FDA Virtual Townhall

Moderator: Irene Aihie

09-23-20/12:15 pm ET

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FDA Virtual Town Hall Series –

Immediately in Effect Guidance on 

Coronavirus (COVID-19) Diagnostic Tests Moderator: Irene Aihie

September 23, 2020

12:15 pm ET

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

listen only mode until the question and answer session of today's conference. 

At that time, you may press star 1 on your phone to ask a question.

I would like to inform all parties that today's conference is being recorded. If 

you have any objections, you may disconnect at this time.

I would now like to turn the conference over to Irene Aihie. Thank you, you 

may begin.

Irene Aihie: Thank you. Hello, I'm Irene Aihie of CDRHs Office of Communication and 

Education. Welcome to the FDA 27th 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, Timothy Stenzel, Director of the Office of In Vitro Diagnostics and 

Radiological Health in the Office of Product Evaluation and Quality. And 
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Moderator: Irene Aihie

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Toby Lowe, Associate Director of the Office of In Vitro Diagnostics and 

Radiological Health, both from CDRH, will provide a brief update.

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

today's discussion. Please remember that we are not able to respond to 

questions about specific submissions that might be under review.

Now I'll give you Timothy.

Timothy Stenzel: Thank you, Irene and welcome everyone to this week's call. We look forward 

to answering questions. And I just have a few brief introductory remarks. 

Mostly this is just going over some reminders.

So, first of all, you know our templates contain important recommendations 

for validation and I encourage you to check those out. And then if folks, 

developers submit a pre-EUA and they ask questions that can be directly 

addressed by the templates, in order to assist us to most efficiently handle all 

of the applications that we get, we are going to typically close those by 

referencing the relevant templates. So we hope that works. If you have 

questions, you know that the templates don’t go into them, that's where we'll 

focus most of our pre EUA response. And also, if there is something that 

you're asking that we haven't yet created a template or posted template, then 

obviously, that's important for us to see and provide feedback on.

And again, the recommendations in the templates are exactly that, they are

recommendations. We’re are open to alternative validation strategies, we 

encourage you to check with us on those alternative strategies. So that we're 

all aligned prior to doing the work.
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And then finally, I just wanted to go over some of the top priorities for review 

and for application processing. This is not an all-inclusive list. But does 

include some of them. There remains a robust interest in pooling and in 

particular kit manufacturers who have pooling submissions that would allow 

those kit users in the labs that use that kit to immediately pool with minimal 

work and perhaps no bench work for their own lab. That obviously greatly 

amplifies our efforts around trying to promote the opportunities for pooling. 

So those would be priority.

And then point of care tests, especially those that are molecular in antigen 

remain high priorities. As to those that help us to expand testing further and

that includes home collection, and home testing, especially for molecular 

diagnostics and antigen testing.

So, with that can then move into the question and answer phase and look 

forward to that.

I don't believe Toby has any updates. So, she's here to assist me today. So, 

operator, we can go into the Q&A session.

Coordinator: Thank you. We will now begin the question and answer session. If you 

would like to ask a question, please press star 1, unmute your phone and 

record your name clearly. Your name is required to introduce your question.

If you need to withdraw your question, press star 2. Again, to ask a question, 

please press star 1.

Our first question comes from (Shannon Clark) from User Wide.
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(Shannon Clark): Good morning. This is (Shannon Clark) from User Wide the Human Factors 

Consultancy. Question about PCR assay submitted for high complexity, 

moderate complexity and waived status. We're wondering if we could secure

the capability for pooling for just high and medium complexity contexts, but 

not for point of care? Does the FDA have any hesitation for approving 

pooling for a product just for the CLIA context, but not the point of care for 

that particular product? Or do you want us to do blanket testing that 

demonstrates that pooling is acceptable in all three contexts?

Timothy Stenzel: So that's a great question, we can carve that out and specify in the instructions 

that's for some high end moderately complex lab situations, there are those 

that have expressed interest in pooling for point of care. It would, in addition 

to the typical analytical and clinical validation for pooling addition, we would 

also want to look at usability in the point of care setting. You're not asking 

that for now, I'm just providing a little bit of additional information for those 

potentially, on the call who are interested. But we, you know, we're open to 

pooling schemes at point of care. But again, we would want to see that those 

untrained, you know, those health care workers in a point of care setting, who 

are not trained laboratorians can accurately carry out the pooling scheme and 

both convolute and deconvolute those and to get accurate results as well. I 

hope that's helpful.

(Shannon Clark): To be clear, if we did want to pursue point of care pooling, you're saying that 

human factors data would be required to demonstrate they're able to follow 

the pooling scheme.

Timothy Stenzel: Yes, in an actual clinical study validation to show they get accurate results 

doing pooling, that they don’t get false negatives and false positives and they 

don't mix up results.
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(Shannon Clark): And are you requesting two separate city, the human factor study and a 

clinical study or just a clinical study that also examines user interaction?

Timothy Stenzel: I think they can be combined.

(Shannon Clark): Okay, thank you.

Timothy Stenzel: Thank you.

Coordinator: Our next question comes from (Alyssa Crustacea). Your line is now open.

(Alyssa Crustacea): Hi, this is (Alyssa) also, from User Wide. I have a question about what 

has been the minimum average review time for authorization of a diagnostic 

PCR assay?

Timothy Stenzel: That does vary considerably because of the notification pathway for these 

tests. We focus our attention on the highest priority items. Everyone within 

two weeks of an EUA submission should have a contact that they can 

communicate with. And those that are the highest priority and there's room on 

a reviewer’s desk, can be moved into that slot.

Once we move into interactive review with the reviewer. If there are no 

outstanding issues, the data is all there and the data looks good, And there's 

no additional testing that may be requested, Those applications move 

relatively quickly.

However, if they’re priority and they get into viewers desk, but there is a 

substantial amount of work yet to be done and additional testing and things 

like that it can slow things down. So, we do encourage developers to, as 
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closely as possible, follow our recommendations and to pre check with us, you 

know, prior to doing any alternatives so that we don't lose time on either the 

developer side or on the reviewer’s side. And also, you know if there are

problems with the review, rather with the application, where there's clearly not 

a match between what our recommendations are and expectations are for 

performance and your actual test, That's going to slow things down as well. 

We do look at the ponderous of evidence, but by and large, we've set our 

recommendations, at what we believe are very appropriate levels. So, we are 

asking all developers to work with us and that will speed things up for all of 

us.

(Alyssa Crustacea): Great, thank you so much. And thank you for doing these town halls. 

They're really helpful.

Timothy Stenzel: You’re welcome.

Coordinator: Our next question comes from (Ariana Trovati). Your line is now open.

(Ariana Trovati): Hi, everybody. So, along the same lines, I was wondering if we do end up 

needing to perform any new studies that were not necessarily indicated in the 

pre-EUA, do we lose our place in the queue by updating our submission? Or 

is it is the review done on a rolling basis?

Timothy Stenzel: So yes, that, you know, is mostly left up to the individual reviewer at this 

time. So, they don't waste time of theirs, they may hand that off to one of our 

other support staff, with the recommended additional study design. And then 

when that comes back in with that data, then that reviewer will be notified that 

the requested additional data has been provided. And then the reviewer as 

soon as they can, can get back to that.
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But in order to manage all the volume of applications as efficiently as 

possible, those reviewers will move on to new applications. So anyways, I 

wanted to provide that clarity to you.

(Ariana Trovati): Thank you very much. And then for the antigen testing, about how long is 

the turn around right now, getting it through the review.

Timothy Stenzel: So, again, it depends, it depends greatly on the application. When we receive 

an application that has everything there and it's well organized, easy to 

understand, the data are acceptable and no additional studies are needed. 

Those move incredibly fast. Obviously, we're having a lot more applications 

right now. Versus in the early days, when we can turn things around in as 

little as a day. Those times are not necessarily with us right now, because of 

the volume. And our desire to work with as many developers as our reviewers 

can handle in moving them along, all along as quickly as possible. So, it does 

vary greatly.

So again, if additional studies are requested, that can slow things down, if 

things aren't clear. If study designs are not clear, we do look at more than the 

data, we look at the study designs to make sure that the studies were 

performed per our recommendations. And in that there are no potential

factors that could influence our review. So, in addition to setting the data, it is 

great to have the study designs there.

So, the fewer questions that we that we identify in the review, the fewer 

questions you the developers get to answer and the faster things go.
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So again, even for direct antigen, when those submissions are well put 

together, well organized, everything looks, you know, shipshape, then those 

can go incredibly fast.

(Ariana Trovati): Thank you very much.

Coordinator: Our next question comes from (Daniel Marcus), your line is now open.

Timothy Stenzel: Hey, Dan how is it going?

(Daniel Marcus): So, my question and I've asked a shade of this before is around EUAs for 

point of care tests. To my knowledge, to date most of them have just been 

platforms that you're familiar with that have basically developed an assay for 

those platforms. I know we mentioned or last time I asked question to the 

nature, I mentioned the notion of there being an assay that requires a pipetting 

step. And that being something that you guys would probably consider to be a 

fairly complex thing. Whereas I've seen other assay that have gotten point of 

care designation that use something that will not, rather not precision 

pipetting, but a transfer pipetting step.

And so that's the specific question, which is, could the substitution of a 

simpler liquid transfer mechanism taken assay from being a highly complex 

assay to a CLIA waived point of care assay? And then the broader question 

is, what are the fundamental components of an assay that you would deem to 

be something that you would authorize for the point of care that isn't an 

existing platform? Because I think there's a lot of developers are trying to 

crack that code. And I know, to date, I don't think I've seen one that that's 

been able to successfully do it. So, I'm just wondering what that looks like.
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Timothy Stenzel: Yes, I'm trying to find the list. We had a list of point of care tests that we've 

authorized recently, and there are quite a few that that we've authorized that 

have not previously been seen by the FDA. And I know that I think the 

molecular template we're updating with point of care studies, but the antigen,

template and I believe the serology template have point of care studies, or vice 

versa, maybe I forget, Toby can probably clarify which, which template has 

the point of care.

Toby Lowe: You're correct.

Timothy Stenzel: So, you can you can look at it, first of all, we can provide those 

recommendations for, for technology point of care that we haven't had posted 

now. It won't be, you know, it won't even be a draft template and just be 

specific recommendations relative to the question, but we absolutely have 

authorized new point of care devices. I'm trying to find that list. Maybe 

Toby, you have that list? I know it was shared recently on an email.

Toby Lowe: Yes. And actually, we were both backwards on the template. So molecular 

template does have point of care, antigen does not but will be updated with it. 

For point of care tests, there are I believe, nine currently authorized. Five 

molecular and four antigen. And I think I want to say that there's about three 

molecular and two antigen, possibly, that are platforms that we have not 

previously seen before the pandemic.

(Daniel Marcus): And what would you say are the commonalities between those as far as how 

you look at complexity, or is it very, very much a case by case thing?
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Timothy Stenzel: No, there's pretty good, you know, if you wouldn't mind indulging us, Toby, 

you could read through those one by one, and I'll tell you whether it's new.

I’m having a hard time finding this list quite easily.

Toby Lowe: The antigen tests that have been authorized for point of care are the Abbott

BinaxNow.

Timothy Stenzel: So, for Abbott we've previously seen that device and authorized it for other 

targets such as the flu, I think. So, we don't ask them to do -- if the 

workflows, basically exactly the same, we don't ask them to do the guard 

band studies for this. I'm forgetting the exact terminology we use. But the 

study is around, you know, what are the volume parameters that are important 

to watch and the time parameters. So, workflows the same, we don't ask them 

to repeat that, that's just a way to speed things to market, but it's a new device. 

And there's a pipetting step. First of all, precision pipetting with the calibrated 

pipette is not something that most CLIA waived labs have and nor are those 

healthcare workers trained in it's correct operation. However, most of the 

point of care devices, if they have a pipetting step, they have a little bulb, 

plastic bulb pipettor is common. You know, and so that's what we look for,

things requiring centrifugation, things requiring vortexing, things requiring 

freezers, those are all you know, a little bit different.

We will take them all one by one and assess them as to whether or not a CLIA 

waived environment worker can properly operate them. We are taking for at 

least this pandemic and in order to speed things along, we are maintaining a 

very open mind. That may, you know, as far as this, it may. And I think we 

are being very flexible and allowing some things that outside of this pandemic 

situation, we might not.
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Again, the designation of waived status here is not - it's deemed, not actually 

formally classified. Formal classification for CLIA waiver would happen 

upon conversion to a full application at some subsequent point if that's what 

the developer does.

So, these are in essence, temporary, deemed waived status, so Toby, if you

continue on.

Toby Lowe: Yes, so the next one is LumiraDX test, which is the only one of the antigen 

tests, I believe, where we had not seen the instrument before the pandemic.

Timothy Stenzel: Yes. So, you know, obviously, they then have done the point of care studies 

that we've recommended for that setting that was a direct antigen test. And 

so, you can look to that IFU to know the studies that they performed.

Okay, next one, and just moving to well, the other antigens are probably 

Quidel and BD Veritor, obviously, we've already authorized waived tests for 

them. So again, we deemed without requiring them to do the repeat point of 

care studies for this pandemic.

Moving to molecular then, Toby.

Toby Lowe: Yes. So, we have the Cepheid Xpert Xpress.

Timothy Stenzel: So that's obviously something that we've waived before very commonly used 

instruments, next.

Toby Lowe: Abbott ID now.

Timothy Stenzel: Again, very commonly used and waived before, next.
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Toby Lowe: Roche Cobas for the Cobas Liat.

Timothy Stenzel: Liat. Yes. So again, we've authorized that for flu and other targets before, 

next.

Toby Lowe: The Mesa Biotech Accula.

Timothy Stenzel: I believe we’ve already authorized the mesa one for flu. So that was not new 

to us. Next.

Toby Lowe: The Cue Health. I believe that was new.

((Crosstalk)

Timothy Stenzel: That was new, and they performed all of the point of care studies. And you 

can look their IFU to see some of the same, and not all the studies that were

performed for that, next.

Toby Lowe: I believe that's all of them.

Timothy Stenzel: Okay, so there were two that were new.

(Daniel Marcus): By my count that’s two. I guess it illustrates my point a little bit.

Timothy Stenzel: What's your point?

(Daniel Marcus): My point is that it's to try to find the commonalities with respect to what's 

considered not complex enough for the least complex to be able to authorize 
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for point of care setting is somewhat, is somewhat opaque. And I guess what

I'm trying to find, is figured out if there's enough, what are the ingredients that 

make something point of care outside of us having all waived them before.

Timothy Stenzel: The bottom line than an untrained user that is a healthcare worker in a CLIA 

Waived of setting, a clinic sort of setting. And now in this pandemic, it could 

be a school setting with a waiver, a certificate of waiver, or a work certificate 

of waiver and not anybody related at all to a health care facility in the prior, 

that they can open up the box, read the instructions perform the test accurately 

and get acceptable results. Bottom line, that's what it is. And they don't have,

they don't have a laboratory setup. So, the more everything is self-contained 

within the kit, the better. The fewer the steps and reading the results and 

interpretation of the results should be straightforward.

Typically, in that kind of CLIA waived of setting, you don't even have a long 

instructions for use. You have a quick user reference instructions, mostly 

pictures. Think of you know self-assembly of some, you know, home you 

know, furniture you might get from a store, from IKEA.

(Daniel Marcus): IKEA may not be your best analogy for your point, but I do get it.

Toby Lowe: And we do have quite a bit of information on our website about how we 

assess tests for complexity outside of pandemic. And while it's not, you 

know, completely the same situation because as Tim explained, these are not 

formally categorized during the EUA review they’re just deemed waived for 

the purposes of the pandemic, we do consider the, you know, the information 

that we consider during a formal complexity review, we just may have a 

slightly different bar, you know, given the risk benefit analysis for the 

pandemic. But there is a lot of information about how we assess the 
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simplicity of a test to determine whether it's appropriate for a CLIA waived 

setting.

(Daniel Marcus): You devoted a lot of time to this, and I appreciate that. So, I'll seed back. But 

thank you. I appreciate it.

Timothy Stenzel: Operator.

Operator. Our next one comes from (Lin Hong).

(Lin Hong): Hi, Dr. Stenzel. Thanks for taking my call. My question is about priorities 

and how you see that potentially evolving over time. Particularly, I think right 

now, it does make sense that, you know, serology is taking a bit of a backseat 

to active virology testing, whether it's PCR or antigen. I was wondering if 

you could comment in a post-vaccine world where folks are getting 

vaccinated, you know, what is the value of testing for serology? And in terms 

of characterizing individual immune response and potentially monitoring 

antibody response over time. Certainly, I recognize some of this data 

continues to evolve. But when you do the math in a post- vaccine world, you 

could see the demand, you know, getting up to millions, if not hundreds of 

millions of tests required.

So anyway, I just was wondering what are your thoughts on that?

Timothy Stenzel: Yes, it's a great question and a little bit more transparency, and not that I didn't 

want to offer it before. But we have three teams, three separate teams, those 

who are expert at molecular, those who are expert at antigen and those that are 

expert at serology. And they are independent of one another and have their 

own priority of it. So, this serology team, you know, is 100% on serology. 

They're not they're not working on antigen; they're not working on molecular. 
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They are 100% serology. And we do have the ability to shift resources from 

one team to another to balance the workload. And we have been actively 

rebalancing, when appropriate. But by and large, there's a core group in each 

of those areas who have a long history of working with developers for their 

specific technology, who are dedicated to those. So, serology for the serology 

team is all they're focused on and they're moving as quickly as they can.

And then I think I may have missed the second part of the question.

(Lin Hong): Yes, I was just wondering, you know, in the post vaccine world, you know, 

that potentially, you know, measuring antibody response, monitoring that 

because I think the data is still coming out and may vary by vaccine may vary 

by ethnicity? How long do people retain those responses? Because I could 

see, or I guess, one could see that, you know, the demand could be quite 

considerable, depending on how the clinical data evolves.

Timothy Stenzel: I think you're absolutely correct. And it's why, you know, we have a team 

dedicated to serology and advancing serology and will remain dedicated to 

that. When you move into a vaccine situation and you then start to potentially 

ask questions or try to answer questions relative to vaccines that does become 

a little bit more complex from a data perspective. And you know, if you want 

to have some sort of claims around, you know, showing response say to a 

vaccine and whether that response is adequate or not, et cetera, et cetera. The 

agencies, you know, we'll take a look at those requests. I can't foretell exactly 

what our response would be. And it frankly, it would not involve just our 

Center and our, you know, our OIR Office, but likely other areas of the FDA, 

as you might expect, so. But again, you know, we remain open to ideas and 

open for business. So, if you want to start having those dialogues with us 

now, we're open to it.
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(Lin Hong): So absolutely, thank you for taking the time and your thoughtful comments. 

Thank you.

Coordinator: Our next question comes from (Peggy McLaughlin). Your line is now open.

(Peggy McLaughlin): Thank you, Dr. Stenzel. For taking questions this morning. In the 

development of an antigen test for home use, we'd like to use a PCR assay

whose intended use is specific for a nasal pharyngeal swab, but due to 

expected patient comfort and compliance, we'd like to use a mid-turbinate

swab. Is this allowable with discussion with the FDA per your guidance? 

And what kind of discussion would that be? Or does the FDA require use of 

only a PCR test? Who has been - which has been authorized for mid 

terminate sampling?

Timothy Stenzel: So, I think you're saying, "Can you use a molecular test off label that's been 

authorized for a validation purposes?" And I think you're looking at 

developing and validating an antigen test in the home. Can I ask you this? It's 

a swab based test you're developing.

(Peggy McLaughlin): Yes.

Timothy Stenzel: And you want to use a mid-turbinate?

(Peggy McLaughlin): Potentially.

Timothy Stenzel: Okay. Well, we are very open to a home mid -turbinate use. And I don't 

know that we've authorized a mid-turbinate, but we've certainly expressed that 

in multiple occasions. The only caveat to that is in the home environment, we 

want to look at whether children would be swapped or not with a midturbinate. And if so, there are stoppers or other devices that can be utilized 
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with a mid-turbinate swab that makes it appropriate for kids and it can be 

removed for adults. So that's the only sort of caveat on mid-turbinate. It 

would be unlikely for a direct antigen test to be more sensitive

than a molecular test in the home situation. So, we want to compare it to an 

authorized version of the test, an EUA test, and typically I think in our 

recommendations, we say a high sensitivity test. And that can be performed 

in a lot of different settings. We're open to entirely in the true truly home 

setting. But you can also do have the users come into a simulated home 

environment and do testing. And then obviously, after they've collected the 

sample for your home test and tested it, they can be swapped by a healthcare 

worker and then sent in for an EUA authorized test.

So probably some of those details that you're talking about, you know, would 

best be worked out with one of our review staff. So, if something is again, an 

alternate sort of pathway, then in our recommendations for the template from 

the home test template, then I would reach out through our templates email 

address and asked those specific targeted questions.

(Peggy McLaughlin): Hey, thank you, Dr. Stenzel.

Coordinator: Our next question comes from (Elliot Cowan). Your line is now open.

(Elliot Cowan): Alright, thanks. This is a question about standard development for 

quantitative anybody assays. So usually, I'm sorry, WHO generates 

internationally recognized standards for infectious disease tests. But it looks 

as though CDC is making its own standards for the antibodies recognizing 

different SARS-CoV-2 proteins. Will FDA have a preference between the 

CDC standard and the WHO standards? Since FDA is usually a key player in 
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WHO standard development? Or will the standards from WHO and CDC be 

aligned?

Timothy Stenzel: You know, that's a question I don't know the answer to right off the top of my 

head. We are open to any - to considering any international standard. We're 

obviously working with the WHO. Toby, are you aware specifically is the 

CDC doing something separate? Because I know that in all likelihood there 

are multiple parties within us government involved in the WHO standard 

development, not just for serology, but for antigen and molecular tests as well.

Toby Lowe: No, I'm not aware, that's probably a question better for the for CDC. And I 

think generally we would, you know, be involved as much as possible and 

evaluate whatever standards are, are put out prior to commenting on them.

(Elliot Cowan): Yes, because Siemens recently released a press release and they talked about 

how they were involved with CDC and development of serology test 

standards.

Timothy Stenzel: Yes, I would, you know, will in will independently reach out to the CDC, but 

I would recommend that you directly approach the CDC and try to and try to 

get some clarity from them. Okay.

(Elliot Cowan): Okay, yes. Thanks.

Timothy Stenzel: You're welcome.

Coordinator: Our next question comes from (Ian McLeod). Your line is now open.

(Ian McLeod), your line is now open.
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(Ian McLeod): Hi, this is (Ian) from Adaptive Bio Scientific. Can you hear me?

Timothy Stenzel: Yes, we can.

(Ian McLeod): Okay, great. So, we submitted our EUA on the 15th of May for panda 

technology, which is a QPCR method which is unaffected by mismatches in 

the primer binding site. And these are known to impact conventional QPCRs 

looks like what we're seeing with the Roche assays, which is starting to fail

due to the IG mutations. Now, since the 15th of May, we submitted three 

amendments, including one for saliva as a sample type. And our customers 

have performed over 65,000 tests using our kits. And we've had no adverse 

events or complaints.

Now, we were initially assigned a reviewer and then told on the fifth of June 

that the assignment had been an error and that no reviewer has been assigned. 

Then since then, we've received no meaningful updates in the last almost four 

months. So, who should we be contacting to request the reviewer be 

assigned?

Timothy Stenzel: So hopefully, you have some sort of contact in our office so that you can ask 

questions and we get updates on a weekly basis, that is my direction. But in 

this particular case, because it's been so long, I would like to understand a 

little bit more detail. So, if you send an email to our cdrh-euatemplates@fda.hhs.gov email, the common email address for this pandemic 

for covid related tests and ask for Doctor Stenzel or Toby Lowe and we will 

look into details and either communicate directly with you or have someone 

else get back to you.

(Ian McLeod): Great, thank you very much for very much appreciate it.
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Coordinator: Our next question comes from Oregon State Public Health Lab. Your line is 

now open.

Man 1: Hi, Dr. Stenzel. Thank you for taking this question. We're developing or 

validating a lamp assay using the CDC PCRS is a reference test and I'm 

wondering, what is the benchmark for sensitivity and specificity for this test? 

It's going to be used as a point of care test. And we're going to try to send. 

You're saying no.

Woman 1: No. It's going to be used as a high complexity test. And we're going to put it 

in the certified high complexity laboratory.

Man 1: Thank you that was Sherry.

Timothy Stenzel: Hi, yes, no, that's fine. You know, we've really recommend that no that no 

viral detection test, single use, you know, whether it's antigen or molecular 

fall below an 80% percent positive agreement of PPA or in other you know 

kind of another term for sensitivity. You know, we ideally would like to see, 

you know, a sensitivity of greater than 95% greater than or equal to 95% in 

comparison to an EUA authorized by sensitivity molecular test. But we can 

authorize, if it falls below that 95. There may be some limitations in the 

language such as negatives may be presumed negative, rather than negatives. 

So, we are open to new technology that fall below that standard molecular 

comparison target, even in the high complexity labs.

Woman 1: Do you, this is (Sherry), a follow up question. Do you have a marker for the 

limited detection, like 100 virus copies or 1000 virus copies, like I know, 

when I looked at your website, it seems like the limits of detection are 

variable.
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Timothy Stenzel: So, you know, each developer performs limited detection studies so that, in in 

their authorized test, users can see not only how they did it, but what the 

termination is. And, and those methods can vary greatly and have been very

varied throughout this pandemic. Early on when samples or all virus was not 

even available. Now, we do recommend that live or inactivated virus be used 

for those LOD studies. And then, we also now have the FDA reference panel. 

So, developers who have a locked down device and would like to initiate the 

testing of their device using our relative LOD FDA reference panel can 

request that panel and on a case by case basis for those who haven't yet 

submitted even in EUA, we will look at that those who have submitted an

EUA can request that now as well. And obviously, those who have an EUA 

authorization, we have been contacting all EUA authorized test developers 

asking for shipping information and then sending them the panel and working 

with them. And working on determining with that panel, what we can say 

about the relative LOD using the FDA panel and then obviously working to 

post those results which we already have.

So long winded answers saying a lot of different things taking pause there if 

you want any clarification.

Man 1: I think we're fine. Thank you very much.

Timothy Stenzel: You're welcome.

Operators: Our next question comes from (Daniel Roth). Your line is now open.

(Daniel Roth): Yes, hi, Doctor Stenzel. Thank you. So, a question here are related to 

positive predictive value for home use diagnostic kit and positive traits value 

for home use surveillance kit. They come in multipack format. Curious how 
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you view the differences between those two uses as well as what is an 

appropriate number of subjects for a usability study for an at home test?

Timothy Stenzel: Is this for serology? Or is this for direct antigen or molecular?

(Daniel Roth): Sure, this is for an antigen test.

Timothy Stenzel: Okay, for antigens. So, and I understood home use diagnosis and then I'm not 

sure if you meant screening when you saying surveillance or are you talking 

truly surveillance as we have defined on our FDA FAQ webpage. 

Surveillance being that you're not really providing a CLIA result. You're 

doing population assessment of the presence or absence and at what level of 

the virus in it, in a targeted population basis. 

(Daniel Roth): Yes, it would be a bit, good thing, to understand the differences, and the 

positive predictive value recommendation for screening, versus diagnostic, for 

at-home use and if the word surveillance means something in this context as a

third category, then it would be good for us to know the numbers you 

recommend for a single test, as well as what's an overall multi pack? 

Assuming it's a two or three multi pack, what the overall positive predictive 

value should be.

Timothy Stenzel: All right, so, yes. So, for truly surveillance purposes as defined in our FAQ,

and you can go there, for this pandemic, the FDA is not reviewing those. We 

do obviously recommend that in those situations an EUA authorized test be 

used, but it's not a requirement. And there are different, you can check with 

CMS and in CLIA, there are different reporting, you know, there I don't 

believe there's reporting requirements, but double check with them.
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So, for home use diagnosis, that’s somebody with symptoms, home use 

screening, for those who may otherwise be at risk and could be asymptomatic 

carriers. There are clear recommendations in our templates, if you go to our 

template at the FDA website for what’s probably called home use testing 

includes both molecular and antigen recommendations for that environment, it 

has all the recommended performance expectation.

When you're talking about PPV, there's difference between PPV and PPA 

positive predictive value versus percent positive agreement. Percent positive 

agreement is when you're comparing your method to some other method. We 

recommend EUA authorized high sensitivity molecular test. That's really 

looking at you know, when the reference test is positive, how many times out 

of 100 is your test that you're developing positive? So, if it's positive, say, 

you know 90% of the time when the high sensitivity molecular test is positive, 

then your PPA or sensitivity would be 90%. Positive predictive value has to 

do with it's more of a population based measure. Yes, we do look at PPV for 

direct antigen tests, but that PPV can vary widely depending on the percent 

positivity in a given population. When a population has a very low incidence 

of active coronavirus infection, you know, a test like indirect antigen test that 

may have a specificity of 99%, would have quite a low PPV. I think I 

mentioned recently, that if the prevalence of SARS infection detectable with a 

direct antigen test is 0.2%. The test is 99% specific, the positive predictive 

value is 16%. So, you know, basically five out of six positive results are false 

positives. And that doesn't mean there's anything wrong with the test. It just 

means that in a low percent positive population, you're going to, even with a 

relatively high specific test, like 99% pretty high. Hard to go above that 

significantly within with a direct antigen test. You just want to confirm those 

results, I think with another test.
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So, we don't have typically a specific recommendation for PPV. We do have 

expectations for specificity and sensitivity or PPA and NPA. Negative 

percentage agreement and positive percent agreement. And we would for 

direct antigen test as for molecular tests in the home environment, when it's 

done by prescription, it's the same expectation as any other and viral detection 

method and that is what I like to see.

For single use, we'd like to see 80% PPA or sensitivity or greater. We are 

open, as we've stated, as (Jeff) and I stated in our recent op ed in the hill, we 

are open to a lower single test PPA. You know, we mentioned 70%. If some 

sort of serial testing, a two- pack, perhaps have the test done on consecutive 

days or in days 1 days 3, is able to in a combined sense, get us to that 80% 

mark, we may indeed find that acceptable.

And again, as I've stated on previous calls, at this forum, we're most interested 

in identifying patients in the first 5 to 7 days of infection, when they have the 

highest viral load. That is viral loads that we think might very likely, although 

it's hard to get at this, corresponds to their ability to infect others. And so, we 

want to make sure we identify those people and we have a test that's sensitive 

to detecting those.

So far as far as you have any clarifying questions?

(Daniel Roth): Sure, that's extremely helpful. And the other question was about an 

appropriate number of subjects for a usability study that we may recommend?

Timothy Stenzel: Yes, it that is that is in the home, I believe that's in the home test template 

that's on our website. And I don't remember I want to be accurate. Toby, 

unless you know, specifically, what that number is. I would just refer you to 

that. And then if you have any follow up questions, if the templates not clear, 
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just send us an email to the templates, email address. Toby do you know. If 

not, that's fine.

Toby Lowe: No, I don't have I don't have the template open.

Timothy Stenzel: Yes, I think Yes, rather than taking time to pull that template up and find that 

section we have. There's a lot of information in those templates. And I would 

appreciate that.

Thanks for your questions.

Coordinator: Our last question comes from (Han Son). Your line is now open.

(Han), your line is now open.

(Han Son): Hello. Can you guys hear me? 

Timothy Stenzel: Yes. can hear you now. Thanks.

(Han Son): Yes. My question is pertaining to point of care testing. With regards to the 

six further components of robustness testing. And one of the elements 

requires the test to be performed at high temperature. I was just wondering 

about how you rationalize the need for doing the test at 40 degrees Celsius 

when the average temperature around here is not even that extreme 

conditions? And is it really required for us to do that type of a temperature 

stress test, for point of care testing?

Timothy Stenzel: So those are our recommendations. If you want to propose alternate, that's 

fine. We may put limitation, temperature limitations, in your instructions for 

use. But we are seeing that these kind of point of care tests sometimes are 

used and in non-healthcare settings now, that may not have air conditioning. 
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And so, in sometimes they’re pop up tents and things like that. So that's the 

reason for asking that kind of temperature variation.

But again, you know, we can label around certain potential, we have the 

option, when everything else looks good to look at whether or not we alter the 

labeling for your product. And it might say if your test, for example, doesn't 

perform well, we might say must be performed in, in temperature controlled 

environment between these temperatures. But it's really working with you to 

figure out when your test performs well. So, you know, so we asked for these 

flex studies. And we want to see if there is any impact on your test 

performance. And then It doesn't necessarily mean if there's an impact that 

we wouldn't authorize your test. It's simply that we want to alert users, that 

certain variables may impact the performance of the test. So, I'll pause there 

in case you have any clarifying questions.

Hopefully that was clear and justifies why we asked those important 

questions.

(Han Son): Okay, thank you. Thank you very much.

Irene Aihie: Thank you. I believe that was our last question. This is Irene Aihie. We 

appreciate your participation and thoughtful questions. Today's presentation 

and transcripts will be made available on the CDRH learn webpage at 

www.fda.gov/training/cdrhlearn by Thursday, October 1.

If you have additional questions about today's presentation, please email cdrheua- templates@fda.hhs.gov. As always, we appreciate your feedback.

Following the conclusion of today's presentation, please complete a short 13 

question survey about our FDA CDRH virtual Town Hall experience. The 
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Moderator: Irene Aihie

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Page 27

survey can be found at www.fda.gov/cdrhwebinar immediately following the 

conclusion of today's live discussion. Again, thank you for participating in 

this concludes today's discussion.

Coordinator: That concludes today's conference. Thank you for participating You may 

disconnect at this time. Speakers, please allow a moment of silence and 

standby for your post conference.

END