In Vitro Companion Diagnostic 

Devices 

 
 
Guidance for Industry and Food and 

Drug Administration Staff 

 
 
 
Document issued on: August 6, 2014 
 
 
The draft of this document was issued on July 14, 2011.  
 
 
For questions regarding this document that relate to CDRH contact Elizabeth Mansfield, at 
301-796-4664, or elizabeth.mansfield@fda.hhs.gov; for questions for CBER contact Office 
of Communication, Outreach and Development (OCOD) at 240-402-7800 or 1-800-835-
4709, or ocod@fda.hhs.gov. For questions for CDER, contact Christopher Leptak at 301-
796-0017, or christopher.leptak@fda,hhs.gov. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health  
Center for Biologics Evaluation and Research 
Center for Drug Evaluation and Research  
  
    Contains Nonbinding Recommendations  
 
Preface 

 
 
Public Comment  

 
You may submit written comments and suggestions at any time for Agency consideration to 
the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, rm. 
1061, (HFA-305), Rockville, MD, 20852. Submit electronic comments to 
http://www.regulations.gov. Identify all comments with the docket number FDA-2011-D-0215. 
Comments may not be acted upon by the Agency until the document is next revised or updated.  
 
Additional Copies 
  
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document 
number (1737)  to identify the guidance you are requesting. 
 
Additional copies of this guidance document are also available from: 

 
Center for Biologics Evaluation and Research (CBER), 
 
Office of Communication, Outreach and Development (OCOD),  

10903 New Hampshire Ave., Bldg. 71, Room 3128, Silver Spring, MD 20993- 0002,  

or by calling 1-800-835-4709 or 240-402-7800, or  email ocod@fda.hhs.gov,  or from 
 
the Internet at 

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInform 
ation/Guidances/default.htm. 
 
or 
 
Center for Drug Evaluation and Research 
Division of Drug Information 
10903 New Hampshire Ave., Bldg. 51, rm. 2201 
Silver Spring, MD 20993-0002 
Tel: 301-796-3400; Fax: 301-847-8714; E-mail: druginfo@fda.hhs.gov 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/de 
fault.htm 
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  Contains Nonbinding Recommendations  
Table of Contents 
 
I.   INTRODUCTION ................................................................................................ 4 
 
II.   BACKGROUND ................................................................................................ 5 
 
III.   DEFINITION AND USE OF AN IVD COMPANION DIAGNOSTIC DEVICE .. 7 
 
IV.   REVIEW AND APPROVAL OF IVD COMPANION DIAGNOSTIC DEVICES 

AND THERAPEUTIC PRODUCTS ........................................................................... 8 
 
A.   Novel Therapeutic Products  .................................................................................................................... 8
  
B.   Approval of a Therapeutic Product without an Approved  or  Cleared IVD Companion Diagnostic 
Device 8  
C.   General Policies ........................................................................................................................................ 9 
 
V.   LABELING ..................................................................................................... 10 
 
A.   Therapeutic Product Labeling............................................................................................................... 10 
 
B.   IVD Companion Diagnostic Device Labeling ....................................................................................... 11 
 
VI.   INVESTIGATIONAL USE.............................................................................. 12 
 
 
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  Contains Nonbinding Recommendations  
Guidance for Industry and 
 
Food and Drug Administration Staff 
 
  
 
In Vitro Companion Diagnostic 

Devices 

  
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking 
on this topic. It does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public.  You can use an alternative approach if the approach 
satisfies the requirements of the applicable statutes and regulations.  If you want to discuss 
an alternative approach, contact the FDA staff responsible for implementing this 
guidance. If you cannot identify the appropriate FDA staff, call the appropriate number 
listed on the title page of this guidance.  
 
 
 
I.  Introduction  
 
This guidance is intended to assist (1) sponsors who are planning to develop a therapeutic 
product1 (either a novel product or an existing product with a new indication) for which the 
use of an in vitro companion diagnostic device (or test) is essential for the therapeutic 
products safe and effective use and (2) sponsors planning to develop an in vitro companion 
diagnostic device that is intended to be used with a corresponding therapeutic product. 
 
Specifically, the guidance intends to accomplish the following:  
 
 	  Define in vitro companion diagnostic device (hereafter referred to as an IVD 
companion diagnostic device) 
 	  Explain the need for FDA oversight of IVD companion diagnostic devices 
 	  Clarify that, in most circumstances, an IVD companion diagnostic device and its 
corresponding therapeutic product should be approved or cleared contemporaneously 
by FDA for the use indicated in the therapeutic product labeling 
                                                           
1 As  used in this guidance,  therapeutic product includes therapeutic, preventive, and  prophylactic drugs and 
biological  products.  Although this  guidance  does not expressly address therapeutic devices intended for use  
with in vitro diagnostics, the principles discussed in this  guidance may also be relevant to  premarket review of  
such devices.  
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  Contains Nonbinding Recommendations  
 	  Provide guidance for industry and FDA staff on possible premarket regulatory 

pathways and FDAs regulatory enforcement policy 

 	  Describe certain statutory and regulatory approval requirements relevant to 
therapeutic product labeling that stipulates concomitant use of an IVD companion 
diagnostic device when use of the IVD is essential to the safe and effective use of the 
therapeutic product 
FDA encourages sponsors considering developing either the therapeutic product or IVD 
companion diagnostic devices discussed in this guidance to request a meeting with both 
relevant device and therapeutic product review divisions to ensure that the product 
development plan(s) will produce sufficient data to establish the safety and effectiveness of  
both the IVD companion diagnostic device and the therapeutic product. 
 
This guidance document does not address the tests performed to establish the matching of a 
donor's blood, blood components, cells, tissue, or organs with that of a potential recipient, 
which are dealt with in the broader regulatory scheme of FDAs regulation of blood and 
human cells, tissues, and tissue-based products.   Although Human Leukocyte Antigen (HLA) 
assays are often used to establish the matching of a donor and a potential recipient, they may 
have other uses as well. When used for such other purposes, HLA assays that are essential 
for the safe and effective use of a therapeutic product would fall within the scope of this 
guidance. 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required.  
 
 
II.  Background 
 
Diagnostic tests have been used for many years to enhance the use of therapeutic products. 
Tests are also used during therapeutic product development to obtain the data FDA uses to 
make regulatory determinations.  After a therapeutic product is commercially available for 
use, health care professionals may use a relevant diagnostic test, for example, to select the 
appropriate therapy for a particular patient or to optimize a dosing regimen.   
 
Recently, the development of therapeutic products for which the use of a diagnostic test is 
essential for the products to meet their labeled safety and effectiveness claims has become  
more common. For example, such a test can identify appropriate subpopulations for 
treatment or identify populations who should not receive a particular treatment because of an 
increased risk of a serious side effect.   These new technologies are making it increasingly 
possible to individualize, or personalize, medical therapy by identifying patients who are 
most likely to respond, or who are at varying degrees of risk for a particular side effect.   
 
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  Contains Nonbinding Recommendations  
When an appropriate scientific rationale supports such an approach, FDA encourages the 
joint development of therapeutic products and diagnostic devices that are essential for the 
safe and effective use of those therapeutic products. Several examples of such approved 
therapeutic/diagnostic pairs exist.2  
 
When results from a diagnostic device are essential in patient treatment, health care 
professionals must be able to rely on those results. Inadequate performance of an IVD 
companion diagnostic device could have severe therapeutic consequences.  Such a device 
might fail analytically (e.g., by not accurately measuring the expression level of a protein of 
interest), or clinically (e.g., by not identifying those patients at increased risk for a serious 
adverse effect). Erroneous IVD companion diagnostic device results could lead to 
withholding appropriate therapy or to administering inappropriate therapy.  Therefore, FDA 
believes that use of an IVD companion diagnostic device with a therapeutic product raises 
important concerns about the safety and effectiveness of both the IVD companion diagnostic 
device and the therapeutic product. Because an IVD companion diagnostic device with 
inadequate performance characteristics3 or other issues related to safety and effectiveness 
could expose a patient to avoidable treatment risks, 4 FDA will assess, through premarket 
review and clearance or approval, the safety and effectiveness of the IVD companion 
diagnostic device as used with the therapeutic product. 
 
To facilitate the development and approval of therapeutic products that are intended for use 
with IVD companion diagnostic devices, as well as the development of the IVD companion 
diagnostic devices themselves, FDA is clarifying relevant policies related to these devices 
and products.  FDA is also developing appropriate internal policies and procedures to ensure 
effective communication among the relevant centers and to promote consistent advice, 
efficient development of IVD companion diagnostic devices and therapeutic products, and 
coordinated product reviews for these devices and therapeutic products.5   
 
                                                           
2 One example of a currently approved  IVD companion diagnostic device that illustrates the importance of  
established performance parameters for both the therapeutic product and the IVD companion diagnostic  device 
is FDA approved HER-2 tests to  determine whether a patient may be a candidate for Herceptin  (trastuzumab) 
therapy, which is indicated  for treatment of  metastatic breast cancer and gastric cancer.  Herceptin lacks 
effectiveness in the HER-2 marker negative  population,  and also  has the possibility of causing severe adverse 
effects. Therefore it is important to use an IVD companion diagnostic device to identify only those patients 
who could benefit from the therapy. 
3 See 21 CFR 809.10  (b)(12). 
4 Avoidable treatment risks may include  adverse reactions, or failure to realize benefit from a different drug.  
5  FDA expects that most therapeutic product and IVD companion  diagnostic device pairs will not meet the 
definition of combination product  under 21 CFR 3.2(e).  It is not  necessary to contact the Office of  
Combination Products about whether a therapeutic product and IVD companion diagnostic device pair is a 
combination product  unless recommended  by CDER, CBER, or CDRH.  FDA intends to  require separate  
marketing applications for a therapeutic product and an  IVD companion diagnostic device intended for use with 
that therapeutic product regardless of whether the products could constitute a combination product.  See 21 CFR 
3.4(c).  The standards for review, approval or clearance would be the same whether or not the therapeutic 
product and the IVD companion diagnostic  device pair were considered a combination product.  For 
information on investigational applications  for these products, see Section VI.   
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  Contains Nonbinding Recommendations  
 
III.  Definition and Use of an IVD Companion Diagnostic 
Device 
 
An IVD companion diagnostic device is an in vitro diagnostic device that provides 
information that is essential for the safe and effective use of a corresponding therapeutic 
product. The use of an IVD companion diagnostic device with a therapeutic product is 
stipulated in the instructions for use in the labeling of both the diagnostic device and the 
corresponding therapeutic product, including the labeling of any generic equivalents of the 
therapeutic product. 
 
An IVD companion diagnostic device could be essential6 for the safe and effective use of a 
corresponding therapeutic product to:  
 
 	  Identify patients who are most likely to benefit from the therapeutic product  
 	  Identify patients likely to be at increased risk for serious adverse reactions as a result 
of treatment with the therapeutic product  
	   Monitor response to treatment with the therapeutic product for the purpose of 
adjusting treatment (e.g., schedule, dose, discontinuation) to achieve improved safety 
or effectiveness  
	   Identify patients in the population for whom the therapeutic product has been 
adequately studied, and found safe and effective, i.e., there is insufficient information 
about the safety and effectiveness of the therapeutic product in any other population  
FDA does not include in this definition in vitro diagnostic tests that are not essential to the 
safe and effective use of a therapeutic product. 7    
  
Ideally, a therapeutic product and its corresponding IVD companion diagnostic device should 
be developed contemporaneously, with the clinical performance and clinical significance of 
the IVD companion diagnostic device established using data from the clinical development 
program of the corresponding therapeutic product.  However, FDA recognizes there may be 
cases when contemporaneous development may not be possible.  An IVD companion 
diagnostic device may be a novel IVD device (i.e., a new test for a new analyte), a new 
version of an existing device developed by a different manufacturer, or an existing device 
that has already been approved or cleared for another purpose. 
  
                                                           
6  When use of a diagnostic device is required  in the labeling  of a therapeutic product, e.g., for selection of 
appropriate patients for therapy, or to select patients who should not  use the product, or for monitoring  patients 
to achieve safety or effectiveness, use of the diagnostic device is considered "essential" for the purposes of this 
guidance.   Uses of  diagnostic devices that are suggested but not  required in therapeutic  product labeling are not  
considered essential.   
7 Examples of such clinical laboratory tests are commonly used and well  understood  biochemical assays (e.g.,  
serum creatinine or transaminases) that are used to monitor organ function,  but are not essential for the safe and 
effective use of a therapeutic product. 
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  Contains Nonbinding Recommendations  
The following section outlines FDAs policy regarding approval of a therapeutic product for 
use with a corresponding IVD companion diagnostic device. 
 
 
IV. 	 Review and Approval of IVD Companion Diagnostic 
Devices and Therapeutic Products 
 
Applications for an IVD companion diagnostic device and its corresponding therapeutic 
product will be reviewed and approved according to applicable regulatory requirements.  The 
IVD companion diagnostic device application will be reviewed and approved or cleared 
under the device authorities of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 
relevant medical device regulations; the therapeutic product application will be reviewed and 
approved under section 505 of the FD&C Act (i.e., drug products) or section 351 of the 
Public Health Service Act (i.e., biological products) and relevant drug and biological product 
regulations. FDA intends to review each IVD companion diagnostic device submission 
within the context of, or in conjunction with, its corresponding therapeutic product, and FDA 
review of the IVD companion diagnostic device and the therapeutic product will be carried 
out collaboratively among relevant FDA offices.   
 
A. 	 Novel Therapeutic Products 
 
For a novel therapeutic product for which an IVD companion diagnostic device is essential 
for the safe and effective use of the product, the IVD companion diagnostic device should be 
developed and approved or cleared contemporaneously so that it will be available for use 
when the therapeutic product is approved. Before approving the therapeutic product, FDA 
will determine that the IVD companion diagnostic device is properly validated and meets the 
applicable standard for safety and effectiveness or for substantial equivalence for the use 
indicated in the therapeutic products labeling.  The use of the IVD companion diagnostic 
device will be stipulated in the labeling of the therapeutic product (i.e., the therapeutic 
product is considered safe and effective only if used with the IVD companion diagnostic 
device). If FDA determines that an IVD companion diagnostic device is essential to the safe  
and effective use of a novel therapeutic product or indication, FDA generally will not 
approve the therapeutic product or new therapeutic product indication if the IVD companion 
diagnostic device is not approved or cleared for that indication. Approval or clearance of the 
IVD companion diagnostic device will ensure that the device has been adequately evaluated 
and has adequate performance characteristics in the intended population.   
 
B. 	 Approval of a Therapeutic Product without an Approved or Cleared IVD 
Companion Diagnostic Device 
 
FDA may decide that it is appropriate to approve a therapeutic product even though an IVD 
companion diagnostic device is not approved or cleared contemporaneously.  Two such 
scenarios are discussed in this section. In general, if a therapeutic product is approved 
without approval or clearance of an IVD companion diagnostic device, FDA expects that an 
IVD companion diagnostic device that is intended for use with the therapeutic product will 
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  Contains Nonbinding Recommendations  
be subsequently approved or cleared through an appropriate device submission, and the 
therapeutic product labeling will be revised to stipulate the use of the IVD companion 
diagnostic device.  In addition, FDA will consider whether additional protections are 
necessary to address the safety issues presented by the use of the therapeutic product without 
an approved or cleared IVD companion diagnostic device.8   
 
1.	 	 New 	Therapeutic	 Products	 to	 Treat	 Serious	 or	 LifeThreatening	 
Conditions 	
 
FDA may decide to approve a therapeutic product even if an IVD companion diagnostic 
device is not yet approved or cleared 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 approved or cleared IVD companion diagnostic device.  This will be 
determined by FDA during product review. 
 
2.	  Already	 Approved 	Therapeutic	 Products 	
 
FDA will generally not approve a supplement to an approved therapeutic product application 
to update that products labeling until the IVD companion diagnostic device is approved or 
cleared. Nevertheless, FDA recognizes that there may be occasions when the labeling for an 
already approved therapeutic product must be revised to address a serious safety issue.  
Under these circumstances, if the benefits from the use of the therapeutic product are so 
pronounced as to outweigh the risks from the lack of an approved or cleared IVD companion 
diagnostic device, FDA does not intend to delay approval of changes to the labeling of the 
therapeutic product until the IVD companion diagnostic device is approved or cleared.  
 
C.  General Policies  
 
If the use of an IVD companion diagnostic device is essential for the safe and effective use of 
a therapeutic product, an approved or cleared IVD companion diagnostic device should be 
available for use once the therapeutic product is approved.  FDA expects that the therapeutic 
product sponsor will address the need for an approved or cleared IVD companion diagnostic 
device in its therapeutic product development plan.  The sponsor of the therapeutic product 
can decide to develop its own IVD companion diagnostic device; the sponsor can partner 
with a diagnostic device sponsor to develop the appropriate IVD companion diagnostic 
device; or the sponsor can explore modification of an existing IVD diagnostic device (its own 
or another sponsors with that sponsors agreement) to accommodate the appropriate device 
intended use. The following general policies apply whether a therapeutic product and its 
IVD companion diagnostic device are developed and manufactured by the same, or different, 
entities:  
 
                                                           
8 Safety measures might include a risk evaluation and mitigation strategy (REMS), or a postmarket requirement, 
if necessary. 
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  Contains Nonbinding Recommendations  
 	  FDA will apply a risk-based approach to determine the regulatory pathway for IVD 
companion diagnostic devices, as it does with all medical devices.  This means that 
the regulatory pathway will depend on the level of risk to patients, based on the 
intended use9 of the IVD companion diagnostic device and the controls necessary to 
provide a reasonable assurance of safety and effectiveness.  Thus, the level of risk 
together with available controls to mitigate risk will establish whether an IVD 
companion diagnostic device requires a premarket approval application (PMA) or a 
premarket notification submission (510(k)).10  FDA recommends that sponsors 
consult early with FDA on the likely regulatory pathway for the IVD companion 
diagnostic device. Premarket review by FDA will determine whether the IVD 
companion diagnostic device has adequate performance characteristics for its 
intended use. 
	   After completing review of the applications for a therapeutic product and an IVD 
companion diagnostic device and after determining that both products are ready for 
approval or approval and clearance, FDA intends to issue approvals or approval and 
clearance for both products at the same time (unless the Agency determines that 
approval of the drug prior to approval or clearance of the device is appropriate, as 
described in Section IV. B, above). FDA strongly encourages sponsors to time their 
clinical developments and premarket submissions to facilitate concurrent review.  
	   If an IVD diagnostic device is already legally marketed and the IVD diagnostic 
device manufacturer intends to market its device for a new use as an IVD companion 
diagnostic device for a novel therapeutic product, FDA would likely consider the new 
use of the IVD diagnostic device with the novel therapeutic product as a new use for 
the device that would require an additional premarket submission (see 21 CFR 
807.81(a)(3)(ii), 814.39(a)). 
	   New IVD companion diagnostic devices intended to be used in the same manner as 
an existing approved or cleared IVD companion diagnostic device (e.g., different 
manufacturer, different technological characteristics) will be reviewed under a PMA 
or a traditional 510(k), as appropriate. 
 
V.  Labeling 
A.  Therapeutic Product Labeling 
 
The FD&C Act requires the labeling of prescription therapeutic and device products to 
include the information health care professionals need to use the products (21 U.S.C. 352(f), 
21 CFR 201.100(c)(1), 801.109(c) and (d)). The labeling often includes information about 
diagnostic tests that determine how, when, or whether a therapeutic product is used.  The 
regulations for drug and biological product labeling expressly recognize the importance of 
diagnostic tests for the safe and effective use of these therapeutic products.  According to the 
                                                           
9  As used here, indications is  considered  a part of  intended use. 

10 Experience indicates that most IVD companion  diagnostic devices will be Class III devices, although there 

may be cases when a Class II classification with premarket notification (510(k)) is appropriate. 

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  Contains Nonbinding Recommendations  
labeling regulations for drugs and biological products (21 CFR 201.56 and 57), product 
labeling must include information about (1) specific tests necessary for selection or 
monitoring of patients who need a drug; (2) dosage modifications in special patient 
populations (e.g., in groups defined by genetic characteristics); and (3) the identity of any 
laboratory test(s) helpful in following a patients response or in identifying possible adverse 
reactions.  The labeling regulations identify labeling sections where such discussion is 
appropriate (e.g., Indications and Usage, Dosage and Administration, Contraindications, 
Warnings and Precautions, Use in Specific Populations).  For example: 
 
 	  If a drug or biological product has been shown to be safe and effective in only a 
certain patient population identified by a diagnostic test, the Indications and Usage 
section must clearly define the patient population in whom the drug is approved (21 
CFR 201.57(c)(2)(i)(B) and (C)). 
 	  If a diagnostic test is essential for monitoring either therapeutic or toxic effects, the 
type of test must be identified under Warnings and Precautions (21 CFR 
201.57(c)(6)(iii)). 
 
Because it is important that the approved labeling for an IVD companion diagnostic device 
and its corresponding therapeutic product be complete and consistent, FDA makes the 
following clarifications: 
 
 	  Ordinarily, information about the use of an IVD companion diagnostic device will be 
included in the labeling of its corresponding therapeutic product when the device 
meets the definition of an IVD companion diagnostic device (see Section III).   
 	  The therapeutic product labeling should specify use of an FDA approved or cleared 
IVD companion diagnostic device, rather than a particular manufacturers IVD 
companion diagnostic device.  This will facilitate the development and use of more 
than one approved or cleared IVD companion diagnostic device of the type described 
in the labeling for the therapeutic product. 
	   In cases when an IVD companion diagnostic device is approved or cleared and is 
marketed after the therapeutic product is approved, the therapeutic product labeling 
should be updated to refer to the use of this type of IVD companion diagnostic device 
(21 CFR 201.56(a)(2)).  
 
B.  IVD Companion Diagnostic Device Labeling 
 
The labeling for an in vitro diagnostic device is required to specify the intended use of the 
diagnostic device (21 CFR 809.10(a)(2)).  Therefore, an IVD companion diagnostic device 
that is intended for use with a therapeutic product must specify the therapeutic product(s) for 
which it has been approved or cleared for use.  In some cases, if evidence is sufficient to 
conclude that the IVD companion diagnostic device is appropriate for use with a class of 
therapeutic products, the intended use/indications for use should name the therapeutic class, 
rather than each specific product within the class. 
 
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  Contains Nonbinding Recommendations  
When an IVD companion diagnostic device has been approved or cleared for use with a 
therapeutic product in one disease or setting, a PMA supplement or new 510(k), as 
appropriate, will be needed to expand the IVD companion diagnostic device labeling to 
include additional IVD companion diagnostic device indications, e.g., use of the same  
therapeutic that is now approved for use in a different disease or setting.  
 
When an IVD companion diagnostic device has been approved or cleared for use with one 
therapeutic product and evidence becomes available that use of the same device is essential 
for the safe and effective use of a different therapeutic product, the IVD companion 
diagnostic device labeling should be expanded through approval or clearance of a new 
premarket submission (PMA or 510(k) as appropriate) or PMA supplement (see Section IV, 
above) to include the new therapeutic product.  Labeling of the therapeutic product should 
also be amended through submission of a supplement. 
 
 
VI.  Investigational Use 
 
IVD companion diagnostic devices used to make treatment decisions in clinical trials of a 
therapeutic product generally will be considered investigational devices, unless employed for 
an intended use for which the device is already approved or cleared.  If used to make critical 
treatment decisions, such as patient selection, treatment assignment, or treatment arm, a 
diagnostic device generally will be considered a significant risk device under 21 CFR 
812.3(m)(3) because it presents a potential for serious risk to the health, safety, or welfare of 
the subject, and the sponsor of the diagnostic device will be required to comply with the 
investigational device exemption (IDE) regulations that address significant risk devices.  
 
If a diagnostic device and a therapeutic product are to be studied together to support their 
respective approvals (or clearance as appropriate for the diagnostic device), both products 
can be studied in the same investigational study, if the study is conducted in a manner that 
meets both the requirements of the IDE regulations (21 CFR Part 812) and the investigational 
new drug (IND) regulations (21 CFR Part 312).  Depending on details of the study plan and 
participants, a sponsor may seek to submit an IND alone, or both an IND and an IDE.  
Sponsors should consult with the therapeutic product center and the relevant device center as 
to which approach is best or necessary for a particular study.  
 
Information about the planned use of an IVD companion diagnostic device and its use in 
clinical trials should be included in an investigational submission.  This information will help 
FDA understand and provide advice on how the IVD device will be used to enroll subjects 
into the trial(s) and how the test will be validated for use.  For therapeutic product INDs that 
contain information about the investigational device, the therapeutic product review center 
(Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research) 
will engage appropriate expertise from the diagnostic product review center (Center for 
Devices and Radiological Health or Center for Biologics Evaluation and Research), and joint 
advice will be provided to the sponsor. 
 
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  Contains Nonbinding Recommendations  
In addition, it will be helpful if both the IVD companion diagnostic device sponsor and the 
therapeutic product sponsor participate in discussions about the proposed IVD companion 
diagnostic device and solicit FDA feedback via the pre-submission process (a consultative 
submission through which device sponsors may obtain information that may help guide 
product development, e.g., information concerning appropriate validation studies) with the 
diagnostic review center. This will enable a more focused and in-depth discussion about the 
validation of the IVD companion diagnostic device and will aid in planning for a device 
PMA or 510(k) that is complete and timely.  When appropriate, expertise from the relevant 
therapeutic product review center will be included in the diagnostic review center meetings. 
 
FDA strongly encourages sponsors considering developing the products discussed in this 
guidance to request a meeting with both relevant device and therapeutic product review 
divisions as early in development as possible. 
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