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Today’s Topic:

Oncology Drug Products Used with Certain In Vitro Diagnostic Tests: 

Pilot Program

Date

December 12, 2023
Oncology Drug Products Used with Certain 

In Vitro Diagnostic Tests: Pilot Program

and

Templates for Collecting and Providing Performance Characteristics 

and Validation Information for Clinical Trial Assays (CTAs)

Timothy Stenzel, MD, PhD

Office Director

Office of Health Technology 7

(In Vitro Diagnostics)

McKenna Tennant, MPH

Policy Analyst

Office of Health Technology 7

(In Vitro Diagnostics)

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

U.S. Food and Drug Administration
Opening Remarks

3

Oncology Drug Products Used with Certain 

In Vitro Diagnostic Tests: Pilot Program

Templates for Collecting and Providing Performance Characteristics 

and Validation Information for Clinical Trial Assays (CTAs)
Final Guidance

• Oncology Drug Products Used with Certain In 

Vitro Diagnostic Tests: Pilot Program

– www.fda.gov/regulatory-information/search-fdaguidance-documents/oncology-drug-productsused-certain-in-vitro-diagnostic-tests-pilotprogram

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Learning Objectives

• Identify the scope and goals of the new voluntary pilot 

program for certain oncology drugs used with certain in 

vitro diagnostic tests

• Describe how to complete FDA templates to provide 

analytical validation and performance characteristic 

information for CTAs used in the pivotal trial(s) for drug 

products under the pilot, when requested by FDA

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Oncology Drug Products Used with 

Certain In Vitro Diagnostic Tests: 

Pilot Program Overview

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Background: Companion Diagnostics (CDx) 

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An in vitro diagnostic (IVD) that provides information that is essential for 

the safe and effective use of a corresponding therapeutic product

Identify patients who are 

most likely to benefit 

from the therapeutic 

product 

Identify patients in the 

population for whom the 

therapeutic product has 

been adequately studied, 

and found safe and 

effective

Monitor response to 

treatment with the 

therapeutic product for 

the purpose of adjusting 

treatment to achieve 

improved safety or 

effectiveness 

Identify patients likely to be 

at increased risk for serious 

adverse reactions as a 

result of treatment with the 

therapeutic product 

Companion 

Diagnostic
Background: CDx (cont.)

The FDA issued final guidance “In Vitro Companion Diagnostic Devices”, August 2014 

(www.fda.gov/regulatory-information/search-fda-guidance-documents/in-vitro-companion-diagnostic-devices )

Ideally, a therapeutic product and its corresponding CDx should be 

developed and authorized contemporaneously,

– With the clinical performance and clinical significance of the companion 

diagnostic established using data from the clinical development program 

of the corresponding therapeutic product

The use of a CDx with a therapeutic product is stipulated in the 

instructions for use in the labeling of both the diagnostic device and the 

corresponding therapeutic product

8
Current Environment

As described in FDA’s CDx guidance, there are specific circumstances where FDA 

may decide to approve a drug without clearing, approving, or authorizing a 

corresponding CDx at the same time.

www.fda.gov/regulatory-information/search-fda-guidance-documents/in-vitro-companion-diagnostic-devices

9
Current Environment (cont.)

• In these cases, tests offered as laboratory-developed tests (LDTs) with 

unknown performance are being used for patient treatment decisions.

• An LDT means an in vitro diagnostic device that is intended for clinical use and designed, 

manufactured and used within a single laboratory certified under the Clinical Laboratory 

Improvement Amendments (CLIA) (42 U.S.C. 263a) that meets the requirements to perform 

tests of high complexity, as described in 42 CFR 493.17(c)(4) and 493.25, and is a location 

that has its own CLIA certificate as described in 42 CFR 493.43(a).

• 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.

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Current Environment (cont.)

• FDA is concerned that LDTs used to identify patient biomarkers may 

not be accurate or reliable

• FDA is particularly concerned that LDTs used to identify patients for 

drug treatment when there is not an FDA authorized companion 

diagnostic may not perform well

• Pilot Program: Recommend minimum performance characteristics for 

tests used to identify patients for certain oncology drugs to address 

safety risks posed by LDTs

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Oncology Drug Products Used with Certain 

In Vitro Diagnostic Tests: Pilot Program

FDA is piloting a new approach to provide 

greater transparency regarding minimum 

performance characteristics that certain tests 

for certain oncology drugs should meet

• One step that may be helpful in reducing the 

risk of using LDTs for oncology drug treatment 

decisions.

• This pilot does not alter the standards for 

approval of the oncology drug products or for 

marketing authorization of the corresponding 

companion in vitro diagnostics.

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Pilot Program Limitations

The scope of this voluntary pilot program is limited to 9 drug sponsors and:

CDER-regulated oncology drug 

products for which FDA determines 

that:

use of an in vitro 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 FDAauthorized companion diagnostic

CDRH-regulated corresponding 

clinical trial assay(s):

for which there is a well-validated 

reference method, well-validated 

comparator method, and/or wellcharacterized materials that can be 

used to support test accuracy

that use the same technology as a 

previously FDA-authorized CDx

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FDA intends to rely on the same pivotal clinical 

trial(s) that support approval of the drug product 

to establish the clinical validity for the clinical trial 

assays (CTAs) used in those trial(s).

Given the type of tests eligible for use in the pilot 

program, 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.

Pilot Program

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Pilot Program

FDA will request performance information for the tests used 

to enroll patients into the clinical trials that support drug 

approval

FDA will post to its website the minimum performance 

characteristics recommended for similar tests that may be 

used to select patients for treatment with the approved drug

Laboratories may use this information to guide their 

development of LDTs to identify specific biomarkers used for 

selecting cancer treatment

This transparency aims to help facilitate better and more 

consistent performance of these tests, resulting in better 

drug selection and improved care for patients with cancer 15
Pilot Program: Templates

CDRH’s website includes a series of templates that oncology drug product 

sponsors may use to facilitate the provision of performance characteristic 

and validation information for CTAs used in the drug product pivotal clinical 

trial(s), when requested by FDA

Templates for Collecting and Providing Performance Characteristics 

and Validation Information for Clinical Trial Assays:

– Next generation sequencing test template

– Polymerase chain reaction test template

– Sanger sequencing test template

– Immunohistochemistry test template

– Fluorescence in situ hybridization test template

www.fda.gov/medical-devices/in-vitro-diagnostics/oncology-drug-products-used-certain-in-vitro-diagnostics-pilot-program 16
Pilot Program: Procedures

• FDA will provide minimum validation and performance 

characteristics for CTAs to enroll the drug product’s 

pivotal clinical trial(s), prior to the start of the trial

• FDA expects the CTAs for trial enrollment will meet or 

exceed these validation and performance 

characteristics

• If the drug is approved, FDA will recommend minimum 

performance characteristics for IVDs to be used with 

that drug based upon performance of the CTAs used in 

the clinical trials

Oncology drug 

pivotal trial(s) 

have not 

started as of 

June 20, 2023

17
Pilot Program: Procedures (cont.)

FDA will work with drug sponsors accepted into pilot to 

review the performance characteristic and validation 

information for each CTA and recommend the 

minimum performance characteristics within the New 

Drug Application (NDA)/Biologics License Applications

(BLA) application review timeframe

Oncology drug 

pivotal trial(s) 

were initiated 

prior to 

June 20, 2023

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Key Takeaways

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

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Oncology Drug Products Used with Certain 

In Vitro Diagnostic Tests: Pilot Program

Templates for Collecting and Providing 

Performance Characteristics and Validation 

Information for CTAs under the Pilot 

Program

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CTA Templates: Scope and Purpose

The templates on CDRH’s website are intended for use by oncology drug product 

sponsors who have submitted the statement of interest (SOI) for the pilot program

- Oncology drug sponsors interested in participating in the pilot should submit an SOI to their 

IND, NDA, or BLA 

The templates should be used to provide the information recommended in the 

templates only when requested by FDA

The templates are to help oncology drug sponsors collect and provide validation 

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

trial(s) for the drug product

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CTA Templates: General Sections

I. General 

Laboratory 

Information

II. General Test 

Information

III. Validation 

Studies IV. Data Tables

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Template Demo: 

Next Generation 

Sequencing 

(NGS) Test 

Template

www.fda.gov/media/169619/download?attachment 23
General 

Laboratory 

and Test 

Information

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Determination of Calling Rules 

and Clinical Cut-off

• Prespecified variant 

classification rule(s) to identify 

presence or absence of 

analytes

• Acceptable sequencing quality 

metrics at the sample, variant, 

and flow cell level (Table 1)

• Summary of the prespecified 

clinical cut-off used to enroll 

subjects 

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Validation Studies 

• Samples used (Table 2)

• Comparator/orthogonal method(s) (Table 3)

• Analytical accuracy – concordance (Table 4)

• Limit of Detection (LoD) (Table 5)

• Precision (Table 6)

• Interfering substances (Table 7)

• Inclusivity/Cross-reactivity

• Stability

• NGS liquid biopsy (LBx) specific information

26
Validation Studies 

• Samples used (Table 2)

• Comparator/orthogonal method(s) (Table 3)

• Analytical accuracy – concordance (Table 4)

• Limit of Detection (LoD) (Table 5)

• Precision (Table 6)

• Interfering substances (Table 7)

• Inclusivity/Cross-reactivity

• Stability

• NGS liquid biopsy (LBx) specific information

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Comparator/Orthogonal Method(s)

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Analytical Accuracy - Concordance

Analytical accuracy of the CTA is determined relative to a reference method or 

validated comparator method (orthogonal method). 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/or previous analytical testing). Well characterized samples 

should be tested with both the CTA and comparator method.

Information Requested:

• Summary of study design to determine analytical concordance

• Details on samples tested to demonstrate accuracy

• If the analytes are not individually validated, details on the samples tested to 

demonstrate panel-wide accuracy for representative panel variants

• Summary of analytical concordance between NGS CTA and comparator for 

variant(s) and gene(s) evaluated for patient enrollment (Table 4)

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Validation Studies 

• Samples used (Table 2)

• Comparator/orthogonal method(s) (Table 3)

• Analytical accuracy – concordance (Table 4)

• Limit of Detection (LoD) (Table 5)

• Precision (Table 6)

• Interfering substances (Table 7)

• Inclusivity/Cross-reactivity

• Stability

• NGS liquid biopsy (LBx) specific information

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Precision

Information Recommended:

• Brief study design

• Number of runs, days, instruments, reagent lots, operators, replicates tested per sample

• Whether precision evaluated at multiple sites

• If details not provided for each analyte, details on samples tested to demonstrate panelwide precision

• If study not conducted with end-to-end workflow, information on part of workflow included 

and rationale

• Summary of statistical/data analysis methods to determine CTA precision

• Summary of PPA and NPA for variant(s) in gene(s) used for patient enrollment and panelwide precision, if applicable (Table 6)

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

procedure to determine the repeatability and reproducibility of the test.
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Validation Studies 

• Samples used (Table 2)

• Comparator/orthogonal method(s) (Table 3)

• Analytical accuracy – concordance (Table 4)

• Limit of Detection (LoD) (Table 5)

• Precision (Table 6)

• Interfering substances (Table 7)

• Inclusivity/Cross-reactivity

• Stability

• NGS liquid biopsy (LBx) specific information

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Limit of Detection (LoD)

The lowest amount of genomic target that the test 

can consistently detect with a stated probability.

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Interfering Substances

Studies that evaluate the effects of potentially interfering 

endogenous and exogenous substances on test 

performance.

36
Inclusivity/Cross-Reactivity

Studies that evaluate the specificity of the primers 

or probes used to target specific genes and/or 

genomic regions.

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Validation Studies 

• Samples used (Table 2)

• Comparator/orthogonal method(s) (Table 3)

• Analytical accuracy – concordance (Table 4)

• Limit of Detection (LoD) (Table 5)

• Precision (Table 6)

• Interfering substances (Table 7)

• Inclusivity/Cross-reactivity

• Stability

• NGS liquid biopsy (LBx) specific information

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NGS LBx-Specific Information

• Quality measures for circulating tumor DNA (ctDNA) samples, 

such as fragment analysis

• Whether germline and/or clonal hematopoiesis of 

indeterminate potential (CHIP) variants were excluded

• Limit of Blank (LoB) study description, if performed

• Description of assessment of interferents (such as short draws 

and unique components derived from the blood collection 

process can contribute to interference)

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Questions and Comments

• Please submit questions regarding the templates and 

CTA validation to OncologyPilotCDRH@fda.hhs.gov

• Please submit comments on the oncology diagnostics 

pilot guidance and templates to the docket 

(www.regulations.gov/docket/FDA-2022-D-2275)

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Summary

• Pilot CTA templates are intended to facilitate the 

provision, when requested by FDA, of analytical 

validation and performance characteristic information 

for CTAs used in pivotal trial(s) for drug products 

under the pilot.

• The pilot program is one step that may be helpful in 

reducing the risk of using unauthorized LDTs for 

oncology drug treatment decisions.

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