Waiver of IRB Requirements for Drug and Biological Product Studies: Guidance For Sponsors, Clinical Investigators, and IRBs

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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
For Sponsors, Clinical Investigators, and IRBs1
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 Agency’s
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 investigator’s
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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