FDA Virtual Townhall

Moderator: Irene Aihie

05-26-21/12:15 pm ET

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FDA Virtual Townhall

Moderator: Irene Aihie

May 26, 2021

11:15 pm ET

Coordinator: Welcome and thank you for standing by. At this time, all participants are in a 

listen-only mode. At the end of today’s presentation, we will conduct a 

question-and-answer session. To ask a question please press Star 1. Today’s 

conference is being recorded. If you have any objections, you may disconnect 

at this time. I would now like to turn the meeting over to Irene Aihie. You 

may begin.

Irene Aihie: Thank you. Hello. I’m Irene Aihie of CDRH’s Office of Communication and 

Education. Welcome to the FDA’s 57th in a series of virtual Town Hall 

meetings to help answer technical questions about the development and 

validation of tests for SARS-CoV-2 during the Public Health Emergency. 

Today, Toby Lowe, Associate director of the Office of In vitro Diagnostics

and Radiological Health and Dr. Timothy Stenzel, Director of the Office of In

vitro Diagnostics and Radiological Health in the Office of Product Evaluation

and Quality, both from CDRH, will provide a brief update. 

Following opening remarks, we will open the line for your questions related to 

development and validation of tests for SARS-CoV-2. Please remember that 
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during this Town Hall we are not able to respond to questions about specific 

submissions that might be under review. Now, I give you Toby.

Toby Lowe: Thanks Irene and thanks everyone for joining us yet again this week. I don’t 

have any particular announcements today, so I’ll start with the questions that 

we received by email ahead of time. The first one that we have is related to 

equivocal evaluation study preparing for a 510(k) submission for a respiratory 

PCI multiplex panel, including COVID-19 Flue A-B and RSV. The question

notes that FDA generally requires that the Flu and RSV comparative methods 

be cleared by 510(k) PCR devices. But they’re getting feedback from many 

CLIA labs that manufacturers have stopped selling their Flu and RSV 

multiplex kits and are only manufacturing their EUA multiplex kits that have 

COVID added into it. 

So, the question is asking whether it would be possible to use an EUA 

respiratory multiplex kit for COVID, Influenza, and RSVP, I’m sorry, RSV as 

the comparator in the clinical study. So, generally we do recommend that the 

respiratory multiplex comparator methods are 510(k) cleared. But we do know 

that that’s, that maybe challenging at the moment, so you could also consider 

using an EUA-authorized, highly sensitive RT PCR assay as your comparator 

method for your clinical evaluation. 

But we do note that the EUA tests are validated with a different level of 

evidence than a 510(k) tests, a cleared test. So, we would probably 

recommend that you use multiple EUA tests in an algorithm to determine

positive and negative comparator test results.

For example, you could use two EUA tests per sample of the comparator and 

if there’s disagreement between those, use a third tiebreaker test. And as 

we’ve mentioned here on this call before, we do recommend that if you’re 
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pursing 510(k) pathway, that you submit a presubmission to discuss your 

proposed comparator method. And, you know, as I’m sure most of you are 

aware when you submit your 510(k), you do need to have a predicate that has 

been cleared or Denovo-granted device. And so, right now that is just the 

BioFire assay so that would be an appropriate predicate, but it does not have 

to necessarily be your comparator method. 

Our next question has to do with a topic that was previously discussed on the 

Town Hall, where the question is stating the FDA mentioned that after 50% of 

clinical specimens for a 510(k) clinical validation study can be frozen

prospective specimens. And they’re asking if we can confirm if frozen

retrospective samples can be used as well if they’re retested on a comparative 

method in the clinical study. 

And if not, to please provide more information on how the frozen prospective

samples should be collected to qualify for the clinical validation study. Such 

as whether they can be US or outside the USA, if they must be collected

during the clinical validation study and not before; whether the concerned

positive-negative status must be known. 

So, generally we do recommend that clinical studies include prospectively

fresh and frozen samples to preserve analyte prevalence. Retrospective

samples are considered to be selected and archived samples that are 

previously frozen usually based on a previous positive result. 

So, since that approach is more than minimally biased since the prevalence is 

generally not preserved, that’s not, not our recommended method. Typically, 

the, or often the archived samples are also very high concentration so they 

would not be near the LOD of the assay and may not be reflective of the 

actual patient population. So, we do agree that sponsors can supplement with 
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retrospective samples but usually only after conducting a prospective study 

which yielded too few samples to demonstrate adequate performance.

In terms of US versus outside the US, we recommend that sponsors conduct 

their prospective clinical studies primarily in the US to support a 510(k) or 

Denovo. Data from outside the US prospective clinical studies can also be 

submitted to supplement the US data, especially in cases where there’s 

difficulty getting enough specimens in the US due to low prevalence with a 

heavily vaccinated population. 

Our next question also has to do with enrichment studies due to the current 

COVID positive cases decreasing here in the US. And mentioning a comment 

in that Dr. Stenzel made on a previous Town Hall about the acceptability of 

enriching studies in order to meet the study requirements. The question is 

asking if we can clarify what would be appropriate for study enrichment. So, 

there are multiple options for clinical study enrichment, and they really should 

be appropriately tailored for your specific test and the claims that you are 

validating. So, we do recommend that we, that you submit a pre-EUA so that 

we can review your proposal and consider the alternate study designs that 

would streamline enrollment of positive subjects when prevalence drops low. 

That would be best appropriate or most appropriate for your, for your 

situation.

Dr. Timothy Stenzel: Yes, and thanks, Toby. And I would add that, the original reason to offer 

enrichment was for stimulating additional development of screening assays. 

You know for screening asymptomatic patients and when it was, when in 

sometimes in populations that’s very low or you have to screen a lot of folks. 

We have now considered doing to allow enrichment for original submissions

where obtaining of positives may be more challenging, symptomatic positives 

even. And, you know, where maybe banked samples are not appropriate or of 
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such. But we would still like to see, you know, a prospective attempt to try to 

get true positives and then looking at supplementing them with a method of 

enrichment. Banked samples is one.

The other is to use some sort of selection where a patient may be and this 

might be more, so for, an asymptomatic carrier then an symptomatic person. 

But it could also be done with an symptomatic person and that is, where they 

are identified as positive with some orthogonal method and some sort of 

routine study or protocol for screening. They would be open to study designs

that try to mitigate the bias in that situation. If the patient themselves knows 

the result of the test and it’s not going to involve self-collection for the 

candidate test, then that may be acceptable. If the patient although is going to 

be doing self-testing with candidate device knowing the previous result, this 

will bias the result.

But, you know, for the situation where they’re not going to be self-collecting 

for the candidate device, the person doing the collection, you know, should be 

blinded to the previous results. The patient should be asked not to identify 

whether they were positive negative and of course, to keep the immigration of 

the study honest and unbiased. A suitable number of negative patients should 

be offered in the same way so that the person doing the testing doesn’t assume 

that it should be positive. This way, bias can be mitigated to a greater extent. 

So, there are multiple paths, and we’re open to multiple paths. 

We do recommend, highly recommend, that you run those strategies by the 

FDA prior to initiating your study. And in order to avoid any sort of 

duplication of studies because study plan and design was not suitable. Back 

over to you, Toby.
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Toby Lowe: Thanks Tim. That’s really helpful, that additional information. Our next 

question is regarding a professional use, rapid antigen test. This sponsor is 

conducting a clinical study and has so far collected some positive samples but 

none of them have CT values over 30. They’re looking for FDA feedback on 

what to do if they’re still not able to get any or enough low positives since 

FDA generally does want to see 10 to 20% of positive samples being low 

positives with a CT over 30 for antigen tests. 

So, we do, generally, we still need to see at least 10 to 20% of low positives as 

observed in other sequentially collected prospective studies. But we, we are 

happy to discuss enrichment strategies that we just talked about in a pre-EUA. 

So, we would request that you a pre-EUA with your proposal and we can give 

comprehensive feedback that way. 

The next question...

Dr. Timothy Stenzel: So.

Toby Lowe: Oh, go ahead Tim.

Dr. Timothy Stenzel: If I could add just a little bit to that.

Toby Lowe: Yes.

Dr. Timothy Stenzel: One thing with an antigen test device, if you’re skewing patients towards 

the early days of symptoms, that may have an effect on comparator CT values. 

We would expect it to be higher once the PCR test is positive. So, we look at 

the scatter of patients across the window of claimed days of sensitivity and 

that may be that collecting more samples further out from symptoms in the 

study is a way to enrich. But if you’re in the situation, we do recommend you 
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come in with a pre-EUA and discuss your challenge and potential solutions

with the FDA team. Thanks. Back over to you, Toby.

Toby Lowe: Thanks Tim. So, the next half of this question is about, for the same rapid 

antigen test, asking about usability in clinical studies for non-prescription, 

over the counter use. The question notes that a couple of products were 

recently granted EUA for over-the-counter serial testing so they’re asking 

questions about whether the usability study and the clinical study need to 

consider serial testing in the study protocols design. 

So, I want to make sure that everyone, including the sponsor, is aware of the 

supplemental template for adding serial testing. That was put out in March, I 

believe, and it does lay out exactly what situations we think we can add serial 

testing including over the counter serial screening, without having 

prospectively collected data on asymptomatic individuals or for serial testing 

specifically. So, for the initial authorization we would not expect to see serial

testing specifically evaluated in your usability or clinical study. 

We would expect you to follow that, you know, the antigen template and then 

that supplemental template which indicates that you would need to 

demonstrate a PPA of 80% with a lower bound of 70% for individual singleuse testing on symptomatic individuals. And based on that performance, we 

would be able to give you the indication of serial testing for asymptomatic

individuals with a post-authorization requirement to validate the 

asymptomatic serial testing claim. And that would be through a protocol that 

we would review interactively with you before you implemented that as your 

post-authorization requirement.

All right. I think we have another question. Oh, go ahead.
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Dr. Timothy Stenzel: Yes. What is the next question? Do you want to just read the next question 

as I may be answering one of these that are coming? It would be the EUA 

letters of authorization question that’s next.

Toby Lowe: Yes. There is a question about EUA letters of authorization containing several 

statements that are required to be included on all descriptive printed matter, 

advertising and promotional materials. And the question is asking for online

advertisements, is it acceptable to omit the statements due to space limitations

if a link to a webpage with the full list of statements is included in the online 

advertisement?

Dr. Timothy Stenzel: Yes. Toby, I didn’t see a prepared answer so I will jump in unless you 

have this one?

Toby Lowe: I think we were planning to get a written response for that one to make sure 

we get all of the legal nuances on that one actually.

Dr. Timothy Stenzel: Oh, yes. Okay. Well, my suggestion was going to be that, you know, that 

is in the letters of authorization. We generally expect that to be followed but if 

there is some sort of situation or that’s hard, we’re open to different ways of 

handing it. So, I would approach the FDA on that but typically we want all the 

important information on all of the materials. Thanks Toby.

Toby Lowe: Yes. Great.

Dr. Timothy Stenzel: Back over to you.

Toby Lowe: Thank you. All right. Let’s see. The next question is about a 510(k) for our 

molecular SARS-CoV-2 RT PCR with claims for asymptomatic population

and asking FDA’s thoughts on comparator method for, for that study. 
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Specifically, whether the comparator assay needs to have asymptomatic

claims and whether the comparator assay needs to be cleared. And as well as 

whether the BioFire RP-2.1 assay is an acceptable comparator. So, we have 

not, we don’t currently have any tests that are cleared with an asymptomatic

claim for SARS-CoV-2 So, at this time we would recommend that you use a 

comparator method consisting of two EUA-authorized, highly sensitive RT 

PCR assays that do have that asymptomatic claim with a third test available as 

a tiebreaker. And as we’ve discussed previously, we do recommend that you 

submit a pre-submission to discuss your individual comparator method prior 

to moving forward with that towards the 510(k). 

And our next question is about clinical evaluation of a point of care or over 

the counter antigen test for an EUA. Asking about due to the declining 

number of positive in the US, whether some or all of the study can be 

completed outside of the US? So, we do, it is acceptable for some of the data 

to come from prospective clinical studies outside the US to supplement a USbased prospective study. If that US data is not sufficient due to low prevalence

in the US simple due to a heavily vaccinated population now. 

However, we would need to understand if the testing is being conducted under 

the exact same protocols and whether the population tested appropriately 

represent the US population. So, we would recommend in that situation to 

submit a pre-EUA to discuss the proposed clinical evaluation to make sure 

that it is appropriately designed and carried out and we can give 

comprehensive feedback to you that way.

Our next question is for, there’s two questions. One about an antibody test, 

asking whether a prospective study is required for antibody, Denovo, or 

510(k) submissions? Or whether a retrospective study can include some 

samples from outside the US? So, we do recommend that sponsors conduct 
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prospective clinical studies primarily in the US to support a 510(k) or Denovo. 

Again, similar to the previous question, data from outside the US prospective

clinical studies can be submitted to supplement the US prospective data. And 

if collection sites outside of the US are chosen, you should document the 

relevance of the studies to the US clinical practice and demographics. 

And the then second part of that question is about an antigen test, Denovo, 

510(k) submission when only claiming use with nasal swabs whether the 

comparator method can be a high sensitivity RT PCR with nasal swabs? Or 

does it need to be an NP swab for the comparator? So, we do, we do. We have 

been accepting nasal and mid-turbinate swabs for the comparator method for 

EUA submissions and I would expect we would do the same for a Denovo or 

510(k). But we do recommend that you submit a pre-submission again to 

discuss that study design so that we can provide comprehensive feedback.

Dr. Timothy Stenzel: In one sample type, Toby, that doesn’t follow that recommendation is 

saliva where we still recommend a NP swab. But for saliva, we’ll also 

entertain a mid-turbinate swab. 

Toby Lowe: Great. Thanks. All right. Speaking of saliva, our next question is about, is 

about saliva noting that on previous Town Halls, we’ve mentioned that saliva 

is a challenging sample type for antigen tests. And asking whether we could 

explain more details on what issues were uncovered. I do want to note that we 

have mentioned that saliva is a challenging sample type, both for molecular 

and antigen tests, not just antigen. And then the other question also notes that 

FDA mentioned that freeze-thaw processes increase sensitivity in saliva 

antigen tests and asking if this is the case for antigen testes detecting the N 

protein or the S protein or both. 
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So, we have seen that saliva is a challenging specimen type. Detection from 

saliva is typically less sensitive than upper respiratory specimens. The freezethaw issues can affect the samples in different ways and in some cases we’ve 

seen where it increases and in other cases, decreases. And so, we have seen 

some variability in the data that we’ve seen from test developers with saliva in 

terms of the ability to appropriately validate it and to get appropriate

performance with saliva. Tim, did you want to add anything?

Dr. Timothy Stenzel: I would add that...

Toby Lowe: More? Yes.

Dr. Timothy Stenzel: Yes. I would add that the freeze-thaw cycle, we recommend it be 

investigated if you’re going to use frozen samples for any EUA authorization

to show that there is no bias in using frozen samples. Okay. Thanks. Back 

over to you.

Toby Lowe: Great. And then the last prepared question that we have is about submitting an 

EUA for a point of care molecular diagnostic test system with an optional app 

to communicate the results of the test to the appropriate authorities if the user 

desires. Asking whether it is a requirement to include validation data for the 

optional app as part of the initial EUA submission. Or if use of the app could 

be filed separately or whether or not it is even necessary to provide validation

data for the optional app. 

So, for that it would depend a little bit on the role of the app and how it 

interacts with the test itself. So, that’s something that we would likely want to 

have a more in-depth conversation with you about. So that we can better 

understand the interaction between the test and the app before we provide that 

feedback, and I would submit a a pre-EUA anyway. Sorry, go ahead, Tim.
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Dr. Timothy Stenzel: I just wanted to wait until you’re done. Are you done?

Toby Lowe: Yes. Go ahead.

Dr. Timothy Stenzel: Okay. I just wanted to say that’s my fault, we passed over on one of the 

questions earlier and I wanted to go back and answer it. And the question had 

to do with when does the FDA anticipate a recommended reference material is 

available for antigen tests. And at this time, we don’t have such a 

recommendation or a panel. There are clear challenges in doing this for 

antigen tests and currently we do not have anything stood up. You know 

that’d be great so we’re obviously thinking about it but nothing right now. 

Thanks, and Toby, I think that might be the end, and can we go to the open 

line for questions?

Toby Lowe: Yes. 

Dr. Timothy Stenzel: Okay. Back to you, Coordinator:

Coordinator: Thank you and at this time if you would like to ask a question, please press 

Star 1. Please unmute your phone and record your first and last name clearly 

when prompted. Your name is required to introduce your question. To 

withdraw your question, you may press Star 2. Once again at this time if you 

would like to ask a question, please press Star 1 and our first question is from 

Alex. Your line is open.

Alex: Hi. This is Alex with UserWise Consulting. We specialize in human factors

and usability testing. My question is about inclusivity testing. Is there any 

expectation that manufacturers of OTC antigen tests include new recent 

strains of the virus in inclusivity testing? Or they can rely on very common 
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strains sourced from Europe, for example? And can you generally explain 

your latest expectations on the quantity of strains and which strains should be 

used for inclusivity testing?

Dr. Timothy Stenzel: Yes. Toby, you can correct if I’m incorrect on the guidance related to 

variants and mutations. Our intention there was for developers to take a look 

at the variants in the US population when they do their validation tests and 

determine whether or not there might be an issue with certain variants. If, you 

know, by informatics analysis, you know, you see where the mutations are, 

you know how your, you know what antigen your antibodies were raised

against. So, you know at least that the area of the virus that you should look 

for potential, you know, issues with certain mutations and variants. 

And apparently, with one of the antigen tests there’s has been, fortunately, in 

low abundance a mutation in the United States but we don’t expect it to 

increase. But it has been in studies shown to not detect a particular, a 

particular mutation, virus with a peak of mutation. So, this has been proven to 

be real already from molecular and now it’s proven to be real for antigen. 

Serology may be a little bit more insensitive to mutations and variants due to 

the polyclonal nature of immune responses. And that may help since there 

would certainly be a clear example that come up in serology as well. 

So, we are currently surveying for tests on the market, molecular, antigen, and 

serology. The information that we received from the developers having to do 

with how their tests were designed allows us to do a first pass, at least for 

antigen, and serology tests for potential issues with inclusivity. You know, 

and false negatives and we are currently reaching out when we have a 

potential concern in engaging those developers. And it is important for those 
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developers to get their hands on some sort of protein molecule with those 

variants. 

We’re open to a different, on what methods to do that. I would suggest that if 

you do determine that there could be false negatives with overall at or above 

the 5% mark in the US population. Or a single variant or mutation that’s at or 

above 5%, that you engage with the FDA on your strategy to assess that preauthorization. So, that we have good assurance that it’s not going to affect

performance of the assay. 

We also have in that guidance asked that you come in when you’re coming in 

with your EUA, that you come in with a plan for how you’re going to, on an 

ongoing basis, assess the risk of false negatives due to variants and mutations. 

And we’ll look to that and get feedback on that because that will be a postmarket commitment that we will require for developers to monitor that 

situation. Toby, anything to add?

Toby Lowe: Yes. That’s, just in addition to what you were covering, I would also note that 

the EUA templates do include recommendations for inclusivity testing. So, I 

would also suggest that you take a look at the template for the specific type of 

test that you’re looking at.

Alex: Thank you.

Coordinator: Thank you. Our next question is from Shannon Clark. Your line is open.

Shannon Clark: Hello. This is Shannon Clark with UserWise Consulting. Thanks for that 

really helpful response just now. Another question. My understanding that is 

in order to obtain over the counter designation for an antigen test kit with a 

mid-turbinate swab. That requires the inclusion of a stopper for child safety to 
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prevent over insertion. First of all is this true? And then is the purpose of this 

stopper to prevent gross over insertion such as the stopper could be located 

four centimeters from tip? Or does it need to prevent insertion past sort of a 

zone for two-year-old’s which is about 1.5 centimeters or a half inch? What is 

the purpose of that stopper and is it required?

Dr. Timothy Stenzel: It is safety related and we’ll take this on a case-by-case basis. For 

example, we’ve had some developers come in say, you know, that they’re 

going to require a mid-turbinate swab. And it’s sort of in the gray zone just 

beyond an interior nares, you know, sort of in the, I don’t know, one inch or 

one centimeter, I forget. You know versus a deeper, a true, you know, right up 

there mid-turbinate swab. But it is a safety consideration so we will take this 

on a case-by-case basis per the device and per the device instructions. So, if 

there’s any questions or potential concern about that engaging with the FDA 

early is good prior to doing your user usability studies and perhaps also in

your clinical studies to make sure that it’s done in a safe manner.

Shannon Clark: Okay. Thanks so much.

Coordinator: Thank you. Our next question is from Jackie Chang. Your line is open.

Jackie Chang: Hey. My question is about the expectation for fully quantitative serology tests 

and also, and also for a fully quantitative neutralizing test. Right now, the two 

templates are for semi-quantitative tests and I’m just wondering if, if the 

validation requirements are just doing everything that is listed for the semiquantitative test. And then also, establishing traceability of the results to the 

who sender.

Dr. Timothy Stenzel: Yes. Establishing traceability is important to the National standards for 

pointing out International units but also, you know, linearity and other issues. 
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So, I believe we’ve authorized one truly quantitative test if I’m correct. So, 

there is some information in that online information about that test, so I’d 

check that out. We are working in this area, it is an area of importance and 

focus for the FDA and the serology team. It’s neutralizing antibodies and fully 

quantitating antibody assays are a top priority, high priority, for serology tests. 

So, if you have, you can submit a pre-EUA and put in there what you think 

based on the prior authorization and how you want to plan it. And then, you 

know, we can provide some feedback on the validation study plans and 

whether our recommendations are more specifically for your device.

Jackie Chang: Thank you.

Toby Lowe: And just to clarify, we have, we’ve authorized semi-quants. We have not 

authorized a fully quantitative test yet, but we do, we are happy to help 

provide feedback through the mailbox or through a pre-EUA.

Jackie Chang: Yes. So, I submitted...

Dr. Timothy Stenzel: Submit a pre-EUA, that’s the way to go.

Jackie Chang: I submitted a question to the mailbox, and I haven’t received any answer yet,

but I really appreciate the answer. Maybe...

Dr. Timothy Stenzel: Send it back through and copy Toby. Ask them to copy Toby and me 

when they reach out to the team. Because the team has put together their 

thoughts on fully quantitative and obviously, we’ve been thinking about it and 

engaging with sponsors already for me with fully quantitative already. So.

Jackie Chang: Okay. Thank you.
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Coordinator: Thank you and as a reminder if you would like to ask a question at this time, 

please press Star 1. Your next question is from Codimode Vanke. Your line is 

open.

Codimode Vanke: Good afternoon. Thank you for taking the question. This question is related to 

the serology tests. I just wanted to find out, I know last year there was an 

umbrella EUA for serology tests, and then the independent validation was 

done at NCI. So, my question is, is it, the NCI has done now the validation or 

is it still the independent validation is in effect? If you could just give me an 

update. I’d love to hear. Thank you.

Dr. Timothy Stenzel: Yes. The NCI is still open for business as they say for those assays that the 

FDA prioritizes for the NCI. And we’ve asked the NCI to stay through a 

period of time where I’d say they’re converted to a full authorization. Or we 

receive a novel application through either a Denovo or a 510(k) pathway 

following the first granting of the Denovo application for serology.

Toby Lowe: And if I could clarify about your question about the umbrella EUA. There was 

an umbrella EUA issues last Spring and last Summer, it was revoked. There 

were no tests that were, that were added under it, so it did not impact any 

specific tests. But the umbrella EUA itself was revoked and we have been 

using the individual EUA pathway instead for serology tests including the 

ones that have been evaluated by NCI.

Codimonte Vanke: Yes. Thanks. My question was for something similar to what the team 

answer, is it still the NCI is doing the independent validations. The question is 

has the backlog of the submitted they have done and then the reports have 

been given. Or are, are there things that are being done at a different lab?
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Dr. Timothy Stenzel: That’s a great question. I don’t have an answer for that today. I know that, 

that we constantly look at priorities, and if there is a priority, we do let the 

NCI know. So, but I don’t, I haven’t tracked lately what that backlog is. I 

can’t respond directly to that...

Codimonte Vanke: Thank you.

Dr. Timothy Stenzel: ...at this time.

Codimonte Vanke: Thanks.

Coordinator: Thank you. Our next question is from Shannon Clark. Your line is open.

Shannon Clark: Oh, hello. Shannon Clark with UserWise Consulting. So, a question about 

vaccinations. So, obviously you can’t run a clinical study for a serological test 

kit with vaccinated individuals as vaccinations may influence the presence of 

antibodies. However, can you include vaccinated individuals with an antigen 

clinical evaluation study?

Dr. Timothy Stenzel: Toby, I believe for antigen, yes. But we would want the data separated out 

with those who have been vaccinated versus those who haven’t. But and the 

performance could differ and in particular, if someone is vaccinated, they 

might have lower levels of virus in their nasal passages. And it could 

potentially impact the performance of the antigen test. 

So, we don’t, I’m not familiar with any data that we have yet on antigen test 

performance in vaccinated information. If somebody is doing some research

on that out there, we should probably ask our antigen team if they’ve seen that 

yet. Because sometimes we keep our nose to the grindstone with the 

applications but it’s a good question. And it’s just a word of caution that, that 
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vaccinated people may not behave the same way on a symptomatic follow up

infection as a primary or natural infection.

Shannon Clark: But it doesn’t necessarily double our sample size. We can just collect the data 

and then analyze the data separately if needed?

Dr. Timothy Stenzel: Yes. You may find that it really drops with performance there and we’d 

like to see the data in the vaccinated population. If it doesn’t really drop the 

performance, we just want to see the data also separately. You may list it 

separately in, you know, together and separately in the IFU.

Shannon Clark: Okay. Thanks so much.

Coordinator: And at this time, I’m showing no further questions. 

Toby Lowe: Thank you. 

Dr. Timothy Stenzel: Okay.

Toby Lowe: Oh.

Dr. Timothy Stenzel: We have a little bit of time so we can, we can just wait a minute or two 

and if there are no further questions, we can give it back to you, Irene, if that’s 

okay. Give it a minute, not too long, but we’re available and ready to answer 

questions.

Coordinator: And as a reminder if you would like to ask a question at this time, please press 

Star 1. We have a question from Codimode Vanke. Your line is open.
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

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Codimode Vanke: Yes. Thanks for taking the question. My question is for serology tests that just 

like how NCI is doing, I mean, has been doing, looking for the binding 

antibodies. At NCI, or are there any other institution that might also do the 

vaccine antibodies? Do you have any plan about having a center that can do 

verification validations for antibodies that can show neutrilizing antibodies are 

protective antibodies?

Dr. Timothy Stenzel: Yes. So, we’re, you know, we recently issued a statement on use of 

serology for vaccinated folks and people that had a natural infection and the 

implications currently for what can be said about protection or immunity. 

Which, you know, studies to our knowledge haven’t been done to support that 

use. So, potentially both neutralizing and non-neutralizing assays could be 

used, mostly likely, through quantitative assays are going to be the assays that 

are going to provide the most important information about that if things go as 

we hope. That we it’s just the presence or absence of antibody in other 

examples where, where a test has been authorized to assess the vaccination. 

But it’s the level of antibody sometimes that, that is important. It’s an obvious 

area for us to look into, getting additional information about the serology 

banked samples at NCI having do with quantification of antibodies and the 

presence or absence of neutralizing antibodies. 

So, it’s certainly an area of active discussion right now but in all, because the 

focus may be more on truly quantitative assays. Those are truly, those are 

usually not going to care about assays although I’m not going to rule it out. 

So, it may be something that we eventually design a blinded panel for if we 

can, you know, depending on how soon we can stand up such a program. But I 

can’t make any promises that one will be stood up and if it is stood up, how 

long it will take to stand it up. But it’s an obvious area for consideration right 

now.
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

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Codimonte Varte: Thank you. But I think in the past when you were mentioning vaccination is 

not diagnostic so do they really need the approval the way in which it is done. 

And, you know, I think it was a positive mention that NCI did a discuss with 

CBER and we will discuss? And also, can you just mention still it is a part of 

CBER team, vaccine and vaccine as we can see is not a diagnostic test. 

Dr. Timothy Stenzel: Oh, it’s very clearly a diagnostic test. It’s just that it, it was moves into 

CBER’s sphere as well and we have an agreement with CBER that we will 

combine our efforts to review applications that have to do with, particularly

that have to do with any claims about immunity or protection. That’s the 

situation we’re really talking about here. Although they are types of assays

that don’t speak to immunity, all other serology assays for COVID that don’t 

speak to immunity or protection would be reviewed within our office and our 

center.

Codimonte Varte: Thank you.

Coordinator: Our next question is from Lonnie Edelman. Your line is open.

Lonnie Edelman: Hi. Thanks. Good morning. I actually haven’t called in a few weeks. It’s good 

to hear all the questions and thanks for continuing the discussion. There was 

no template for a reader to get an EUA, so we submitted a pre-EUA a couple 

of months ago, maybe three months ago. I was wondering how the flow is 

going. You had a surge going at the beginning of the year. Are you, I guess 

what I want to know, if are you going to get to the pre-EUA anytime soon? Or 

are you still really backed up?

Dr. Timothy Stenzel: So, I think, you know, sorry for the delay in getting back to you and 

certainly I’m not sure that I’m aware or Toby’s aware of your pre-EUA. So, if 

you could forward that to our templates email address and make sure that your 
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

Page 22

submission a few months ago is seen by Toby and I? We will look into it and 

we’ll get back to you. One of us or one of the team members will get back to 

you. One thing with readers is in order to assess readers, we do recommend 

that it comes in with a candidate test. 

Lonnie Edelman: Sure.

Dr. Timothy Stenzel: And that’s how you assess it. So, I guess this is for general, but I don’t 

know what you put in your submission but that’s just for a general 

consumption. That the only way we can evaluate a reader is in the specific 

application in use with a test. We just don’t know on the readers how, how 

portable they are, from test to test, right? 

And we clearly have seen some issues with some readers and we’re not quite

sure why. It could be your individual software applications aren’t robust 

enough but we, for example, we’ve seen variable performance across different

makes and models. That gives us pause and, you know, something isn’t robust 

enough to work across several makes and models, it may not be as useful. 

Because, you know, there’s a lot of makes and models of Smartphones out 

there if you have a Smartphone application. And we do want to see a 

validation plan that incorporates diversity of Smartphone and even software

version use on those Smartphones for obvious reasons.

Lonnie Edelman: Yes. That’s, I have, I’m in full agreement. The system was designed with a 

captive phone so anyway, I don’t want to turn this into an infomercial. So, we 

will, we’ll send in the email and hopefully. Yes. Yes. I will.

Dr. Timothy Stenzel: And Toby and I will make sure you get a response.
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

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Lonnie Edelman: Great. Thanks again for continuing to do these meetings. You know it kind of 

feels like things are straightening up and, you know, maybe there’s no need. 

But there’s a still at least for us.

Dr. Timothy Stenzel: For developers, I completely agree, and I have recommended to FDA 

leadership that for non-COVID, after we’re done with COVID, that we have 

some kind of forum like this for all IVD and developing. It probably won’t be, 

probably won’t be a weekly call, probably will be a monthly call. But you 

know.

Lonnie Edelman: Great.

Dr. Timothy Stenzel: My desire and the FDA’s desire is to give a ready access to developers to 

ask questions and to make that as easy as possible. So, it’s part of our overall 

customer service.

Lonnie Edelman: Yes. That’s great. Yes. Good to hear. Thanks so much.

Dr. Timothy Stenzel: You’re welcome.

Coordinator: Our next question is from Ashwood. Your line is open.

Ashwood: Thank you. I’d just like to build on the statement that you made last week on 

antibody testing and on the fact that all currently approved ones should not be 

used for verifying immunity from vaccines. Do you foresee a series of new 

tests or other ones in the pipeline that would be vaccine-specific, i.e., they 

would be detecting specific antibodies to the Pfizer, Moderna or Johnson 

vaccine? And would they need to be labeled to be matched with their 

vaccines?
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

Page 24

Dr. Timothy Stenzel: Yes. It’s, I don’t have a crystal ball that tells me how this is all going to 

work out. It’s my hope that measuring antibody response to vaccines and postinfection, natural infection will afford some ability to speak to immunity and 

protection based on clinical study data. Clinical studies are being performed. 

They’re obviously easier to perform relative to specific vaccines because you 

know the prior history because of, you know, studies because you’ve done,

the investigators have done serology testing to know prior to vaccination that 

they haven’t been exposed and are currently positive say a molecular test 

when they get vaccinated. 

And then you know exactly when they get vaccinated, so you know the start 

of the immune process to raise antibody and the level of antibodies, whether 

or not there’s neutralizing antibodies present. 

So, those studies, you know, in determining outcomes from that vaccination or 

any sort of, obviously, infection are easiest to carryout in the vaccinated 

population for obvious reasons. And I hope that we don’t link it to a specific 

vaccine but that we link it to something that is, can be universalized. This is 

my hope, there’s no promises, but say a certain level of binding antibody to, 

you know, to the appropriate antigen with use of the appropriate antigen and a 

serology test that cross reacts with vaccine. And almost all the vaccines, well, 

all the ones authorized in the US are protein vaccines right now. You know I 

hope that there’s standardization through the International WHO standard so 

that we can say, you know, this cut point or this level of antibody and above is 

protective. And we can roll that out as for use by developers in updating 

appropriate tests without them having to do their own outcome study with 

their own test. 

So, the only way I can think about doing it now and I’m open to other ways is 

to actually utilize the WHO standard to link the study assays using these 
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Moderator: Irene Aihie

05-26-21/12:15 pm ET

Page 25

clinical trials to the International standard. And then from there, go back 

through the International standard for any other developed tests. I think it 

would be ideal if we had a bank of immune plasma serum that could also be 

used to perhaps send out and blindly test developers as part of the process. 

Perhaps as part of the post-marked authorization process to ensure, ensure that 

the information that’s being assessed is accurate and useful and can be 

counted on. So, it’s a long-winded answer, a complex area right now, but one 

of obviously intense thought within the FDA.

Ashwood: All right. Thank you.

Coordinator: And at this time, I’m showing no further questions.

Dr. Timothy Stenzel: And we’re at the end of the hour so it’s good time to turn it back over to 

Irene.

Irene Aihie: Thank you. This is Irene Aihie. We appreciate your participation and 

thoughtful questions during today’s Town Hall. Today’s presentation and 

transcript will be made available on the CDRH Webpage at 

www.fda.gov/training/cdrhlearn by Wednesday, June 2. If you have additional 

questions about today’s presentation, please email cdrh-euatemplates@fda.hhs.gov. 

As you we continue to hold these virtual Town Halls, we would like to, we 

would appreciate your feedback. Following the conclusion of today’s virtual

Town Hall, please complete a short 13-question survey about you FDA 

CDHR virtual Town Hall experience. The survey can be found now on 

www.fda.gov/cdrhwebinar. Again, thank you for participating and this 

concludes today’s virtual Town Hall.
FDA Virtual Townhall

Moderator: Irene Aihie

05-26-21/12:15 pm ET

Page 26

Coordinator: Thank you for participating in today’s conference. All lines may disconnect at 

this time.

END