Virtual Town Hall Series - Monkeypox Test Development and Validation

September 21, 2022

Moderator: Joseph Tartal

Joseph Tartal: Hello, and welcome everyone, to today's Virtual IVD Town Hall for Monkeypox Test 

Developers in which we'll discuss and answer your questions about diagnostic tests in response to the 

monkeypox public health emergency. Thank you for joining us today. I'm Joseph Tartal, Deputy Director 

in the Division of Industry and Consumer Education in CDRH's Office of Communication and Education. 

And I will be your moderator for today's town hall. 

Our panelists for today's town hall are Dr. Timothy Stenzel, Director of the Office of In Vitro Diagnostics, 

which is also referred to as the Office of Health Technology number 7 or OHT7 in CDRH's Office of 

Product Evaluation and Quality, or OPEQ. Toby Lowe, Associate Director for Regulatory Programs in 

OHT7. And Dr. Kristian Roth, Deputy Director of the Division of Microbiology Devices, also in OHT7. 

For today's town hall, we'll begin with Toby providing opening remarks, followed by answering your 

previously emailed questions and then we will proceed to address your live questions. A recording of 

today's town hall and transcript will be made available on CDRH Learn under the section title "Specialty 

Technical Topics," and then the subsection title "Public Health Emergencies." A recording and transcript 

of last week's webinar on the policy for monkeypox tests has been posted. 

We will continue holding these town halls weekly, every Wednesday. Therefore, the next scheduled IVD 

Town Hall will be on Wednesday, September 28, 2022, from 12:05 to 1:00 PM Eastern Standard Time. 

This will be a combined town hall for both topics of monkeypox and COVID test developers. We will then 

hold town halls on October 5th and October 12th for monkeypox test developers specifically. 

Future dates for town halls will be announced once they have been confirmed. Please refer to our 

Medical Device Webinars and Stakeholders Call webpage for details on upcoming IVD Town Halls. A link 

to this web page has been provided on the bottom of this slide. 

And lastly, I have one administrative reminder. For those of you participating live in today's town hall, 

please be sure you have joined the town hall via the Zoom app and not through a web browser to avoid 

any technical issues. 

I'd now like to welcome Toby, who will provide today's opening remarks on important dates. Toby, the 

floor is yours. 

Toby Lowe: Thanks, Joe. And hi everyone. Thanks for joining us again. So we just wanted to go over the 

dates that are noted in the guidance that we thought test developers should be well aware of. So 

October 13, 2022 is 30 days after the publication of the notice of availability of the guidance. So the 

guidance posted on our website on October-- I'm sorry, on September 7th. But the notice of availability 

published in the Federal Register on September 13. So 30 days after that is October 13. 

And that is important for the policies both in section IV.A.1 and IV.A.2. So for the prioritization of review 

of EUA requests, the guidance notes that we will intend to prioritize tests from developers that inform 

FDA of their intent to submit an EUA request within 30 days after publication of the notice of availability 

of the guidance. 
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And then for Section IV.A.2, which talks about the notification to FDA for certain diagnostic tests 

developed and performed by laboratories, we intend to accept notifications within that same 30 days. 

And we ask that laboratories notify FDA within five business days of offering their test that the lab has 

appropriately validated the test. And in most cases, we do not intend to object to the laboratory offering 

that test for clinical use without an EUA request, without submitting any EUA request. 

And those intent to submit and the notifications can be sent to the MPXDx@fda.hhs.govmailbox, where 

you can also send any questions that you may have. 

Joseph Tartal: OK, thank you Toby, for those remarks. 

We'll now answer your previously emailed questions. Please note we do receive some questions that are 

too detailed or to test case specific that we will not address today. For those questions, we'll try to send 

a response in writing within a few days. If you submitted a question and do not hear it addressed today, 

please look for a written response. If you do not receive a response within a few days, please feel free to 

reach back out to the MPXDx@fda.hhs.govmailbox for an update. 

Toby, I'll be directing these questions to you. And the first question is, what FDA cleared or authorized 

monkeypox tests are available? 

Toby Lowe: Thanks, Joe. So the Centers for Disease Control and Prevention, CDC, Non-variola 

Orthopoxvirus Real-Time PCR Primer and Probe Set is the only monkeypox test that is currently FDA 

cleared through the 510(k) regulatory pathway. It is a real time PCR test that detects non-variola 

Orthopoxvirus DNA, including monkeypox virus. And the CDC test is available in designated CDC 

Laboratory Response Network laboratories and other CDC designated laboratories, which at this point 

are LabCorp, Quest, Mayo, Aegis, and Sonic. 

Additionally, there is currently one test that has received an EUA. That's the Quest Diagnostics 

Monkeypox Virus Qualitative Real-time PCR Assay. And that detects DNA from the monkeypox virus, 

clade II, or the West African clade, and non-variola Orthopoxvirus. 

Joseph Tartal: Thank you. And what test is detected by the Quest Diagnostic Monkeypox Virus 

Qualitative Real-Time PCR assay? 

Toby Lowe: So I think that's what target is detected by that assay. And the Quest Monkeypox Virus assay 

targets both non-variola Orthopoxvirus and monkeypox virus. The non-variola Orthopoxvirus target 

detects a region of Orthopoxvirus DNA polymerase gene E9L, which detects several members of the 

Orthopoxvirus genus, including monkeypox, vaccinia, and ectromelia viruses. 

And then the monkeypox target detects a region of the monkeypox virus, clade II, the TNF gene, or the 

Tumor Necrosis Factor receptor gene. There's also additional information on the Quest assay in the EUA 

summary that's posted on FDA'S EUA Monkeypox page. 

Joseph Tartal:OK, thank you on both those answers with regards to available tests. Our next question 

has to do with sampling. Is there any evidence of whole blood sample detection and its consideration for 

sampling for monkeypox tests? 
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Toby Lowe: We're not aware of any other validated specimen types for diagnosing monkeypox at this 

time, other than lesion swab samples. And so currently, the recommended specimen type is skin lesion 

material. We have the most experience with this sample type and it has generally been performing well 

in the current outbreak. We encourage any test developers that are interested in claiming nonconventional sample types to submit a pre-EUA to obtain feedback on their proposed analytical and 

clinical study designs. 

Joseph Tartal: OK, thank you for that answer on samples. The next question is actually a three-part 

question. And I'll do each part individually. So the first part is, when will FDA publish a template for 

monkeypox rapid tests? 

Toby Lowe: We did discuss this briefly in the previous monkeypox webinar last week. We are working on 

a rapid antigen template and will provide that as soon as possible. In the meantime, we encourage 

interested test developers to apply to the NIH Monkeypox ITAP program, which NIH announced last 

week. And they have already begun accepting applications. 

Joseph Tartal: OK, thank you. The next part is, will FDA consider over-the-counter use for monkeypox 

rapid tests? 

Toby Lowe: So we are continuing to consider the ongoing testing needs to address the public health 

needs and increase the availability of tests that will have the biggest impact on the nation's ongoing 

monkeypox outbreak. And we encourage test developers that are interested in over-the-counter 

monkeypox rapid tests to apply to the NIH Monkeypox ITAP program. And you can also submit a preEUA to discuss any of your innovative proposals with FDA. And Tim, do you want to add anything on that 

one on over-the-counter? 

Timothy Stenzel: Yeah. Hopefully, they can hear me. So we do encourage innovation. It may be that 

rapid antigen tests are not going to be sensitive enough for monkeypox. We don't know yet. Once we 

start getting applications for rapid antigen tests, we'll see. But we do know that molecular tests are 

sensitive enough. 

And so, I think there is an area of innovation for over-the-counter tests on higher sensitivity rapid tests. 

Now, that may be molecular technology. We did authorize three OTC molecular tests for COVID. 

However, we do understand that those testing technologies right now are more expensive than rapid 

antigen tests in the home. 

So one of the unmet needs for over-the-counter, and even for point of care, probably, are lower-cost 

molecular test options that have-- that bridge the gap between high-sensitivity molecular tests and 

lower-cost rapid antigen tests. So just throwing that out there. Thanks, Toby. Back over to you. 

Joseph Tartal: OK. Thank you, Tim, and thank you, Toby. Our next question-- the next part of this 

question is what does FDA recommend using as a comparator for validation? 

Toby Lowe: Thanks Tim and Joe. Alright, so we do have some discussion of comparators for validation in 

the templates. And importantly, the templates do note that at this time our initial validation 

recommendations are for clinical validation with contrived specimens. And if clinical samples become 

more widely available, we may revise this recommendation. 
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If you do have access to clinical samples, or want to pursue that option, we generally recommend using 

a high-sensitivity FDA cleared or EUA authorized RT-PRC assay, which uses a chemical lysis step, 

followed by solid phase extraction of nucleic acid, such as silica bead extraction as the comparator test. 

And it's important that comparator test be one that has been validated with clinical specimens. 

At this point, the CDC cleared assay is the only one that meets that, but, hopefully, there will be 

additional options in the future. Since only certain laboratories may perform the currently cleared test, 

as well as authorized, you may consider reaching out to one of those laboratories using that test and 

they may be able to provide leftover samples that other developers can use for validation. And when 

doing that, they can usually provide the test results from the cleared or authorized test, along with the 

Ct values observed for each sample upon request. 

And if you have any questions about choosing the appropriate comparator or are encountering 

difficulties accessing the comparator testing, you can reach out to FDA through the MPXDx mailbox. And

Tim, did you want to add anything on this one? 

Timothy Stenzel: No, I think that's great. Thanks, Toby. 

Toby Lowe: Sure. 

Joseph Tartal: OK, Thank you, guys. We'll go on to our next question. And this has more to do with our 

process. What happens after a test developer informs FDA of its intent to submit an emergency use 

authorization request? 

Toby Lowe: Yeah, so when FDA receives an email from a developer informing FDA of the developer's 

intent to submit an EUA request, we will generally log that in as a pre-EUA. So then the developer would 

receive a response with a pre-EUA number for tracking purposes. Then FDA will consider the 

information that the developer provided regarding whether or not FDA would prioritize a future EUA 

request for that test. 

After the FDA's consideration, FDA will respond back to the developer indicating whether or not FDA 

intends to prioritize a future EUA request if submitted for that test. We intend for that response to 

inform the developer's plans and decisions regarding whether to submit a future EUA request. And if we 

respond that we would not intend to prioritize review for the test, we do plan to include high-level 

reasons why, but it is important to note that it's not a substantive review of the test, so it won't include 

any deficiencies related to validation that may have been provided to the FDA in that email. 

And then, of course, the full authorization pathways, such as 510(k), are also an option for developers. 

Joseph Tartal: OK, thank you Toby. Our next question, and this kind of links back to your opening 

remarks, can test developers still submit an emergency use authorization request later if they do not 

inform FDA of their intent to submit an emergency use authorization within the 30-day window from 

when the guidance was issued? 

Toby Lowe: Thanks Joe. So as discussed in the guidance and in my opening remarks, we do intend to 

prioritize review of EUA requests for certain types of monkeypox diagnostic tests, including those from 

manufacturers who inform FDA within 30 days after publication of the notice of availability of the 
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guidance in the Federal Register. We do plan to monitor the situation and may adjust the prioritization, 

including shortening or lengthening that time period as appropriate. 

And importantly, developers may submit an EUA request at any time while a 564 declaration is in effect, 

which is discussed in the guidance. And as discussed in the guidance, we will consider-- FDA will consider 

whether or not to review and process that EUA request based on a variety of factors related to whether 

the action is necessary to protect the public health in an emergency. 

Joseph Tartal: OK, very good. Thank you, Toby. We'll move to our next question. Can FDA clarify what 

you consider to be high throughput and high manufacturing capacity for monkeypox emergency use 

authorization review prioritization? 

Toby Lowe: Yeah, so as we stated in the guidance document, we do plan to prioritize review of requests 

of high throughput diagnostic tests from experienced developers with high manufacturing capacity 

where authorization would significantly increase testing capacity to address public health needs. Since 

these are two of several factors considered for prioritization, and as we noted in the guidance, we 

recommend that developers send information, including their test throughput manufacturing capacity 

and the other information noted in the guidance to FDA indicating their intent to submit an EUA request 

for a monkeypox diagnostic test. And we intend to respond, noting whether FDA intends to prioritize 

review of the proposed test. 

And so as we've discussed previously, that information can be sent by email to MPXDx@fda.hhs.gov

with the subject line “Diagnostic Test for Monkeypox – Intent to Submit EUA Request - Test Summary 

Information.”

Joseph Tartal: Thank you. And we'll move on to our next question. This has to do with getting hold of a 

comparator. Can FDA clarify how test developers can obtain the FDA cleared CDC non-variola 

Orthopoxvirus test from CDC to use as a comparator test? 

Toby Lowe: Yeah, so this goes back to the previous question. And I believe we also discussed this on the 

town hall last week. Since only laboratories that are designated by the CDC may perform the FDA 

cleared CDC test, we recommend that you reach out to one of those laboratories for assistance with 

that. And those laboratories may be able to provide leftover samples to use for validation. And they can 

provide that with the CDC test results and the Ct values observed for each sample. 

But also, as we've discussed, initial validation can be done on contrived samples and you can also reach 

out to FDA at MPXDx@fda.hhs.gov if you have difficulty accessing comparator testing. 

Joseph Tartal: Thank you, Toby. And this actually was the last question that was pre-sent and wraps up 

the previously submitted questions portion of our town hall today. 

So we'll now take your live questions. To ask a live questions, please select the Raise Hand icon at the 

bottom of your Zoom screen. When you are called on, please follow the prompt in Zoom and select the 

blue button to unmute your line. Then identify yourself and ask your question. Please remember to limit 

yourself to asking one question only. If you have additional questions, you may raise your hand again to 

get back into the queue and then I will call on you as time permits. 
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So with that, let's get to the first question. Wenli, I'm going to unmute your line. Now, please unmute 

yourself and ask your question. 

Wenli Zhou: Thank you very much. This is Wenli Zhou from XYZ Laboratory. And yeah, I have a question 

here. I realize from the policy that the FDA is doing, the [INAUDIBLE – priority or early] review for the 

submission, the FDA notification submission. So I'm just wondering how long is it taking to get a 

response from the FDA now for the manufacturer to know if their project is a prioritized or not? 

Timothy Stenzel: So, typically, we can do a pretty quick review of that. But we may, in some cases, want 

to see all of the submissions that we get for interest and test development through the open window for 

that before we make final decisions. So we'll get back to you as soon as possible. And we'll get back to 

you certainly, if not within that 30-day window, shortly thereafter. 

Wenli Zhou:OK, thank you very much. 

Joseph Tartal: Alright, let's go to our next question, which is from Jennifer. Jennifer, I'm unmuting your 

line. Please unmute yourself and ask your question. 

Jennifer Stanford: Thank you very much. This is Jennifer Stanford from Hopkins MedTech Compliance. 

And I have a question regarding if we would like to try to do a retrospective enrollment study with 

patients who have already been diagnosed and bringing them back in. That was one of the options in 

the guidelines. If we did that, would we be able to use one sample, such as if we collect one lesion 

sample with a 3 mil VTM solution, to use to test both the investigational PCR test as well as the 

comparator? Or do we need to do two separate swabs from the same lesion? 

And the reason I ask is because you might actually do the swab in a slightly different location in that 

same lesion and potentially have different viral loads. So we were just trying to figure out what would be 

the best methodology for that. 

Timothy Stenzel: Yeah, I think that if you're concerned about consistent swabbing from a lesion, 

because the FDA will allow transport media that's been validated for an amp assay in a submission, that 

as long as the comparator test allows that same VTM you can, perhaps, split the sample. You want to 

make sure that the comparator test has enough volume and you can communicate with whoever is 

doing that testing to make sure that that's going to be sufficient. 

Right now, the only comparator test available is the FDA cleared CDC assay run at the LRN Labs and the 

five major reference labs that are testing with it. The CDC has requested that we don't send repeat, any 

sort of repeat testing, where a patient's already been diagnosed in, because that would utilize additional 

kit reagents. And they're trying to manage that and meet the response needs. 

So obtaining a residual sample material from any of the LRN Labs or any of the five reference labs that 

are testing with the CDC-- FDA cleared kit is probably one of the best options for your device, as long as 

those kind of samples are acceptable to you. That way, you get what you need. It probably is easier to 

do. 

It can be retrospective. We are going to look at things like were possible consecutive samples selected 

from those resources from those labs? And we'll want to know if there's any gaps and why there are 
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gaps in those consecutive series of samples, so that there is a limitation on any sort of bias. Hopefully, 

that addresses your question. 

As we authorize additional tests that have been validated with actual patient samples, then there will be 

more comparator tests available. 

Jennifer Stanford: OK, so just to clarify, it sounds like you're not encouraging us to do the retrospective 

model, where we would take patients who've already been diagnosed and bring them back in for 

retesting, simply because of the shortage of reagents and we already know they're positive. So you 

would rather us use contrived samples for this testing. 

Timothy Stenzel: Yeah, if you can’t easily obtain actual patient samples then a contrived is a better 

route to take right now because of the availability of the CDC test for this prospective, retrospective look 

that you're talking about. Because if these patients have already been diagnosed, particularly with those 

CDC assay, then they don't need it for diagnosis. However, if the CDC assay--if you're doing a study 

where the CDC assay is ordered as the test of record and the comparator is one in the same, then that 

would work if that's easier for you to use. But I think you're correct on your assessment. Thanks.

Jennifer Stanford: OK, thank you very much. 

Joseph Tartal: Thank you for your question, Jennifer. And thank you Tim, for the response. Our next 

question is from Homer. Homer, I'm going to unmute your line. Please unmute yourself and ask your 

question. 

Homer Wu: Hi, this is Homer Wu from Hopkins MedTech Compliance. I have a separate question, which 

is, in the template we mentioned that we can use home collection kit. But there's no instruction on how 

we validate the home collection kit. Or can we just use like approved COVID-19 home collection kit? 

Timothy Stenzel: So they may or may not be suitable, since this is a lesion swab versus another type of 

swab. And if it would involve something like saliva, then we would want to see, as mentioned earlier, 

that we'd want to see your plans for validating that. We are working on a home collection template. It 

wasn't ready to be released at the time of the guidance. And so we are working on that. And we will get 

that cleared and posted as soon as possible. 

Homer Wu:OK, just follow up on this. Since we want to be the priority and that is one of the options, to 

do the home collection kit, so can we-- when we submit, can we claim that we're going to have a home 

collection kit, but—

Timothy Stenzel: Yeah, in the 30-day-- in the 30-day window, if you're a test developer and you want to 

develop something, then that can go in there that you want to develop a home collection kit. And we'll 

want to know what assay you're going to use with that home collection kit. And that can go into an 

email to the FDA and we can assess that, on whether or not we would invite you to submit an EUA. And 

then we'll work with you-- if we do invite you, we'll work with you going forward on how to do that 

validation. 

Homer Wu: Alright, great thank you. 
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Toby Lowe: To add to what Tim was just saying, the 30 days is not to submit your EUA request. The 30 

days is to inform us that you intend to submit an EUA request. 

Homer Wu: This is Toby, right? So I do have a question. Based on the current template, if we can 

complete the performance in the lab and if we can perform the contrived sample, actually, according to 

the templates, then we can submit the EUA, right? 

Timothy Stenzel: You can submit an EUA after you've said that you would like to and get a positive 

response from the FDA. That's how we're doing the prioritization for any kit manufacturers. So it is best 

before you do any validation to go ahead and make sure that we would prioritize your EUA when it does 

come in. So please go back to the guidance document and that can explain all these details. Thank you. 

Homer Wu: Alright, thank you. 

Joseph Tartal: OK, thank you. Our next question is from Om Singh. I'm unmuted your mic. Please 

unmute yourself and ask your question. 

Om Singh: Thank you for the opportunity to ask the question. If a lab is certified with the CLIAand they 

have these validated testing and everything, do they still need to go through the EUA process in order to 

commercialize the kit? 

Timothy Stenzel: So if you're talking about a lab developed test for a single site that is using PCR to test 

lesions, that individual lab just needs to have notified the FDA within the time periods that are spelled 

out in the guidance, and which Toby went over, again, at the top of the hour. If a developer is 

developing a kit, then it needs to be EUA authorized before it can be distributed. 

Om Singh:OK, so a lab can do it individually, but if a developer, who's putting the kit in the market, need 

EUA certification. Am I getting it right? 

Timothy Stenzel: Go ahead, Toby. 

Toby Lowe: Yeah, so if you are a high-complexity CLIA certified laboratory, and you are developing your 

own test in-house, and using that test in-house at your single site, and it's a PCR test, lesion swab 

specimens-- all of the details for this are laid out in the guidance document-- then we ask that you notify 

us within five days of offering the test that you have appropriately validated the test. And we do not 

expect you to submit an EUA request. 

If you are intending to distribute that test, whether it's--whether you're considering it to be a kit or 

otherwise, we do expect that you submit an EUA request and get authorized prior to distributing any 

test. 

Om Singh: Thank you, appreciate it. 

Timothy Stenzel: Yeah, and Toby mentioned that the 30-day window for LDT notification of the FDA and 

kit manufacturer email, one, expressing interest in developing an EUA authorized test. That 30-day 

window closes on October 13. 

OK, I think we can go to the next question. 
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Joseph Tartal: We'll move to the next question. Dennis, I'm going to open up your line. Please unmute 

yourself and ask your question. 

Dennis Repella: Hi, Dennis Repella, Smith Associates, FDA consultants in Crofton, Maryland. What's the 

current estimate of how many of these monkeypox cases will be identified in the next 12 to 18 months? 

Timothy Stenzel: The number of cases is that are being identified with sufficient testing in the United 

States is going down. It is now around a little bit over 200 cases a day and that's down from a high of 

probably more than double that in the U.S. In the world, the number of cases are going down as well. 

Currently, it's 600. 

So we would love to see this outbreak end sooner than later. And if you were to just draw a straight line 

on what the curve is doing right now, the emergency may end sooner than later. But it's really hard to 

predict. The CDC has given guidance on how to limit the spread of the disease. They're getting that word 

out as best they can. 

There are vaccines available to the high-risk populations that is going forward. And all of those efforts, 

combined with testing, hopefully will drive this response to a close in the U.S.sooner than later. But I 

cannot predict. I do not have a crystal ball. I don't know if our efforts will continue to have the success 

they have so far. 

Dennis Repella: Well, thank you very much. I appreciate the answer. 

Joseph Tartal: OK, with that, that was our last live question for today. Thank you everyone for your 

participation today. And I want to, again, thank our panelists, Tim, Toby, and Kris. 

A recording of today's webinar and transcript will be posted to CDRH Learn under the section title 

"Specialty Technical Topics," and then the subsection titled "Public Health Emergencies." To access 

those materials, please visit CDRH Learn at the link provided on this slide. 

For additional questions about today's town hall and monkeypox IVD topics in general, you may send an 

email to MPXDx@fda.hhs.gov. 

Please remember to join us for the next IVD town hall for monkeypox and COVID test developers on 

Wednesday, September 28, 2022, from 12:05 to 1:00 PM Eastern time. 

Thank you again for joining us. This concludes today's town hall. Have a nice day. 

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