Information Sheet Guidance 

For IRBs, Clinical 

Investigators, and Sponsors 

FDA Institutional Review 

Board Inspections 

Additional copies are available from: 

Good Clinical Practice Program, HF-34 

Office of Science & Health Coordination, Office of the Commissioner 

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) (301)-827-3340 

http://www.fda.gov/oc/gcp/guidance.html

U.S. Department of Health and Human Services 

Food and Drug Administration 

January 2006 

 
Contains Nonbinding Recommendations

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Information Sheet Guidance 

 For IRBs, Clinical Investigators, and Sponsors1

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 FDA’s 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 Agency’s 

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 

 

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 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). 

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 65 FR 56477, September 19, 2000. 
Contains Nonbinding Recommendations

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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 IRB’s 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 FDA’s 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 IRB’s 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 
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• 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, 
Contains Nonbinding Recommendations

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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 Agency’s 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 FDA’s 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 .