CDRH Virtual Town Hall #98

Monkeypox and COVID‐19 Test Development and Validation

November 30, 2022

CDR Kim Piermatteo: Hello and welcome everyone to today's Virtual Town Hall Number 98 for

monkeypox and SARS‐CoV‐2 test developers. Today, we will discuss and answer your questions about

diagnostic tests in response to the monkeypox and COVID‐19 public health emergencies.

This is Commander Kim Piermatteo of the United States Public Health Service, and I am the Education

Program Administrator within the Division of Industry and Consumer Education in CDRH's Office of

Communication and Education. I'll be your moderator for today's Virtual Town Hall.

Our panelists for today are Dr. Timothy Stenzel, Director of the Office of In Vitro Diagnostics, which is

also referred to as the Office of Health Technology Number 7, or OHT 7, in CDRH's Office of Product

Evaluation and Quality, or OPEQ.

Joining Tim is Toby Lowe, Associate Director for Regulatory Programs in OHT 7, and Dr. Kristian Roth,

Deputy Director of the Division of Microbiology Devices in OHT 7 as well, and Dr. Noel Gerald, Branch

Chief for Bacterial, Respiratory, and Medical Countermeasures in OHT 7 as well.

For today's Virtual Town Hall, we'll begin with opening remarks. Then, we'll answer your previously

emailed monkeypox and COVID‐19 test questions. And then, lastly, we will address your live questions.

As a friendly reminder for those of you participating live in today's Virtual Town Hall, please be sure you

have joined us today via the Zoom app and not through a web browser to avoid any technical issues.

Our last scheduled Virtual Town Hall for the calendar year 2022 will be on December 14th for both

monkeypox and COVID‐19 test developers. You may refer to our webpage titled “Virtual Town Hall

Series ‐ Test Development and Validation During Public Health Emergencies for COVID‐19 and

Monkeypox” webpage for details on all upcoming Virtual Town Halls. Links to both of these pages have

been provided on this slide.

The presentation and transcript for our last Virtual Town Hall for monkeypox test developers

specifically, which was held on November 9th, 2022, has been posted to CDRH Learn. I have provided a

screenshot on this slide of where you can find those materials within CDRH Learn.

I'd now like to welcome Toby, who will provide today's opening remarks. Toby, the floor is yours.

Toby Lowe: Thank you, Kim. Thanks everyone, for joining us for another town hall. Our initial update is

we just have one update to provide, and that is to share that, yesterday, we posted EUA templates for

antigen diagnostic tests for mpox, and those are available on our website, which is showing on the slide

right now. So that's the same place where the molecular templates are on our website as well. And with

that, we can move into the questions.

CDR Kim Piermatteo: Great. Thank you, Toby. We'll now answer your previously emailed questions

about monkeypox and COVID‐19 test development and validation. As always, please note, we do receive

some email questions that are too detailed or test case specific that we will not address during today's

Virtual Town Hall. For those questions, we will try to send a response in writing within a few days. If you

have submitted a question and do not hear it addressed today, please look for a written response. If you
                                   

                  

                             

                                     

                  

                                 

                               

                             

                    

                                   

                               

                            

                                     

                                

                                     

                                   

                                  

                                 

                               

                           

                                   

                            

                               

                               

                      

                               

          

                             

                       

                                 

                

                           

                                   

                    

                                 

                                 

                             

do not receive a response within a few days, please feel free to reach back out to the

MPXDx@fda.hhs.gov mailbox or the COVID19Dx@fda.hhs.gov mailbox for an update.

Toby, I'll be directing this previously emailed question about monkeypox test development to you. The

question is what are FDA's long‐term plans with the monkeypox EUA? Is there a time frame to keep it

open, since cases are decreasing in the United States?

Toby Lowe: Thanks, Kim. So as we've discussed here and in the guidance document, there is currently an

EUA declaration in place under Section 564 of the FD&C Act which declares that circumstances exist

justifying the authorization of emergency use of in vitro diagnostics for detection or diagnosis of

monkeypox. We cannot anticipate when that declaration may be terminated.

It's important to note that EUA declarations have historically been left open for quite a while to ensure

that public health needs are addressed, and this is seen with several previous public health emergency

declarations, including Zika, Ebola, and, obviously COVID‐19, which have not been terminated to date.

And we at FDA are committed to help ensure that the public has access to appropriate test options for

monkeypox, and we will continue to review EUA requests as needed to address public health needs.

CDR Kim Piermatteo: Thanks, Toby. As a second part to that question, the question is in the instance the

EUA is kept open, what would happen to the authorized ones in the case that any potential future

product is cleared? Will this affect and/or limit the status or validity of the previously authorized EUAs?

Toby Lowe: Thanks. So as with all EUA declarations and EUAs, unless revoked, the EUAs are in effect

until the EUA declaration is terminated. And those EUAs, the tests that are authorized under those

EUAs, should be maintained in accordance with the conditions of authorization. Clearance of future

products does not automatically mean that EUAs for other products will be revoked. As we can see with

the COVID tests, we can clear a 510(k) without revoking EUAs for other tests.

And, notably, for mpox, we already have a cleared 510(k) for a non‐variola Orthopoxvirus test that

detects monkeypox virus, and that test has been cleared since before the EUA declaration was made.

And we also do welcome additional premarket submissions for mpox tests.

CDR Kim Piermatteo: Thank you, Toby. We will now move to address your previously emailed questions

related to COVID‐19 test development.

Toby, the first question for COVID‐19 test development is would a multi‐analyte rapid molecular test

that can detect multiple common respiratory pathogens, including SARS‐CoV‐2, be prioritized for

review? What is the most effective method prior to submitting an EUA request to determine if a COVID‐

19 test would meet FDA's priorities for review?

Toby Lowe: Thanks, Kim. So we may consider prioritizing EUA requests for multi‐analyte rapid molecular

tests, and we encourage developers of such tests to engage with us early through a pre‐EUA to discuss

prioritization as well as validation plans and approaches to consider.

As is discussed in our policy for COVID‐19 tests during the public health emergency, which is the

guidance document that was updated earlier this fall, we do generally intend to prioritize review of EUA

requests from experienced developers for diagnostic tests that are likely to have a significant public

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health benefit or are likely to fulfill an unmet need. So the types of tests that are considered to meet

those priorities may change as the public health needs change. And we will consider each request on its

own merits to determine whether or not to prioritize review of that test.

To follow up or to get questions answered on priorities, we recommend that test developers email the

COVID mailbox. That's COVID19DX@fda.hhs.gov, and that's the same mailbox we've been using this

whole time. We've often referred to it as the EUA mailbox or the EUA templates mailbox. It all goes to

the same place. So you can email that mailbox with questions regarding whether your test meets FDA's

review priorities, and when you send that email, we recommend including sufficient detail regarding

your test so that we can provide informed feedback.

CDR Kim Piermatteo: Thanks, Toby. For our next previously emailed question related to COVID‐19 test

development, I'll direct that to you, Tim. So Tim, the question is on November 1st, 2022, the FDA revised

the authorized uses for all currently authorized SARS‐CoV‐2 rapid antigen tests to include repeat or

serial testing on symptomatic patients. Is the FDA planning to provide information for healthcare

providers or laboratories that order or perform antigen tests regarding how to implement this change in

their testing regimens?

Timothy Stenzel: Thank you, Kim. In August of this year, FDA issued a safety communication titled At‐

Home COVID‐19 Antigen Test‐‐ Take Steps to Reduce Your Risk of False Negative, recommending

increased serial testing for users of at‐home COVID‐19 antigen tests and, in fact, this is now our

recommendations for all antigen tests based on available data showing the need for repeat testing after

a negative result to increase the chance of an accurate test result of catching those true positive results.

Then, as stated on November 1st of this year, revision of all authorized antigen tests followed the August

safety communication updating the authorized uses of all antigen tests to include necessary serial

testing. Both the safety communication and the revision letter include information on how to perform

this serial testing. Symptomatic individuals who receive an initial negative result should test at least

twice over three days with 48 hours between tests. And asymptomatic individuals who receive an initial

negative test result should test at least three times over five days with 48 hours in between tests.

These instructions will also be included in each test labeling as it is updated further requirements in the

revision letter. It is important for all users, including healthcare providers, laboratories, home users to

follow the authorized instructions for use. However, the test can be mixed and matched. So the same

antigen test doesn't have to be used in all of the serial testing for a given patient. You can start out with

manufacturer A and move to manufacturer B.

Also, the second test does not have to be performed in a clinic. If the clinic decides that a patient can go

home and do the subsequent repeat testing if the first test in the clinic is negative, that meets the spirit

and letter of the safety and labeling updates. So hopefully that addresses the questions that were at

hand here, and we appreciate everybody working with us to make sure that antigen testing is as

accurate as possible.

Thanks. And I think we're what, Kim, going to live questions now?

CDR Kim Piermatteo: Yes, we are, yep. So thanks Tim. That does wrap up our previously emailed

questions for both monkeypox and COVID‐19 test development. We will now take your live questions.

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As a reminder, to ask a live question, please select the Raise Hand icon at the bottom of your Zoom

screen. When you are called on, please follow the prompt in Zoom and select the blue button to unmute

your line. Then identify yourself and ask your question. Please remember to limit yourself to asking one

question only. If you have an additional question, you may raise your hand again to get back into the

queue and I will call on you as time permits.

So it looks like our first question is coming from Kal. Kal, I have unmuted your line. Please unmute

yourself and ask your question.

Kal: Can you [INAUDIBLE] hear me OK?

CDR Kim Piermatteo: You're very muffled and staticky.

Kal: OK, I apologize. I'll try to do my best.

CDR Kim Piermatteo: That's better, yes.

Kal: OK, so my question is that how many flu A and flu B positive samples are required for a 510(k)

submission for an antigen‐based multi‐analyte test intended for home use, and are there pre‐

authorization and post‐authorization targets for the samples?

Timothy Stenzel: Yes, and you're talking about not an EUA submission but a 510(k) or since we have not

yet authorized an antigen test, fully authorized and tested, it would be a De Novo submission. Is that

what you're talking about, a full authorization submission?

Kal: Correct, yes.

Timothy Stenzel: Yeah, so we are recommending that you submit a Pre‐Sub or a Q‐Sub—Pre‐Submission

or a Q‐submission. This is free. That is the process that we're going through and making

recommendations to developers for that full authorization submission. We've been doing that all along

here, and that is the process. You can look for the Q‐Submission or Pre‐Submission guidance document,

and that spells out how you go about submitting that. But again, there's no cost for that. Kris, anything

to add on that?

Kal: OK.

Kristian Roth: No, we're glad to give you those target numbers in the context of Pre‐Sub because we

want to make sure that we kind of paint the whole picture of the clinical study in there because there's

more details than just what actual numbers we're expecting.

Kal: So for like EUA, would it still be 50 for flu A and 30 for flu B.

Timothy Stenzel: Kris, can you answer that? It's whatever is in the templates is what our

recommendations are.

Kristian Roth: Yeah, that's right. Those are numbers that are in the template for EUA, and I think that

continues to be our recommendation.

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Kal: Because we just wanted to get clarity because we got some feedback from FDA recently, and there

seems to be some confusion about total of 100 samples for each with pre and post, so we just want to

be really clear how many is it still 50 and 30 or now has anything changed from a target point of view.

Timothy Stenzel: Yeah, we're going to need to move on to the next caller, and you're asking very specific

questions about a submission or a Pre‐Submission, so if you have any questions on any directions that

you've already had, and you've established with the FDA, go back to your lead reviewer, and they can

address your question because we look at specific circumstances. There's a lot going on. Do you have an

EUA authorized test already‐‐ if so, what amount of that data can be applied to a full submission? So

these it's important that these responses be individualized to best help each developer, OK.

Kal: Got it, thanks.

CDR Kim Piermatteo: OK, thank you Kal. And thank you, Tim, and Kris, for that response. Alright, our

next caller is Ashfaaq I have unmuted your line. Please unmute yourself and ask your question.

Ashfaaq Ismail: Thank you very much for this town hall meeting. My question is a general one, but still

sort of related to the topic at hand. But if this is already available in any guidance that the FDA have

provided, then my sincere apologies in advance. In the event that an EUA expires, what level of

additional documentation might need to be provided for the formal submission to allow a product or

device for mpox or COVID‐19 to clear?

And what sort of timeline would the FDA allow‐‐ if I remember rightly, normally for a 510(k) submission,

it's about 90 days? Please do correct me if I'm wrong. But I was just wondering what kind of timescale

would a legal manufacturer have on the clock with regards to getting formal clearance after in the event

that EUA expires.

Toby Lowe: So the EUA doesn't actually expire. The EUA declaration has to be terminated proactively.

And we have two transition guidances. One of them is applicable here, regarding the transition for

devices that have received EUA for COVID. And the transition guidance is out in draft, and it will be

finalized. It talks about the transition from EUA to the post‐emergency state, and it contemplates a 180‐

day advanced notice of termination of the EUA declaration and provides information on the

enforcement policies that FDA is considering putting into place to provide sort of an extended runway

for developers to transition to full marketing.

So I suggest take a look at that. And if you have additional questions about how to proceed, you can

send those into the mailbox and we'll take a look and get back to you.

Ashfaaq Ismail: That's great, thank you very much for that.

CDR Kim Piermatteo: Thank you Ashfaaq for that question and thank you, Toby, for that response. Our

next question is coming from Kathy. Kathy, I have unmuted your line. Please unmute yourself and ask

your question.

Kathy Barnecut: Hi, my name is Kathy Barnecut. I'm calling from Becton Dickinson. My question is a two‐

part question related COVID‐19. The first part is for a multi‐analyte SARS‐CoV‐2 assay molecular assay,

can the FDA comment on how to deal with the extremely low flu B prevalence and the lack of available

clinical samples for the validation and the testing? And for the second part is will the FDA accept

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contrived flu B samples in lieu of clinical specimens once we have already extended the clinical trial as

our due diligence.

Toby Lowe: Thanks for that. So I can start, and then I'll ask Kris to jump in. So we have discussed this a

bit on previous town halls, and we do recommend that you submit a pre‐EUA to discuss different

options. Generally, we would expect you to attempt prospective collection and then discuss with us

alternative options if that's not successful. Kris, do you want to talk a little bit more about how we're

looking at things there?

Kristian Roth: Sure, yeah. Thanks, Toby. We do recognize that the current situation with flu B will result

in not being able to likely collect enough positives. Flu A though is on the rise, and I think if you look at

the recent instructions for use, which include some of the performance numbers from the Lucira test

that was just authorized, you'll see that, of course, there's, I think, no prospective flu B in that particular

label. There is some prospective flu A. So if your data set is close to what the data is in that instructions

for use, in the Lucira instructions for use, I'd say put that together for us and submit that, and we can

chat with you about paths forward for your particular test.

Kathy Barnecut: Thank you. Thank you so much.

CDR Kim Piermatteo: Thanks, Kathy, and thanks, Kris. Our next question is coming from Ling Koh. Ling

Koh I have unmuted your line. Please unmute yourself and ask your question.

Ling Koh: Hi, this is Ling Koh calling from BD. I have a COVID‐19 related question specifically around

sequencing. So in previous town halls, we've heard that originally 10 positive samples were required to

be sequenced that contain currently circulating variants at the time of submission. That number was

then revised to 30 positive sequenced samples collected before March 1st.

And I was just wondering if the FDA could comment on the current thinking around that, and if there‐‐

we've heard the language areas of low variant prevalence versus high variant prevalence. If you can

comment on some definitions there and just provide some guidance about what the current thinking is

on that topic. Thank you.

Timothy Stenzel: Yeah, so we did see a drop in performance with omicron, and so we are wanting to see

30 omicron samples. As far as the details of the sequencing, Kris, can you provide any more details? I

mean, the sequencing is largely just to confirm that it is omicron samples that we are at. But we have a

date, beyond which, if the samples are collected in the U.S., or the 30 samples, then you don't have to

sequence. So it's 30 omicron but there‐‐ and I forget the exact date. Kris may remember that‐‐ but we're

well past that now. Go ahead, Kris.

Kristian Roth: Yeah, March 1st of last year. So if you got 30 prospective samples collected after March 1st

of 2022, then we're not asking for additional sequencing data. And I think we're fairly flexible on the

sequencing data that you do provide. Of course, you want it to be the final sequence to be put through

the Pango‐‐ get a Pango lineage and show us that. But as long as you're using relatively modern

sequencing techniques, I think that's something we've been accepting.

Timothy Stenzel: Yeah, but that's only if your samples were collected partially or completely before

March 1 of this year‐‐ in the U.S. So we just looked at the variants across the country and decided at

what point on the calendar all the sequence data that has been submitted on COVID was above a

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threshold that we could just assume that the vast majority of COVID positive samples after March 1st

were, in fact, omicron.

Ling Koh: Thank you, and that makes sense for U.S.‐based samples. I think that answered it very

succinctly for OUS samples. We had gotten feedback basically around the clinical studies performed in

areas of low variant prevalence, then it's recommended you still perform sequencing. Is there a

threshold percentage prevalence for omicron that you would consider low versus high variant

prevalence?

Timothy Stenzel: Yeah, unfortunately, we don't track the variant thresholds outside of the U.S. in the

same way we do in the US. And so we really can't make that blanket. So have a specific conversation

with your lead reviewer or when you do get assigned one about that, OK?

Ling Koh: OK, thank you.

CDR Kim Piermatteo: Thanks, Ling for that question. Alright, our next question is coming from Annabel.

Annabel, I have unmuted your line. Please unmute yourself and ask your question.

Annabel: Thank you very much. My question is regarding a COVID antigen test for full marketing

clearance. We submitted a Q‐Sub and received the draft recommendations for that full marketing

clearance for a POC test. So our question is regarding a reproducibility study. We understand that the

study should be performed at three POC sites with nine operators, so three operators per site. So we

wondered, is it acceptable to include a site that is point of care, but has less than three healthcare

providers at that site and to bring in a representative operator, such as a retired doctor or a traveling

nurse to that site to round out the required number of operators at that site for the reproducibility

study?

Timothy Stenzel: Again, this is very specific question, so I would encourage you to go back to your lead

reviewer. I mean, we have pretty standard responses to Pre‐Sub and Q‐Sub submissions. And so if you

have any specific questions after you've gotten that pretty standard response, which applies to

everybody, just do go back and ask the lead reviewer and we can handle that sort of thing. The focus for

full authorization and those sites is to actually look at busy regular clinics.

So we're really looking at healthcare workers that are not trained laboratorians. They're busy. They're

doing their normal work. And on top of it, they're doing testing. Why do we do this? We do this because

we want to make sure that the tests are simple enough, accurate enough in that setting to give a result

that will yield a clear way of determination, which is what you want.

So bringing in somebody who's not normally in the workflow and they're just doing the testing and

they're not busy with their other activities doesn't really tell us, in that busy clinic setting, are you able

to get accurate results in that setting? That's the purpose.

Annabel: OK, thank you. The reason I asked this was that we had put in a Pre‐Sub supplement and had

pinged our reviewer. I was just hoping this would be another way to get a faster answer, so I appreciate

your taking the time to answer this. Thank you.

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Timothy Stenzel: Yeah, and probably no one on the phone. Maybe Kris does, but I don't know the

details of that and the discussions. And it's just we want to give you the very best response and in the

context of our communication with you, OK?

Annabel: Of course, thank you.

CDR Kim Piermatteo: Thank you, Annabel, and thank you, Tim. Alright, our next question is coming from

Lisa. Lisa, I have unmuted your line. Please unmute yourself and ask your question.

Lisa Diamond: Yes, thank you. My question is how does FDA view the priority of data infrastructure for

capturing and analyzing results from at‐home testing? Is that something you consider a high priority at

this point?

Timothy Stenzel: So is this for regular testing or is this in a clinical study setting where you're capturing

data?

Lisa Diamond: No, this is for everyday testing. I mean, with the shift to at‐home testing, we lost a lot of

visibility into test results, and the question is it a high priority to develop methods to be able to capture

the results from a wide range of testing, including at‐home testing?

Timothy Stenzel: Yeah, I'm curious, who are you with? Who are you representing?

Lisa Diamond: A company called [INAUDIBLE] Bioscience, and we're actually proposing to build this kind

of infrastructure that could be used.

Timothy Stenzel: Oh, perfect. Perfect. I'm so happy that you're interested in this, and I would

recommend that you send an email into our COVID box and ask to speak with Dr. Sara Brenner‐‐ S‐A‐R‐A

B‐R‐E‐N‐N‐E‐R. So she is heading up our connectivity for this, and she would, I'm sure, love to talk to you

about this.

So the FDA is encouraging that there is greater and greater connectivity so that we can track‐‐ we being

healthcare providers and the healthcare system and the U.S. government can track disease more easily.

For COVID at‐home tests in particular, if a connectivity or a reporting function‐‐ which doesn't have to

be the device connecting. It can be an app that the consumer simply logs in and says my result was

positive, my result was negative. So that is not something that we evaluate for the authorization of the

test decision for any EUA for COVID, but it is something that if it's not available at launch at

authorization, we do ask developers to develop that. So that is very important. And so there probably is

an opportunity to help a lot of developers in this area. So anyways, talk to‐‐ send an email, ask to speak

with Dr. Sara Brenner, and she can help you out.

Lisa Diamond: Thank you, very helpful.

CDR Kim Piermatteo: Thanks, Lisa. Alright, our next question is coming from Amanda. Amanda, I've

unmuted your line. Please unmute yourself and ask your question.

Amanda: Hi, thank you. This is Amanda from BD, and my question is regarding COVID‐19. Regarding the

serial testing labeling updates from November 1, when does FDA expect to provide feedback to antigen

test developers who submitted their serial testing labeling changes on November 15th, and should test

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developers start to apply that same recommended labeling changes to tests that are currently in

development‐‐ i.e., at‐home antigen tests and multi‐analyte tests?

Timothy Stenzel: So multi‐analyte tests will be only on symptomatic patients. That is a really good

question because for the non‐COVID analytes, we're going to have to figure out what that is. But if the

test is negative, everything else is negative, and they're symptomatic, we do want them to serial test.

But the serial testing in that multi‐analyte panel is going to be for COVID only, we have no indication

that for flu or RSV, you need to do serial testing if you're symptomatic and first test is negative.

So would this apply to all future antigen tests for COVID? Yes, it does it does apply. Timing‐‐ so there

were 51 antigen tests on the market when that went out. Newer authorizations that you've seen us

make in the recent days included that serial testing in the initial authorization. So we have 51 companies

we're working with, and we're just going to get through those as quickly as we can, but really, the

labeling‐‐ we do want the labeling reviewed by the FDA. We'll update your authorization, and we'll move

on that as quickly as we can. Kris, do you want to add anything else about that?

Kristian Roth: No, I think that's what I would say as well. We've got a lot of authorizations to work

through. So we're getting through them as fast as we can.

Amanda: OK, thank you.

CDR Kim Piermatteo: Thank you for that question, Amanda, and thank you, Tim and Kris. Alright, our

next question is coming from David. David, I have unmuted your line. Please unmute yourself and ask

your question.

David: Oh, hi. This is David from Mecca Consulting. I have a question regarding the monkeypox antigen

test. So FDA published the template for monkeypox antigen test yesterday. Does that indicate FDA will

reopen applications for monkeypox EUA, or the template is only to be used among developers who have

already submitted their EUA intent before the October deadline? Thank you.

Timothy Stenzel: So I mean, the window for monkeypox did close, and whoever had reached out and

proposed a plan, we've I think we've communicated with all of those folks about whether or not we

would prioritize their submissions. However, you can always submit a pre‐EUA. We just can't make any

promises that it will meet our priorities because we take a look at the totality of developers that we've

already given green lights to and we monitor their progress, and we're trying to meet the needs. And, of

course, thankfully, monkeypox numbers are way, way down. So there are certain challenges with that,

especially for antigen tests.

CDR Kim Piermatteo: Thank you, Tim, for that response. Thank you, David, for that question. Alright, our

next question is coming from Homer. Homer, I've unmuted your line. Please unmute yourself and ask

your question.

Homer Wu: Hi, this is Homer Wu from Hopkins MedTech Compliance. I'm just following the question

from, I guess, Kathy from BD about the multi‐analyte antigen tests for COVID plus flu A and flu B, either

OTC or POC. Does the FDA still allow us to do the flu B with a sample, banked sample or retrospective

samples?

Timothy Stenzel: Is this a molecular test or an antigen test?

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Homer Wu: Antigen test.

Timothy Stenzel: So bank samples with antigen tests are really challenging. We have been open to dry

swabs. So that is a very specific question. I think we're‐‐ as Toby covered, the multi‐analyte with COVID,

flu A/B and/or RSV or other analytes about how we would handle those. So we would ask you to come

in with a Pre‐Submission and make sure that we would prioritize your product for review. And then, if

so, we can really get into the details about how you might do that. But it's really‐‐ right now, there's

significant flu A, but there's almost no flu B, and so that's a real challenge to test that. They really do

require direct swab to be able to evaluate them. Kris, anything else to add?

Kristian Roth: No. And I think if your test uses a transport media, they generally we’re more open to

banked samples. If the test doesn't have a transport media, just saline or VTM then it's going to be a lot

more challenging.

Timothy Stenzel: And we don't necessarily encourage the use of VTM for antigen tests because we have

seen significant issues in the COVID pandemic with VTM, and most of the antigen tests have really

moved away from allowing transparent media because of those false positive issues.

Homer Wu: Right. If we can find flu B patients, can we call them back?

Timothy Stenzel: So you're really talking about an enrichment strategy, and we've recommended for

any sort of enrichment strategy that you check with the FDA first on your plan to make sure that any

potential biases are mitigated to the extent they can be and that the FDA is fine with your study plan.

We're open to enrichment, but we want to make sure that it's a good plan, one that we can support an

authorization with.

Homer Wu: OK, thanks. We do have a Pre‐Sub for this before, but was closed, and we still can't follow‐

on, pre‐EUA.

Timothy Stenzel: You have a pre‐EUA, and what's the status? You got responses back?

Homer Wu: We got response, and we‐‐ I guess like this follow‐on question, can we still use that case?

Timothy Stenzel: So I don't know the details. You're asking about details of a specific submission. So I

would go back to whoever responded to you and ask whatever questions you have about the status.

Homer Wu: OK, alright. Thank you.

CDR Kim Piermatteo: Thank you, Homer, and thank you, Tim. Alright, our next question. We're circling

back to Ashfaaq. You have another question. I have unmuted your line. Please unmute yourself and ask

your question.

Ashfaaq Ismail: Hi, thank you very much. My question was I read a media release from Swiss Medtech

that the Swiss authorities had passed a resolution which moves one step closer to recognizing and

accepting FDA approval on medical devices and IVDs, et cetera. So basically, if a medical device has been

approved by the FDA, then that will make it easier for a device to enter into the Swiss market. Now my

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question was, will the same apply for emergency use authorizations, EUAs, that the FDA have issued as

well. Do you know, by any chance, any information with regards to that?

Timothy Stenzel: I think we would have to reach out ourselves and speak to the Swiss authorities. It's

not uncommon for other countries to recognize the good work that our FDA team does, and they're the

ones that would say that the FDA does have‐‐ is working hard with other regulatory bodies around the

world to see if we can't get to a single submission program, but we're not anywhere close to achieving

that desired goal. There's a lot of work to do still. So I think the Swiss would be the people to reach out

to, or any other country, and what they would recognize for what purpose is not for the FDA to say.

Ashfaaq Ismail: OK, sure, no problem. I just thought I'd put the question out that in light of what I'd read

just recently. But no, thank you very much for that.

CDR Kim Piermatteo: OK, at this time, I see no more raised hands, so I'm going to make a call out. At this

time, if anyone else has a question, please raise your hand.

Alright, we have a question. I will apologize ahead of time. I don't know if I'm going to pronounce your

name correctly. Dhanalakshmi, I unmuted your line. Please unmute yourself and ask your question.

Dhanalakshmi Nair‐Schaef: Thanks, I'm Dhana. And I'm calling from [INAUDIBLE] Diagnostics. I had a

quick question of whether the FDA is recommending serial testing for a clinical trial that would be

performing for a 510(k) for COVID‐19?

Timothy Stenzel: So I would urge you to submit a Q‐submission or a Pre‐Submission for the same thing.

Follow the guidance on this to get a formal response. But I would say, in general, that because of the

NIH‐sponsored study that was done in collaboration with FDA review of the protocol and performed by

the University of Massachusetts, some of the data has been published. Some of it hasn't. It has informed

us on the benefits of serial testing in both symptomatic and asymptomatic. Because of that work, we

want to leverage that work and not require developers to have to repeat that work. So what we're

looking for‐‐ to refer to that data is that you have a test that performs well enough on symptomatic

patients to qualify that.

Kris, do you have anything any more details to add? But the real details should be under a Q‐Sub or Pre‐

Sub submission. I'm just giving you a very high‐level philosophy here. Kris?

Kristian Roth: Yeah, certainly. We want to avoid‐‐ we understand that clinical trials of serial testing are

going to be costly and very intense, so we do want to try to leverage as much information we have

already existing. And like Tim said, we can talk about that specifically with you in the context of Pre‐Sub.

Dhanalakshmi Nair‐Schaef: OK, thank you.

CDR Kim Piermatteo: Dhana, do you have another question?

Dhanalakshmi Nair‐Schaef: I do.

CDR Kim Piermatteo: Go ahead.

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Dhanalakshmi Nair‐Schaef: Sorry. So I know that the recommendations that were put out by the FDA

say that we have to test the LoD on the most recent strains that are available in preparation for any

510(k) submissions. My question really was can we do most of the testing with whatever strain is

available right now and then do just LoD testing with strains that come out as we're preparing for the

submission, or do we have to wait for the strain of concern being available before we submit our

package?

Timothy Stenzel: No, we realize that the latest variants aren't deposited in banks that can be utilized.

You can always take a patient sample and sequence it to make sure what it is and dilute that down for

your studies. But Kris can maybe add a little bit more flavor here, but we realize that you only can get

access to some of the variants, and there's a delay before they're deposited in one of the banks, so that

the very, very latest is usually not always available. Kris?

Kristian Roth: Yeah, I think that's‐‐ I totally agree with that. Also, is this an antigen test or a molecular?

Dhanalakshmi Nair‐Schaef: Sorry, this is an antigen test.

Kristian Roth: Antigen test, OK. Try to get the most modern strain you can, of course, and that LoD study

for a 510(k) is really one of those foundational studies that drives the concentration for the other

studies you're going to perform, such as reproducibility, all the interference study. So it's not necessary

to kind of redo it right before you send in your 510(k) because there's really no point. Really, that 510(k)

study‐‐ or sorry, the LoD study is there to guide you for the rest of your analytical studies. So once your

analytical studies are done, that's kind of your data package, and there's no need to update your LoD

with the latest string.

Dhanalakshmi Nair‐Schaef: OK, thank you.

CDR Kim Piermatteo: OK, thank you for your questions. Our next question is coming from Richard.

Richard, I have unmuted your line. Please unmute yourself and ask your question.

Richard Montagna: Yeah, thank you. Tim, this is Richard Montagna with Rheonix. You just mentioned

the ability to leverage the serial testing work that was done at Massachusetts. Can you repeat that

citation so we can‐‐ is it published, or how do we find it?

Timothy Stenzel: Yeah, the data is not fully published yet. So in either you're pre‐EUA or your

conversations for an EUA test, or for full submission, just refer to the NIH UMass data on serial testing.

Richard Montagna: OK, thank you very much.

Toby Lowe: I can also just add that if you look at the safety communication from August and the

November 1 letter of authorization revising the antigen tests, there are citations to at least the preprint

for that study.

Richard Montagna: OK, thank you very much, Toby.

Timothy Stenzel: Yeah, for some of the data. The data is not completely presented. We're working on

final publications.

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Richard Montagna: Thank You.

CDR Kim Piermatteo: Great. Thank you, Richard, and thank you, Tim, and Toby. At this point, that was

our last live question for today. Thank you everyone for your participation. And I want to, again, thank

our panelists, Tim, Toby, Kris, and Noel. We appreciate everyone.

Today's Virtual Town Hall presentation and transcript will be posted to CDRH Learn under the section

titled "In Vitro Diagnostics" and then the subsection titled "Virtual Town Hall Series."

If you have additional questions about monkeypox test development, you may send an email to

MPXDx@fda.hhs.gov, and for specific questions about COVID‐19 test development, you may send an

email to COVID19Dx@fda.hhs.gov.

As a friendly reminder, our next Virtual Town Hall will be for monkeypox and COVID‐19 test developers

on Wednesday, December 14th, 2022, from 12:05 to 1:00 PM Eastern time. We are hope you able to join

us.

This concludes today's Virtual Town Hall. We hope you have a wonderful day.

**********

END

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