Oncology Drug Products Used with Certain In Vitro Diagnostic Tests: Pilot Program

December 12, 2023

Moderator: CDR Kim Piermatteo

CDR Kim Piermatteo: Hello and welcome everyone to today's CDRH webinar. Thanks for joining us. This 

is Commander Kim Piermatteo of the United States Public Health Service, and I serve as the Education 

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

Communication and Education. I'll be the moderator for today's webinar. 

Our topic today is the final guidance titled "Oncology Drug Products Used with Certain In Vitro 

Diagnostic Tests, Pilot Program," which was issued on June 21, 2023. This guidance is intended to pilot a 

new approach to provide greater transparency regarding performance characteristics that certain tests 

for oncology biomarkers used with certain oncology drug products should meet.

During today's webinar, we will explain the scope and goals of the new voluntary pilot program for 

certain oncology drugs used with certain in vitro diagnostic tests. We will describe how to complete the 

CDRH templates for collecting and providing performance characteristics and validation information for 

clinical trial assays under the pilot program. And answer your questions about this program. 

Before we begin, I'd like to provide a few reminders for the webinar. First, please make sure you've 

joined us through the Zoom app and not through a web browser to avoid technical issues. Second, the 

intended audience for this webinar is industry. Trade press reporters are encouraged to consult with the 

CDRH Trade Press Team at CDRHTradePress@fda.hhs.gov. And members of national media may consult 

with the FDA's Office of Media Affairs at FDAOMA@fda.hhs.gov. And lastly, we look forward to 

interacting with you during the live question-and-answer segment of today's webinar. If you have a 

question, please wait, and raise your hand at the end of today's presentation to get into the queue.

I now have the pleasure of introducing our presenters for today's webinar, Dr. Timothy Stenzel, Office 

Director of the Office of Health Technology Number 7, or OHT 7, for In Vitro Diagnostics within the 

Office of Product Evaluation and Quality, or OPEQ, in CDRH, and McKenna Tennant, Policy Analyst in

OHT 7 and OPEQ as well.

We'll begin with opening remarks from Dr. Stenzel, then a presentation from McKenna, and then field 

your questions about our topic. Thank you all again for joining us. I'll now turn it over to Tim to start 

today's presentation. 

Timothy Stenzel: Hi. I am Tim Stenzel, Director of the Office of In Vitro Diagnostics. Thank you all for 

being here today. We are excited to have the opportunity to host this webinar to walk through FDA's 

new voluntary pilot program for certain CDER-regulated oncology drug products used with certain in 

vitro diagnostic tests. Given the public health importance of such in vitro diagnostic tests for 

determining a patient's cancer treatment, the guidance was implemented immediately. 

We will first start by providing an overview of the scope and goals of the pilot program and then turn to 

walking through our recommendations for how to complete the pilot program's templates for collecting 

and providing performance characteristics and validation information for clinical trial assays, when

requested by the FDA.
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We thank you for joining today's webinar and look forward to the live Q&A at the end of the 

presentation. McKenna Tennant will now continue with the slide presentation. McKenna?

McKenna Tennant: Thank you, Tim. As mentioned, this webinar will focus on the final guidance for 

immediate implementation, "Oncology Drug Products Used with Certain In Vitro Diagnostic Tests, Pilot 

Program," issued earlier this year. 

Thank you all for joining today's webinar on the oncology diagnostics pilot and associated clinical trial 

assay, or CTA templates. There are two key learning objectives for today. The first is to identify the 

scope and goals of the new voluntary pilot program for certain oncology drugs used with certain in vitro 

diagnostic tests. And the second is to be able to describe how to complete CDRH's templates for 

collecting and providing performance characteristics and validation information for CTAs under the pilot 

program, when requested by FDA.

I will start today's talk with a very brief overview of some of the key features and highlights of FDA's 

companion diagnostics policy and program for relevant background, talk about one of the challenges we 

face within the current companion diagnostics program, and then talk about the scope and goals of the 

new voluntary pilot program that is aimed at helping address that challenge.

As some of you may know, FDA defines a companion diagnostic as an in vitro diagnostic device that 

provides information that is essential for the safe and effective use of a corresponding therapeutic 

product. Companion diagnostics can have different uses. They can be for identifying patients who are 

most likely to benefit from the therapeutic product, identifying patients likely to be at increased risk for 

serious adverse reactions as a result of treatment with the therapeutic product, identifying patients in 

the population for whom the product has been adequately studied and found to be safe and effective, 

or, in other words, for treatment selection when there is insufficient information about the safety and 

effectiveness of the therapeutic product in any other population, or monitoring response to treatment 

with a therapeutic product for the purpose of adjusting treatment to achieve improved safety or 

effectiveness.

As described in FDA's final guidance document from 2014, "In Vitro Companion Diagnostic Devices," 

some key features of FDA's companion diagnostic policy that are most relevant to today's presentation 

include that ideally, a therapeutic product and its corresponding companion diagnostic should be 

developed and authorized at the same time, and the use of a companion diagnostic with a therapeutic 

product is stipulated in the instructions for use in the labeling of both the diagnostic device and the 

corresponding therapeutic product. 

The current companion diagnostics program continues to help assure that patients have access to safe, 

effective, and high-quality FDA-authorized companion diagnostic devices. One challenge that arises in 

the current environment, however, is the use of laboratory developed tests, or LDTs, in circumstances 

where there is not an FDA-authorized companion diagnostic. 

As described in FDA's companion diagnostic guidance, there are specific circumstances where FDA may

decide to approve a therapeutic without authorizing a corresponding companion diagnostic at the same 

time. And as stated in the companion diagnostic guidance, this happens when the therapeutic product is 

intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment 
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exists and the benefits from use of the therapeutic product are so pronounced as to outweigh the risks 

from the lack of an FDA-authorized companion diagnostic. 

In use cases, tests offered as LDTs with unknown performance are being used for patient treatment 

decisions. For the purposes of FDA's guidance, "Oncology Drug Products Used with Certain In Vitro 

Diagnostic Tests, Pilot Program," the term LDT means a type of in vitro diagnostic device that is 

designed, manufactured, and used within a single-site CLIA-certified laboratory that meets the 

requirements for high-complexity testing. Historically, FDA generally has exercised enforcement 

discretion with respect to most LDTs such that, except in certain circumstances, FDA generally has not 

enforced applicable requirements with respect to most LDTs. 

For tests that provide information that is essential for the safe and effective use of a therapeutic 

product, in circumstances where FDA decides to approve a therapeutic without authorizing a 

corresponding companion diagnostic at the same time, LDTs are being used. And while in these cases, 

the benefits from use of the therapeutic product were considered to outweigh the risks from the lack of 

an FDA-authorized companion diagnostic, that doesn't mean there are no risks. There are risks, including 

the use of LDTs that might not work as intended. 

While LDTs play an important role in our health care system, the FDA has become increasingly 

concerned that LDTs currently used in the US might not provide patients with accurate and reliable 

results. For example, recent publications have documented LDTs that are inaccurate, including those 

used to identify patients for treatment with specific drugs. Use of inaccurate test results can negatively 

impact treatment decisions. One step that may be helpful in reducing the risk of using LDTs is to 

recommend and make transparent minimum performance characteristics for tests used to identify 

patients for drug treatment. 

That's why, in June of this year, FDA issued a final guidance to announce and describe a new voluntary 

pilot program for certain oncology drug products used with certain corresponding in vitro diagnostic 

tests. The guidance titled "Oncology Drug Products Used with Certain In Vitro Diagnostic Tests, Pilot 

Program" can be found on FDA's website. As described in the guidance, FDA is piloting a new approach 

to provide transparency regarding minimum performance characteristics that certain tests should meet 

if they are to be used to select treatment with certain oncology drug products. As I mentioned on the 

previous slide, we believe this is one step that may be helpful in reducing the risk of using LDTs for 

oncology drug treatment decisions when there is not an FDA-authorized companion diagnostic. 

The pilot program does not alter the standards for approval of the oncology drug products reviewed 

under the pilot program or for marketing authorization of corresponding companion diagnostics. Since 

the majority of therapeutic products that require use of an in vitro diagnostic test for patient selection

but are approved without contemporaneous approval of a companion diagnostic, are in the oncology 

space, piloting this approach for oncology drug products is a logical place to start. Further, since the 

majority of FDA-cleared and approved companion diagnostics are for oncology drug products, we have 

the most experience with in vitro diagnostic tests used in the selection of such treatments and are 

therefore most comfortable piloting such an approach in this space. 

Before we dive into the details of the pilot program, it's important to understand the scope of the 

program, which is limited to certain scenarios. Specifically, the pilot program is limited to nine drug 

sponsors and CDER-regulated oncology drug products for which FDA determines use of in vitro 
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diagnostic test is needed to identify the intended patient population. No satisfactory alternative 

treatment exists, and the anticipated benefits from the use of the drug product are so pronounced as to 

outweigh the anticipated risks from approval of the drug product without an FDA-authorized companion 

diagnostic. 

The corresponding clinical trial assays are limited to CDRH-regulated tests for which there is a wellvalidated reference method, well-validated comparator method, and/or well-characterized materials 

that can be used to support test accuracy and that use the same technology as a previously FDAauthorized companion diagnostic for any indication. 

Although the initial phase is for nine drug sponsors, if appropriate based on the experience during the 

initial phase, FDA anticipates it may expand the pilot to evaluate additional sponsors for acceptance. 

Now let's talk a little bit about the pilot program at a high level. As is the case for FDA-authorized 

companion diagnostics, under the pilot program, if the FDA concludes that the drug product meets the 

applicable standards for its approval, FDA intends to rely on the same pivotal clinical trials that support 

approval of the drug product to establish the clinical validity for the clinical trial assays used in those 

trials. Given the limited type of tests eligible for use in the pilot program, as described on the prior slide, 

FDA believes that in general, the clinical validity of these CTAs can be extrapolated to additional tests of 

the same type with similar analytical performance when established through properly conducted 

validation studies. 

Under this pilot program, the FDA will be making transparent on its website recommended minimum 

analytical performance characteristics that would support extrapolating the clinical validity established 

in the drug trials to additional tests of the same type. FDA anticipates that the approved drug labeling 

will specify that the drug is indicated for patients identified as exhibiting a named biomarker by in vitro 

diagnostic tests that have FDA's recommended performance characteristics. 

CDRH intends to provide on its website the recommended minimum performance characteristics for 

these tests. FDA also anticipates that both the approved drug labeling and CDRH's website will specify 

relevant test characteristics for the in vitro diagnostic tests for use with the drug, such as the biomarker 

detected and test method, including the specimen type. 

So how does this happen logistically? In circumstances where the FDA approves a drug without approval 

of a companion diagnostic at the same time, the FDA will request the drug sponsor provide performance 

information for the tests used to enroll patients into the clinical trials that support drug approval. Based 

on an assessment of that information, the FDA will post to the FDA website the minimum performance 

characteristics recommended for similar tests that may be used to select patients for treatment with the 

approved drug. 

Providing transparency of minimum recommended performance characteristics aims to help facilitate 

better and more consistent performance of these tests, resulting in better drug selection and improved 

care for patients with cancer. 

To be considered for the voluntary pilot program drug sponsors should submit a statement of interest to 

their investigational new drug application, new drug application, or biologic license application. Upon 

receipt of the statement of interest, FDA will follow up with no more than nine sponsors to request 
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specific information to enable FDA to make a decision concerning acceptance into the pilot, based on 

certain factors described in the guidance. One of those is the oncology drug sponsor being able to 

collect and provide the analytical validation data and performance characteristics, as recommended in 

FDA's templates, for all CTAs used for the enrollment of the pivotal clinical trial. 

On its website, the FDA has provided a series of templates that oncology drug product sponsors, when 

requested by the FDA, can use to facilitate the provision of performance characteristic information on 

the CTAs used in their clinical trials. These templates describe the performance characteristic 

information that should be provided by the oncology drug product sponsors when requested by the 

FDA, which drug sponsors would need to obtain from the test developers. 

The templates available on the website are based on test technology. And currently on our website, 

there is a next-generation sequencing test template, a PCR test template, a Sanger sequencing test 

template, an immunohistochemistry test template, and a fluorescence in-situ hybridization test 

template. We will turn to more details on these templates during the second half of this presentation. 

Drug development programs from drug product sponsors accepted into the pilot program will fall into 

one of two buckets, the oncology drug pivotal trials are not started at the time the guidance was issued 

on June 2023, or the oncology drug pivotal trials were initiated prior to June 20, 2023. We sometimes 

call this the prospective approach and retrospective approach. Procedures for the pilot and accepted 

sponsors vary based on whether the programs are prospective or retrospective. For pivotal trials that 

have not started as of June 20th of this year, FDA will provide minimum validation and performance 

characteristics for CTAs to enroll the drug product's pivotal clinical trial prior to the start of the trial. FDA 

expects the CTAs for trial enrollment will meet or exceed these validation and performance 

characteristics. And if the drug is ultimately approved, FDA will recommend minimum performance 

characteristics for IVDs to be used with that drug based on performance of the CTAs used in the clinical 

trials. 

For trials that were initiated prior to June 20th of this year, FDA will work with the drug sponsors 

accepted into the pilot to review the performance characteristics and validation information for each 

CTA and, provided the data are sufficient, recommend the minimum performance characteristics within 

the NDA or BLA application review time frame. 

In summary, the key takeaways for the pilot program described today are that FDA believes 

transparency regarding minimum recommended performance characteristics will help facilitate 

development of better and more consistently performing tests, resulting in better drug selection and 

improved care for patients with cancer. However, this pilot program will not assure that LDTs available 

to patients are safe and effective. Separately, FDA issued a notice of proposed rulemaking, proposing a 

policy under which FDA intends to phase out its general enforcement discretion approach for LDTs. 

Now we will move on to learning objective two and focus on the pilot program templates for collecting 

and providing performance characteristics and validation information for CTAs under the pilot program.

As previously touched on, the pilot templates on CDRH's his website are intended for use by oncology 

drug product sponsors who have submitted the statement of interest for the pilot program. We 

encourage oncology drug sponsors interested in participating in the pilot to submit a statement of 

interest to their IND, NDA, or BLA. 
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These templates should only be used to provide information that should be submitted to FDA, only 

when requested by FDA. The templates are to help oncology drug sponsors to collect and provide 

validation information and performance characteristics for each CTA used in the pivotal clinical trials for 

drug products under the pilot program. 

The information recommended in the templates is largely technology specific, so, it varies by template. 

However, there are four general sections in each of the CTA templates, general laboratory information, 

general test information, validation studies, and data tables. 

Five templates are available on CDRH's website for download as Word documents, with various free text 

and yes-or-no selection box options for filling out requested information. We aim to make these 

templates as user friendly as possible to simplify the process. And for today's webinar, we will walk 

through elements of the Next-Generation Sequencing, or NGS TTA template. Please note that FDA's 

collection of the validation and performance characteristic information for CTAs used under the pilot 

does not mean we are authorizing or deeming acceptable the performance of these assays. 

So, the template first asks for general laboratory and test information. In the general laboratory 

information section, you should fill out information about the laboratory performing the CTA, relevant 

contact information for that laboratory, and the test name. As shown on this slide, the template 

includes a question that asks whether the CTA is commercially available. If yes, you would provide the 

kit and manufacturer name as well as describe any modifications that may have been made to the kit, 

for example, to specimen type. If the CTA is not commercially available as described in the template, you 

should provide the analyte or analytes detected, such as single-nucleotide variants for T790M and the 

EGFR gene in DNA. And describe the test method, including the specimen type, for example, hybridbased capture from formalin-fixed paraffin-embedded, or FFPE breast tumor tissue. 

As described in the template, regardless of whether the test is commercially available, we recommend 

you provide the following information, CTA components: such as probes, reaction mixes, and enzymes; 

extraction methods; instrument or platform used; minimum tumor content and nucleic acid amount and

range; description of the positive and negative control, their respective use, and what they respectively 

measure; and a summary of the bioinformatic workflow used for the test, including the sequence 

alignment, germline filter, and variant calling processes. 

The general test information section recommends providing your determination of calling rules, 

acceptable sequencing quality metrics, and clinical cutoff. For calling rules, please provide the 

prespecified variant classification rules used to identify the presence or absence of the analytes that the 

CTA is intended to detect. As described in the template, we recommend you provide your sequencing 

quality metrics for run acceptability at the sample, variant, and flow cell level using a table, as 

exemplified by table one. These include coverage uniformity, based quality score, mapped reads, strand 

bias, variant allele frequency, minimum number of mutant reads, percent pass quality filter, percent 

greater than Q30, and any other metrics you may have implemented for run acceptability. We also 

recommend you briefly summarize the prespecified clinical cutoff that was used to enroll subjects in the 

clinical trial. 

We are now moving on to the validation studies section of the template. While we are not going to go 

through all of these subsections today in detail, at a high level, the validation study section of the NGS
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template requests information on samples used in the validation studies, for example, a summary on 

how surrogate samples were constructed if used, information on the source of reference samples or 

materials if used, and the number of different types of samples used in each validation study. 

Information is also requested on comparator or orthogonal methods, analytical accuracy of the CTA, 

limit of detection determined, precision studies, interfering substances studies, inclusivity, crossreactivity studies, stability studies, and NGS liquid biopsy specific information. 

I'm first going to discuss requested information on comparator and orthogonal methods and analytical 

accuracy of the CTA. Comparator or orthogonal methods are used to characterize samples and/or 

validate the CTAs. For this section of the template, please provide information on any comparator and 

orthogonal methods used to characterize samples and validate the CTA. And the studies they were used 

for in table three, for example, analytical accuracy, limit of detection, precision, and interfering 

substances for orthogonal or comparator methods used for sample selection and characterization, and 

analytical accuracy when used for validation. If LDTs were used as comparators, we recommend you 

provide the laboratory's name and address, as well as the stated accuracy of the comparator methods. 

Now turning to the analytical accuracy concordance piece of the validation studies section of the 

template and what is recommended. Analytical accuracy of the CTA is determined relative to a 

reference method or validated comparator method or orthogonal method. For NGS-based tests, 

accuracy represents the degree of concordance or agreement of results between a sequence obtained 

from the test and the same sequence determined by the valid comparator method, or between a 

reference sample run on an NGS-based test and the high confidence sequence of the reference. 

If a comparator method is used, it should have similar panel content and sensitivity to that expected 

from the CTA, based on the test method and previous analytical testing. Well-characterized samples 

should be tested with both the CTA and comparator method. 

So, for this section of the template please provide a brief summary of the study design, including the 

statistical data analysis methods used to determine analytical concordance. Details on the samples 

tested to demonstrate accuracy, of which the requested information varies by variant type, so variant 

allele frequency for SNVs and indels, chimeric reads for rearrangements and fusions, and copy numbers 

for CNVs. Please also provide, if the analytes are not individually validated, details on the samples tested 

to demonstrate panel-wide accuracy for representative panel variants, including variant allele frequency 

for SNVs and indels, chimeric reads for rearrangements and fusions, and copy number for CNVs, as well 

as a summary of analytical concordance between the NGS CTA and comparator for variants and genes 

evaluated for patient enrollment. 

We will now look at the recommended concordance summary data on the next slide. 

For analytical accuracy, we recommend you calculate positive percent agreement, or PPA, and negative 

percent agreement, NPA, between the CTA and the comparator method for representative variants in 

genes and for panel-wide accuracy as applicable. And provide concordant summary data in table 4, as 

you see here. The top part of the table is where you would input information on specific variants that 

have been individually validated. For example, SNV EGFR T790M. The bottom part of the table is where 

you would input information on panel-wide accuracy as applicable. 

PPA is the ability of the test to correctly identify variants that are present in a sample and reflects the 

frequency of false negatives. NPA is generally defined as the proportion of correct calls by the assay for 
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the absence of a genetic variant. More specifically, for genetic tests, NPA is the probability that the assay 

will not detect a sequence variation when none are present. At this time, the table does not include 

calculations for PPA and NPA. As described in the template, we recommend you provide your calculated 

PPA and NPA in table four. 

We're now going to look at the requested precision information in the validation studies section of the 

template. 

Precision studies are performed to evaluate sources of variation in the test procedure to determine the 

repeatability and reproducibility of the test. Reproducibility for NGS-based tests involves measuring test 

variability under a variety of specified conditions, such as when using different operators, different 

operating conditions, different days of measurement, different instruments, et cetera, using the same 

sample, including samples around the test cutoff, and accounting for major sources of variability in the 

test. 

Repeatability involves measuring test result variability when using the same operators, the same 

measuring system, the same operating conditions, and the same location, and replicating measurements 

on the same or similar objects over a short period of time. 

For the precision section of the template, please provide a brief study design; the number of runs, days, 

instruments, reagent lots, operators, and replicates tested per sample; whether precision was evaluated 

at multiple sites, and if details are not provided for each analyte, details on samples tested to 

demonstrate panel-wide precision; if the study was not conducted with the end-to-end workflow, 

information on the part of workflow included and rationale; a summary of statistical data analysis 

methods to determine CTA precision; and a summary of PPA and NPA for variants and genes used for 

patient enrollment, and panel-wide precision, if applicable. Now, looking at the table to provide this 

information on the next slide.

We recommend using table six in the template to provide summary variant PPA and NPA information for 

precision. The top part of the table is where you would input information on specific variants that have 

been individually validated-- for example, EGFR T790M. The bottom part of the table is where you would 

input information on panel-wide accuracy as applicable. 

We will now go through requested information on limit of detection, interfering substances, and 

inclusivity cross-reactivity studies. 

Limit of detection, or LOD, is the lowest amount of genomic target that the test can consistently detect 

with a stated probability. LOD can be stated as the lowest variant allele frequency the test can detect for 

short variants, such as SNVs and indels, the lowest number of chimeric reads that the test can detect for 

gene fusions and large rearrangements, and the lowest copy numbers that the test can detect for 

chromosome amplifications, and the lowest number of rearrangements and CNVs the test can detect for 

structural variants. 

LOD may also be based on tumor content. As described in the template, for the LOD section, please 

provide a brief summary of the study design, including the statistical data analysis methods used to 

determine LOD, a list of how many reagent lots were used in the LOD establishment and confirmation 
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study, and a summary of your precision study results. We recommend using table five of the template 

for the summary of your LOD study results. 

Moving on to the interfering substances piece of the validation study section of the template, interfering 

substances studies evaluate the effects of potentially interfering endogenous and exogenous substances 

on test performance, for example, hemoglobin. As described in the template, for the interfering 

substances section, we recommend providing a brief study design summary, including statistical data 

analysis methods used to evaluate interference and a summary of results for each interfering substance 

tested in table seven. As shown here and in the template, table seven includes the LOD levels used, the 

number of samples, replicates per sample, failure rate, detection rate, and call rate. 

Looking at the inclusivity/cross-reactivity section. Inclusivity/cross-reactivity studies evaluate the 

specificity of the primers or probes used to target specific genes or genomic regions. Specifically, these 

studies assess the potential for cross-reactivity of known cross-reactive alleles and homologous regions, 

such as pseudogenes, based on the targets interrogated by the test. We recommend you provide a brief 

description of the inclusivity/cross-reactivity study performed and a summary of the in silico crossreactivity with nontargeted regions. While not on this slide, as described in the template, we also 

recommend that stability studies be conducted to support storage conditions, including the duration of 

storage for specimens, and stored intermediate products, as applicable. In the template, we recommend 

providing the stability for primary specimens, including the conditions and durations, and the stability 

for intermediate specimen products, such as library prep. 

There is specific information requested in the templates for if the CTA uses liquid biopsy. 

If this is applicable to your CTAs, in the NGS liquid biopsy specific information in the template, please 

describe any quality measures for the circulating tumor DNA samples, such as fragment analysis. Please 

document whether germline or clonal hematopoiesis of indeterminate potential, or chip variants, were 

excluded. Please describe the study to establish the CTA's Limit of Blank, or LoB, if LoB was performed 

for your CTA. LoB is determined as the highest measurement result that is likely to be observed with a 

stated probability for a blank sample, for example, analyte negative. And then, lastly, please describe 

how interference for the blood-based tests were assessed. For blood-based tests, short draws and 

unique components derived from the blood collection process could contribute to interference. 

If you have any questions when using the template, please feel free to reach out to the CDRH mailbox in 

the guidance, OncologyPilotCDRH@fda.hhs.gov. Also, if you wish to comment on the guidance or the 

templates, we encourage you to submit a comment to the pilot program guidance document.

We hope that you found this template demonstration helpful. And to summarize, our goal is to make 

the collection and provision of test validation and performance characteristic information as easy as 

possible. The pilot CTA templates provided on our website, for which we walked through one of five 

available templates today, are intended to facilitate the provision when requested by FDA of analytical 

validation and performance characteristic information for CTAs used in pivotal trials for drug products 

under the pilot. This pilot program is one step that may be helpful in reducing the risk of using 

unauthorized LDTs for oncology drug treatment decisions. 

CDR Kim Piermatteo: Thanks for that presentation, McKenna. Now we will transition to our interactive 

question-and-answer segment for today's webinar. 
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Before we begin, I'd like to go over how we'll manage this segment and a few reminders. To ask a 

question, please select the Raise Hand icon, which should appear on the bottom of your Zoom screen.

I'll announce your name and give you permission to talk. When prompted, please select the blue button 

to unmute your line and then ask your question. When asking your question, please remember to limit 

yourself to asking one question only and try to keep it as short as possible. We appreciate that you may 

have a very specific question involving your device or scenario; however, we might not be able to 

answer such specific questions today. Therefore, we'll try to frame a broader response based on what's 

described in the final guidance and the pilot. After you ask your question, please lower your hand. And if 

you have another question, please feel free to raise your hand again to get back into the queue, and I'll 

call on you as time permits. 

So, at this time, please go into Zoom, and you can select the Raise Hand icon to ask Tim and McKenna a 

question related to this pilot program. 

Our first question is coming from Dun. Dun, I have unmuted your line. Please unmute yourself and ask 

your question. 

Dun Liang: Thank you. Can you hear me?

CDR Kim Piermatteo: Yes, we can. 

Dun Lian: This is Dun from Loxo@Lily. So, I have just one question. Is it necessary to collect performance 

characteristics, and how should one fill that template for an FDA-approved test or device?

CDR Kim Piermatteo: Thank you, Dun, for that question. I'm going to turn it over to McKenna to provide 

you a response.

McKenna Tennant: Hi. Thank you, Dun. So, yes, as part of the pilot program, if requested by FDA, we will 

be requesting validation and performance characteristic information from the CTAs used for enrollment 

in the trial, as that information will be used by FDA, provided that it's appropriate, to develop the 

recommended minimum performance characteristics should the drug be approved under the pilot 

program. Does that answer your question?

Dun Liang: Yes. Some of those tests, in our preparation for the pilot, is that they are actually FDAapproved, right. So probably not with the indication for this particular investigational drug, but they are 

approved. So, my question is, can we, do we need to extract those information, and how can we do 

that? Are we looking at those approved SSED or decision summary? You know, I'm asking those LDTs--

that are being approved. 

McKenna Tennant: Yeah. So, if FDA-authorized kits are used for enrollment of the pivotal clinical trial, 

and it's not used as the approved indication for use, then, yes, labs should submit, or the drug sponsor 

should submit performance data. So, again, it would be when requested by FDA, we would expect the 

analytical validation data and performance characteristics for all CTAs used for enrollment, including if 

it's a kit. One thing to note is that the drug sponsor will need a right of reference from the owner or 

owners of the CTA data, such as the kit manufacturer. 
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Dun Liang: Thank you. 

Timothy Stenzel: And I would also add, this is Tim, that if you make any modifications to the kit, a new 

sample type, maybe a new extraction method, we would want to see validation around that you do just 

normally.

Dun Liang: Thank you. 

CDR Kim Piermatteo: Thank you Dun for your question. And thank you, McKenna, and Tim, for providing 

a response. Our next question is coming from Lynne. Lynne, I have unmuted your line. Please unmute 

yourself and ask your question. 

Lynne: Hi there. Can you hear me? 

CDR Kim Piermatteo: Yes, we can. 

Lynne: Sure. I wanted to know if this pilot program and any of the LDTs that are put through this 

program, once the drug is approved, or prior to the drug approval, does this pilot program remove the 

need for the drug manufacturer to bring forth an approved CDx?

McKenna Tennant: Thank you for that question, Lynn. So, for drugs approved under the pilot program, 

FDA will determine the need for a post marketing commitment for the development of a companion 

diagnostic on a case-by-case basis. But I want to emphasize, in general, we would not expect a 

companion diagnostic or a post marketing commitment for the development of a companion diagnostic 

for drugs approved under the pilot program where FDA would be able and would be recommending and 

posting on its website minimum performance characteristics for the in vitro diagnostic test used to 

identify patients. So generally, we would not expect a PMC if we are able and will be recommending 

NPCs under the pilot program for that drug. 

Lynne: OK, thank you. 

Timothy Stenzel: And this is Tim. I would add that any drug sponsor that wants to discuss this in a little 

bit more detail, just reach out at the email address posted on the presentation and we'd love to engage 

in a dialogue about it as needed. Thanks.

Lynne: Thank you. 

CDR Kim Piermatteo: Thank you for your question, Lynne. Alright, our next question is coming from 

Staci. Staci, I have unmuted your line. Please unmute yourself and ask your question. 

Staci J Kearney: Yes, hi, thank you, Staci Kearney from Elevation Strategic Development. You may not be 

able to answer this question yet, but if finalized, how could the proposed rule, going into effect, affect 

the drug label when an LDT is used to support drug approval, but an FDA-approved CDx does not yet 

exist? 

McKenna Tennant: Thank you for your question, Staci. As we stated, this webinar is only about the pilot 

program.
12

Staci J Kearney: OK. Thank you.

McKenna Tennant: Thank you. 

CDR Kim Piermatteo: Thanks, Staci. Our next question is coming from Valerie. Valerie, I have unmuted 

your line. Please unmute yourself and ask your question. 

Valerie M Bella: Hello. Can you hear me?

CDR Kim Piermatteo: Yes, we can. 

Valerie M Bella: Hello. My name is Valerie, I'm from Johnson & Johnson. I have a question. If the clinical 

trial is enrolled based on a local test, but you centrally confirm your results using an FDA-authorized 

test, would the NPCs be based off of the local test data or the central test? Or would it be a combination 

of both? 

Timothy Stenzel: Can I ask a follow-up question before we answer? And that is, what is the test of 

record for enrollment in the study? 

Valerie M Bella: It is, enrollment will be based on the local test results. 

Timothy Stenzel: OK. Thank you. McKenna, do you want to handle this one? 

McKenna Tennant: Yep. If enrollment will be based on the local test results, then we would expect 

analytical validation performance characteristic data from those local test results, and we would be 

recommending NPCs based on the performance of those local test results used for enrollment.

Valerie M Bella: Thank you. 

McKenna Tennant: Thank you. 

CDR Kim Piermatteo: Thanks, McKenna. Thanks, Valerie. Our next question is coming from Jean. Jean, I 

have unmuted your line. Please unmute yourself and ask your question.

Jean Y Chen: Hi, thanks. Hi, this is Jean Y Chen from Loxo@Lily. I have a question about collecting the 

local laboratory test data. So, as you know, the laboratory frequently change their tests, and the 

performance may change as those tests are changed. So how can the performance data be accurately 

collected for a specific version of the test that's used in the trial?

Timothy Stenzel: That's a challenging question. Generally hoped that an enrollment assay would not 

change during a drug trial. If it's necessary to make a change, it would be great to have information 

about those changes and also provided with the collection of local assay information so that the FDA can 

assess the original and any subsequent changes in their potential impact on performance. McKenna, 

anything else to add about my response? 
13

McKenna Tennant: Nope. I think that sounds good. We would just still expect the validation 

performance characteristic information for that modified version of the assay because the goal of the 

pilot is if the drug is approvable, we would set the minimum performance characteristics based on the 

actual performance of the tests used for enrollment.

Timothy Stenzel: Yeah, and I can imagine that some of those changes might be minor and not impactful 

of performance. But still, we'd like to be aware of them.

Jean Y Chen: Thank you. And just to follow up, sometimes the trials may take a very long time to 

complete. And over time, as the performance of the tests change, how does FDA expect the sponsor to 

capture that?

Timothy Stenzel: You know, this is, perhaps should be expected, given long trials. I think, you know, if 

you could send us an email at OncologyPilotCDRH@fda.hhs.gov asking this question, I think having an 

offline conversation about this, especially internally so that we can give you the best answer, is going to 

be best at this point.

Jean Y Chen: Thank you. 

CDR Kim Piermatteo: Thanks, Jean, for your question, and thanks, Tim, and McKenna. Our next question 

is coming from Carly. Carly, I have unmuted your line. Please unmute yourself and ask your question.

Carly McWilliams: Hi. This is Carly McWilliams with Roche Diagnostics. Can you hear me, OK? 

CDR Kim Piermatteo: Yes, we can. 

Carly McWilliams: Thank you. I have understood from a meeting that this pilot could potentially lead to 

down-classifications of companion diagnostics. And I wanted to know if there was anything that you 

could say about that?

Timothy Stenzel: McKenna, you want to handle that? 

McKenna Tennant: Yes. I am happy to. So, this pilot program may facilitate regulatory submissions to 

FDA because the minimum performance characteristics developed through the pilot could be leveraged 

to support Premarket Application, or PMA approval, but the NPCs could also be leveraged to support the 

development of special controls. 

I do want to note the pilot doesn't alter the standards for marketing authorization of companion 

diagnostics. So, kit manufacturers will still be required to obtain FDA authorization, which is typically 

currently sought through the PMA pathway for companions, but this pilot might help open up the De 

Novo pathway and, subsequently, the 510(k) pathway, if the statutory criteria for the De Novo pathway 

are met. And we are aware that many labs are interested in using FDA-authorized kits when available. 

And also, the availability of the De Novo or 510(k) pathways may also incentivize voluntary submissions 

for LDTs. 

Carly McWilliams: Thank you very much. 
14

CDR Kim Piermatteo: Thanks Carly for your question. Our next question is coming from Aaron. Aaron, I 

have unmuted your line. Please unmute yourself and ask your question.

Aaron Schetter: Hi, this is Aaron Schetter from AstraZeneca. And I just had a question about the 

interactions and the timings for companies to get feedback on clinical trial assay. As we start planning 

studies [inaudible].

CDR Kim Piermatteo: Aaron, you're breaking up a little bit. Would you mind speaking...

Aaron Schetter: Oh. 

CDR Kim Piermatteo: There you go. 

Aaron Schetter: OK. Yeah, I want to ask a question about, what do you foresee the interactions and the 

timing of those interactions for us, for companies to get feedback on one of the clinical trial assays 

they've selected would be sufficient? And the idea would be we would need to proactively plan to use 

them in our studies and get answers kind of in real time to be able to take advantage of it. 

McKenna Tennant: Thank you for your question. So, we can't speak to kind of the timeline of reviews of 

statements of interest and acceptance of participants into the pilot. I will say that for accepted drug 

sponsors with prospective programs or programs that have not yet begun enrollment, as stated in the 

guidance, you know we will work with that sponsor to provide written feedback regarding validation of 

performance characteristics for the CTAs used for enrollment prior to the trial initiation. We can't speak 

to specific timing you know right now, but we will definitely be working interactively with the sponsor. I 

hope that gets at the question. Thank you. And I see Tim is also.

Timothy Stenzel: Yeah. I just want to add that we want to turn this around quickly when we have 

inquiries about this. And we know that it's important to increase certainty and decrease uncertainty in 

your decisions and we want to make this as easy as possible for you to decide whether or not to 

participate.

Aaron Schetter: OK, thank you. 

CDR Kim Piermatteo: Thank you, Aaron, for your question. Looks like I'm going to circle back to Jean. 

Jean, do you have another question? I've unmuted your line. Please ask your question. 

Jean Y Chen: Hi, thank you. Yes, I have another question. So, will all the analytical performance data that 

is submitted by the sponsor be public, be publicly available on FDA's website, or will any of the details or 

any of the data or information that we collect be publicly available?

McKenna Tennant: Thank you for your question. So, on CDRH's website, we will not be providing 

specific information about specific tests or labs. So, on our website, we will just be providing the 

minimum performance characteristic recommendations by technology type and per approved drug 

under the pilot program. Thank you. 

Jean Y Chen: Thank you. 
15

CDR Kim Piermatteo: Thanks, McKenna. Thanks, Jean. Our next question is coming from Shannon. 

Shannon, I have unmuted your line. Please unmute yourself and ask your question.

Shannon Bennett: Thanks. It seems like the guidance is really driven by the drug companies. If there is a 

laboratory that would be interested in participating in a pilot, how might they get involved?

McKenna Tennant: Thank you for your question. So, the pilot program is specifically for oncology drug 

product sponsors. So, we're going to be accepting, you know the scope is just for accepting drug 

sponsors. So, I just want to flag that. However, you know, we do get the question, are labs or drug 

sponsors supposed to fill out the templates? This is up to the oncology drug product sponsor. But the 

oncology drug sponsor should submit that information. If you have comments or questions on the 

guidance with respect to input from the lab community, we suggest you reach out to the CDRH inbox on 

the slides, or also submit comments to the docket of the guidance. 

Timothy Stenzel: And, Shannon, I would also add that, certainly, you can make your desire known to 

participate to drug sponsors. I would expect you know a lot. 

Shannon Bennett: Thank you. 

CDR Kim Piermatteo: Thank you for that question. Our next question is coming from Songbai Wang. I've 

unmuted your line. Please unmute yourself and ask your question. 

Songbai Wang: Hi, this is Songbai. Thanks. Can you hear me? 

CDR Kim Piermatteo: Yes, we can. 

Songbai Wang: OK. So, can FDA clarify what's the timing for recommended minimum performance 

characteristics? Specifically, is it before the clinical trial in the pilot to start or after the trial start, after 

the trial finish and the drug is approved?

McKenna Tennant: Thank you. So, FDA intends to recommend the minimum performance 

characteristics within the time frame for review of the NDA or BLA application. And we expect to post 

the minimum performance characteristics on our website at the time of drug approval. 

Songbai Wang: OK. Thanks. From your presentation, I believe I saw somewhere that you indicate that 

said you would recommend NPC for the CTA, is, but that's.

Timothy Stenzel: Yeah. 

McKenna Tennant: Yes, I can, oh, go ahead, Tim. 

Timothy Stenzel: No, no. You now know what he's asking. So, thanks. 

McKenna Tennant: Thank you. So, you are correct. And this was in the slide presentation, the discussion 

between, about the process difference for retrospective and prospective programs. So, for trials that 

have not yet begun enrollment and for accepted drug sponsors, we will work with the sponsor to 

provide our feedback in the form of minimum validation and performance characteristics for CTAs to be 
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used for enrollment prior to the start of the trial. We would only be providing those recommendations 

to that accepted drug sponsor. And then we would expect that the CTAs used for enrollment would 

meet or exceed those recommendations. And at the conclusion of the trial, and if acceptable, the drug is 

deemed approvable, we would develop the minimum performance characteristics and publicly 

recommend those based on the actual performance of the CTAs. 

Timothy Stenzel: And then, McKenna, if you could you know address the, what we call retrospective in 

the guidance and how that differs. 

McKenna Tennant: Yes. So, we consider, to clarify the difference between retrospective and prospective 

programs, retrospective programs are those that have already begun enrollment. And actually, it's those 

that have begun enrollment at the date of the guidance publication, which is June 20th of this year. 

And then prospective programs are those that have not yet begun enrollment, where we would work 

with the sponsor to provide feedback regarding CTA validation prior to the trial enrolling.

Timothy Stenzel: So, if the trial has already begun enrolling, then we would want you to collect the 

information, the drug sponsor would collect the information about the CTA, clinical trial assay, test 

performance characteristics. But if we interact with you before you start the trial, then we'll work with 

you to set those expectations so that the labs that enroll know you know what the expectation is. 

Songbai Want: OK, thanks. That's very helpful. If I understood correctly, you mean that your final NPC 

that's recommended, that you post as final, that's after community trial, after drug review, after 

everything that's reviewed, right? But during the discussion with the sponsor for the prospective trial, 

you would recommend, and the validation, analytical validation, and the minimum performance 

characteristics. But that can change, sort of you are, your recommendation with that specific sponsor. 

And that may change and different, or that may be different than what you eventually, after you see all 

those clinical trial data and, finally, you post on your website for the NPC. 

Timothy Stenzel: Yeah, yeah. So, we'll need to move on to probably at least one more question. Yes, the 

final performance expectations will be set after the drug is reviewed. You could imagine that we might 

set minimums before the trial begins but, when we're actually looking at the assays in the study, that 

they're well above the minimums and so, the minimums may be different. It's too hard to predict at this 

point. Thank you.

Songbai Wang: OK, thanks. 

Timothy Stenzel: Time for one more question, maybe?

CDR Kim Piermatteo: Yes. The next person we're calling on is Kaben. Kaben, I have unmuted your line. 

Please unmute yourself and ask your question.

Kaben Schwartz: Yes. Good afternoon and thank you for the discussion. I just wanted to ensure I'm 

capturing a couple of key takeaways from this.

So, if a sponsor is conducting a clinical trial with an investigational drug that enrolls patients using a 

validated biomarker, and the sponsor wishes to rely on a commercially available CDx that is FDA-
17

authorized, then the sponsor may need to provide clinical data that was described in this webinar, along 

with a right of reference from the manufacturer. Is that correct? 

McKenna Tennant: So, if the trial is using, sorry, if the trial is using local tests from labs, and those local 

tests are kits from manufacturers, then the right of reference would need to extend to both the 

laboratory running the test as well as the kit manufacturer. Does that get at your question? 

Kaben Schwartz: Yes, yes, it does.

McKenna Tennant: Yes. Thank you. 

Timothy Stenzel: Do we have time for one more question? 

CDR Kim Piermatteo: Sure. We do, Tim. Alright, our next question is coming from Yaji Xu. I have 

unmuted your line. Please unmute yourself and ask a question. 

Yaji Xu: Yeah, hello. This is Yaji Xu from Johnson & Johnson. I have a question related to some previous 

questions. Just, for example, if the drug sponsor decides to use not-yet-approved commercialized assay 

for trial enrollment, does this case fall into the scope of the pilot program?

McKenna Tennant: Thank you for your question. So, regarding the scope of the pilot program, the CTA 

has to use a technology of the same type as a previously FDA-authorized companion diagnostic, 

regardless of indication. And then there also has to be the availability of a well-characterized or wellvalidated reference method, comparator method, or other materials to support test accuracy. So that's 

the kind of scope of CTAs. With respect to can you use a kit or not, those are the only CTA scope 

limitations. And we would just expect that you be able to provide the validation and performance 

characteristic information from that kit if used as a CTA for your assay. So, again, just to reiterate, we 

expect the validation performance characteristic information for all the CTAs used for enrollment, which 

can include kits.

Yaji Xu: Thank you. 

McKenna Tennant: Thank you. 

CDR Kim Piermatteo: Thank you for that question, and thank you, McKenna, for your response. At this 

time, that wraps up our question-and-answer segment for today. Thank you all for your questions and 

for your engagement today. At this point, I'd like to turn it back over to McKenna to provide her final 

thoughts. McKenna? 

McKenna Tennant: Thanks, Kim. So, yes, I want to thank you all again for joining, and we hope you 

found this pilot program overview and template demonstration helpful. If there are any questions that 

you didn't get to today, please feel free to submit them to the CDRH mailbox in the guidance, 

OncologyPilotCDRH@fda.hhs.gov.

Again, to summarize this pilot program is one step that might be helpful in reducing the risk of using 

unauthorized LDTs for oncology drug treatment decisions. And regarding the templates, our goal is 
18

really to make the collection and provision of test validation and performance characteristic information 

as easy as possible when requested by FDA. So, thank you again for joining. 

CDR Kim Piermatteo: Thanks McKenna for those final thoughts. To go over a few admin items, just for 

your information, printable slides of today's presentation are currently available on CDRH Learn at the 

link provided on this slide under the section titled In Vitro Diagnostics. A recording of today's webinar 

and a transcript will be posted to CDRH Learn under the same section in the next few weeks. And a 

screenshot of where you can find these webinar materials has been provided on the slide as well. 

If you have additional questions about today's webinar, feel free to reach out to DICE at 

DICE@fda.hhs.gov. And lastly, we hope that you are able to join us for a future webinar. You can find a 

listing of all of our upcoming webinars via the link provided on the bottom of this slide at 

www.fda.gov/CDRHWebinar. 

Thank you all again for joining us. This concludes today's CDRH webinar.

**********

END