Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and fda staff



Yüklə 80,37 Kb.
Pdf görüntüsü
tarix26.02.2017
ölçüsü80,37 Kb.

Guidance for Sponsors, 

Institutional Review Boards

Clinical Investigators   

and FDA Staff 

 

Guidance on Informed Consent 

for In Vitro Diagnostic Device 

Studies Using Leftover Human 

Specimens that are Not 

Individually Identifiable 

 

 

Document issued on April 25, 2006

 

For questions regarding this document contact Sally Hojvat, Ph.D., at 240-276-0496 or by 



email at sally.hojvat@fda.hhs.gov. 

 

 

 



U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Devices and Radiological Health 

Office of In Vitro Diagnostic Device Evaluation and Safety 

 

Center for Biologic Evaluation and Research 

                                                                                Office of Blood Research and Review 

 

 

OMB Control No. 0910-0582

  

Expiration Date: 



04/30/2016

See additional PRA statement in Section 8 of this guidance

Contains Nonbinding Recommendations 

 

2



Preface

 

 



Public Comment 

 

Written comments and suggestions may be submitted at any time for Agency 



consideration to Division of Dockets Management, Food and Drug Administration, 5630 

Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852.  Alternatively, electronic 

comments may be submitted to 

http://www.fda.gov/dockets/ecomments

.  Please identify 

your comments with the docket number 2006D-0150.  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 at: 



http://www.fda.gov/cdrh/oivd/guidance/1588.pdf

, or to receive this document by your fax 

machine, call the CDRH Facts-On-Demand system at 800-899-0381 or 301-827-0111 

from a touch-tone telephone.  Press 1 to enter the system.  At the second voice prompt, 

press 1 to order a document.  Enter the document number (1588) followed by the pound 

sign (#).  Follow the remaining voice prompts to complete your request.   

 

For questions regarding the use or interpretation of this guidance contact:  Sally Hojvat, 



PhD at 240-276-0496, or by email at sally.hojvat@fda.hhs.gov. 

 

 



 

Contains Nonbinding Recommendations 

 

3



 

Table of Contents 

 

 

1.

 

INTRODUCTION............................................................................................................. 4

 

2.

 

SCOPE ............................................................................................................................... 5

 

3.

 

BACKGROUND ............................................................................................................... 6

 

4.

 

IN WHAT CIRCUMSTANCES DOES FDA INTEND TO EXERCISE 



ENFORCEMENT DISCRETION AS TO THE REQUIREMENTS FOR 

INFORMED CONSENT FOR USE OF SPECIMENS IN FDA-

REGULATED IVD STUDIES?....................................................................................... 7

 

5.

 

WHAT TYPE OF RECORDS SHOULD BE KEPT FOR THESE TYPES OF 

STUDIES? ......................................................................................................................... 9

 

6.

 

SHOULD SPONSORS CONSIDER ANYTHING ELSE IN DECIDING 

WHETHER OR NOT TO CONDUCT A STUDY THAT MAY FALL 

WITHIN THE EXERCISE OF ENFORCEMENT DISCRETION 

CONTEMPLATED BY THIS GUIDANCE? ................................................................ 9

 

7.

 

WHAT SHOULD IRBS DO WHEN REVIEWING THE TYPES OF IVD 

STUDIES THAT ARE THE FOCUS OF THIS GUIDANCE?.................................... 9

 

8.

 

PAPERWORK REDUCTION ACT OF 1995.............................................................. 10

 

 



Contains Nonbinding Recommendations 

 

4



Guidance for Sponsors, Institutional Review 

Boards, Clinical Investigators and FDA Staff 



 

Guidance on Informed Consent for In 

Vitro Diagnostic Device Studies Using 

Leftover Human Specimens that are Not 

Individually Identifiable 

 

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.  

1. Introduction 

FDA is issuing this guidance to inform sponsors, institutional review boards (IRBs), 

clinical investigators, and agency staff that the FDA intends to exercise enforcement 

discretion, under certain circumstances, with respect to its current regulations governing 

the requirement for informed consent when human specimens are used for FDA-

regulated in vitro diagnostic (IVD)

1

 device investigations.  As described below, FDA 



does not intend to object to the use, without informed consent, of leftover human 

specimens -- remnants of specimens collected for routine clinical care or analysis that 

would otherwise have been discarded -- in investigations that meet the criteria for 

exemption from the Investigational Device Exemptions (IDE) regulation at 21 CFR 

812.2(c)(3), as long as subject privacy is protected by using only specimens that are not 

individually identifiable.  FDA also intends to include in this policy specimens obtained 

from specimen repositories

2

 and specimens that are leftover from specimens previously 



collected for other unrelated research, as long as these specimens are not individually 

identifiable. 

                                                           

1

 In vitro diagnostic products are those reagents, instruments, and systems intended for use in the diagnosis 



of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, 

treat, or prevent disease or its sequelae.  Such products are intended for use in the collection, preparation, 

and examination of specimens taken from the human body.  21 CFR 809.3(a). 

2

 A specimen repository is a common site for storage of collections of human biological specimens 



available for study. 

Contains Nonbinding Recommendations 

 

5



 

Under FDA’s current regulations governing the conduct of IVD device studies, the 

definition of human subject includes individuals on whose specimens an investigational 

device is used [see 21 CFR 812.3(p)].  Because these regulations require informed 

consent for FDA-regulated human subject research, except in limited circumstances 

specified in the regulations,

3

 informed consent is required before specimens can be used 



in FDA-regulated research [see 21 CFR part 50].  

 

 This aspect of FDA’s human subject protection regulations has created confusion and 



difficulty for persons developing IVDs.  Many clinicians, research hospitals, and 

companies have viewed the requirement for informed consent for IVD studies using 

leftover specimens as unnecessary for the protection of human subjects and as overly 

burdensome and costly.   

 

FDA’s recent “Critical Path



4

” initiative has also focused the agency’s concern on 

unnecessary obstacles to medical product development.  The agency has received 

comments from trade associations and research institutions that identify the challenge of 

obtaining informed consent for the use of leftover specimens as an unnecessary obstacle 

and expense for investigational efforts.  When leftover specimens are available, it is often 

difficult, if not impossible, to locate the donor and obtain consent.  This difficulty may 

deter a manufacturer’s research efforts that would bring safe and effective IVDs to 

market more quickly.  At the same time, many researchers maintain that for this 

particular type of study, the human subject protection values that informed consent is 

intended to ensure either are not implicated, or can be adequately safeguarded through 

less burdensome measures.  

 

The confusion regarding the application of informed consent requirements to IVD studies 



and concerns about unnecessary obstacles to product development have prompted FDA 

to issue this guidance document.  The agency believes this guidance will facilitate 

product development in a manner consistent with the values of human subject protection. 

FDA intends that the exercise of enforcement discretion expressed in this guidance begin 

immediately.  In accordance with the agency’s Good Guidance Practice regulations, 21 

CFR 10.115, you may submit comments on this guidance at any time.  The agency will 

consider your comments and determine whether to revise the guidance at a later date. 

2.

 

Scope 

This document applies only to IVD device investigations regulated by FDA in 

accordance with section 520(g) of Federal Food, Drug, and Cosmetic Act (the Act), 21 

USC 360j(g), that are exempt from most requirements of the IDE regulation (21 CFR 

812) under 21 CFR 812.2(c)(3), and that use leftover specimens that are not individually 

                                                           

3

 See 21 CFR 50.23(a) and 50.24.  



4

 

"



Innovation or Stagnation? -- Challenge and Opportunity on the Critical Path to New Medical Products" 

FDA Report issued on March 16, 2004.  This document may be found at: 

http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

 

 



Contains Nonbinding Recommendations 

 

6



identifiable. A leftover specimen is the remnant of a human specimen collected for 

routine clinical care or analysis that would otherwise have been discarded.  A specimen is 

not individually identifiable when the identity of the subject is not known to or may not 

readily be ascertained by the investigator or any other individuals associated with the 

investigation, including the sponsor. (See Section 4, below.)   This guidance also applies 

to specimens that were previously collected for other unrelated research and that are not 

individually identifiable. 

 

This guidance will be implemented on the date it is issued.  It applies to investigations 



using leftover specimens that are already existing on the date the guidance is issued and 

investigations using specimens that will be collected after the issuance of this guidance, 

so long as both the specimens and the investigations meet the circumstances outlined 

below (see section 4).

 

3.

 

Background 

FDA's investigational device regulations are intended to encourage the development of 

new, useful devices in a manner that is consistent with public health and safety and with 

ethical standards. (See 21 U.S.C. 360j(g)).  Investigators should have freedom to pursue 

the least burdensome means of accomplishing this goal.  However, to ensure that the 

balance is maintained between product development and the protection of public health 

and safety and ethical standards, FDA has established human subject protection 

regulations addressing requirements for informed consent and IRB review that apply to 

all FDA-regulated clinical investigations involving human subjects.  In particular, 

informed consent requirements further both safety and ethical considerations by allowing 

potential subjects to consider both the physical and privacy risks they face if they agree to 

participate in a trial. 

 

Under FDA regulations, clinical investigations using human specimens conducted in 



support of premarket submissions to FDA are considered human subject investigations 

[see 21 CFR 812.3(p)].  Many IVD studies are exempt from most provisions of 21 CFR 

part 812, Investigational Device Exemptions, under 21 CFR 812.2(c)(3), but FDA’s  

regulations for the protection of human subjects (21 CFR parts 50 and 56) apply to all 

clinical investigations that are regulated by FDA [see 21 CFR 50.1; 21 CFR 56.1; 21 

U.S.C. 360j(g)(3)(A) & (D)]. 

 

FDA does have narrow exceptions from the general requirements of informed consent for 



certain emergency and military research,

5

 but FDA regulations do not contain exceptions 



from the requirements of informed consent on the grounds that the specimens are not 

identifiable and

 

or that they are remnants of human specimens collected for routine 



clinical care or analysis that would otherwise have been discarded.  Nor do FDA 

regulations allow IRBs to decide whether or not to waive informed consent for research 

involving leftover or unidentifiable specimens. 

 

                                                           



5

 21 CFR 50.23 and 50.24. 



Contains Nonbinding Recommendations 

 

7



Leftover specimens are frequently used in feasibility studies and studies to characterize 

the performance of new in vitro diagnostic devices for several reasons.  The evaluation of 

new devices often requires the use of specimens with specific laboratory characteristics, 

e.g., positive or negative for a particular disease marker,

 

in order to meet the study 



inclusion criteria. Routine clinical care testing can provide information about the 

laboratory characteristics of the specimen that permit investigators to quickly ascertain 

whether the specimen will meet the study inclusion criteria. The remnants of these 

specimens thus become valuable to research at a point when they are of no value to the 

patient and are ready to be discarded.  The lower cost of these specimens, compared to 

the cost of specimens collected prospectively for research, makes studies using leftover 

specimens more affordable, permitting manufacturers to conduct studies that otherwise 

may not be done. In addition, banked leftover specimens are a source for unique and 

possibly rare specimens in sufficient quantity to permit the rapid completion of 

investigations that would be difficult if not impossible to conduct in a reasonable 

timeframe without these specimens. 

 

FDA believes that it is possible in certain circumstances for IVD device investigations to 



be conducted using leftover specimens obtained without informed consent while 

protecting the human subjects who are the source of such specimens.  When IVD study 

sponsors use leftover specimens for which the subject cannot be identified and where 

results of the investigational test are not communicated to or otherwise associated with 

the identified subject, concerns associated with privacy are minimized.  In addition, these 

studies do not pose new medical risks to subjects from whom the specimens were 

originally collected: Any risks from specimen collection were incurred prior to the 

involvement of the patient as a subject in an investigation, when the specimen was 

obtained for the patient's own clinical needs, and no risks from erroneous test results are 

presented because the results of the testing are not used for clinical management of the 

subject.  Like leftover specimens that have been collected for routine clinical care, the 

investigational use of leftover specimens previously collected for other research purposes 

involves no additional medical risk, and privacy risks are mitigated by limiting the 

applicability of this guidance to specimens that are not identifiable.  



4.

 

   In what circumstances does FDA intend to exercise 

enforcement discretion as to the requirements for 

informed consent for use of specimens in FDA-

regulated IVD studies? 

FDA intends to exercise enforcement discretion as to the informed consent requirements 

for clinical investigators, sponsors, and IRBs if an in vitro diagnostic device investigation 

is performed and all of the following are true:  

 

a)

 



The investigation meets the IDE exemption criteria at 21 CFR 812.2(c) (3). 

 


Contains Nonbinding Recommendations 

 

8



b)

 

The study uses leftover specimens, that is, remnants of specimens collected for 



routine clinical care or analysis that would have been discarded. The study may 

also use specimens obtained from specimen repositories or leftover specimens 

that were previously collected for other research purposes.  

 

c)



 

The specimens are not individually identifiable, i.e., the identity of the subject is 

not known to and may not readily be ascertained by the investigator or any other 

individuals associated with the investigation, including the sponsor.  If the 

specimen is coded,

6

 it will be considered to be not individually identifiable if 



neither the investigator(s) nor any other individuals associated with the 

investigation or the sponsor can link the specimen to the subject from whom the 

specimen was collected, either directly or indirectly through coding systems.   

 

d)



 

The specimens may be accompanied by clinical information as long as this 

information does not make the specimen source identifiable to the investigator 

or any other individual associated with the investigation, including the sponsor. 

 

e)

 



The individuals caring for the patients are different from and do not share 

information about the patient with those conducting the investigation.     

 

f)

 



The specimens are provided to the investigator(s) without identifiers and the 

supplier of the specimens has established policies and procedures to prevent the 

release of personal information.  

 

g)



 

The study has been reviewed by an IRB in accordance with 21 CFR Part 56, 

except as described in section 7 of this guidance document.   

 

Studies that do not fall within the intended enforcement discretion expressed in this 



guidance include (but are not limited to) studies where any of the following is true: 

 



 

The study does not meet the IDE exemption criteria at 21 CFR 812.2(c)(3); 

 

the specimens are individually identifiable, i.e., the identity of the subject is 



known to or may be readily ascertained by the investigator or any other 

individuals associated with the investigation, including the sponsor. 

 

the specimens were collected specifically for the proposed investigation.  That is, 



the specimens are not leftover from routine clinical care or analysis or leftover 

from other research. 

 

the amount of specimen needed for the study is more than would be leftover from 



what is usually collected for routine clinical analysis 

   or,  


                                                           

6

 For the purposes of this document, coded means that: 1) a number, letter, symbol, or combination thereof 



(i.e., the code) has replaced identifying information (such as name or social security number) that would 

enable the investigator or any other individuals associated with the investigation, including the sponsor to 

readily ascertain the identity of the individual to whom the specimen pertains; and 2) a key to decipher the 

code exists, enabling linkage of the identifying information to the specimen.   

 


Contains Nonbinding Recommendations 

 

9



 

the test results will be reported to the subject’s health care provider.  For example, 



in the course of comparative studies involving B. anthracis detection devices, it 

would be inappropriate not to report positive results if they occur in the course of 

an investigation. 

5.

 

  What type of records should be kept for these types 

of studies?  

We recommend that sponsors maintain written documentation regarding the factors 

described in section 4 (a)-(g) of this guidance, including the policies and procedures 

followed by the specimen provider to ensure that the subject cannot be identified.  FDA 

may request to inspect this documentation.  FDA recommends that IRBs review this 

documentation before approving an investigation paying particular attention to privacy 

and confidentiality, and the potential for use of information from the investigation for 

clinical patient management.    



6.

 

  Should sponsors consider anything else in deciding 

whether or not to conduct a study that may fall 

within the exercise of enforcement discretion 

contemplated by this guidance?  

Sponsors should consider whether a study exhibiting the factors relevant to the exercise 

of enforcement discretion described in section 4 will generate sufficient data to support 

the product application they are considering. Although FDA does not intend to reject data 

from a study exhibiting the factors described in section 4 solely because it was conducted 

without complying with the informed consent requirements found in 21 CFR part 50, 

FDA also does not guarantee that the data generated from a study with those 

characteristics will be sufficient to support a premarket clearance or approval.    FDA 

may determine that additional clinical information is important in order to evaluate test 

results. For some studies, masking of clinical information may be problematic and may 

bias data collection. Sponsors should understand that by choosing to conduct an 

investigation without informed consent, even in a manner consistent with this guidance, 

they accept the risk that they may not be able to provide sufficient information to satisfy 

FDA's premarket review needs.  

 

7.

 

  What should IRBs do when reviewing the types of 

IVD studies that are the focus of this guidance? 

To facilitate IVD device development, FDA intends to exercise enforcement discretion 

toward IRBs who approve IVD investigations that are consistent with the factors in 

section 4 of this guidance, with respect to the IRB's duties under 21 CFR part 56 

regarding informed consent for those studies. (Noncompliance with requirements of 21 


Contains Nonbinding Recommendations 

 

10



CFR part 56 not related to informed consent is not subject to enforcement discretion 

under this guidance.) We recommend that the IRB review the sponsor's documentation 

regarding the factors described in Section 4, (a) through (f), including the policies and 

procedures followed by the specimen provider to ensure that the subject cannot be 

identified.

 

 IRBs should apply existing FDA regulations, including all informed consent 



requirements, to any other investigational IVD study. We encourage IRBs to contact 

FDA if they have questions about the guidance or a specific study under review (see FDA 

contact information on the title page of this guidance.) 

8.

 

  Paperwork Reduction Act of 1995 

This guidance contains information collection provisions that are subject to review by the 

Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501-3520). 

 

The time required to complete this information collection is estimated to average 4 hours 



per response, including the time to review instructions, search existing data sources, 

gather the data needed, and complete and review the information collection.  Send 

comments regarding this burden estimate or suggestions for reducing this burden to: 

 

     Department of Health and Human Services



     Food and Drug Administration

     Office of Chief Information Officer

     Paperwork Reduction Act (PRA) Staff

     1350 Piccard Drive, Room 400

     Rockville, MD 20850   

 

 



 

 

An agency may not conduct or sponsor, and a person is not required to respond to, a 



collection of information unless it displays a currently valid OMB control number. The OMB 

control number for this information collection is 0910-0582, expires 04/30/2016. 




Yüklə 80,37 Kb.

Dostları ilə paylaş:




Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©azkurs.org 2020
rəhbərliyinə müraciət

    Ana səhifə