Information Sheet Guidance 
For Sponsors, Clinical 
Investigators, and IRBs 
 
 
 
 
Waiver of IRB Requirements for Drug 
and Biological Product Studies 
 
 
 
 
 
 
 
Additional copies are available from: 
 
Office of Good Clinical Practice  
Office of Special Medical Programs, Office of Medical Products and Tobacco  
Food and Drug Administration 
10903 New Hampshire Avenue 
WO32-5103 
Silver Spring, MD 20993 
(Tel) 301-796-8340 
(Fax) 301-847-8640 
 
http://www.fda.gov/oc/gcp/guidance.html 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
 
January 2006 
Updated October 2017  Information Sheet Guidance For 
Sponsors, Clinical Investigators, and 
IRBs 
 
Waiver of IRB Requirements for Drug 
and Biological Product Studies 
 
 
 
 
Note: FDA made the following updates to this guidance in October 2017. 
  The last paragraph of Section V was deleted to clarify that a sponsor does not need to 
apply for a waiver of local IRB review when a centralized IRB review process is used. 
  New Section VIII When Is An IRB Waiver for Individual Patient Expanded Access 
Use Of An Investigational Drug Appropriate? was added. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
 
January 2006 
Updated October 2017 
    Contains Nonbinding Recommendations  
   
 
 
 
 
Information Sheet Guidance 
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For Sponsors, Clinical Investigators, and IRBs
 
Waiver of IRB Requirements for Drug and Biological Product 
Studies 
 
 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You can 
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  To 
discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title 
page.   
 
 
 
I.  INTRODUCTION 
 
This guidance is intended to provide information for sponsors and sponsor-investigators2 about 
requesting a waiver of Institutional Review Board (IRB) requirements for drug and biological 
product studies regulated by the Food and Drug Administration (FDA).  This document 
supersedes Waiver of IRB Requirements (September 1998) Office of Health Affairs, Food and 
Drug Administration.  That document has been revised to make it consistent with the Agencys 
good guidance practices regulations (21 CFR 10.115). 
 
In general, FDA's guidance documents 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. 
 
 
 
                                                           
1 This guidance document was developed by the Office of Good Clinical Practice in coordination with the Agency 
centers. 
2 For the purpose of this guidance, the term sponsor will be used to refer to both sponsors and sponsor-investigators. 
See 21 CFR 56.102 (j) and (k) for definitions. 
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    Contains Nonbinding Recommendations  
   
 
II.  TO WHICH STUDIES DOES THIS GUIDANCE APPLY? 
 
This guidance applies to clinical investigations regulated by FDA under section 505(i) of the 
Federal Food, Drug, and Cosmetic Act (the Act). 
 
 
III.   WHEN CAN IRB REQUIREMENTS BE WAIVED? 
 
IRB review and approval is generally required before a study can be initiated under an 
Investigational New Drug Application (IND) (56.103(a)).3  FDA may waive any of the IRB 
requirements for specific research activities or for classes of research activities otherwise 
covered by the IRB regulations (56.105), but FDA believes that this waiver provision should be 
used only when alternative mechanisms for ensuring protection of the rights and welfare of 
human subjects are acceptable.  The most common circumstance for which FDA receives a 
waiver request is when a sponsor wishes to conduct a foreign clinical study under an IND.  In 
this case, typically sponsors utilize an Independent Ethics Committee (IEC) that operates in 
accordance with Good Clinical Practice (GCP).4   Although its membership and functions for 
assuring human subject protection are comparable to those of an IRB, an IEC may not meet all 
the IRB requirements contained in Part 56. 
 
IV.  ARE THERE ANY REQUIREMENTS FOR WHICH A WAIVER IS NOT 
AVAILABLE? 
 
Because the waiver provision in 21 CFR 56.105 applies only to the requirements in Part 56, it 
does not apply to the informed consent requirements addressed in 21 CFR Part 50. 5 
 
V.  WHEN IS IT UNNECESSARY TO REQUEST A WAIVER OF IRB 
REQUIREMENTS? 
 
A sponsor does not need to apply prospectively for a waiver of the IRB requirements for the 
emergency use of a test article6, provided that such use is reported to the IRB within 5 working 
days (56.104(c)).  Any subsequent use of the test article at the institution, however, is subject to  
   
                                                           
3 IRB review may be conducted by the local IRB or by a central IRB.  The IRB regulations expressly provide for 
joint or centralized IRB review for multi-institutional studies.  (21 CFR 56.114).  See the FDA Guidance: Using a 
Centralized IRB Review Process in Multicenter Clinical Trials 
(https://www.fda.gov/regulatoryinformation/guidances/ucm127004.htm) for more information. 
4 Sponsors seeking additional guidance on GCP should consult ICH E6 Good Clinical Practice: Consolidated 
Guideline, 62 FR 25692, May 9, 1997 (https://www.gpo.gov/fdsys/pkg/FR-1997-05-09/html/97-12138.htm). 
5 Please note that FDA will not waive the requirement of IRB review for investigations of medical devices 
conducted under section 520(g) of the Act because IRB review is a statutory requirement for such studies.  See 
520(g)(3)(A)(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360j(g)(3)(A)(i)). 
6 "Test article" is defined at 21 CFR 56.102(l). 
 
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    Contains Nonbinding Recommendations  
   
 
IRB review.  See the FDA Information Sheet Guidance: Emergency Use of an Investigational 
Drug or Biologic for more information. 
 
VI.  WHAT SHOULD SPONSORS SUBMIT IN AN IRB WAIVER REQUEST? 
For domestic studies, an IRB waiver request should contain the following: 
 
1.   The specific requirement or requirements in the IRB regulations from which the 
sponsor is requesting a waiver and the reason the sponsor believes that the waiver 
is necessary 
 
2.   A description of the alternate mechanisms for assuring human subject protection 
that the sponsor intends to use 
For foreign studies, an IRB waiver request should contain a description of the alternative 
mechanisms the sponsor intends to use to assure that the rights and welfare of the subjects are 
protected.  As noted above, it would generally be acceptable for a waiver request to state that the 
sponsor intends to use an IEC that complies with GCP instead of an IRB that complies with 21 
CFR Part 56. 
 
The sponsor should submit the waiver request to the IND under which the study will be 
conducted in the appropriate review division in the Center for Drug Evaluation and Research 
(CDER) or in the Center for Biologics Evaluation and Research (CBER). 
 
VII.  HOW WILL THE SPONSOR BE NOTIFIED? 
 
FDA [generally] will notify the sponsor in writing as to whether the waiver request is denied or 
granted.  If a waiver is granted, sponsors should have investigators attach a copy of the letter 
granting the waiver to the signed investigator statement (Form FDA-15727) in the investigators 
records. 
 
VIII.  WHEN IS AN IRB WAIVER FOR INDIVIDUAL PATIENT EXPANDED ACCESS 
USE OF AN INVESTIGATIONAL DRUG APPROPRIATE? 
 
A physician submitting an individual patient expanded access IND using Form FDA 39268 may 
select the appropriate box on that form to request a waiver under  56.105 of the requirements in 
 56.108(c), which relate to IRB review and approval at a convened IRB meeting at which a 
majority of the members are present.  FDA concludes that such a waiver is appropriate for 
individual patient expanded access INDs when the physician obtains concurrence by the IRB 
chairperson or another designated IRB member before treatment use begins (no separate IRB 
                                                           
7 For information about completing Form FDA 1571, see 
https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm432757.htm 
8 For additional information regarding Form FDA 3926, see FDA Guidance for Industry, Individual Patient 
Expanded Access Applications: Form FDA 3926. 
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    Contains Nonbinding Recommendations  
   
 
approval process or notification to the IRB would be needed). A physician submitting an 
individual patient expanded access IND using Form FDA 1571 may include a separate waiver 
request with the application.9 
                                                           
9 For information about completing Form FDA 1571, see 
https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/ucm432757.htm 
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