The White House’s recent announcement that the Biden Administration plans to end the public health emergency on May 11th, 2023.

In a statement released on January 31st, 2023, the FDA indicates that manufacturers with Emergency Use Authorizations (EUAs) should consider the premarket submission process in order to stay on the U.S. market. The agency stated:

“Manufacturers are encouraged to pursue premarket submissions through the appropriate regulatory pathway (for example, 510(k), De Novo request, PMA) during the public health emergency so that devices authorized under an EUA can remain on the market after the EUA is no longer in effect” (read more).

While the public health emergency (319 PHE declaration) is ending, EUAs may still be granted (under section 564 declarations), but it is a good time to move towards traditional market pathways (510k, De Novo, PMA). If you will seek full FDA pre-market authorization and need any assistance with the application process, our team at CSSi LifeSciences is here to help. Simply reach out to us for support.

We understand that these changes can be overwhelming and want to ensure that you have all the information you need to make informed decisions. The FDA has provided a FAQ section with additional information, which you can access by clicking the link below:

 If you have any questions, please don’t hesitate to reach out to Damian Daszynski at ddaszynski@cssilifesciences.com. We are here to help.

Below are the key points discussed during the town hall meeting with the Agency regarding COVID test kits.

1. The SARS-CoV-2 reference panel for LoD is not available at this time.
2. 510(k) vs EUA
   1. No premarket authorizations have been granted; therefore, the first submission will be a de novo.  Once the de novo is cleared, product code established, and special controls written, all future submissions will be 510(k).
   2. Prior to submission of the premarket authorization, submit a presubmission including:
      1. Planned testing.
      2. Usability and label comprehension proposed testing.
      3. Proposal on plans to use testing from EUA for the 510(k) submission.
      4. OTC clinical data from EUA can be used to support 510(k) for both OTC and POC.
      5. If planning to leverage the analytical and clinical data used to support the EUA for the 510(k), need to fully explain how all data collected.  Of importance in the clinical will be the comparator used.  For analytical testing, multiple lots need to be tested.  Again, this information should be provided in the presubmission package.
   3. No separate CLIA waiver is needed if OTC or POC was authorized under EUA.
3. Timeline for conversion from EUA to full authorization
   1. Unlike the public health emergency that needs to be renewed every 3 months, the EUA declaration remains in effect until terminated by the HHS secretary.  The declaration is independent of the public health emergency.
   2. Companies are encouraged to move forward with plans for full clearance and should submit presubmission to the Agency.
   3. The question was asked if the transition from EUA to full authorization will occur in July.
      1. There is no end date for the EUA at this time.  Any closing dates being discussed are simply based on speculation and rumor.
      2.  The draft transition guidance needs to be finalized and published before the transition process can begin.
      3. Cannot predict when the final guidance will publish.
      4. The Agency will allow a transition period to allow products to stay on the market during the transition period.
      5. No transition date has been announced.  The final guidance will outline the timeline.
      6. The Agency is accepting EUA applications.  However, the Agency again reiterated that companies should proceed with submitting pre-subs for full authorization.
4. Data from current prospective clinical studies show large rates of low viral loads with omicron, in the range of 30-40%, resulting in lower performance by the OTC kits.  In the past the low viral load rate was 10-20%.  If the clinical study is completed and the low viral load is >20%, may be able to recalculate performance.  Submit all data and apply new analysis.  ( No details were provided on the new analysis.  Perhaps look at low viral load performance separately.)  If the clinical study has not started, submit a plan for analysis to discuss how data will be analyzed if high percentage of low positive.
5. For those companies interested in multiplex COVID and Flu testing
   1. Only prospective, freshly collected clinical samples can be used for the performance study.  The only exception they would consider is samples frozen in saline, however, they do not believe these samples exist.
   2. Flu A is present in the US; Flu B is not.  For Flu B, consider going to the southern hemisphere to get samples.
   3. Flu is not considered pandemic, only COVID, so the focus should be on COVID.  If sufficient samples have been obtained for COVID and not the flu, submit the results to the Agency and if authorized, mask the flu aspect of the test when released until sufficient flu data is available.
6. Kit Manufacturing
   1. There are limited QMS requirements at this time, but the Agency plans to expand the requirements.
7. Timeline to review EUA and PEUA
   1. The Agency continues to be challenged by the number of EUA and PEUA submissions.  EUA take priority over PEUA. If weeks have passed without a response, send email to templates.  Reviewer assigned should provide regular updates.
8. Q-Sub
   1. Not accepting all pre submissions at this time, with the exception being for COVID.
   2. The goal is to review all Q-subs, but not there yet, as COVID Q-subs take priority.  Therefore, the timing for other Q-subs is extended.
   3. The Agency prefers to respond to Q-subs via email.  Meetings take a long time and are reserved for those when email will not suffice.  This is due to resource limitations at the Agency.

Below are the key points discussed during the town hall meeting with the Agency regarding COVID test kits.

1. FDA is seeing a slow upswing in the prevalence of COVID-19, at approximately 5% in the US.  Therefore, the Agency does not see issues in obtaining positive samples from patients for either POC or OTC clinical performance testing.  Only freshly collected samples can be used, no frozen samples.
2. Agency is receiving 130/month PEUA and EUAs. They recently hired more staff and hope to reduce the expert review time for the EUA to 10 days.  Submissions will be prioritized based on submission data and production capabilities.  If questions are sent to the sponsor after the expert review, the Agency wants a response ASAP.
3. Expiration dating – Up to 6 months will be allowed based on accelerated tested.  Real time data is needed to extend the self-life beyond 6 months.
4. FDA prefers the OTC kits to have as few steps as possible.  They prefer OTC with pre-filled tubes.  They have seen usability issues when the lay user needed to add the diluent or buffer to the collection tube.  They have reports of people using the diluent as eye drops and dexterity issues adding the liquid.
5. Any non-COVID IVD submissions will have a longer review time.
6. Although the Agency requires a minimum of 500,000 kits/week be produced within 3 months of authorization, their expectations are for a much higher production capability.
7. For the POC kits, they are noticing some kits are not performing as well when symptoms have been present for 7 days versus 5 days.
8. For POC tests, the site should be able to perform high volumes of testing easily.
9. High sensitivity RT-PCR comparator – Agency said to confirm acceptance of the proposed test prior to starting the clinical study.  They would not confirm what the cut off was to be considered high sensitivity.  Stated they would confirm in PEUA.
10. Must report the Ct for the RT-PCR samples.
11. The GMP requirements for the CMO are more than previously needed.  The authorization letter will detail the GMP requirements for the product.  They stated if the CMO is experienced with manufacturing IVD kits, the GMP requirements should not be an issue.  If changing CMO or location of the CMO, submit update to the FDA.
12. On the call this week, unlike prior weeks, the FDA agents answered most questions referring participants to the guidance.