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



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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 

2  


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

 

3  



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 

product

1

 (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 

product’s 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. 

4  


Contains Nonbinding Recommendations 

   Provide guidance for industry and FDA staff on possible premarket regulatory 

pathways and FDA’s 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 FDA’s 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. 

5  


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.

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 characteristics”

3

 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.

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.

See 21 CFR 809.10 (b)(12). 



Avoidable treatment risks may include adverse reactions, or failure to realize benefit from a different drug. 

 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.  

6  


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 essential

6

 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. 

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. 

7  


Contains Nonbinding Recommendations 

The following section outlines FDA’s 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 product’s 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 

8  


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.



1. 

New Therapeutic Products to Treat Serious or Life‐Threatening 

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 product’s 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 sponsor’s with that sponsor’s 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. 

9  


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 use

9

 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 

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. 

10  


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 patient’s 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 manufacturer’s 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. 

11  


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. 

12  


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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