Virtual Town Hall #80

March 9, 2022

Moderator: CDR Kimberly Piermatteo

CDR Kimberly Piermatteo: Hello and welcome to virtual IVD Town Hall number 80 for SARS-CoV-2 test 

developers, in which we'll discuss and answer your questions about diagnostic tests in response to 

COVID-19. Thank you for joining us today. 

I am Commander Kimberly Piermatteo of the United States Public Health Service. I am the Education 

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

Communication and Education. And I'll be moderating today's Town Hall. 

A recording of today's Town Hall and transcript will be made available on CDRH Learn, under the section 

titled Specialty Technical Topics, and then the subsection titled Coronavirus COVID-19 Test Development 

and Validation, Virtual Town Hall Series. 

The February 23rd IVD Town Hall recording and transcript have been posted. 

The next scheduled IVD Town Hall will take place on Wednesday, March 23, 2022. 

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

Radiological Health, or OIR, in CDRH's Office of Product Evaluation and Quality, and Dr. Kristian Roth, 

Deputy Director of the Division of Microbiology Devices, also in OIR. 

For today's Town Hall we'll begin with a few opening remarks from our panelists, followed by answering 

your previously emailed questions, and then proceed to answer your live questions. 

I'd now like to welcome Tim, who will provide the first opening remarks. Tim, the floor is yours. 

Timothy Stenzel: Thank you Kim, and welcome everyone. This is our 80th IVD Town Hall and we'll 

continue these series as long for COVID IVDs as long as there is a need and strong interest. Just wanted 

to let you know that. And we do have a lot of questions that were submitted ahead of time having to do 

with transition from EUAs to full authorizations, and Kris will go over those. 

We are continuing to encourage submissions for full authorizations. We are accepting Pre-Subs, Q-Subs, 

regular Pre-Subs, Q-Subs, for them, and encourage them. And we want to do our part to help this 

transformation or this transition. 

And so, with that I'm going to go into next a couple of web updates. So we did update the FDA's website 

and the links are in the PowerPoint and will obviously be available after the meeting too. And some of 

the website's updates are regarding serology, one of them is fairly straightforward and providing 

recommendations for traceability to an international standard. If someone is developing a quantitative 

test or wants to trace their semi-quants or other tests to international standard. 

And then also we continue to get questions about whether or not SARS-CoV-2 antibody tests should be 

used to assess whether a person is protected from COVID, and the current FDA thinking is still that no, 

the current antibody tests should not be used for this purpose. We are still awaiting sufficient data to 
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establish thresholds for immunity and protection and should we have those, and when we have those, 

that will be a different situation entirely. 

The other website update has to do with our COVID test basics web page. And this is largely focused on 

consumers. What is a diagnostic test? Was is a serology test? And how do you use them and what are 

they good for? So please check into those if you are interested. 

OK, with that, I'll turn it over to Kris. 

Kristian Roth: OK great. Thank you Tim. 

I just want to highlight a couple of safety communications that recently that came out on March 1st. So 

these safety communications are CDRH warning folks not to use these tests, which have the same or 

similar names as FDA authorized tests. 

I think the first we want to discuss is the Celltrion DiaTrust COVID-19 test. We are warning people not to 

use certain Celltrion USA, Inc. DiaTrust COVID-19 Ag rapid tests. People should not use this particular 

Celltrion test if it is in a green and white packaging. 

The second test is the SD Biosensor Standard Q COVID-19 Ag home test. We are warning people not to 

use the SD Biosensor Standard Q COVID-19 Ag home test. This test is packaged in a white and magenta 

box and has not been authorized, cleared, or approved by the FDA for the distribution or use in the 

United States. 

And the last one is a test from ACON Laboratories. We are warning people should not use the ACON 

Laboratories test named FlowFlex SARS-CoV-2 Antigen Rapid Test in parentheses Self-Testing, and this is 

packaged in a dark blue box. 

For more information about these particular safety comms and what to be done if you come across 

these products, please go to these links and it's very thoroughly described within that text. 

With that, I will turn it back over to Kim. Thank you. 

CDR Kimberly Piermatteo: Thank you Tim and Kris for those opening remarks. 

We'll now answer your previously emailed questions about COVID-19 Test Development and Validation. 

Please note we receive some questions that are too detailed or test case specific that we will not 

address during today's 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

CDRH-EUA-Templates@fda.hhs.gov mailbox for an update. 

Now let's get to the questions you sent in advance of today's Town Hall. Kris, I'll be directing these 

questions to you. 

The first question is, would real-world data also be considered acceptable for subsequent marketing 

applications of other EUA products, such as molecular in-vitro diagnostic tests? 
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Kristian Roth: Yeah, Thanks Kim. We are open to considering existing data to support a regulatory 

submission if you believe that you have real-world data that can be used to establish performance of 

your test. We're glad to engage in a discussion to appropriately leverage that real-world use and 

experience as part of your marketing application. 

CDR Kimberly Piermatteo: Thank you Kris. The next question we received is, will FDA prioritize De Novo 

and 510(k) submissions that were formally granted EUA, or will FDA review all serology submissions, 

including those for qualitative and semi-quantitative assays? 

Kristian Roth: Yeah. Thank you. So I think there's two parts here. For the first part, FDA will review all 

MDUFA files that are submitted, and we're working hard to meet the established MDUFA timelines. 

For the second part, we'd like to note that an international standard material for SARS-CoV-2 antibodies 

is available. Qualitative or quantitative tests should be considered in a manner similar to premarket 

submissions for other analytes which have international standard materials and that allow quantitative 

claims. These other examples are hepatitis and rubella. 

CDR Kimberly Piermatteo: OK. Thank you. Our next question is, can FDA clarify whether a De Novo or 

510(k) guidance document for serology tests will be issued prior to the announcement of EUA 

terminations? 

Kristian Roth: Yeah, we can't comment on any future guidance or policy documents that may be in the 

works at this time or in draft, being drafted, however we will provide further details as additional 

information becomes available. Test developers interested in pursuing full marketing authorization for a 

serology test are encouraged to submit Pre-Submission to discuss your approach. 

CDR Kimberly Piermatteo: Thank you, alright. The next question, is FDA currently reviewing any De 

Novo submissions for serology tests? If so, would it be possible to share recommendations provided to 

developers at this time? 

Kristian Roth: So again, we're not going to comment on any submissions that may be under review, 

however if you intend to pursue a De Novo regulatory pathway for your serology test, we recommend 

that you submit a Pre-Submission with your study protocols, in order for FDA to provide appropriate 

feedback. 

CDR Kimberly Piermatteo: All right our next question looks like it has two parts, so I'll read those two 

parts completely and then turn it over to you Kris for your responses. So the first part of this question is, 

for a De Novo or 510(k) serology test, would it be acceptable for the intended use to include monitoring 

of immune response to SARS-CoV-2 vaccination, or will claims be limited to use as an aid in identifying 

individuals with an adaptive immune response to SARS-CoV-2 infection? The second part of this 

question is, if testing of vaccinated individuals is not acceptable, would clinical studies of infected 

individuals require that vaccinated individuals be excluded? 

Kristian Roth: Sure, thank you for that. Tim did discuss this a little bit at the intro and maybe I can add a 

little bit more in the context of this question. So currently, authorized SARS-CoV-2 antibody tests have 

only been authorized for use as an aid in identifying individuals with an adaptive immune response and 

have not been evaluated to assess the level of protection provided by an immune response to COVID-19 

vaccination. 
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We have previously released safety communications stating that currently authorized SARS-CoV-2 

antibody tests should not be used to evaluate a person's level of immunity or protection from COVID-19 

at any time and especially after the person received a COVID-19 vaccination. While positive antibody 

test results can be used to help identify people who may have had a prior SARS-CoV-2 infection, more 

research is needed studying individuals who have received the COVID-19 vaccination. 

FDA's feedback on EUAs, Pre-Submissions, De Novos, 510(k)s, have been consistent with the safety 

comm, and we continue to recommend that test developers do not include vaccinated individuals in 

their clinical evaluation. 

CDR Kimberly Piermatteo: Thank you very much Kris. Alright, so our last pre-submitted question is, due 

to the recent decline in COVID-19 positivity rates, is it acceptable to test archive samples to supplement 

the positives tested during the clinical evaluation for an antigen point-of-care test? 

Kristian Roth: Yes, thanks. So if pursuing an enrichment approach, which is really what this question is 

describing, you should appropriately tailor the study design for your specific test and you'll clearly 

document and describe how any bias associated with your proposal is minimized. We strongly 

recommend that you submit a pre-EUA with a detailed clinical study protocol prior to implementing any 

enrichment activities, such as using big samples. 

CDR Kimberly Piermatteo: Great. Thank you Kris. That wraps up the previously submitted questions. We 

will now take your live questions. To ask a live question, please select the Raise Hand icon at the bottom 

of your screen. When you are called on, please identify yourself and ask your question promptly. Also 

please note, we are not able to discuss specific submissions under review. 

Our first live question is from Sam. Sam I'm going to unmute you, please unmute yourself and ask your 

question. 

Sam Ali: Yes, hello, hi, you hear me, OK? 

CDR Kimberly Piermatteo: Yes we can. 

Sam Ali: Alright great. So this is Sam at Intune.bio. The question is about self-testing usability studies. So 

we're running clinical trials for tests that are substantially similar to other tests that have been recently 

approved, and the question is how extensive are the usability study requirements for tests that have 

very similar workflow and process and interpretation of results, and even the instructions are primarily 

similar. 

Timothy Stenzel: This is Tim and Kris may want to add something. So do check our current template for-

- I think you're talking about an over-the-counter test--

Sam Ali: That's right, yeah. 

Timothy Stenzel: --test at home, and probably antigen, I'm thinking, right? 

Sam Ali: Yes, correct, yes. Yes, correct. 
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Timothy Stenzel: OK well take a look at the template, if you think that it's substantially equivalent to 

what we've authorized before, follow the template and then in your submission you can justify why you 

think that is the case. And you can at least reduce the user testing. I don't know the cost of this. It would 

vary depending on whether you do it yourself and how you do it yourself versus using some sort of 

external party. Kris, anything to add to my response? 

Kristian Roth: No, thank you. 

Sam Ali: OK, thank you. Thank you so much. 

Timothy Stenzel: You're welcome. 

CDR Kimberly Piermatteo: Thank you Tim. Our next question will be coming from Ron. I'm going to 

unmute your line, so please be sure to unmute yourself and ask your question. 

Ron Domingo: Hello, can you hear me? 

CDR Kimberly Piermatteo: Yes we can. 

Ron Domingo: Alright. Thanks Tim and Kris. I have a client with a respiratory panel molecular diagnostic 

PCR based assay that includes COVID, flu A/B, and RSV, and they are currently conducting a clinical trial 

that started in February of this year. However, the prevalence of the viruses has dropped significantly 

since the December, January time frame. Even with prospective all comers collection it is likely that all of 

the category one samples will be negative. Would the agency comment on the acceptability to support 

an EUA as long as the required minimum number of positives outlined in the EUA template are achieved 

if the positive COVID samples are category 2 and flu and RSV positive samples are category 3, and what 

percentage of samples for the trial need to be category 1? Thank you. 

Timothy Stenzel: Kris, you feel comfortable trying to respond to this question? 

Kristian Roth: Sure. I think we all understand that certainly flu and RSV right now are particularly low in 

prevalence, and so I think we're open to different category sample types for those analytes. And you can 

look at some of the other decision summaries for multi-analyte EUAs that have been published and they 

describe sample types. I think the best and most accurate answer we can probably give you would be via 

email, and so really if you can kind of outline the difficulty that you're having, I'm sure we can come to a 

path forward. This is not the first time that we've encountered this and I think we do have a couple of 

ideas of what's acceptable and likely to be a balance between what you can provide pre-authorization 

and post-authorization. 

Timothy Stenzel: And Kris, anything specific about COVID, about SARS-CoV-2? 

Kristian Roth: For COVID, yeah. Taking archive samples is completely acceptable for the suspected 

population. If you're looking for a screening claim, that may be a little bit different but certainly for that 

suspected population archive samples are perfectly fine. 

Ron Domingo: Hello.

Timothy Stenzel: All right. Ron is that you? 
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Ron Domingo: Yeah, just as a follow up, you asked me to send an email. Could I highlight on the subject 

Tim and Kris? 

Kristian Roth: Sure. Please do. 

Ron Domingo: OK thank you very much. 

CDR Kimberly Piermatteo: OK. Thank you Ron. 

Ron Domingo: Sure.

CDR Kimberly Piermatteo: We're going to go ahead. Our next question is from Sue. Sue, I'm unmuting 

you now. Please unmute yourself and ask your question.

Sue Hart: OK my name is Sue Hart from Hemex Health and I have two questions, if that's OK. I'm 

wondering if, this is for antigen POC, if an investigational use device that you're putting into a clinical 

study can be used at a site that doesn't have a CLIA waiver?

Timothy Stenzel: So that's not necessarily what we're recommending here because we're trying to look 

at performance within an actual CLIA site. And with the kind of personnel that you see at a CLIA site, 

presumably a busy clinical practice, where the staff there are juggling seeing patients, taking care of 

those patients, and doing any CLIA waived tests and that that's the scenario that we're trying to-- that 

we're recommending. 

So that we know, in that busy environment, can they get an accurate test result? And I'll allow a follow 

up question there. But that has been our recommendation for a long time now. 

Sue Hart: OK because we've got a POC site that is doing-- its a drive-through PCR site, PCR test site. But 

they don't have a CLIA waiver because they're doing the PCR testing at their laboratory that is a few 

miles away. 

Timothy Stenzel: Say that again. You're doing the candidate device testing at a drive-thru setting. 

Sue Hart: Yeah because we're rapid and they do the collection of the PCR swabs at the drive-thru site 

and it's pretty busy, but the lab for PCR testing itself is a few miles away so they bring the swabs there. 

Timothy Stenzel: Yeah so the comparator testing, that's pretty standard that you'd have to transport 

that somewhere else. Again we're looking for a standard POC site so, Kris, you may be able to add on to 

this, but I think if you're going to have multiple sites and one of those sites is such a site that's fine. But 

the drive-thru site should have, first of all should have a CLIA certificate if they're doing CLIA lab testing. 

So unless they're doing just collection and sending to a central facility but if it's going to be a 

nonstandard point-of-care testing site that you want to use, or at least one site that you want to use, I 

would recommend you submit a pre-EUA that includes your clinical study design and your method for 

testing, and verify with the FDA that that's acceptable. 
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Sue Hart: OK the second question has to do with an OTC submittal and antigen submittal. If you also 

want a POC claim, do you need a study, an additional study, that includes the intended POC user and 

that environment? 

Timothy Stenzel: No. So we'd recommended a long time ago that those that are ultimately interested in 

going over-the-counter, they just do the over-the-counter studies. They don't have to do-- there are all 

the flex studies but they don't have to do-- we don't recommend doing clinical studies within a point-ofcare if you're going to do the home user study. If something works well in home user hands, we expect 

to work well in point-of-care user hands. And that just comes with it, you don't necessarily have to have 

a point-of-care version of the test but you can have a professional use of the test and you don't need 

any additional clinical study data to support the point-of-care in that case. 

Sue Hart: OK, alright. And in that case, in your intended use, do you not say CLIA waived for that 

environment? You just say point-of-care environment? 

Timothy Stenzel: So it depends on you and what you want and typically a professional use kit is going to 

have a lot more tests than an over-to-counter kit, so you would, in all likelihood, have two separate 

authorizations with one submission. 

Sue Hart: Yeah, OK. 

Timothy Stenzel: We would assign a second EUA number for the point-of-care kit, you would have 

different kit sizes, their labeling would be a little bit different, how you describe the setting where it 

happened. And then on the FDA website for a successful test, you will have both over-the-counter 

designation on the website, as well as CLIA waived, moderate and high complexity settings. 

Sue Hart: OK so would you submit two sets of labels in that case also? 

Timothy Stenzel: Yes. 

Sue Hart: OK. 

Timothy Stenzel: Yes. 

Sue Hart: Thank you. Oh that's awesome. 

Timothy Stenzel: You're welcome. 

Sue Hart: Thank you. 

CDR Kimberly Piermatteo: Thank you, Sue. Thank you, Tim. Our next question comes from Ray. Ray, I'm 

going to unmute your line. Please unmute yourself and ask your question. 

Ray Bandziulis: Hello, thank you for taking the question. My name is Ray Bandziulis from LGC Biosearch 

Technologies. This question is in the category of additional conditions of authorization that FDA issued 

related to-- for molecular tests that were already authorized related to the monitoring of variants. And 

for the request, the conditional authorization was for manufacturers to submit reports on how their 

monitoring programs were structured, as well as some labeling modifications to the existing materials. 
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In the case of LGC, those materials were due December 21st. Does FDA still intend to provide feedback 

on the manufacturer’s program? And related to that, in the absence of feedback, should manufacturers 

continue to provide regular updates on the program even if prevalence is not detected at or above 5% 

occurrence? Thank you. 

Timothy Stenzel: So yeah, you're welcome. So we've got a guidance out there and we've also updated 

the authorizations as you mentioned. I think this-- Kris, if you want to handle this, it'd be an excellent 

one for you to handle. 

Kristian Roth: Yeah so we do have a rather large backlog of these particular files, so you may have not 

heard back from the review team yet on your supplement. I think we really only are interested if you 

detect changes in reactivity. If you continue to monitor the publicly available databases and there's no 

change, there's no reason to report. We will of course, be doing the same thing on our side and if there 

is some changes that we detect, we will likely reach out to you as well. So I would just say, keep doing 

your typical monitoring that you are doing and if there's no signal that things are changing then certainly 

we want to keep those reporting activities at a minimum. 

Ray Bandziulis: Great, thank you. 

CDR Kimberly Piermatteo: Alright thank you. Our next question is coming from Tracy. Tracy, I'm 

unmuting you now. Please unmute yourself and ask your question. 

Tracy: Hello doctors. My name is Tracy, Tracilynn Kidd, they call me Tracy. I'm independent quality 

consultant, and I had a question about the submissions on the clinical testing kits or systems for 

submission for emergency use authorization. How is the validation approach for determining the shelf 

life where the expiration date is being monitored? 

Timothy Stenzel: So there's different expiration dating experiments that can be done. I think our 

templates that are on the FDA website speak to some of these. 

You really want to start with the target date for your unopened kits at least for ultimately where you 

want your expiration dating to be. Let's just say you want it to be two years for molecular and/or rapid 

antigen tests or a serology test, then you plan your expiration dating experiments out beyond that date. 

You want to go one time point beyond those dates. And then there's been a lot of interest to seeing 

date extension for expiration dating for COVID tests, so that especially when there's drop off in cases, 

perhaps only temporarily, product doesn't go bad in the intervening period, and labs have stocks and 

individuals that have stocks of tests. 

So we are encouraging that all developers extend their dates. And so in the early months you may want 

to have more time points. Once you get up to say one year, you may want to go quarterly in real time 

work up to a year, and then you might drop off to every six months or something. That's up to the 

sponsor. 

But we like to see real time-- we'd like to see accelerated stability testing for the submissions so that we 

know that we can give at least six months dating at additional authorization. And then as you do your 

real-time stability testing and have updates, those are supplements and submissions. The FDA reviews 

the data and if it looks good, can authorize it. 
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And then also we've displayed extreme flexibility for kits that are already in the field, that may be 

expiring because they have an earlier expiration date or a shorter expiration date than has just been 

authorized. And so we do work closely with firms to address that issue. So that kits in the field with FDA 

authorization can be used beyond the original dating with information provided by the developer. I'm 

not sure if that addresses all your questions. I mean, to get into a detail response on how to do that 

would be too much for this call. Do look at the templates and then if you have questions beyond that 

you can submit those as part of a pre-EUA.

Tracy: Great thank you, and thank you Kimberly. 

CDR Kimberly Piermatteo: Thank you. Our next question is from Murthy. Murthy I am unmuting your 

line. Please unmute yourself and ask your question. 

Murthy Talasila: Hi, can you guys hear me? 

CDR Kimberly Piermatteo: Yes, we can. 

Murthy Talasila: Thank you. My question is around the EUA timeline as we try and plan for our market 

approach. So I don't think any of you would be talking about our specific case submission, but I'd like to 

understand what is a typical timeline once we're in an active review process?

Timothy Stenzel: So that's typically not information that we give out. We're still receiving upwards of 

about 100 original EUAs and pre-EUAs a month, so we remain very busy. The surge has largely returned 

to their original spots within the Center, but we have been able to hire very well through the pandemic 

with additional funding provided by Congress. So the DMD Division, the Microbiology Division, is 

substantially larger than it was pre-pandemic. 

And so we do have our priorities that were listed at the November 15, 2021 guidance update. You can 

see what those priorities are. If you meet those priorities and your submission is excellent, meaning that 

the data support the test authorization and the data is presented in a way that's easily understood and 

complete and all the protocols are provided, that you used, and they're able to be understood, those 

submissions go through very quickly. Sometimes very quickly, even now. However if we have questions, 

that can involve a lot of back and forth. And that's going to extend. So those submissions that are well 

done in all aspects really benefit from that focus to making sure that it's a well-done submission. 

Murthy Talasila: OK thank you. 

CDR Kimberly Piermatteo: Alright our next question is coming from Jennifer. Jennifer, I'm unmuting you 

now. Please unmute yourself and ask your question. 

Jennifer Stanford: Hi, this is Jennifer Stanford from Hopkins Med Tech Compliance, and my question is 

regarding over-the-counter rapid antigen tests. We have been using NP swabs as our standard of care 

for PCR testing, and on other calls we've talked about the potential of switching to anterior nasal swabs. 

So if we did an anterior nasal swab for our PCR, and then we also did an anterior nasal swab for the 

over-the-counter test, would you all want to see a randomization between those two types of swabs? 

Timothy Stenzel: OK so this is a clinical study protocol where you have a candidate antigen tests. 
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Jennifer Stanford: Yes. 

Timothy Stenzel: And Kris may want to answer, add some additional to this. So first of all, the sample 

type for the comparator test has to be authorized. It has to be an EUA-authorized test to be used as a 

comparator and we want it, we recommend it to be a high sensitivity. So we are recommending that the 

developers do check with the FDA to make sure that the particular molecular comparator test is of 

sufficient sensitivity for your study. That's a pretty easy direct question if you're not going to have any 

other questions that can probably be handled by an email rather than a pre-EUA. 

And then if the antigen test, if you want to go with an anterior nasal swab, then as long as the anterior 

nasal swab is acceptable and validated and authorized for the molecular comparator, comparing the two 

is just fine. It may be clear to you already but sometimes it's not clear. And then there are different 

approaches to this as far as you can-- oh randomize, this is an OTC test, so we don't like to have the 

users biased, at least immediately biased. I mean most everybody has had some sort of swab done on 

them but sometimes they forget. And we're really evaluating, for an OTC test, you know how does that 

user approach that test with just the instructions that are provided with the test without any help. And 

so the comparator test of swabbing could give them a little bit of education right before they do the 

antigen test. 

So the best situation here that we recommend, if you want to do something other than this, then I 

would recommend that you submit a pre-EUA with your clinical study design. There may be other 

questions you have. Is to first give the candidate test to the subject, and have them do that, and then 

have a short washout period of, we would recommend 15 minutes, and then you come back with the 

comparator test. So since most of these tests, if the user goes ahead self-swabs, runs the test, it's going 

to be at least 15 minutes already. So it's really as soon as they're done performing that OTC antigen test, 

you can then direct them into getting their comparator test swab done. 

Jennifer Stanford: OK. Thank you. 

CDR Kimberly Piermatteo: Alright thank you very much. It looks like we're going to receive another 

question from Sam. Sam I'm going unmute your line and you can ask your question. 

Sam Ali: Yes, this is Sam again from Intune.bio. Thank you for taking my second question. This is a 

follow-up question to something that was mentioned last time at the last Town Hall, about enrichment 

in clinical trials. As you know, the numbers, the number of cases are going down, and for, again the 

question is for OTC self-testing antigen tests, can you give us maybe an example-- I think Kristian 

mentioned the enrichment last time, but it was a bit vague, but is there an example of an acceptable 

enrichment approach for antigen tests? 

Timothy Stenzel: Yeah so a lot of this has to be individualized because there's specifics that are 

important. What we want to do is eliminate bias, and enhancing the performance of the test through 

that bias, so since this is an over-the-counter antigen test it's really important that the user doesn't 

know the results of-- it's important that they don't know whether they're positive or negative with the 

test of record or comparator test. 

So first of all, antigen tests are directed at symptomatic people, so obviously someone has symptoms 

and can define those symptoms, that can help you enrich. If there's a way that you can have a quick-- I 
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think it's probably good for you to come in with a pre-EUA and suggest some things. But those are the 

important elements, and it all depends on what the comparator test is, how quickly you can, or the test 

of record, if it's the same thing, as compared to how quickly you know that result, and then what's 

ethical and when you provide that result to the user, relative to when they are tested. One possibility is, 

if the local IRB would approve, is that you bring people back to give them their results of their testing. If 

they, at the time of the original testing, say they're willing to be part of a study, and you bring back both 

people who tested positive on the test of record, as well as tested negative so there isn't a bias there. 

And so they don't know whether they were positive with the comparator test or not. But that's just one 

idea, it's not necessarily the recommended approach, it's just to get your creativity going here on how 

you might do it and to lay out the importance of avoiding bias. 

Sam Ali: Yes. Yes, I understand. Thank you so much. 

Timothy Stenzel: Mm-hmm. 

CDR Kimberly Piermatteo: Alright our next question is coming from Zakir. Zakir, I am unmuting your line 

now. Please unmute yourself and ask your question. 

Zakir Murtaza: Hello, good morning. Yeah, this is Zakir Murtaza from Applied Biomedical. I have a 

question regarding cross-reactivity to be recommending it, we have to have an organism, inactivated 

organism but some of them are not available. Is there any recommendation where we can acquire those 

kind of samples? 

Timothy Stenzel: So I think you're talking about cross-reactivity testing. 

Zakir Murtaza: Right, yes. 

Timothy Stenzel: ---that can be done wet. Some can be cultured and some can't. And the type of tests 

that you're developing is, I presume an antigen test, then? 

Zakir Murtaza: Antigen test, yes. 

Timothy Stenzel: Yeah, so it's a little bit more difficult to do in silico analysis. I'm not going to say it's 

impossible, but you know I'm not sure that science is there yet. So that's the sort of thing that you could 

ans--

Zakir Murtaza: We are using recombinant but not all of them are available. So some of them are 

available. So we are planning to do that, but some of them recombinant proteins are available. So that's 

what we are planning to do unless we find some real organisms. 

Timothy Stenzel: Yeah. Yeah, so I think we have a pretty standard list that we know are available. 

Zakir Murtaza: Yeah. 

Timothy Stenzel: And then those that aren't available, I don't know that I'm up to speed on the use of 

recombinant for those. Kris, are you? 
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Kristian Roth: Yeah, I don't think we've accepted recombinant quite yet. EEI has quite a few clinical lab 

collaborators that you can engage with. There are other sample banks that provide samples as well. So 

you can always [INTERPOSING VOICES] just and always discuss your due diligence with us and say, well 

hey we looked and we can, in some cases we can point you in other directions. 

Zakir Murtaza: OK, very good. Thank you. 

Timothy Stenzel: Yeah so, I was just going to recommend that you write you write up your crossreactivity study protocol and the suggestions that you want to do and the rationale, you send that in as 

a pre-EUA for us to review. 

Zakir Murtaza: OK. Thank you. 

Timothy Stenzel: Thank you.

CDR Kimberly Piermatteo: Thank you for that question. Our next question is coming from Wen Li. Wen

Li I'm going to unmute your line. Please unmute yourself and ask your question.

Wen Li: OK thank you, can you hear me? 

CDR Kimberly Piermatteo: Yes we can. 

Wen Li: Yeah thank you. Yeah, I'm Wen Li Zhou from XYZ Laboratory, and I just have a question on when 

we do the analytical performance for the antigen OTC kits and from the antigen template. We use this 

spike in the quantified virus inactivated. So right now, for the EUA application we have all been using 

this, the commercially available from ATCC and such other places. And to do this study, and recently 

there's a WHO standard that come out, so I just wondering for the De Novo or 510(k) are you expecting 

us to use this WHO standard for that or we still use the same way as the EUA studies? 

Timothy Stenzel: No. This is for an antigen test or is this for a molecular? 

Wen Li: Antigen. Antigen. 

Timothy Stenzel: Yeah, so I don't think we would be recommending that you use WHO standard unless, 

a WHO standard, unless you were interested in developing something that you wanted to link to 

international standard units. Rather, following the existing templates and obtain inactivated virus that's 

been in use and do and do your studies with that. Kris, anything different than that from you? 

Kristian Roth: No. In fact, WHO doesn't recommend use of their material in that manner anyways. They 

are providing that primary standard to folks that they're making a secondary standard and then using 

that secondary standard for further investigation. So really that primary standard for WHO really should 

be used according to instructions that WHO provides. 

Timothy Stenzel: Yeah. So they don't have an under limited amount of international standards. So we 

don't recommend that be used for other than the intended purposes for that standard. 

Wen Li: OK. Great, thank you. 
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CDR Kimberly Piermatteo: Thank you. Our next question is coming from D. Rafferty. I have unmuted 

your line. Please unmute yourself and ask your question. 

D. Rafferty: Hi. Good afternoon. Thank you for taking my question. In reference to previous Town Hall 

meetings, on February 9th we actually heard information about the sequencing of at least 10 positive 

samples. And in regards to that, if it comes for the OTC or the POC antigen test, can the-- because 

currently the lab where we currently work in, they unfortunately they don't do sequencing, and we were 

wondering if these sequencing samples, even if they are collected in the United States, if they can be 

processed outside the United States. And I have another question, but I would like to hear the panel's 

opinion for that.

Timothy Stenzel: Is the study being conducted in the United States? 

D. Rafferty: Yes, sir. 

Timothy Stenzel: Mm-hmm OK, well there should be plenty of opportunities to get a sequence within 

the United States. We do ask that it's been a well-validated method of sequence analysis. And then as 

long as you collect, as long as the study is conducted when omicron is essentially 100%, which it still is, 

in a region of the country or world where you, well in this case, the country recommended, then we 

don't need to see the sequence information at the submission. That can be verified later. So we don't 

want to hold up the submission unnecessarily if the sequence information isn't back, as long as you've 

collected the samples. If you haven't even started your study and you start your study now, it's mostly 

going to be omicron. We just want to verify that at least 10 of those pre-authorization are omicron. And 

then again that sequence information can be submitted as soon as you can get it if it's not quite ready 

when you submit your file. 

D. Rafferty: Thank you so much, Dr. Stenzel. And second question, if I may ask, can the accelerated 

study or the real time study for the stability, can part of it be supplemented with a study done and 

performed outside the United States, while we continue performing our tests within the United States? 

Timothy Stenzel: Yeah, so if you've launched your test outside of the United States and the test is 

unchanged from what you're using, what you're going to submit to the United States, then that 

information can be applied to the current test as long as there's no changes to the test. 

D. Rafferty: Great, excellent. Thank you so much for your time. 

Timothy Stenzel: Mm-hmm. 

CDR Kimberly Piermatteo: Thank you. Our next question will be from Nancy. Nancy I'm unmuting your 

line now. Please unmute yourself and ask your question. 

Nancy Rector: Hi, thanks I'm Nancy Rector from Recuro Health. I have a real quick question about EUA 

templates. Is there one that is specific for the submission of digital test data for digital interpretation of 

over-the-counter rapid test results? 

Timothy Stenzel: Digital test interpretation for over-the-counter tests?

Nancy Rector: Yeah, test results. 
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Timothy Stenzel: Yeah, so you mean that, say a smartphone would capture an image and call the result 

as either positive or negative--

Nancy Rector: Yes 

Timothy Stenzel: or failed, or--?

Nancy Rector: Yes exactly. 

Timothy Stenzel: And do we have recommendations? So I don't know how extensive the 

recommendations currently are in the template, but there is some direction there, I know. And then we 

do have a team that's focused on the review of those digital submissions, and they're pretty up to 

speed. So if you want to think about what-- if it's smartphone based, versus you have an instrument that 

does it right, that's dedicated for your test, if you want to use smartphones they've got to figure out 

which smartphones are going to be allowed to be used with the test, then have a validation plan for 

those different smartphones and also take into account different models within that family of 

smartphones. So if you want to go ahead and put together a protocol for validation of that and submit 

that as a pre-EUA that digital team can provide some feedback to you. 

Nancy Rector: Great, thanks. We've been taking photos for a while, so we just are looking how to move 

forward. So thank you so much for all that you all do, for sure, and you've answered my question. 

Thanks. 

Timothy Stenzel: OK thank you. 

CDR Kimberly Piermatteo: Thank you Tim. We will try to get in two more questions. Our next question is 

going to be from William. William, I have unmuted your line. Please unmute yourself and ask your 

question. 

William W.: How are you doing? My name's William from Texas, and my background is procurement 

and quality control. So, quick question, will Chinese-made OTC antigen tests be on the priority test? 

Timothy Stenzel: National origin doesn't determine our priority. Our priority is listed on our guidance 

update on November 15, 2021, established what the priorities are. Many of the recent authorizations 

have been outside the US, have been manufactured outside the US. 

William W.: Thank you, that's it. I really appreciate the answers. 

CDR Kimberly Piermatteo: Thank you, William. Thank you, Tim. Alright we will move on to our last live 

question for today. That will be from Sousan. Sousan I am unmuting your line. Please unmute yourself 

and ask your question. 

Sousan Sheldon: Hello, this is Sousan Sheldon. I'm an independent consultant. Thank you Tim and Kris 

for doing all you do, and the rest of the team at OIVD. 

I have a question regarding the usability study for over-the-counter test that's going to be done in the 

US. Is it sufficient to have the final instruction for use for the patients to go through the testing and then 
15

give them the 15 minutes, washout and sample the one for the comparator test and the study would be 

just that. Otherwise, I have thought about adding a questionnaire to the study protocol where the 

patients respond about the ease of the test, how difficult it was, and things like that to be able to tweak 

the instruction for use after the study. And if that happens, do I need to redo another usability study? 

Timothy Stenzel: Yeah, so first of all, collection of the comparator test you can do exactly as you 

described. I think I mentioned that earlier on this call. Where you give them the kit and current 

instructions and they run the test without help, and then as soon as they're done obviously you can 

collect a competitor sample and not bias that. 

If you don't think you have locked down instructions in your usability study creates questions about 

whether you should change your instruction. I mean that's really, could be material. And so its why 

traditionally, people do usability studies ahead of the clinical study. Because if they make any changes 

there's no impact on the clinical study. 

If developers have high confidence there doesn't need to be a change that they have their protocol and 

their test locked down, it's going to perform well, then there's probably low risk and you save a lot of 

time if you combine things. But if you really want to know, is the test easy to use and will it, with the 

current instructions work, it may be best to do the usability study ahead of the clinical study. 

Sousan Sheldon: Great, thank you so [INAUDIBLE] that's very helpful. 

Timothy Stenzel: Yep. You're welcome. 

CDR Kimberly Piermatteo: Alright. Thank you Tim. That was our last live question for today. And thank 

you to all of our panelists for providing responses to these questions. We greatly appreciate everyone's 

participation. 

As I mentioned earlier, a recording of today's Town Hall and a transcript will be made available on CDRH 

Learn. Please visit CDRH Learn at the link provided on this slide. You will find the recording and 

transcript under the section titled Specialty Technical Topics, and then the subsection titled Coronavirus 

COVID-19 Test Development and Validation Virtual Town Hall Series. 

For additional questions about today's Town Hall and COVID-19 IVD topics in general, please email 

CDRH-EUA-Templates@fda.hhs.gov.

Lastly, please remember to join us for the next IVD Town Hall scheduled for Wednesday March 23, 2022. 

Thank you. This concludes today's Town Hall and have a nice day. 

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