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NWX-FDA OC

Moderator: Irene Aihie

March 2, 2020

2:00 pm CT

Coordinator: Hello and thank you for standing by. At this time I’d like to inform all 

participants that today’s call is being recorded. If you have any objections 

you may disconnect at this time. You have been placed in listen-only mode 

until the question-and-answer session of today’s call. At that time we are 

taking calls over the phone only. And if you would like to ask a question 

please press Star 1 and please make sure that your phone is unmuted and 

record your name clearly when prompted so I may announce you for your 

question. Thank you and you may begin with your host Ms. Irene Aihie.

Irene Aihie: Hello and welcome to today’s FDA webinar. I am Irene Aihie of CDRH’s 

Office of Communication and Education. On February 29, the FDA issued 

the immediately in effect guidance titled Policy for Diagnostics Testing in 

Laboratories Certified to Perform High Complexity Testing Under CLIA prior 

to Emergency Use Authorization for Coronavirus Disease 2019 during the 

Public Health Emergency. 

This guidance provides a policy for novel coronavirus molecular diagnostic 

tests developed and used in laboratories certified to perform high complexity 
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testing under the Clinical Laboratory Improvement Amendments prior to 

issuance of emergency use authorizations for such tests. 

Today Timothy Stenzel, Director in the Office of In Vitro Diagnostic and 

Radiologic Health in the Office of Product Evaluation and Quality here in 

CDRH will present an overview of the guidance document. Following the 

presentation we will open the line for your questions related to information 

provided during the presentation. 

Additionally there are other center subject matter experts here with us today to 

assist with the Q&A portion of our webinar. Now I give you Timothy. 

Timothy Stenzel: Welcome. It’s great to share this new policy with you today. This policy is 

for diagnostic testing, in laboratories certified to perform high complexity 

testing under CLIA, prior to EUA authorization. The agenda today will be to 

go through the background summary of the immediately in effect guidance 

and then of course take questions and provide some answers. 

The objective today is to explain this new policy for molecular diagnostic 

testing and high complexity Clinical Laboratory Improvement Amendments 

(CLIA) certified labs prior to emergency use authorization for coronavirus 

disease 2019 and now the coronavirus during this public health emergency.

Some background. This guidance was issued on February 29, 2020. It 

describes a policy regarding certain laboratories immediately using tests they 

have developed and validated in order to achieve a more rapid testing capacity 

in the United States. 

With the COVID-19 public health emergency the FDA has determined that 

prior public participation for this guidance is not feasible or appropriate. And 
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issued this guidance without prior public comment. This guidance document 

is immediately in effect but remains subject to comment in accordance with 

the FDAs good guidance practices. 

Scope. This policy is limited to laboratories certified to perform high 

complexity testing consistent with the requirements under the clinical 

laboratory improvement amendment and is for molecular diagnostics for the 

SARS-COV-2 virus. The new policy does not impact requirements under 

CLIA, does not impact CDC recommendations for who should be tested. 

Policy. The guidance includes recommendations regarding validating newly 

developed coronavirus tests prior to clinical use, notifying the FDA when 

clinical use of a validated test begins, confirming the first five positive and 

negative samples with EUA authorized tests, indicating in test reports that the 

test has been validated but independent review by the FDA is not complete, 

submitting EUA within 15 days of initiating testing and, finally, steps to take 

if any specimen fails confirmatory testing or if the FDA is unable to authorize 

the EUA. 

Test validation. The guidance includes recommendations regarding the 

minimal testing to be performed for validation. These include Limit of 

Detection or LOD, clinical evaluation, inclusivity, cross reactivity. And then 

comments on the limited viral materials that are available to the FDA, 

BARDA, and the CDC of prioritized and coordinated shipments to labs when 

ready to validate. 

You can address this by sending an email to the FDA email as listed later in 

this presentation. This is limit of detection testing under this guidance defined 

as the lowest concentration in which at least 19 of 20 replicates are positive. 

The methods include we recommend testing dilution series with three 
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replicates at each concentration in order to find the range of the LOD for your 

assay. And then when you have done this confirm the final concentration with 

20 replicates. And this is – and do these 20 replicates after you’ve initially 

identified the LOD. And again 19 of these 20 replicates at least – so 19 or 20 

are to be positive to pass this limit of detection criteria. 

The samples they can be pooled negative clinical samples or artificial matrix. 

If multiple specimen types are included the most challenging of these should 

be evaluated, for example sputum. This slide describes the recommended 

clinical evaluation testing. At least 30 contrived reactive specimens and 30 

non-reactive specimens should be tested. The contrived reactive specimens

can be created by spiking in viral RNA or an activated virus into leftover 

clinical specimens. 

Twenty of these contrived specimens should be spiked at a concentration of 

between 1X and 2X of your determined LOD for your assay with the 

remainder of the specimen spanning in the assay testing range. Acceptable 

performance for this clinical evaluation is 95% agreement at the 1 to 2X of 

LOD. 

So again that means 19 or 20 positives out of those near LOD samples. And 

then 100% agreement for all concentrations that are above the 1 to 2X LOD 

and for all negative samples. 

Inclusivity testing recommendations. Inclusivity can be conducted with in 

silico analysis of the percent identity matches against publicly available novel 

coronavirus sequences that can be detected by the proposed and developed 

molecular assay. One hundred percent of published sequences should be 

detectable with the selected primers and probes for your assay. 
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Cross reactivity testing is recommended that you conduct an in silico analysis 

of the assay primer and probes compared to common respiratory flora and 

other viral pathogens. There should be greater than 80% homology between 

one of the primers and probes and any sequence present in the targeted 

microorganism. 

It is recommended that you follow recognized laboratory procedures for any 

additional cross reactivity testing in the context of the sample types intended 

for testing. 

I wanted to give you an update of the EUA tests. First of course the CDC was 

given an EUA authorization on February 4 for their tests and their kits. This 

also under the CDCs EUA there is another covered test and that is the IDT 

2019 novel coronavirus kit. We are doing a lot of qualification tests. The 

CDC rather is doing a lot of qualification testing. And the lot that is already 

passed from a QC at the CDC is Lot No. 000500383. 

If you are a laboratory that has this kit lot and can use it according to federal, 

local and state laws and regulations, you can go ahead upon verification that 

you normally perform when you receive a kit. You can go ahead and begin 

clinical testing on this lot. Stay tuned as additional IDT lots are undergoing 

qualification by the CDC and that information will be made known publicly as 

soon as possible. 

In addition you may have noted that the FDA has issued a second EUA 

authorization for New York State Wadsworth Center on February 29, 2020.

And finally, the CDC, FDA and BARDA are working with multiple IVD 

manufacturers and laboratories to enable additional EUA authorizations as 

soon as possible. You can monitor this at our Web site. We will post all new 
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EUA authorizations as soon as those authorizations occur. So you can keep 

track of this. 

How do you perform your submissions to the FDA? First of all once you 

have validated your assay according to these recommendations and met the 

performance criteria, laid out in this webinar and in our guidance, you can 

begin testing as soon as you notify us of that. Your notification can be sent to 

this email address – CDRH-EUA-templates@fda.hhs.gov. Include the name 

of your laboratory, the name of the laboratory director, your address and a 

contact person. 

This is also the same email that you can use to ask any inquiries of this 

process. Request through the FDA, BARDA and CDC access to viral RNA 

for virus that is currently being managed by a number of entities. The EUA 

should be submitted then. That is the completed package 15 days after your 

initiating clinical testing. And you can send that to the email address here –

OIR-operations@fda.hhs.gov. And should include the following information 

on these forms and the completed EUA template. 

I should back up and say that upon submission of a notification to the 

notification email we will receive a response back. You should receive a 

response back and if you haven’t please contact us so that we have received 

that notification email. 

Finally I think is the last slide. Here are some resources that you can utilize in 

this process for the COVID-19 guidance, general EUA guidance documents 

and FDA’s novel coronavirus Webpage. I would like to also relay an 

important announcement that some of our public health lab officials have 

asked that we do. I am just pulling up that email right now – is the delay. 
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This concerns public health reporting. And I think we’re all in the same boat 

here and we really encourage you to help us out in meeting this emergency 

need. We strongly encourage laboratories seeking testing under this policy to 

contact their state public health department as early as possible in the process. 

Perhaps even before receipt of any orders or samples to help ensure they have 

capacity for the validation testing described in the guidance and have the 

information necessary to support case investigations. We also encourage 

laboratories to be sure they are familiar with state and local laws maintaining 

reporting of diseases and conditions of public health significance. And that 

ends that statement that we wanted to make.

So for any questions you can address them to this email address – CDRH-euatemplates@fda.hhs.gov or call us at 301-348-1778. To receive the slide 

presentation transcript and webinar recordings you can go to this link which 

will be up shortly after this webinar. And with that I believe we’ll open up for 

questions. 

Coordinator: Thank you. It is now time for the question and answer session of today’s call. 

Again if you would like to ask a question over the phone please press Star 1. 

Please make sure that your phone is unmuted and record your name when 

prompted. If you wish to withdraw your question you may press Star 2. 

Thank you, please give a second for me to get the names. First question comes 

from (Pamela Martiniak) your line is open.

(Pamela Martiniak): Hi. I’d like to know if there’s any recommendations or guidance on the 

procedure codes that will need to be used to bill for the testing and, you know, 

if there are any out there that are specific to the kits that you mentioned.

Timothy Stenzel: That’s an excellent question. That would not be under FDA’s purview. I 

would suggest that you reach out to CMS to get a response for that. 
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(Pamela Martiniak): Thank you. 

Coordinator: Thank you. Next question comes from (Richard Montegna) your line is open. 

(Richard Montegna): Yes thank you. I noticed that in the EUA template the contrived samples 

numbered 50 either 50 contrived or 50 clinical and in this webinar you just 

mentioned 30. So has that number changed or is this only for CLIA labs 

because we’re an IVD manufacturer?

(Uwe Scherf): Yes, this is (Uwe) from Division of Microbiology Devices. Yes this number 

has changed in order to address the validation challenges associating with

verifying devices – yes going forward the number of samples have been 

reduced.

(Richard Montegna): Okay thank you. And related to that we are trying to establish the limit of

detection. And we have been working with Zeptometrix in Buffalo who 

frequently is able to get these viral samples from CDC or others. And as of 

right now BEI Resources is shipping only to BSL3 labs and not allowing them 

to reship inactivated viruses. So that’s make it a little difficult for those of us 

in the industry because we have BSL2 labs but not BSL3 labs. So, my 

question is is there anything being done to address that or secondly it looks, 

like we might be able to use viral RNA that I understand is now available to 

set LODs.

Timothy Stenzel: Yes. So you can request viral RNA if you’re not a BSL3 facility who can 

handle live virus. And right now you can request that from BEI and UTMB. 

Now there is currently a limitation on the availability. And if you are 

requesting that you have access to that if you have any issues in ordering that 
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from those two entities, please send us an email to CDRH-EUAtemplates@fda.hhs.gov and we will work with you.

(Richard Montegna): Okay.

Timothy Stenzel: Also the procedures for validation in this new guidance are suggestions and 

recommendations. If you have ideas for alternative approaches, please reach 

out to that same email and we will work with you in cases such as this where 

you cannot easily access viral isolates or viral RNA. 

(Richard Montegna): Okay thank you very much, appreciate the help.

Coordinator: Thank you. Next question comes from (Ali Nori). Your line is open sir.

(Ali Nori): Thank you very much. Just a quick question. I’m wondering if you can tell 

us, you know, anything as to which of the reagents was the problematic one in 

the initial kits issued by CDC. There’s some report suggesting they were the 

primers in the N3 reaction. There’s other reports suggesting it was something 

that was creating false positives. I’m just wondering if you can sort of 

elucidate some of that. 

Timothy Stenzel: Sure this is what I can tell you that we believe that the design of the original 

CDC assay that was reviewed under the EUA application is solid. We have a 

lot of confidence in that. And that includes the N1, N2 and N3 and the control 

reaction – the RP control reaction. 

And as regard to CDC assay we have worked closely with them. And we 

believe we have resolved the manufacturing issues. And so now kits are again 

being shipped to public health labs. And as I mentioned earlier we are 

working with more than one manufacturer. But the one we can publicly 
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announce today is IDT. And we have a process to qualify those lots. And as 

soon as lots are available our laboratories can contact IDT and purchase those 

kits for their uses. 

If you purchase those kits under IDT that have been lot qualified, you will not 

need to submit your own EUA. That’s the beauty of this approach. You can 

simply do the normal verification testing upon receiving a new kit as if it’s 

another EUA authorized kit. 

(Ali Nori): So the primer sequences are the same then.

Timothy Stenzel: The primer sequence in the IDT reaction are exactly the same as the CDC 

primers yes. And the IDT kit includes N1, N2, N3 and the control reaction. 

(Ali Nori): So was it just a bad lot initially? Was that creating the problem the design 

was good but there was something wrong with one of the lots?

Timothy Stenzel: The design is good. It was a manufacturing issue that we have now resolved. 

That we have resolved I should say in conjunction with the CDC resolve and 

the FDA did provide assistance in that. 

Coordinator: Okay thank you. Next question comes from Dr. (Manad Salem). Your line is 

open. 

Dr. (Manad Salem): Hi thank you so much for the great presentation. I just have a general 

question about notifying FDA for clinical use of laboratory developed tests. 

Is it included for every laboratory developed test or is it specifically for the

SARS COV coronavirus detection?
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Timothy Stenzel: No this new policy was only for the novel coronavirus. However I will add 

that your design does not need to be the CDC’s design. It can be whatever 

design you choose as long as it’s properly validated. 

Dr. (Manad Salem): Thank you so much.

Coordinator: Thank you. Next question comes from (Arthur Kowaski). Your line is open. 

(Kawasaki) sorry.

(Arthur Kawasaki): Thank you. I just have two questions. One, I would like to confirm the 

notification when starting initial clinical studies is not required if an industry 

member is already engaged in FDA and the Pre-EUA, EUA interactive 

review. And the second question is regarding the EUA proposals for any 

differences or deviations from the policy or guidance that does not have to be 

notified as it will be done under interactive review if an industry member has 

initiated that. 

Timothy Stenzel: So are you in a CLIA-certified high complexity laboratory?

(Arthur Kawasaki): No not specifically. We’re just an industry member and we actually 

haven’t engaged FDA are thinking of engaging FDA with the Pre-EUA, EUA 

interactive review. 

Timothy Stenzel: Okay you can submit inquiries to the same email address and we will work 

closely with you, interactively with you to assist you in any way we can with 

validating your assay under the EUA provisions. 

(Arthur Kawasaki): Okay, thank you.

Coordinator: Thank you. Next question comes from (Ali Burken). Your line is open. 
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(Ali Burken): Hello. I was wondering how does the FDA guidance impact test kit 

manufacturers who wish to immediately sell a test kit to hospitals or airports, 

you know, for detecting the coronavirus?

Timothy Stenzel: So under this guidance high complexity, CLIA labs can purchase RUO

components and validate them according to these recommendations. And 

once that has happened you can notify us and begin testing. That is at the 

moment under this policy – that is under this policy what can be done with 

manufactured reagents. Also if you’re a CLIA certified high complexity lab 

you can develop your own reagents and follow the guidance.

(Ali Burken): Yes I understand that. At that point we can begin testing after validation and 

notification. But I’m talking about in terms of selling a kit to third parties to 

allow them to perform the testing. 

Timothy Stenzel: Again test developers can purchase RUO reagents for their test development 

purposes. Manufacturers if they want to distribute their kits will still need to 

be coming through the EUA process. Please email us at cdrh-eua-templates 

and we will work through it with you in order for you to achieve that EUA 

authorization. 

(Ali Burken): All right thank you very much. 

Coordinator: Thank you. Next question comes from (Douglas Shanay). Your line is open. 

Can you check the mute function on your phone please? Okay next question 

comes from (Nahed Mosin). Your line is open.

(Nahed Mosin): Yes hello. This is (Nahed Mosin). I just have a question for you. After – so 

getting – while we’re getting the EUA authorized assay application, we need 
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to evaluate, to do the clinical testing. The question that we have how are we –

yes we are the manufacturer. We’re not the clinical laboratory, high 

complexity clinical laboratory. So our question in order to validate that and 

confirm our assay, how are we going to get those positive clinical specimens 

or negative clinical specimens to do the clinical testing itself?

Timothy Stenzel: All right. So we understand that this material right now can be – in the U.S. 

can be limiting. You can send us an email request at cdrh-euatemplates@fda.hhs.gov. And we will add you to the list of entities that would 

like to obtain these materials. You can also work interactively with our staff 

in order to determine if there are alternate pathways that you can take to 

validate your assays. 

(Nahed Mosin): Okay. The other question that we have if you don’t mind. We have done our 

instrument. We have gotten approval for one instrument to other assays with 

FDA which is basically a PCR instrument. The question is we can go ahead 

and use other instruments as well? 

Woman 1: No that instrument is also approved for LDTs use...

((Crosstalk))

(Nahed Mosin): Yes but it’s not through FDA use, you know, it is not approved yet by FDA. 

Can we use those assays on these instruments?

Timothy Stenzel: So I would ask you to send some of these details to the cdrh-eua email 

address. And we will respond with – will ask for probably more details and 

will respond as quickly as we can which we are doing a great job right now in 

providing you specific information that is directly related to the instruments 

you’re interested in.
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(Nahed Mosin): Okay one more question. What’s the timeline for approval estimated?

Timothy Stenzel: So once we have a complete package if you’re an IVD test manufacturer we 

suggest that you start sending in portions of your submission under what’s 

called the Pre-EUA process. That will allow us to have a rolling review of 

your information so that when you submit the final part of the application our 

assessment is at that time only going to review the final part. And that can 

happen relatively quickly. So say that for both the CDC and for the New 

York State EUA authorizations most of those were handled in a similar 

manner. And those final authorizations came within about 24 hours of the 

final submission being made. 

Woman 1: Okay. So we are currently – have an assay developed, we use for 

nasopharyngeal swabs and nasal swabs, UGM transport medium. And if we 

want to because the difficulty is to secure some clinical sputum samples. Is it 

possible we can submit the first – just one use, one kind of matrix and follow 

up with the more expansion of the matrix?

Timothy Stenzel: No the EUA authorization is – it can absolutely be amended and updated over 

time. So again for specific questions for IVD manufacturers, I would 

recommend you send an email to the cdrh-eua. I would ask that traditional 

IVD manufacturers that they do this. This call is really to describe the policy 

for lab developed tests at CLIA high complexity labs. So I want to make sure 

that in the time allotted that I can address all of the CLIA lab questions. 

(Nahed Mosin): Okay. 

Woman 1: Okay, thank you. 
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Coordinator: Thank you. And please going forward please limit yourself to one question. If 

you would like to ask another question you can rejoin the queue. Thank you. 

Next question comes from (Breanna Sewell) your line is open. 

(Breanna Sewell): Hi sorry. So we have a question regarding registration in the BEI. We are not 

currently registered but we want to be able to order some viral RNA. But 

does it makes sense for us to get a draft in order to send to you all to start the 

review process before worrying about registering to order the RNA or how do 

you suggest we handle that?

Timothy Stenzel: I would suggest you reach out right away to the email address and put that 

request in. If you have any questions about how you register we perhaps can 

help you. While in parallel you develop your plan or your validation if you 

have any questions about how you approach that. You can also send those 

email questions to us.

(Breanna Sewell): Okay yes I already did an email. I received an email back today with how to 

go ahead and register. That’s why I was just wondering. I wasn’t really clear 

which I should, you know, prioritize.

Timothy Stenzel: I would work on all things that you can at the same time in parallel.

(Breanna Sewell): Okay thank you. 

Coordinator: Thank you. Next question comes from (Sevems Betha) your line is open. 

Please check the mute function on your phone. Next question comes from 

(Chen Zen) your line is open.

(Chen Zen): Yes my question is whether FDA’s considering expanding the scope of EUA 

to non-molecular based tests for IVD matures in labs. If yes are you partnering 
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with manufacturers or labs to develop a template for non-molecular based 

tests?

Timothy Stenzel: Let me turn that over to Uwe if you could comment. I’m thinking that if it’s a 

non-molecular test I think we’d want to know something more about it and the 

more traditional EUA process to start this off might be good by asking 

questions by sending emails to us. But I’ll turn it over to Uwe to see if he has 

any comments. 

(Uwe Scherf): I think you understand of course that the molecular approach has opportunities 

that other technologies will not offer. So I suggest that you work with us in the 

pre-EUA process to then describe to us what you are planning to do and we 

will provide you the appropriate feedback on the next steps. And again 

requests can be done with the email address that (Tim) mentioned those times 

already. 

(Chen Zen): Yes we did send (Tim) an email, you know, giving them a description of the 

lysis. But the response we got is that you are still – your resources are strictly 

focusing on the molecular based tests. So it seems you’re not ready to take 

non-molecular based tests. Is that true? Do you have a timeline that you can 

expand the scope to other tests?

(Uwe Scherf): Well we are working as fast as we can getting all of the requests done. But I 

cannot give you a specific timeline. 

(Chen Zen): Okay.

( Uwe Scherf): But individuals here are trying to assure that all of the requests and all of the 

technologies can be supported the appropriate way.
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Timothy Stenzel: And here the technology that you believe can be helpful in this situation either 

in the shorter term or the longer term, I would suggest that you continue to 

develop your product. And our team will get back to you as soon as they can. 

I do want to encourage all types of diagnostic development here. 

(Chen Zen): Okay thank you. 

Coordinator: Thank you. Next question comes from (David Perlin) your line is open.

(David Perlin): Oh hi thank you for this. I wanted to ask you about clinical CLIA lab, about a 

limit of detection and clinical specimens that you’re recommending for the 

validation. In terms of limit of detection do you have a number in mind? Is it 

10 particles genome, 100 for your limit of detection? And you mention 

sputum as well in clinical specimens. Are you also - are you looking at nasal 

washes, bronchial washes, sputum? Can you give a little more guidance on 

that?

(Uwe Scherf): Yes. I mean the sensitivity you can imagine that the performance needs to be 

evaluated towards that concept. And except viral load we will not be able to 

provide you with a number. But the material that you are spiking will have a 

certain concentration. And we would like to assure that the assay is sensitive 

enough for the performance. Regarding the specimen that you said again of 

course nasal washes and nasal pharyngeal washes are also specimens that 

clearly are needed for evaluation. 

The concept here if you are limited with material and you want to really then 

also go into lower respiratory specimens that you could consider using that as 

the most challenging matrix that you are evaluating. Assuming then the other 

matrixes will be performing similarly and you can move forward with the 

testing.
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Timothy Stenzel: As you begin your testing and you start to get results for what your LOD is 

that you think it may be, please don’t hesitate to contact us at the email 

address and check in with us if you have any questions about...

(David Perlin): You know because we’re doing spike in studies now and we’re just trying to 

understand what sort of thresholds you’re looking for for LOD. 

Timothy Stenzel: Yes. So we’re still very early in this process with this virus and this disease. 

And it is why we’re focusing first on molecular techniques because at the 

moment we want very sensitive techniques to be able to detect the virus. So 

standard molecular detection LODs for viruses in nasopharyngeal and 

oropharyngeal specimens are, you know, in the range especially if you know 

anything about coronavirus in general that would be another place to start. 

(Uwe) do you have anything else to add to that?

Uwe Scherf: I think that captures it, yes.

Timothy Stenzel: Okay thank you.

Coordinator: Next question comes from (Kazi Masira) your line is open. 

(Kazi Masira): Hi. I have a follow up question from the previous question regarding the 

LOD validation. So if you are doing the validation with wild RNA we are 

doing it BSL2 level. But once you have the samples and your patient samples 

you move back BSL3 level. Is my understanding correct?

Timothy Stenzel: You know I think that is a CLIA question as to what it is. Let me just check 

and see if we can provide any comment on that. So do check with CLIA but I 
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believe at that point BSL2 level testing is still appropriate. But please do 

check with CLIA.

(Kazi Masira): Okay thank you.

Coordinator: Thank you. Next question comes from (B.J. Dacall) your line is open.

(B.J. Dacall): Hello. We have a question about the IDT lots. Which ones are approved and 

where do we find that list of approved lots of IDT? And can you elaborate 

around that EUA that you authorized if we’re buying an approved lot from 

IDT? We’re good to start clinical testing without validation. 

Timothy Stenzel: So if it’s a lot that’s been qualified by the CDC under their EUA authorization 

you do not need to submit your own EUA. We are still working on how we’re 

going to make that information public. So stay tuned and stay in touch with 

IDT. At this moment that’s what I recommend. They were expecting that 

they might receive some inquiries about this. And as of now we only have 

one kit left to announce but again stay tuned. 

(B.J. Dacall): Thank you.

Timothy Stenzel: Let me just follow up on the previous caller’s question. It is not 

recommended obviously that you try to culture virus if you’re only BSL level 

2. Probably only those labs that are really expert in this and are a BSL level 3

and above should be even contemplating this. So that’s the level BSL three 

that if you’re dealing with a cultured live virus. Okay ready for the next 

question.

Coordinator: Thank you sir. Next question comes from (Donna Ferguson) your line is 

open. 
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(Donna Ferguson): Hi I have some questions about false negative due to inhibitory 

substances. And our physicians are concerned because some of these patients 

are receiving breathing treatments. And they want to know if they take a 

specimen after a breathing treatment if that could lead to false negative.

(Uwe Scherf): Since these are nucleic acid-based tests that are moving forward, I mean we 

have a good understanding about the extraction approaches that normally 

these substances are not enough interfering with the assay. So I mean we need 

to have a compromise – enough approaches available and can be quickly 

validated. So that was the step that we took in order to allow a faster kind of 

access to the testing here in our laboratories. 

Timothy Stenzel: And to add to that you certainly can take non-reactive samples that are 

samples in that way and spike in and see if that affects your LOD in any way.

(Donna Ferguson): Thank you. 

Coordinator: Thank you. Next question comes from Dr. (Michael Milhoff) your line is 

open.

Dr. (Michael Milhoff): Hi. My question is in regards to who is eligible to purchase the 

kits from IDT? Can only governmental labs purchase these kits or can any lab 

or entity purchase directly from IDT?

Timothy Stenzel: We would – it’s not just public health labs that can purchase this. In fact it’s 

probably – but it is let me say that it is any lab qualified to do this testing can 

certainly order this test from IDT.

Dr. (Michael Milhoff): And the qualification is just a high-complexity lab correct?
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Timothy Stenzel: High complexity CLIA certified lab yes. 

Dr. (Michael Milhoff): Correct, thank you.

Coordinator: Thank you. Next question comes from (Richard Montegna) your line is open.

(Richard Montegna): Yes thank you for taking the second question. It has to deal with the 30 

contrived samples. If we wanted to look at these oral swabs – oropharyngeal 

swabs and sputum is that 30 of each of those or total of 30?

(Uwe Scherf): Yes, in this case it would be for one of the most challenging matrixes. So if 

you go for sputum I mean that would be the one that you’d go for. 

(Richard Montegna): Okay, thank you very much.

Timothy Stenzel: I want to update my response to the last caller. There may be traditional 

manufacturers who would also like to get a EUA authorized kit through any of 

the manufacturers who have an EUA authorization such as IDT who has it 

under the CDC. You know we understand that having such a kit may be 

helpful in your test allotment process. And I don’t want to exclude those 

entities from being able to purchase the kit. Okay ready for the next question.

Coordinator: Thank you sir. Next question comes from (William Glover) your line is open.

(William Glover): Hi. Thank you for the question. I just want a clarification answer regarding 

for high complexity CLIA laboratories that are using the IDT CDC kit. So it 

was my understanding under the guidance that those laboratories would have 

to send the first five positive and the first five negatives to another laboratory 

to get those results confirmed. Is that still the case? If not public health 
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laboratories that are using the CDC EUA have to send their results to CDC to 

get confirmed and are presumptive?

Timothy Stenzel: Yes. I understand for public health labs that that is the process. This new 

guidance has to do when you’re developing your own tests in a laboratory 

developed test, if you were using one that’s already authorized by the FDA in 

this case IDT has authorization under the CDC EUA, this guidance does not 

apply to you. That test has already been developed. It’s already been qualified 

per lot. And again all that you need to do if you get one of those qualified lots 

from IDT or any of the follow on manufacturers have an EUA, you simply 

receive that kit or those kit lots in your lab and follow your normal laboratory 

procedures when you receive a new kit before you begin testing. There is no 

notification of the FDA that is required. 

But if you were on the call when I mentioned that the public health labs would 

like to hear, we encourage you to let them know even before you receive an 

order for a specimen that you have contact with them to let them know that 

you’re going to be initiating testing so they can prepare for dealing with 

potential positives that you would have. 

(Uwe Scherf): I think just to add that the presumptive positives that are then identified after 

you did your validation and your normal testing, it’s clear that they still need 

to do – need to be sent to the public health labs for confirmation or to the 

CDC. So I think that’s – so to be clear that this is the case. 

(William Glover): Thank you.

Timothy Stenzel: I think the best thing is we encourage you to reach out to your local or state 

public health lab to get further guidance on that. 
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(William Glover): Thank you.

Coordinator: Thank you. Next question comes from (Tom Griss) your line is open.

(Tom Griss): Hi. I just want to clarify when looking at the LOD – one to two fold LOD is 

that speaking in log as in tenfold, a hundred fold above or do you literally 

mean from 1,000 to 2,000 copies that sort of relationship?

(Uwe Scherf): It’s from 1 to 2,000. It’s close to really the appropriate evaluation there. So if 

what you’re describing is correct it’s not necessarily...

((Crosstalk))

(Uwe Scherf): ...yes.

Timothy Stenzel: Yes not (unintelligible) mix. So if your LOD is 1,000 those 20 samples near 

LOD would have to be in the range of 1,000 to 2,000. 

(Tom Griss): Right and then spike in for the positives would be intended to also be around 

that level for...

(Uwe Scherf): That’s correct, yes. 

(Tom Griss): And does that imply then you can use the LOD as part of your spike in?

Timothy Stenzel: Can you rephrase the question please?

(Tom Griss): If you get 19 or 20 of 20 is that 20 of the 30 spike in that you need to do then 

you need 10 additional?
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(Uwe Scherf): No, I think the concept would be that remember we described that for the 

LOD study you can actually use a combined matrix, you know, combined 

samples that are pooled samples. For the clinical study it’s important to have 

individual samples evaluated because it will give you then the appropriate 

evaluation tools – the differences in samples. And really what you’re doing is 

you are spiking material into these individual samples to really mimic the 

appropriate clinical evaluation. 

Timothy Stenzel: So to rephrase when you’re doing your LOD studies your initial dilution and 

your final verification of what your LOD is analytically, you can use pooled 

or clinical samples and non-responsive test negative samples to pool them and 

do your spike ins and dilution. But when it comes to clinical evaluation you 

would spike in viral RNA at the levels that are described. But each of those 

replicates would be in unique negative clinical samples.

(Tom Griss): That makes sense, thank you.

Coordinator: Thank you. Next question comes from (John Baines) your line is open.

(John Baines): Hi yes I believe that you answered it earlier. But if you’re getting the IDT kit 

that have the CDC EUA guidance, the LOD studies and the cross reactivity 

those are not steps that you need to take in order to begin clinical testing 

correct?

Timothy Stenzel: That’s correct. When you have an EUA authorized test then this new policy is 

not for you. And, you know, obviously the availability of such kits certainly 

would make it much easier for labs to get up and going because they don’t 

have to develop the tests themselves. So we encourage that if that’s possible 

for you.
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(John Baines): Perfect, thank you. 

Coordinator: Thank you. Next question comes from (Laurel Glaser) your line is open. 

(Laural Glaser): I’m calling from a CLIA lab. I just have a question. If we’re using a 

manufacturer’s kit where we don’t know the precise sequences of the primers 

and probes, can we use in silico LFS if we’re going to use it as an LDT? 

Timothy Stenzel: So if you’re developing a product, you know, I think that’s a great question to 

take offline and send us the question to our email address because we want to 

get a little bit more specifics but (Uwe Scherf) you can add anything. 

(Uwe Scherf): Yes, I mean the point there would be we need to have the sequence 

information. If the manufacturer is not willing to give it to you, I mean the 

opportunity from the FDA perspective to contact that manufacturer and get 

into kind of master file submitted so we have an opportunity to assess it. 

Because again the concept that we are describing here is nucleic acid base you 

have to have certain kind of blasts for them so evaluations done. And from 

our side that means that we accomplish that.

Timothy Stenzel: And we encourage those manufacturers to come in for EUA authorization. 

Coordinator: Thank you. Next question comes from (Sopheny Gene) your line is open.

(Sopheny Gene): I believe my questions have already been answered. But I’ll rephrase and ask 

you to confirm. If you are a high complexity, CLIA certified lab using the 

CDC kit with approved lot numbers you are not required to submit an EUA or 

to submit notification to the FDA, you can begin clinical testing following 

verification. My understanding from what you said is that there are no 

published guidelines but we would use CLIA guidelines on verification. 
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My second question is if you are validating specimens that are not currently 

claimed on the CDC kit, i.e., stool, that would require an EUA notification, et 

cetera per this policy. 

Timothy Stenzel: Let me address the stool question first. Yes if you’re going to use a sample 

type that has not been covered under the existing or existing EUAs, we 

suggest that you send an email to us to discuss how you can make a 

modification to that. If you’re using already an EUA authorized kit, I think 

the validation required for that will be obviously much more straightforward 

because much of the work has been done to validate that kit. But we would 

like to make sure that a novel matrix that hasn’t been authorized is going to 

function adequately and your extraction procedures are good. I will turn this 

over to (Uwe Scherf) to finish anything on the question. Anything else?

(Uwe Scherf): No, I think you captured.

Timothy Stenzel: Okay. On the first question having to do with what do you need to do if you 

have an EUA authorized kit. Yes all you need to do is do your normal 

verification when you receive that kit. You do not need to file an EUA 

submission or notification with us. 

And the second part of that question had to do with guidelines. Could you 

rephrase that question?

(Sopheny Gene): Oh I was just confirming that we can use standard CLIA guidelines for 

verification.

Timothy Stenzel: Yes. 

(Sopheny Gene): Great, thank you.
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Coordinator: That was our last question. I would now like to turn the call back over to Miss 

Irene Aihie.

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

thoughtful questions. Today’s presentation and transcript will remain 

available on the CDRH Webpage at www.fda.gov/training/cdrhlearn by 

Friday, March 13. If you have additional questions about today’s presentation 

please use the contact information provided at the end of the slide 

presentation. As always we appreciate your feedback. Following the 

conclusion of today’s webinar please complete a short 13-question survey 

about your FDA CDRH webinar experience. The survey can be found at 

www.fda.gov/cdrhwebinar immediately following the conclusion of today’s 

live webinar. 

Again thank you for participating. This concludes today’s webinar. 

Coordinator: This concludes today’s conference. You may disconnect at this time and thank 

you for joining. 

END