Next: The guidance documents are only temporarily in force, and will be revoked following the conclusion of the Public Health Emergency (PHE) declaration. At that time, it’s not clear how device manufacturers who have invested in new technological capabilities for their devices, such as wireless connectivity, will be able to re-introduce these products to market.

Regulatory Background

Under the Medical Device Amendments of 1976 (MDA), medical devices are stratified into three regulatory categories based on their risk profile and intended use. This categorization determines the types of regulatory submissions that a device’s developer is required—or not required—to submit to the agency.


Class I and II devices (low to moderate risk) must generally submit a Premarket Notification, or 510(k) submission, to the agency to gain market access unless they are otherwise exempted. This application type requires that a device show its similarity (“substantial equivalence”) to an already-marketed “predicate” device—a standard which generally requires a relatively small amount of data. In contrast, the Premarket Approval (PMA) process, used with Class III devices, generally requires new clinical evidence about the device’s safety and efficacy.


Under Congressional direction, the FDA typically takes a “least burdensome” approach to device regulation, so several well-understood and very low-risk device types are exempted entirely from the 510(k) process so that the agency can redirect its resources to reviewing higher-risk or higher-impact devices.


Changes to a 510(k)

Developers that have a 510(k) cleared by the agency may update their devices over time to reflect current best practices, such as a new material that is more readily in supply or updates to a product’s software. While some small changes can be implemented under a standing 510(k), any “major change or modification” does require the submission of a new 510(k).


There is a defined, regulatory threshold that determines when a change is “major” and would require a new 510(k). Examples of major changes include modifications to the device’s “design, material, chemical composition, energy source, or manufacturing process.” This approach is meant to conform to an approach mandated by Congress which requires the FDA utilize a “least burdensome” process to review medical devices.


The types of changes that require a new 510(k) submission are things that will fundamentally alter the device or its use—such as a new manufacturing process, a new kind of material, or the addition of a new technology. Small changes like security updates in software typically do not require a new submission.


Regulatory Context

The COVID-19 pandemic has led to the FDA to release a significant amount of guidance documents and policies intended to support the development of new treatments and the increased availability of existing treatments.


For some medical devices, the FDA has offered significant new flexibilities often intended to waive the need for new submissions to update a product cleared under an existing 510(k). These policies, although typically limited to design or manufacturing changes (e.g., using a new source material or updating manufacturing processes to allow for greater distribution), could serve to expand the number of FDA-cleared devices that are available to providers.


The agency has also focused on provider safety—specifically allowing the use of Bluetooth or other remote-accessible technology into equipment so that providers are not in close contact with a patient infected with COVID-19. To date, the FDA has issued guidance allowing for modifications to respiratory equipment and accessories, ventilators, and personal protective equipment (PPE), as well as non-invasive remote monitoring devices themselves.


In addition to allowing modifications to cleared devices without new submissions, each of these guidance documents from the FDA calls for Emergency Use Authorizations (EUAs) from manufacturers or entities that don’t have a cleared product on the market. This would expand the number of products on the market by lowering the bar for new entrants. While for some products—such as N95 respirators—the agency has issued a blanket EUA covering all devices that have been cleared by certain other global regulators (e.g., the European Union), sponsors of other product types are encouraged to submit independent EUAs.


What’s New

In the last week, the FDA has issued four guidance documents expanding its flexible regulatory approach to additional products types.


These guidance documents cover Extracorporeal Membrane Oxygenation (ECMO) and Cardiopulmonary Bypass devices, Ophthalmic Assessment and Monitoring devices, infusion pumps and their accessories, and electronic thermometers. The documents are only in effect temporarily, and will be revoked following the conclusion of the Public Health Emergency (PHE) declaration.


ECMO and Bypass Devices

Extracorporeal (i.e., outside the body) breathing circuits, including ECMO machines and their accessories, are regulated under 21 CFR 870.411 as Class II devices. Cardiopulmonary bypass devices fall under several regulatory definitions and vary in Class accordingly.

These devices are intended to pump or oxygenate blood. COVID-19 infections often result in significant respiratory distress and low blood oxygen levels leading to acute patient distress or mortality. The devices can help mitigate the symptoms and effects of COVID-19 in lieu of an approved therapeutic to treat the disease.


In its new guidance, the FDA said it will exempt three ECMO device product codes from the usual requirement that the developer submit a new 510(k) for a “limited” change to the product. Additionally, the agency is exempting 31 product codes related to cardiopulmonary bypass devices, accessories and components from the same requirement. These products are regulated either as Class I or Class II devices, with several exempt from the 510(k) process.


Because cardiopulmonary devices represent circuit systems—requiring pumps, controls, valves, reservoirs, rollers, motors, and filters, among other components—each part of the typical circuit is included individually.


As with the previous guidance documents, the FDA outlines that any modifications for which the agency will not require a new 510(k) should be for a “limited modification” to the device’s design or indication and should not create undue risk. Aligning with previous policy, manufacturers need to clearly indicate which uses are cleared and which are not on the product’s labeling, and should provide a description of how the modification could be performed and factors that indicate a device should be changed out.


For these device types, the agency considers “limited modifications” to be changing a cardiopulmonary bypass device’s indication to support using it with an ECMO circuit for the treatment of COVID-19 patients. This includes indicating it for treatment of in individuals in acute respiratory failure and/or acute cardiopulmonary failure or to indicate its use for longer than currently allowed (6 hours) when used within the ECMO circuit. Additionally, manufacturers of both device types could alter the types of accessories cleared to use in the circuit (e.g., cannulae, tubing, filters, connectors) to support its use in a circuit, as long as those types of accessories don’t affect the blood flow rate.


The agency is also calling for EUA submissions for ECMO devices or cardiopulmonary bypass devices intended for use for more than six hours that are not currently cleared in the US. If authorized, the agency expects significant conditions of authorization to apply, including provider information about the product’s marketing status, monitoring and reporting of adverse events, and recordkeeping and reporting.


Ophthalmic Assessment and Monitoring

On March 22, the FDA issued guidance exercising enforcement discretion over modifications to remote monitoring products, excluding those for ophthalmic assessment and monitoring. On April 7, the agency expanded the policy to include these device types. Unlike the other recent guidance documents, those on remote patient monitoring devices are intended not to increase the supply of products needed to respond to the emergency but rather to help ensure provider safety by allowing them to keep physical distance from certain patients and reduce the risk of infection.

The scope of the new guidance is limited to certain visual acuity charts, visual field devices and general-use ophthalmic cameras, all of which are Class I devices that are exempt from 510(k) submission requirements. The guidance also covers tonometers (i.e., devices to measure interocular tension), which are Class II and subject to the 510(k) requirements.


Under the new policy, the Class I devices will be further exempt from meeting quality system regulation (QSR) requirements, reporting corrections and removals, and unique device identifier (UDI) requirements.


The limited modifications that the agency will allow without a 510(k) will be new indications allowing the product to be used in a separate location than originally intended (e.g., home use and/or consumer use), as well as fairly significant changes to the indication. These changes could include permitting the use of the device for a telemedicine visit or adding software or hardware that could facilitate remote access by providers, such as the addition of Bluetooth.


Tonometers, however, will still be subject to the QSR and other applicable requirements, although requiring a new submission for modifications that would have required a new 510(k) will be waived. The types of modifications that the FDA will be allowed are those that would be intended to support or provide adjunctive recommendations for ocular condition prevention, diagnosis, or treatment. That is, the device simply provides information to a provider, which they then independently review as a basis for treatment or diagnosis. This does not, notably, include any modifications to the device components that actually touch a patient’s eye, nor does it apply to any modifications that change the actual functionality of the device.


Aligning with previous policy, manufacturers need to clearly indicate which uses are cleared and which are not on the product’s labeling, and should provide detailed instructions for use that highlight the differences.


Infusion pumps and accessories

Although there are no FDA-approved treatments for COVID-19, patients with the virus are likely to require continuous infusion therapies when hospitalized (e.g., fluids, nutrition and medication) as it can cause organ system distress.


The new guidance extends the same type of enforcement discretion to these products, including four Class II infusion pump device types regulated under 21 CFR 880.5725 and 22 accessories, regulated under several citations and including both Class II and Class I products, as well as three 510(k) exempt Class I products.


Under the policy, the FDA will again waive the requirement that certain modifications to the device necessitate the submission of a new 510(k). This may increase the supply of products available to health care workers and encourage firms to develop innovations that could help minimize the exposure of healthcare workers to COVID-19.


The FDA will also allow modifications to the design and materials of the pumps or accessory systems to allow alternate accessories or suppliers. Further, the agency will allow the products to be used past their indicated shelf life and cleared duration of use. Both changes are intended to reduce potential shortages of essential components.


Aligning with previous policy, manufacturers need to clearly indicate which uses are cleared and which are not on the product’s labeling, and should provide a description of how the modification could be performed and factors that indicate a device should be changed out.


The agency is also calling for EUA submissions for infusion pumps and accessories from entities not currently engaged in medical device manufacturing, as well as manufacturers of devices that are not currently cleared in the US. If authorized, the agency expects significant conditions of authorization to apply, including provider information about the product’s marketing status, monitoring and reporting of adverse events, and recordkeeping and reporting.


Electronic thermometers

Fever is a common symptom of COVID-19, making electronic clinical thermometers a vital screening and diagnostic tool.


Clinical electronic thermometers are regulated as a Class II device under 21 CFR 880.2910.

Under this guidance the FDA will not require any entity to submit a 510(k) before making and distributing clinical electronic thermometers. In order to meet the distribution standards, the thermometer would need to either be authorized in another regulatory jurisdiction (e.g., European CE Mark) or meet the FDA’s thermometer standards.


These entities will also not be subject to additional regulatory requirements, including: UDI requirements, reports of Corrections and Removal, and registration and listing.


What’s Next

The FDA’s rapid-fire guidance issuance indicates that the agency is working to respond to device shortages in real time. As more hospitals and health systems face limited supplies while the outbreak continues, expect additional guidance from the FDA waiving certain specific regulatory requirements.


One interesting aspect to the guidance documents is how the FDA is weighing existing regulatory concerns with critical user concerns. For example, the FDA has recently warned companies about the use of Bluetooth technologies in their products due to potential cybersecurity concerns. However, the guidance documents permit the use of Bluetooth technologies to facilitate the remote use or monitoring of products by healthcare workers caring for patients with COVID-19. 


Although the guidance documents do state that the modifications to integrate wireless capacity into an existing device should include a cybersecurity plan, responding to those difficulties is notoriously difficult.


Even as the FDA moves to permit greater flexibility by companies, it’s not clear what impact these policies may have on patient access. Even simple changes to a device may take weeks or months to implement. Supplies may be difficult to ship internationally. Physicians may choose to modify devices on their own, such as New York physicians working to “split” ventilators to allow them to be used by multiple patients. Even if the FDA permits a device to be marketed, there may not be supportive payment policies in place.


In short: Much is beyond the control of the FDA, despite its efforts.


One other challenge facing companies is that the guidance documents will expire at the end of the Public Health Emergency declaration. However, it’s not clear how the modified devices will be tracked, or if they will be required to be removed from the market immediately. Based on their performance, the FDA could continue to allow some products to be used, or some companies may wish to seek clearance or approval for their devices.


It’s also unclear what the standards for legal liability might be for these devices, since they could fall under “failure to warn” lawsuits unless given proper legal liability protection (such as under an EUA).


Key Documents and Dates

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