Guidance for IRBs, Clinical 
Investigators, and Sponsors 
 
IRB Responsibilities for Reviewing 
the Qualifications of Investigators, 
Adequacy of Research Sites, and the 
Determination of Whether an 
  
IND/IDE is Needed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice (OGCP) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
 
August 2013 
Procedural 
 
   
Guidance for IRBs, Clinical 
Investigators, and Sponsors 
IRB Responsibilities for Reviewing the 
Qualifications of Investigators, 
Adequacy of Research Sites, and the 
Determination of Whether an IND/IDE 
is Needed 
 
Additional copies are available from: 
Office of Communications 
Division of Drug Information, WO51, Room 2201 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Silver Spring, MD 20993  
Phone: 301-796-3400; Fax: 301-847-8714 
druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
 Office of Communication, Outreach and Development, HFM-40  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
1401 Rockville Pike, Rockville, MD 20852-1448  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm   
(Tel) 800-835-4709 or 301-827-1800 
and/or 
Office of Communication, Education and Radiological Programs 
Division of Small Manufacturers Assistance, WO66-4613 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Silver Spring,  MD 20993 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm 
Email: dsmica@cdrh.fda.gov; Fax: 301.847.8149 
(Tel) Manufacturers Assistance: 800.638.2041 or 301.796.7100 
(Tel) International Staff Phone: 301.827.3993 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
 August 2013 
Procedural 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  DISCUSSION .................................................................................................................... 2 
1.  Must an IRB review the qualifications of clinical investigators who conduct FDA-
regulated research? ................................................................................................................................. 2 
2.  Is any information publicly available from FDA about a clinical investigators 
inspectional history? ................................................................................................................................ 4 
3.  Must an IRB review the adequacy of the research site? ................................................................... 4 
4.  What are the IRBs responsibilities with respect to verifying the determination of whether 
an IND or IDE is required for an FDA-regulated investigation? ......................................................... 5 
 
 
  Contains Nonbinding Recommendations 
1
Guidance for IRBs, Clinical Investigators, and Sponsors  
IRB Responsibilities for Reviewing the Qualifications of 
Investigators, Adequacy of Research Sites, and the 
Determination of Whether an IND/IDE is Needed 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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  
 
All of the parties who conduct or have oversight responsibilities for biomedical 
researchsponsors, clinical investigators, and institutional review boards (IRBs)have 
responsibility for ensuring that the research complies with applicable laws and 
regulations and that risks to subjects are minimized.  Although selection of clinical 
investigators and research sites, and determining if an investigational new drug 
application (IND) or investigational device exemption (IDE) is required are viewed 
primarily as sponsor responsibilities, FDA is issuing this guidance to clarify IRBs' 
responsibilities related to these activities and to encourage all parties to work together in 
order to protect the rights and welfare of study subjects. 
 
FDAs guidance documents, including this guidance, 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 the word should in agency guidances means that 
something is suggested or recommended, but not required.  
 
To enhance protection of human subjects and reduce regulatory burden, the Department 
of Health and Human Services (HHS) Office for Human Research Protections (OHRP) 
and FDA have been actively working to harmonize the agencies regulatory requirements 
and guidance for human subject research.  This guidance document was developed as a 
part of these efforts and in consultation with OHRP.  
 
                                                 
1 This guidance was prepared by the Office of Good Clinical Practice (OGCP) in the Office of the 
Commissioner, with input from the Center for Drug Evaluation and Research (CDER), the Center for 
Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and 
the Office of Regulatory Affairs (ORA).  
  1 Contains Nonbinding Recommendations 
II.  BACKGROUND 
 
Many of the recommendations in this guidance have appeared in other FDA guidance 
documents2 or have been communicated to IRBs who have contacted the agency directly 
about these issues.  FDA has also provided instructions to its field investigators on the 
types of records that should be reviewed during an IRB inspection to determine whether 
the IRB performed an evaluation of an investigator's qualifications, assessed the 
adequacy of a site, and questioned whether an IND or IDE is necessary.3  FDA has 
compiled the recommendations from these various sources into this guidance to ensure 
that all IRBs have access to it.  In addition, FDA provides guidance on how IRBs may 
efficiently fulfill these important responsibilities.  
 
The recommendations in this guidance are applicable to any IRB, independent or 
affiliated with an institution, whether serving as a local IRB or as the central IRB for 
other IRBs or institutions participating in a centralized review process for multi-site 
studies.  The recommendations are general in order to provide IRBs with necessary 
flexibility in developing agreements for cooperative research as described in 21 CFR 
56.114.  As discussed in Guidance for Industry - Using a Centralized IRB Review 
Process in Multicenter Clinical Trials,4 FDA recommends that IRBs and institutions 
participating in a centralized review process agree on how to divide and carry out these 
responsibilities, and that such agreements be in writing to help ensure that the rights and 
welfare of study subjects are protected. 
 
 
III.  DISCUSSION     
 
1.  Must an IRB review the qualifications of clinical investigators who conduct FDA-
regulated research? 
 
Yes.  Although FDA's regulations place responsibility on the sponsor to select clinical 
investigators who are "qualified by training and experience as appropriate experts" to 
investigate the test article,5 IRBs also have a role in reviewing an investigator's 
qualifications.6  The regulations at 21 CFR 56.107(a) require that an IRB "...be able to 
ascertain the acceptability of the proposed research in terms of institutional commitments 
and regulations, applicable law, and standards of professional conduct and practice..."  In 
addition, the regulations at 21 CFR 56.111 require that an IRB determine that the 
proposed research satisfies the criteria for approval, including that "...risks to subjects are 
                                                 
2 ICH E6 Good Clinical Practice: Consolidated Guidance, 3.1.3 and 4.1.1 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM07312
2.pdf. 
3 Compliance Program Guidance Manual (CPGM) 7348.809, Institutional Review Boards, November 28, 
2011, generally, and Section III.J, K, and U;   
http://www.fda.gov/downloads/ICECI/EnforcementActions/BioresearchMonitoring/UCM133768.pdf. 
4 http://www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm.  
5 21 CFR 312.53(a); see also 21 CFR 812.43(a). 
6 See 21 CFR 56.102(g), (h), and (j) for definitions of IRB, investigator, and sponsor, respectively; 
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm155713.htm.  
  2 Contains Nonbinding Recommendations 
minimized...[and] reasonable in relation to anticipated benefits, if any, to subjects..."  In 
order to fulfill these responsibilities, the IRB needs information about the qualifications 
of the investigator(s) to conduct and supervise the proposed research. Depending upon 
the nature and risks of the proposed research and the relationship between the IRB and 
the investigator or the institution where the proposed research is being conducted, this 
may be relatively simple and straightforward or it may entail a more involved assessment.   
 
In many cases, the IRB may have previous experience with an investigator or institution 
that would allow the IRB to readily determine that the clinical investigator is 
appropriately qualified to conduct and supervise the proposed research.  In other cases, 
the IRB may need additional information; however, the IRB should be able to obtain a 
statement confirming the investigators qualifications from an administrator of the 
institution.  For example, for proposed research to be conducted at a hospital where only 
credentialed hospital staff may conduct research, the IRB may be able to rely on another 
office at the institution (e.g., the credentialing office, the clinical investigators medical 
department) for information about the clinical investigators qualifications.  For proposed 
research to be conducted by a university faculty member (e.g., at an affiliated hospital or 
clinic), the IRB may be able to obtain a statement regarding the investigators 
qualifications from the chair of the investigators department.  
 
On the other hand, if the reviewing IRB has no knowledge of either the clinical 
investigator or the institution (e.g., the IRB is not affiliated with the institution where the 
research will be conducted; the IRB has no previous experience with the investigator), the 
IRB would likely need to take additional steps to evaluate the investigators 
qualifications.  Such steps may include, as appropriate, reviewing the curriculum vitae of 
the investigator, subinvestigators, and other necessary study staff, verifying professional 
associations and medical licensure, or reviewing relevant publications and the 
investigator's training in good clinical practice.   
 
The IRB may also need to assess the investigators training and experience specifically 
related to the proposed study, particularly if the proposed research involves higher risks, 
vulnerable subjects, or novel technologies.  For such proposed research, the IRBs 
determination that the investigator is qualified may need to include a review of the 
investigators previous specific experience as demonstrated by recent presentations or 
publications, and prior clinical experience with the test article or study-related 
procedures.  In addition, the IRB should pay particular attention to an investigators 
qualifications to conduct a study submitted for approval to the IRB if the study involves 
one or more of the following: 
 
  a sponsor-investigator;7  
                                                 
7  FDAs regulations (21 CFR 312.53(a) and 21 CFR 812.43(a)) require that a sponsor select clinical 
investigators who are "qualified by training and experience" to investigate the test article.  In a sponsor-
investigator (S-I) clinical trial, the S-I assumes the responsibilities of both the sponsor and the investigator 
(see 21 CFR 312.3(b) and 21 CFR 812.3(o)); therefore, there is no independent assessment of the clinical 
investigators qualifications by the study sponsor.  In this case, the IRBs review of the investigators 
qualifications is particularly important to the determination that the risks to subjects are minimized and 
reasonable in relation to anticipated benefits, if any, to subjects. 
  3 Contains Nonbinding Recommendations 
  a study that is outside of the investigator's area of expertise; or 
  any study design features or other characteristic(s) that may significantly increase 
potential risks to subjects.  
 
If any concerns remain, the IRB may also elect to observe, or have a third party observe, 
the consent process and the research (21 CFR 56.109(f)).  
 
Appropriately trained IRB support staff may assist in obtaining and assessing information 
about an investigator's qualifications.  FDA recommends that the IRB's written 
procedures describe the IRB's process for evaluating the investigator's qualifications to 
conduct and supervise the study. 
 
2.  Is any information publicly available from FDA about a clinical investigators 
inspectional history? 
 
Yes.  IRBs may check the lists posted on FDAs website to determine whether a clinical 
investigator has been the subject of an inspection by the agency8 and the results of such 
inspections (e.g.,Warning Letters).9  FDA also posts on its website a listing of all 
investigators who have been notified of the initiation of a disqualification proceeding or 
have been disqualified.10  FDA recommends that IRBs routinely check FDAs 
Inspections, Compliance, Enforcement, and Criminal Investigations website11 for 
information related to clinical investigator inspections, Warning Letters, disqualification 
proceedings, and debarments.  
 
3.  Must an IRB review the adequacy of the research site? 
 
Yes.  FDAs regulations require that before an IRB can approve research covered by the 
regulations, the IRB must "...be able to ascertain the acceptability of the proposed 
research in terms of institutional commitments and regulations, applicable law, and 
standards of professional conduct and practice..."12  The regulations also require that each 
IRB have sufficient information to determine that the proposed research satisfies the 
criteria for approval.13   
                                                 
8 Lists of investigators who have been inspected by FDA for CDER are posted at: 
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ComplianceEnforcement/defaul
t.htm;    
for CBER: 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ComplianceActi
vities/ucm165743.htm.  Investigators who conducted a device study from 2009 to present are included in 
the Inspection Classification Database maintained by FDAs Office of Regulatory Affairs at: 
http://www.accessdata.fda.gov/scripts/inspsearch. 
9 See the agencys Electronic Reading Room, including Warning Letters 
(http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm). 
10 See 
http://www.accessdata.fda.gov/scripts/SDA/sdNavigation.cfm?sd=clinicalinvestigatorsdisqualificationproc
eedings&previewMode=true&displayAll=true  
11 See http://www.fda.gov/ICECI/default.htm.  
12 21 CFR 56.107(a). 
13 21 CFR 56.111(a). 
  4 Contains Nonbinding Recommendations 
 
In the great majority of instances, an IRB will be familiar with the research site or 
institution at which the clinical investigator has proposed to conduct the research; in such 
cases, additional assessment of a site's adequacy will probably not be necessary (for 
example, if the research is to be conducted at the IRB's affiliated institution).  In other 
cases, the IRB may need additional information to assess the site where the proposed 
research will take place to ensure it can adequately execute the protocol requirements.  
Depending upon the nature and risks of the proposed research and the IRB's prior 
knowledge of or relationship to the institution or other site at which the research will take 
place, this may be relatively simple and straightforward or it may entail a more involved 
assessment.    
 
For example, if a proposed clinical investigation involves administration of medical 
procedures by qualified healthcare providers using medical equipment, the IRB should be 
prepared to assess the adequacy of the facilitys staff and equipment, including the 
availability of emergency or specialized care, should the need arise.  If the proposed 
research site is part of a major medical institution, the IRB may be able to simply note 
that fact.  If, however, the IRB is unfamiliar with the proposed investigational site (e.g., 
research facility, hospital, physician's office, dental clinic), the IRB may need to confirm 
whether the site is appropriately staffed and equipped to conduct the proposed research.  
The IRB should be able to obtain a statement from an appropriate person or persons at the 
research site or institution stating that the facilities are adequate.  Alternatively, the IRB 
could ask that the investigator provide a description of the facility where the research will 
take place, including its staffing and resources relevant to the research under review.   
 
Appropriately trained IRB support staff may assist in obtaining and assessing information 
about the adequacy of the research site.  FDA recommends that the IRB's written 
procedures describe the IRB's process for carrying out these evaluations. 
 
4.  What are the IRBs responsibilities with respect to verifying the determination of 
whether an IND or IDE is required for an FDA-regulated investigation?  
 
In general, the IRB should ask the investigator if he/she considered whether an IND or 
IDE is required and the basis for that determination.  The IRB's specific responsibilities 
may vary, however, depending on the product that is the subject of the study, as discussed 
below. 
 
Drug and Biologics Studies.  FDA regulations require sponsors14 and sponsor- 
investigators (of individual investigator-initiated studies) to determine whether an IND is 
required for a particular study.15  The sponsor should be able to determine whether the 
IND regulations apply to a planned clinical investigation as required under 21 CFR 
                                                 
14 See 21 CFR 312.3(b), definition of "sponsor-investigator."  In this section, when "sponsor" is used, the 
term includes "sponsor-investigator." 
15 See 21 CFR 312.2, 312.20, 312.50, and 320.31(c).  Studies that are exempt from the IND requirements 
are required, however, to comply with 21 CFR Part 50 (Protection of Human Subjects) and Part 56 
(Institutional Review Boards). 
  5 Contains Nonbinding Recommendations 
312.2(a).  If a sponsor is uncertain whether an IND is required, we recommend that the 
sponsor contact the appropriate review division (i.e., for the therapeutic area being 
studied) in the appropriate FDA Center for advice (21 CFR 312.2(e)).  FDA issued for 
public comment, Draft Guidance for Industry: Investigational New Drug Applications 
(INDs)  Determining Whether Human Research Studies Can Be Conducted Without an 
IND.16  When finalized, the guidance will represent FDAs current thinking on this topic. 
 
When reviewing a proposed study, IRBs should ask the clinical investigator whether the 
sponsor determined that an IND is or is not required and the basis for the determination.  
If the sponsor has determined that an IND is not required, the IRB may request that the 
investigator provide a copy of any available supporting documentation (e.g., letter from 
the sponsor or FDA, other basis for that determination).  If during its initial review of a 
study, the IRB questions whether an IND is required, but is unable to resolve this issue, 
the IRB should follow its procedures for resolving controverted issues (e.g., notifying the 
clinical investigator in writing of the IRBs concerns17 and delaying approval of the study 
until the matter is resolved).   
 
Organizational charts listing the review divisions for the Center for Drug Evaluation and 
Research (CDER) and the Center for Biologics Evaluation and Research (CBER) and 
their phone numbers are available on FDAs website.18  If the relevant review division is 
not known, the sponsor may contact CDER or CBER directly: 
 
CDER:   Office of Communications, Division of Drug Information 
    Center for Drug Evaluation and Research 
    Food and Drug Administration 
    10001 New Hampshire Avenue, 4th Floor   
    Silver Spring, MD  20993   
    (Tel) 301-796-3400 
 
CBER:  Office of Communication, Outreach and Development19 
Center for Biologics Evaluation and Research 
Food and Drug Administration 
1401 Rockville Pike, Suite 200N 
Rockville, MD  20852-1448 
(Tel) 800-835-4709 or 301-827-1800 
 
Device Studies.  For studies involving an investigational device, the sponsor20 is 
responsible for determining whether submission of an IDE application to FDA is required 
                                                 
16 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM22917
5.pdf. 
17 21 CFR 56.109(e) 
18 CDER: http://www.fda.gov/AboutFDA/CentersOffices/OrganizationCharts/ucm135674.htm;  
CBER:  http://www.fda.gov/AboutFDA/CentersOffices/OrganizationCharts/ucm135943.htm. 
19 
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm106001.ht
m. 
  6 Contains Nonbinding Recommendations 
before a study may proceed.21  The IDE regulations (21 CFR 812) describe three types of 
device studies: significant risk (SR), nonsignificant risk (NSR), and exempt studies.22  SR 
device studies must have an IDE application approved by FDA and have IRB approval 
before they proceed, and they must follow all of the IDE requirements.23  NSR device 
studies must follow the abbreviated IDE requirements at 21 CFR 812.2(b), including 
informed consent and IRB review, and do not require submission of an IDE application 
to FDA. 
 
The sponsor is responsible for making the initial risk determination, SR or NSR, and 
presenting it to the IRB.24  If the sponsor has determined that a device study is NSR, the 
IRB must review the sponsors determination.25  If the IRB disagrees with the sponsors 
NSR assessment and decides the study is SR, the IRB must inform the clinical 
investigator and, where appropriate, the sponsor.26  The IRB should also document its 
SR/NSR determination in the IRB meeting minutes. 
 
FDA is available to assist sponsors, investigators, and IRBs in making these 
determinations.  For information on how to request such assistance, please see the 
guidance Procedures for Handling Inquiries Regarding the Need for an Investigational 
Device Exemptions Application for Research Involving Medical Devices.27  Sponsors, 
clinical investigators, and IRBs who need assistance in making a risk determination for a 
medical device may also contact: 
 
IDE Staff 
Office of Device Evaluation 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Avenue 
Silver Spring, MD 20993-0002 
(Tel) 301-796-5640  
 
Based on the information provided, FDA will determine if a device study is SR, NSR, or 
exempt from the IDE requirements found in 21 CFR Part 812.  If FDA makes the SR, 
NSR, or exempt determination for a study, the agency's determination is final.  
Additional information may be found in the Information Sheet Guidance for IRBs, 
                                                                                                                                                 
20 See 21 CFR 812.3(n) and 812.3(o); in this section, when "sponsor" is used, the term includes "sponsor-
investigator." 
21 21 CFR 812.2(b)(1)(ii). 
22 With the exception of 21 CFR 812.119, exempt studies are not subject to the IDE regulations.  21 CFR 
812.2(c).  Exempt studies are required to comply with 21 CFR Part 50 (Protection of Human Subjects) and 
Part 56 (Institutional Review Boards).  
23 21 CFR 812.20(a)(1) and (2).   
24 21 CFR 812.2(b)(1)(ii). 
25Ibid. 
26 21 CFR 812.66. 
27 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm126598.htm. 
  7 Contains Nonbinding Recommendations 
Clinical Investigators, and Sponsors - Significant Risk and Nonsignificant Risk Medical 
Device Studies.28  
 
FDA recommends that the IRB have written procedures that explain how the IRB makes 
an SR/NSR determination. 
  
 
                                                 
28 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf. 
 
  8