Information Sheet Guidance 
For IRBs, Clinical Investigators, 
and Sponsors 
 
FDA Institutional Review  
Board Inspections  
  
 
 
 
 
 
 
 
Additional copies are available from: 
 
Office of Good Clinical Practice 
Office of Special Medical Programs, Office of the Commissioner 
Food and Drug Administration 
10903 New Hampshire Ave., WO32-5129 
Silver Spring, MD 20993-5129 
(Tel) (301)-796-8340 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126555.pdf 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
 
January 2006  Contains Nonbinding Recommendations 
 
 
 
 
Information Sheet Guidance 
1
 For IRBs, Clinical Investigators, and Sponsors
FDA Institutional Review Board Inspections
  
 
 
 
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 it 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 provide information about FDA inspections of Institutional Review 
Boards (IRBs) conducted under FDAs Bioresearch Monitoring (BIMO) Program.  This 
document supersedes another document, "FDA Institutional Review Board Inspections," issued 
in September 1998, by the former Office of Health Affairs, FDA. This document has been 
revised to provide updated information and is being issued in accordance with the Agencys 
regulations on Good Guidance Practices (21 CFR 10.115)2. 
 
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 
 
                                                 
1 This guidance document was developed by the Good Clinical Practice Program in the Office of the Commissioner 
(OC) in coordination with the Center for Biologics Evaluation and Research (CBER), the Center for Devices and 
Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the Office of Regulatory 
Affairs (ORA).  
 
2 65 FR 56477, September 19, 2000. 
  1 Contains Nonbinding Recommendations 
 
 
 
FDA regulations generally require IRB review and approval of research involving FDA 
regulated products (e.g., investigational drugs, biological products, and medical devices) (21 
CFR Part 56). 
 
FDA developed its BIMO Program to ensure the protection of the rights, welfare, and safety of 
human subjects and the quality and integrity of data submitted to the Agency.  Among other 
things, the FDA BIMO Program involves site visits to IRBs, clinical investigators, sponsors, 
monitors, contract research organizations, nonclinical (animal) laboratories, and bioequivalence 
analytical laboratories.  This document addresses site visits to IRBs that review clinical 
investigations that are regulated by FDA under 21 USC 355(i) and 21 USC 360(j) and clinical 
investigations that support applications for research or marketing permits for products regulated 
by FDA. 
 
III.  WHEN ARE IRB INSPECTIONS CONDUCTED? 
 
FDA conducts IRB inspections to determine if IRBs are operating in compliance with current 
FDA regulations and statutory requirements and if the IRBs are following their own written 
procedures.  The FDA regulations pertinent to IRBs include 21 CFR Part 50 (Protection of 
Human Subjects), Part 56 (Institutional Review Boards), Part 312 (Investigational New Drug 
Application), and Part 812 (Investigational Device Exemptions).  
 
FDA inspections of IRBs generally fall into one of two categories: 
  Surveillance inspections  periodic, scheduled inspections to review the overall 
operations and procedures of the IRB.   
  Directed inspections  unscheduled inspections focused on the IRBs review of a specific 
clinical trial or trials.  Directed inspections generally result from a complaint, clinical 
investigator misconduct, or safety issues pertaining to a trial or site.   
 
IV.   HOW ARE IRB INSPECTIONS CONDUCTED? 
 
FDA personnel from one of FDAs District Offices contact a responsible individual at the 
institution, usually the IRB chairperson to schedule the site visit.  FDA personnel issue a notice 
of inspection (Form FDA 482) and present their credentials to the most responsible individual 
before the inspection begins. They interview appropriate people and obtain information about the 
IRB's policies and procedures.  Usually, the IRB's performance is evaluated by tracking one or 
more studies that are subject to IRB review under FDA regulations.  Also, the IRBs procedures 
and membership rosters are examined to determine whether they conform to current FDA 
regulations (21 CFR Part 56, subparts A-D).  During the inspection, FDA personnel typically 
review and copy:  
  Records of IRB membership  
  IRB procedures and guidelines  
  Minutes of IRB meetings for the past year 
  2 Contains Nonbinding Recommendations 
 
 
 
  Documents related to the studies given by the clinical investigator to the IRB  
  Documents related to the studies sent by the IRB to the clinical investigator  
  Any other materials about these studies  
 
V.   WHAT HAPPENS AFTER AN INSPECTION? 
 
At the end of an inspection, FDA personnel conduct an exit interview with responsible 
institutional and IRB representatives.  At this interview, FDA personnel who conducted the 
inspection review and discuss the findings from the inspection and, if deficiencies are found, 
issue a written Form FDA 483 (Inspectional Observations; 483) to the most responsible IRB 
representative.  The 483 describes any inspectional observations that, in the opinion of the FDA 
personnel conducting the inspection, represent deviations from applicable statutes and 
regulations. The IRB may respond to the 483 observations verbally during the exit interview 
and/or respond in writing after the inspection.  If the IRB/responsible institution chooses to 
respond in writing to the deficiencies listed on the 483, the response should be directed to the 
FDA District Office listed in the upper left corner of the 483.  A list of FDA District Offices is 
also posted on FDA's website (http://www.fda.gov/ora).   
  
Following the inspection, the FDA personnel who conducted the IRB inspection prepare a 
written Establishment Inspection Report (EIR).  The EIR, 483 (if issued), copies of any materials 
collected during the inspection, and any IRB response are forwarded to the appropriate FDA 
Center for further evaluation.  After this review, one of the following types of letters is typically 
sent from the Center to the IRB chairperson or other responsible institutional official:   
 
1.  A letter that generally states that FDA observed no significant deviations from the 
regulations.  Note that a letter is not always sent when FDA observes no significant 
deviations.    
 
2.  An informational or untitled letter that identifies deviations from statutes and regulations 
for which voluntary corrective action is sufficient. Occasionally, such letters request a 
response from the IRB. 
 
3.  A Warning Letter that identifies serious deviations from applicable statutes and 
regulations.  A Warning Letter generally requests prompt correction by the IRB and a 
formal written response to the Agency.   
 
Letters may also be issued in accordance with 21 CFR 56.120.  In such cases, the Agency will 
require that the IRB or parent institution respond to the letter within a time period specified by 
FDA and describe the corrective actions that will be taken by the IRB or the parent institution, or 
both, to achieve compliance.  Based on the response from the IRB or institution to these letters, 
FDA may schedule a reinspection to confirm the adequacy of corrective actions.  In addition to 
issuing these letters, FDA can take other administrative actions against IRBs, or their institutions, 
  3 Contains Nonbinding Recommendations 
 
 
 
for noncompliance with applicable statutes and regulations (21 CFR Part 56, subpart E).  Until 
the IRB or parent institution takes appropriate corrective action, FDA may (for studies subject to 
FDA's IRB regulations): 
 
  Withhold approval of new studies that are conducted at the institution or reviewed by the 
IRB 
  Direct that no new subjects be added to ongoing studies 
  Terminate ongoing studies when doing so would not endanger the subjects 
  Notify relevant State and Federal regulatory agencies and other parties with direct interest 
in the Agencys action of the deficiencies in the operation of the IRB in instances when 
the apparent noncompliance creates a significant threat to the rights and welfare of 
human subjects 
 
The FDA Commissioner can also begin proceedings to disqualify an IRB or the institution if the 
IRB has refused or repeatedly failed to comply with FDAs IRB regulations (21 CFR Part 56) 
and the noncompliance adversely affects the rights or welfare of the human subjects in a clinical 
investigation. 
 
VI.  WHO CAN PROVIDE MORE INFORMATION? 
 
If, during an inspection, an IRB official has any questions the FDA personnel conducting the 
inspection has not answered, either the District Office Director or the contact person at the 
Center that assigned the inspection can be contacted.  The FDA personnel conducting the 
inspection should be able to provide the name and telephone number of the District Office 
Director and the Center contact person.  
 
In addition, the FDA Compliance Program Guidance Manual for Institutional Review Board 
Inspections (Program 7348.809), used by FDA to conduct these inspections, is available on the 
Internet at http://www.fda.gov/ora/cpgm/default.htm#bimo .  
 
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