R&Q's May 2020 webinar focused on FDA Emergency Use Authorization (EUA) process and EU MDR Article 59 to release devices needed for prevention and treatment of COVID-19. In this blog post, our knowledgeable FDA and EU MDR regulatory experts sat down to provide answers to your questions from the webinar and we hope that they will shed some light on similar questions that you may have on the topic.
In response to the COVID-19 global pandemic, health authorities are taking the necessary steps to allow for greater access to and use of critical medical devices and PPE that are in short supply. However, some manufacturers lack the necessary regulatory approvals needed to make their medical devices/PPE available. In situations such as these, both the United States (FDA) and European Union (European Commission) have legislation in place to help bring these critical products to patients and healthcare workers for emergency applications.
R&Q is here to help address any other questions that you may have regarding EUA or EU MDR Article 59 related topics. Contact us today to find out how we can help! If you were not able to attend this webinar, here's a link where you can sign up to view the on-demand version (and download the slides).
Q: Should we consider a modification to the product for a new 510(k) submission?
A: Yes, after the EUA is terminated, all unapproved devices will need to be recalled. Any changes which were made during the pandemic and not submitted to FDA will still require a 510(k). If you want to continue to market product incorporating the modification afterward, now is a good time to consider your regulatory strategy and approach for getting it cleared through FDA.
Q: Do you see the recently revised MDR updating Article 59 to be used as part of the roll out of the MDR?
A: Yes, this is already in use. The revised EU MDR was adopted on April 23, 2020 and entered into force on April 24, 2020, including Article 59. Implementation of the common specifications was rescheduled from May 26, 2020 to May 2021 due to Coronavirus. However, to allow for greater response to the pandemic and public need, Article 59 was made active on April 24, 2020.
It is difficult to trace exactly what devices are being brought to the EU market via Article 59, due to EUDAMED not currently being active. But most likely there are emergency use devices already being distributed in member states, as approved by the associated Competent Authority.
Q: Any FDA emergency approval avenues for Telehealth/Digital Health solutions? Some of these classify as medical devices but often are not in the diagnostic space but could provide reimbursable monitoring solutions that may/may not need FDA compliance.
A: Currently, there do not appear to be any EUAs but there are several Guidance Documents focused on Telehealth/Digital Health, including “Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency” issued in March and updated in June. If your device can help address the pandemic, we recommend first identifying if your device is included in the scope of any of the relevant Guidance Documents.
Q: If a medical device for reconstitution and transfer is required for COVID-19, how long and what are the minimum requirements to be approved under EUA?
A: Unless otherwise specified, the EUA will remain in effect for the duration of the EUA declaration under which it was issued. The minimum requirements are dependent on the specifics of the device. As of writing this answer, there does not appear to be an active EUA or Device Specific Guidance Document for the device you are describing. If eligible for an Emergency Use Authorization, the FDA will establish the conditions of Authorization that must be met to sell the product. We recommend submitting a pre-EUA notice to FDA to see if your device qualifies.
Q: Can you make modifications to your device after your EUA is authorized?
A: Yes, some modifications can be made to the device under the same EUA if they are agreed upon with the FDA.
Q: In your experience, how much advanced notice does the FDA give manufacturers before the EUA is revoked?
A: Per Section 564(b)(3) of the Federal Register, the Secretary of Health and Human Services must provide advance notice that is sufficient to allow for the disposition of an unapproved product, and of any labeling or other information provided related to unapproved use of an approved product. Historically, we have seen these termination or revocation letters typically give two days of notice. However, most emergencies in the past have had relatively few EUAs issued and most were for therapies or IVDs. The FDA reviewers that we are in contact with have told us that the conditions and timing of EUA terminations for the COVID-19 emergency are under discussion per Senior FDA Management.
Q: If you distribute a product under EUA now, then submit 510k, can you keep the product under EUA in the market until you get 510k clearance? Or do you need to recall devices after pandemic in the interim period?
A: The device can only be distributed if the EUA is still active or if the device has 510(k) clearance. If the EUA is terminated and the device has not received 510(k) clearance, the device will need to be recalled. However, please note that the FDA is encouraging companies to submit their 510(k) and have stated that they will review products intended to address COVID-19 as quickly as possible.
Q: EUA for therapeutics, still require clinical studies or can EUA be used as FIM for previously approved therapeutic with a different route of administration?
A: Depending on the therapeutics, this could be possible if there are no other available treatments. We have seen situations where FDA has expanded access for IND therapeutics to allow for increased availability for patients and providers. Additionally, EUAs with very limited Phase 3 clinical studies for therapeutics have been authorized for a set of different indication for use. It is important to note that to obtain expanded access or an EUA, you will still need to demonstrate that the treatment may be effective and that the risk-benefit profile is acceptable.
Q: Do you have experience with registering a ventilator under the exemptions for EU and US for a company that does not have ISO 13485/21 CFR 820 systems?
A: Yes, we have experience with ventilator applications and other medical device applications in the United States and European Union. While most GMP (21CFR 820) requirements are waived under the EUA, it is not possible to obtain approval in the EU under Article 59 without ISO 13485 certification.
Q: Would Hydroxychloroquine fall into the “May be effective” category (i.e. approved for malaria, but not for COVID-19), considering that Hydroxychloroquine "MAY BE EFFECTIVE" and has 65 years of safety data?
A: As of June 15, 2020 the FDA has revoked the EUA and released the followed statement, that can also be found on their website here:
"June 15, 2020 Update: Based on ongoing analysis and emerging scientific data, FDA has revoked the emergency use authorization (EUA) to use hydroxychloroquine and chloroquine to treat COVID-19 in certain hospitalized patients when a clinical trial is unavailable or participation is not feasible. We made this determination based on recent results from a large, randomized clinical trial in hospitalized patients that found these medicines showed no benefit for decreasing the likelihood of death or speeding recovery. This outcome was consistent with other new data, including those showing the suggested dosing for these medicines are unlikely to kill or inhibit the virus that causes COVID-19. As a result, we determined that the legal criteria for the EUA are no longer met. Please refer to the Revocation of the EUA Letter and FAQs on the Revocation of the EUA for Hydroxychloroquine Sulfate and Chloroquine Phosphate for more information."
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1) U.S. Food & Drug Administration (FDA). FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. Content current as of 07/01/2020. Accessed 07/06/2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or
2) U.S. Food & Drug Administration (FDA). Emergency Use Authorization: Emergency Use Authorization (EUA) information, and list of all current EUAs. Content current as of 07/06/2020. Accessed 07/06/2020. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization
3) U.S. Food & Drug Administration (FDA). Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency (Revised). Content current as of 06/05/2020. Accessed 07/06/2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-non-invasive-remote-monitoring-devices-used-support-patient-monitoring-during