Contains Nonbinding Recommendations 
 
 
Oncology Drug Products Used with 
Certain In Vitro Diagnostic Tests: 
Pilot Program 
Guidance for Industry, Clinical 
Laboratories, and Food and Drug 
Administration Staff 
 
 
Document issued on June 20, 2023. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For questions about this document regarding CDRH-regulated devices, contact the Office of In 
Vitro Diagnostics at OncologyPilotCDRH@fda.hhs.gov.  For questions about this document 
regarding CDER-regulated oncology drug products, contact Reena Philip (OCE) at 301-796-
6179, or by email at Reena.Philip@fda.hhs.gov.  
  
 
            U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health (CDRH) 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
 
     
  Contains Nonbinding Recommendations 
Preface  
 
Public Comment 
 
This guidance is being issued to announce a voluntary pilot for oncology drug products, which 
treat serious and life-threatening disease, and certain corresponding in vitro diagnostic tests. This 
guidance is being implemented without prior public comment because the Food and Drug 
Administration (FDA or Agency) has determined that prior public participation for this guidance 
is not feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic 
Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented 
immediately, but it remains subject to comment in accordance with the Agencys good guidance 
practices. Comments may be submitted at any time for Agency consideration. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to 
https://www.regulations.gov. All comments should be identified with the docket number FDA-
2022-D-2275 and complete title of the guidance in the request. 
 
Additional Copies 
 
CDRH 
Additional copies are available from the Internet.  You may also send an email request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance.  Please include the document 
number 22001 and complete title of the guidance in the request. 
 
CDER 
Additional copies are available from the Center for Drug Evaluation and Research (CDER), 
Office of Communication, 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor, Silver 
Spring, MD 20993-0002, or by calling 1-855-543-3784 or 301-796-3400, by email, 
druginfo@fda.hhs.gov or from the Internet at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
 
 
 
 
 
   
     
  Contains Nonbinding Recommendations 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SCOPE ............................................................................................................................... 3 
IV.  PILOT PROGRAM .......................................................................................................... 4 
V.  PARTICIPATION AND PROCEDURES ...................................................................... 4 
A.  Participation ................................................................................................................................... 4 
B.  Procedures ...................................................................................................................................... 5 
VI.  AVAILABILITY OF TEMPLATES AND PERFORMANCE 
CHARACTERISTICS .................................................................................................................. 7 
     
  Contains Nonbinding Recommendations 
Oncology Drug Products Used with 
Certain In Vitro Diagnostic Tests: 
Pilot Program 
 
Guidance for Industry, Clinical 
Laboratories, and Food and Drug 
Administration Staff 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on 
FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
or Office responsible for this guidance as listed on the title page. 
 
 
 
I.  INTRODUCTION  
 
FDA is issuing this guidance to announce and describe FDAs voluntary pilot program for 
certain Center for Drug Evaluation and Research (CDER)-regulated oncology drug products1 
used with certain in vitro diagnostic tests, as described in the scope below. 
 
Given the public health importance of such in vitro diagnostic tests for determining a patients 
cancer treatment, this guidance is being implemented without prior public comment because 
FDA has determined that prior public participation for this guidance is not feasible or appropriate 
(see section 701(h)(1)(C) of the FD&C Act). This guidance document is being implemented 
immediately, but it remains subject to comment in accordance with the Agencys good guidance 
practices. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
 
1 For the purposes of this guidance, references to oncology drug products include both human drug products and 
biological products regulated by CDER, unless otherwise specified. This pilot is currently only available for 
oncology drug products within CDER. 
  1  Contains Nonbinding Recommendations 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
An in vitro companion diagnostic test (also known as an in vitro companion diagnostic device 
and hereafter referred to as an in vitro companion diagnostic) provides information that is 
essential for the safe and effective use of a corresponding therapeutic product.2 As described in 
the FDA guidance titled In Vitro Companion Diagnostic Devices3 in most circumstances, an in 
vitro companion diagnostic should be granted marketing authorization4 contemporaneously with 
the approval of the corresponding therapeutic product for the use indicated in the therapeutic 
product labeling. As also described in that guidance, FDA may decide to approve a therapeutic 
product even if, at the time of the therapeutic products approval, an in vitro companion 
diagnostic has not yet received marketing authorization, when the therapeutic product is intended 
to treat a serious or life-threatening condition for which no satisfactory alternative treatment 
exists and the benefits from the use of the therapeutic product are so pronounced as to outweigh 
the risks from the lack of an in vitro companion diagnostic with marketing authorization.5 
Consistent with this policy, FDA has approved some oncology drug products that require use of 
in vitro companion diagnostics without contemporaneous marketing authorization of a 
corresponding in vitro companion diagnostic. In these cases, tests offered as laboratory 
developed tests (LDTs)6 are being used for patient treatment decisions. FDA has generally 
exercised enforcement discretion for LDTs, meaning that, at this time, FDA generally does not 
exercise its authority to enforce the regulatory requirements for these devices, although it 
maintains that authority. 
 
FDA intends to pilot a new approach to provide greater transparency regarding performance 
characteristics that certain tests for oncology biomarkers should meet. Through this transparency 
FDA seeks to support better and more consistent performance of certain LDTs used to identify 
 
2 For the purposes of this guidance and as used in FDAs In Vitro Companion Diagnostic Devices: Guidance for 
Industry and Food and Drug Administration Staff (August 2014), references to therapeutic product includes 
therapeutic, preventive, and prophylactic drugs and biological products. This includes oncology drug products. We 
update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
3 See the guidance for industry and Food and Drug Administration Staff In Vitro Companion Diagnostic Devices 
(August 2014), page 8. 
 
4 For purposes of this guidance, the term marketing authorization means FDAs approval of a premarket approval 
application, granting of a de novo request, or clearance of a premarket notification (510(k)). 
 
5 See the guidance for industry and Food and Drug Administration Staff In Vitro Companion Diagnostic Devices 
(August 2014), page 9. 
 
6 For the purposes of this guidance, the term laboratory developed test (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). 
  2  Contains Nonbinding Recommendations 
patients for treatment with certain oncology drug products, resulting in better drug selection and 
improved care for patients with cancer. 
 
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. 
 
 
III.  SCOPE 
 
This guidance document and the pilot program described herein are intended for drug product 
sponsors with regard to: 
 
(1) CDER-regulated oncology drug products for which FDA determines that 
 
(a)  use of an in vitro diagnostic test is needed to identify the intended patient 
population, 
 
(b)  no satisfactory alternative treatment exists, and 
 
(c)  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; and 
 
(2) corresponding clinical trial assay(s) 
 
(a)  that use the same technology as a previously FDA-authorized companion 
diagnostic for any indication (e.g., next generation sequencing, 
immunohistochemistry, and fluorescent in situ hybridization)7; and 
 
(b)  for which there is a well-validated reference method, well-validated comparator 
method, and/or well-characterized materials (e.g., appropriate clinical samples, 
cell lines) that can be used to support test accuracy.  
 
This pilot is intended for the tests described above because FDA believes that, in general, they 
are the tests for which it is appropriate to extrapolate clinical validity of the test(s) used in a drug 
trial to other tests of the same type with similar analytical performance.  
 
Many tests used in selection of oncology drugs in clinical practice employ established 
technologies and have appropriate methods and materials to support leveraging clinical validity 
established for another test of the same type. Further, there is an urgent public health need to 
recommend minimum performance characteristics for tests used to identify patients for oncology 
treatment to address safety risks posed by the use of LDTs that are not properly validated and/or 
are unable to identify the appropriate population for the corresponding drug products. 
 
 
7 https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-
in-vitro-and-imaging-tools  
  3  Contains Nonbinding Recommendations 
IV.  PILOT PROGRAM   
 
This pilot is intended to improve oncology patient care by providing transparency regarding 
minimum performance necessary for in vitro diagnostic tests used with oncology drug products 
enrolled into the pilot program. Under this pilot, if FDA concludes that the drug product meets 
the applicable standards for its approval,8 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). Further, FDA intends to recommend minimum analytical 
performance characteristics for other tests that, when established through properly conducted 
validation studies, FDA believes would support extrapolation of the clinical validity of the 
CTA(s) to additional tests of the same type. If FDA approves an oncology drug product enrolled 
in this pilot program, FDA expects that at the time of drug product approval, it will recommend 
minimum performance characteristics for in vitro diagnostic tests to be used to identify patients 
for treatment with that drug product.  
 
The minimum performance characteristics are intended to serve as a benchmark for test 
developers seeking to design tests that are accurate and reliable for such use. Test developers 
would be able to leverage the clinical validity of the CTAs established through the drug trial to 
help streamline validation of additional tests for the same use. Ultimately, this may bring new 
treatment options to appropriate patients sooner.  
 
Under this pilot program, 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 FDAs recommended performance characteristics. FDAs Center for Devices and 
Radiological Health (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 CDRHs 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(s). The specified test characteristics will be determined based on the 
characteristics of the CTAs used for enrollment of the pivotal clinical trial(s) which helped to 
define the indicated biomarker-selected patient population for which that use of the drug is 
approved, including the validation and performance characteristic information reviewed for those 
tests. For example, if all CTAs detect [DNA biomarker] in formalin-fixed paraffin-embedded 
(FFPE) tissue by polymerase chain reaction (PCR), the drug labeling and CDRH website would 
specify tests for the detection of [DNA biomarker] in FFPE tissue by PCR. 
 
 
V.  PARTICIPATION AND PROCEDURES 
 
A.  Participation  
 
Drug product sponsors may be accepted into the pilot program, starting June 20, 2023, based on 
evaluation of the following factors: 
 
 
8 See FD&C Act Section 505 and PHS Act Section 351. 
  4  Contains Nonbinding Recommendations 
1.  CTAs for the enrollment of the pivotal clinical trial(s) are of a test type described 
in the scope above.  
 
2.  The oncology drug sponsor agrees to discuss with FDA analytical validation data 
and performance characteristics for clinical trial assays prior to enrollment of the 
pivotal clinical trial(s). 
 
3.  Pivotal clinical study protocol(s) use tests that have specified performance 
characteristics recommended by FDA for acceptance into the pilot.  
 
4.  The oncology drug sponsor is able to collect the analytical validation data and 
performance characteristics as recommended in FDA templates (see section VI) 
for all CTAs used for the enrollment of the pivotal clinical trial(s). 
 
5.  The owner(s) of the data supporting the safety and effectiveness of the oncology 
drug product and CTAs agree to FDAs use of such data to recommend minimum 
analytical performance characteristics for tests used to identify patients for 
treatment with the oncology drug product. Such minimum recommended 
performance characteristics will be publicly available on FDAs website and 
could be used by test developers, including in premarket submissions, for tests 
with the same use.  
 
Pivotal clinical trials can take months to years. To begin the pilot program as soon as possible, 
FDA may opt not to consider factor (2) for oncology drug products where the pivotal clinical 
trial(s) started prior to June 20, 2023. Further, FDA recognizes that there may be circumstances 
in which obtaining the analytical validation data may not be possible. Drug product sponsors that 
are able to collect and provide validation data and performance characteristics for virtually all 
CTAs, provide a scientifically and statistically sound justification for any missing validation 
data, and demonstrate that the missing information does not impact the ability to determine 
minimum performance characteristics for the tests used to demonstrate that the drug product is 
safe and effective, might also be accepted into this pilot. If adequate validation data are not 
available for a sufficient number of CTAs used in the trial, the drug product likely will not be 
accepted into this pilot.  
 
B.  Procedures 
 
In the initial phase of the pilot, FDA will evaluate no more than 9 sponsors for possible 
acceptance into the pilot. FDA anticipates the initial phase to last up to one year. Evaluation of 
the pilot program will occur at set timepoints with review of comments submitted to the docket, 
evaluation of the experience of the pilot participants, and a public meeting within three years.  
 
To be considered for the voluntary pilot program, drug product sponsors should submit 
correspondence titled a Statement of Interest in Participation in the Oncology Drug Products 
Used with Certain In Vitro Diagnostic Tests: Pilot Program with their Investigational New Drug 
(IND) applications, New Drug Applications (NDA), or Biologic License Applications (BLA), as 
  5  Contains Nonbinding Recommendations 
appropriate. Submission of this statement affirms the sponsors commitment to provide the 
following information, if subsequently requested by FDA: 
 
1.  Status of the enrollment of the pivotal trial(s). For example, complete, initiated 
but not complete, not initiated. For those that are complete or initiated but not 
complete, the date the trial(s) start and number of enrolled patients should also be 
provided.  
 
2.  IND, NDA, or BLA number if already submitted to FDA or a timeline for 
submission of an IND, NDA, or BLA if not already submitted.  
 
3.  List of clinical trial assays that were used or are planned for use for enrollment of 
the pivotal trial(s). The number of subjects enrolled into the trial by each CTA, 
the total number of subjects enrolled into the trial, and the total number of 
subjects that were evaluated by each CTA but not enrolled into the trial should 
also be provided for completed trials.  
 
4.  Analytical validation and performance characteristic information recommended in 
the templates available on FDAs website for each CTA (see section VI). 
 
5.  Right of reference from the owner(s) of the data supporting the safety and 
effectiveness of the oncology drug product and the CTAs, agreeing that (a) FDA 
may use the provided analytical validation data and performance characteristics to 
recommend minimum performance characteristics that FDA will make publicly 
available on CDRHs website, (b) clinical laboratories may use in developing 
LDTs, and (c) FDA may reference to approve, authorize or clear premarket 
submissions for in vitro companion diagnostic tests. 
 
Upon receipt of the statement of interest, FDA will follow up with no more than 9 sponsors to 
request specific information to enable FDA to make a decision concerning acceptance into the 
pilot, based on evaluation of the factors outlined in section V.A. and provide written feedback 
that either accepts or rejects the drug product for the pilot program.  
 
For oncology drug products where the pivotal clinical trial(s) have not started as of 
June 20, 2023, FDA will work with each sponsor to provide feedback in the form of 
recommended minimum validation and performance characteristics for CTAs to be used to enroll 
the drug products pivotal clinical trial(s), prior to the start of the trial. FDA expects that the 
CTAs to be used for enrollment in the trial will meet or exceed these validation and performance 
characteristics. In the event that the drug is ultimately approved, FDA will recommend minimum 
performance characteristics for in vitro diagnostic tests to be used with the approved oncology 
drug product based upon submission of data and information regarding performance of the CTAs 
actually used in the clinical trials that supported the drugs approval, as these CTAs may have 
exceeded the minimum recommendations for performance provided prior to trial enrollment. 
 
For oncology drug products where the pivotal clinical trial(s) were initiated prior to 
June 20, 2023, FDA will work with drug product sponsors accepted into the pilot program to 
  6  Contains Nonbinding Recommendations 
review the performance characteristic and validation information for each CTA and, provided the 
data are sufficient, recommend the minimum performance characteristics within the timeframe 
for review of the NDA/BLA application. 
 
Based on the experience during the initial phase, FDA intends to update this guidance to include 
more specific procedures with specific information to provide the Agency and anticipates 
expanding the pilot to evaluate additional sponsors for acceptance into the pilot. 
 
 
VI.  AVAILABILITY OF TEMPLATES AND PERFORMANCE 
CHARACTERISTICS  
 
FDA has made available through download from CDRHs website a series of templates that 
oncology drug product sponsors who have submitted the statement of interest described above 
may use to facilitate the provision, when requested by FDA, of performance characteristic and 
validation information for CTAs used in the pivotal clinical trial(s) for the drug product. FDA 
will also make available on CDRHs website the minimum recommended performance 
characteristics for in vitro diagnostic tests to be used with each approved drug product under the 
pilot. 
  7