The Food and Drug Administration (FDA or the Agency), the US regulating authority responsible for medical devices regulation, issued guidance dedicated to extracorporeal membrane oxygenation and cardiopulmonary bypass devices in the context of the Coronavirus Disease 2019 (COVID-2019) caused by the “novel coronavirus” – the virus “SARS-CoV-2”. Due to the public health emergency announced in the US earlier in March 2020, the document is intended to be implemented immediately without prior public discussion, while the industry representatives would still be allowed to submit their suggestions and feedbacks. It is also important to mention that the present enforcement policy would remain effective only during the public health emergency.
ECMO Regulation Overview from the FDA
The document is intended to implement the measures necessary to ensure the availability of the extracorporeal membrane oxygenation (ECMO) devices used in the appropriate therapy.
The scope of the guidance covers extracorporeal circuits and accessories thereto used to treat patients with long-term respiratory/cardiopulmonary failure. In particular, the devices of this type are used to sustain extracorporeal circulation and physiologic gas exchange of the patient`s blood. These devices are regulated under 21 CFR 870.4100 and are intended to be used for more than 6 hours, while the scope of the document also covers the cardiopulmonary bypass devices subject to regulation under the Subpart E thereof, intended to be used for relatively shorter periods (up to 6 hours).
The document addresses the devices used to pump blood or oxygenate blood by maintaining its movement to pumping/oxygenating components, keeping control over the pump speed, gas flow or temperature of the blood.
The FDA explicitly states that medical devices intended to remove extracorporeal carbon dioxide are falling outside of the scope of the enforcement policy while the manufacturers may apply for the Emergency Use Authorization (EUA) – a special procedure to make critical supply medical devices available within the relatively short period of time.
ECMO Devices Enforcement Policy from the FDA
The importance of the devices providing long-term extracorporeal oxygenation increased significantly due to the numerous cases of the acute respiratory failure caused by the novel coronavirus. Thus, the FDA focused on ensuring the availability of ECMO devices to healthcare institutions. At the same time, the Agency states that approved cardiopulmonary devices could be also used for long-term extracorporeal oxygenation (longer than 6 hours) instead of ECMO devices.
As an extraordinary measure, the authority also stated that it would not object to certain changes to the design and/or indications of the devices covered by the scope of the guidance, that have been previously approved by the FDA unless such modifications result in a significant increase in risk to the patients` health. This allows medical device manufacturers to implemented changes and modifications to the FDA-approved devices without the submission of the 510(k) Premarket Approval Application (PMA). The Agency also emphasizes the importance of taking into consideration the compatibility issues since cardiopulmonary bypass systems could include numerous elements and components.
To assist medical device manufacturers in making modifications in compliance with applicable regulation and also the additional requirements and exclusions set forth by the present enforcement policy, the Agency provides a list of changes to the cardiopulmonary bypass devices that are not leading to excessive risk including, inter alia, the following ones:
- Changes to the indications regarding the use of the device as an element of the ECMO circuit,
- Changes to the indications regarding the possibility to use the device for a period of time exceeding 6 hours (which is the basic limit for this type of devices in accordance with the general rules),
- Changes to the dimensions of tubing or other accessories that are not affecting the flow rate (this provision is also applicable to the ECMO devices).
At the same time, the authority also provides examples of modifications that could lead to a significant increase in risk to the patients` health that is unacceptable:
- Any changes to the coating,
- Modifications impacting the gas transfer performance of the device, including changes to the dimension of the gas exchange fiber or its type, as well as any changes to the surface area of the fiber mat.
Additional Requirements for ECMO and Cardiopulmonary Bypass Devices
According to the guidance, any changes to the FDA-cleared device should be clearly indicated in its labeling. In particular, the following requirements should be applied to the labeling of the device subject to the limited modifications:
- The detailed information on the amended indications or characteristics of the device, including the description of the performance of the device, durability testing and clinical performance, and also the information on potential risks associated with the use of the device for ECMO treatment purposes.
- The detailed description of signs indicating that the device should be changed out without regard to the period of time it has been used.
- Details on use conditions.
- The information explicitly outlining the FDA-cleared indications from those changed by the manufacturer without applying for prior approval.
- An indication stating that certain changes have not been approved by the regulating authority.
The Agency also recommends implementing any changes and modifications in accordance with the applicable international harmonized standards recognized by the FDA. The manufacturers shall also properly document any changes made to the device. Such information should be duly kept and provided to the regulating authority upon demand.
Under the general rule, it is advised to use FDA-cleared devices. At the same time, the authority acknowledges the importance of expanding the scope of the devices available to avoid shortcomings. For this purpose, the manufacturers producing ECMO and cardiopulmonary bypass devices could apply for the Emergency Use Authorization (EUA) allowing them to make their devices available under the accelerated procedure. To commence the process for both domestic and foreign medical devices, the manufacturers should submit to the authority the following information:
- The information about the manufacturer, including the name, address and contact information.
- The information about the device in question, including the name and brand name, model, and also the details on marketing authorization obtained in the country of origin.
- Sample of the labeling of the device.
- Copies of marketing authorization certificates and additional documents demonstrating conformity with safety and performance requirements.
- Data on the performance of the device regarding its availability for long term use.
- Indication of the recognized standards the device complies with.
- Information regarding power supply and compliance with the applicable US standards.
The authority would assess the information provided and contact the manufacturer to inform about the further steps to be taken if the device would be found suitable for the EUA application. At the same time, the Agency is entitled to notify the applicant that it would not object to making the device in question available in the US during the preparation and review of the EUA request.
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