Impact of Certain Provisions of the 
Revised Common Rule on  
FDA-Regulated Clinical Investigations 
 
 
 
Guidance for Sponsors, Investigators, and 
Institutional Review Boards 
 
 
 
Submit one set of either electronic or written comments on this guidance at any time. Submit 
electronic comments to https://www.regulations.gov.  Submit written comments to the Dockets 
Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD  20852.  You should identify all comments with the docket number FDA-2018-
D-3551. 
 
Additional copies are available from the Office of Good Clinical Practice, Office of Special 
Medical Programs, Office of Medical Products and Tobacco, Food and Drug Administration, 
10903 New Hampshire Avenue, Silver Spring, MD 20993 or by calling 301-796-8340, or from 
the Internet at  
https://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformati
onSheetsandNotices/ucm219433.htm 
 
For questions regarding this document, contact Karena Cooper, Office of Good Clinical Practice, 
301-796-1612. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice (OGCP) 
 
  October 2018 
 
 
 
    Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  INFORMED CONSENT .................................................................................................. 3 
IV.  EXPEDITED REVIEW PROCEDURES AND LIST ................................................... 3 
V.  IRB CONTINUING REVIEW ........................................................................................ 4 
VI.  FURTHER CLARIFICATION ....................................................................................... 4 
APPENDIX.....................................................................................................5    Contains Nonbinding Recommendations 
 
Impact of Certain Provisions of the Revised Common Rule on  
FDA-Regulated Clinical Investigations 
 
 
Guidance for Sponsors, Investigators, and IRBs
 
 
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 staff 
responsible for this guidance as listed on the title page. 
 
I.  INTRODUCTION 
 
FDAs regulations on human subject protection (21 CFR part 50) and Institutional Review 
Boards (IRBs; 21 CFR part 56) help to ensure that the rights, safety, and welfare of human 
subjects participating in FDA-regulated clinical investigations are protected.  These regulations 
generally conform to the Department of Health and Human Services (HHS) Federal Policy for 
Protection of Human Research Subjects (45 CFR 46, Subpart A; the Common Rule), which 
sets forth requirements for the protection of human subjects involved in research that is 
conducted or supported by HHS.   
 
In a final rule published on January 19, 2017, HHS and a number of federal departments and 
agencies made revisions to the Common Rule.1 The general compliance date for the revised 
Common Rule is January 21, 2019.2 
 
FDA intends to undertake notice and comment rulemaking to harmonize, to the extent 
applicable, FDAs regulations with the revised Common Rule.  Because FDA has not revised its 
regulations, FDA is issuing this guidance to reduce confusion and burden associated with 
complying with two different sets of human subject protection regulations.  This guidance is 
intended to address questions from stakeholders regarding the impact of certain provisions of the 
revised Common Rule on FDA-regulated clinical investigations during FDAs rulemaking 
process.3    
 
If a clinical investigation is conducted or supported by HHS and involves an FDA-regulated product, 
then the study is subject to both 45 CFR part 46 and 21 CFR parts 50 and 56.  As FDA has 
                                                 
1 82 FR 7149, January 19, 2017; https://www.gpo.gov/fdsys/pkg/FR-2017-01-19/pdf/2017-01058.pdf. 
 
2 83 FR 28497, June 19, 2018; https://www.gpo.gov/fdsys/pkg/FR-2018-06-19/pdf/2018-13187.pdf. 
 
3 For more information on related guidances, see FDAs Web page Clinical Trials Guidance Documents, available 
at https://www.fda.gov/RegulatoryInformation/Guidances/ucm122046.htm. 
 
 
1    Contains Nonbinding Recommendations 
 
previously described in guidance concerning the protection of human subjects, where the regulations 
differ, the regulations that offer the greater protection to human subjects should be followed.4  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required. 
 
II.  BACKGROUND 
 
FDAs regulations on human subject protection (21 CFR part 50) and Institutional Review 
Boards (IRBs; 21 CFR part 56) help to ensure that the rights, safety, and welfare of human 
subjects participating in FDA-regulated clinical investigations are protected.  HHS, through its 
application of the Common Rule, regulates human subject research that is conducted or 
supported by HHS. The purposes of the Common Rule are to promote uniformity, understanding, 
and compliance with human subject protections and to create a uniform body of regulations 
across the federal departments and agencies.  The Common Rule has been adopted by 16 other 
federal departments and agencies, and, in 1991, FDA amended its regulations in 21 CFR parts 50 
and 56 to conform to the Common Rule,5 with a few exceptions because of differences in FDAs 
mission or statute.   
 
On December 13, 2016, the 21st Century Cures Act (Cures Act) was signed into law.6  Section 
3023 directs the Secretary of HHS, to the extent practicable and consistent with other statutory 
provisions, to harmonize differences between the HHS human subject regulations and FDAs 
human subject regulations. The Cures Act supports HHS and FDAs longstanding efforts to 
harmonize the human subject protection regulations to reduce burdens on sponsors, investigators, 
and IRBs while protecting research subjects. 
 
As previously mentioned, on January 19, 2017, HHS published a final rule, which revised the 
Common Rule.7  The revisions to the Common Rule (2018 Requirements) have created certain 
differences between FDAs human subject regulations and HHS human subject regulations.  
Many sponsors, investigators, and IRBs are involved in both HHS-regulated research and FDA-
regulated clinical investigations.  Some FDA-regulated clinical investigations may also be 
                                                 
4 See, e.g., Use of Electronic Informed Consent Questions and Answers: Guidance for Institutional Review Boards, 
Investigators, and Sponsors, (December 2016), https://www.fda.gov/downloads/drugs/guidances/ucm436811.pdf. 
 
5 56 FR 28025, June 18, 1991. 
 
6 Public Law 114-255, enacted December 13, 2016; https://www.gpo.gov/fdsys/pkg/PLAW-114publ255/pdf/PLAW-
114publ255.pdf.  
 
7 The January 19, 2017 final rule that revised the Common Rule had an effective and general compliance date of 
January 19, 2018 (82 FR 7149).  By an interim final rule published on January 22, 2018, the effective and general 
compliance dates were delayed for a 6-month period, until July 19, 2018 (83 FR 2885).   On June 19, 2018, a final 
rule was published to delay the general compliance date until January 21, 2019 (83 FR 28497).   The revised 
Common Rule, including technical amendments made by the January 22, 2018 interim final rule and the June 19, 
2018 final rule, is referred to as the 2018 Requirements. 
2    Contains Nonbinding Recommendations 
 
conducted or supported by HHS, and would therefore be subject to both sets of regulations.  As a 
result, many sponsors, investigators, and IRBs would need to be familiar and comply with both 
HHS and FDAs regulations.  While FDA intends to undertake rulemaking to harmonize, to the 
extent practicable and consistent with other statutory provisions, its regulations with the 2018 
Requirements consistent with Section 3023 of the Cures Act, we recognize the potential for 
confusion in the interim.  This guidance is intended to clarify the impact of certain provisions of 
the 2018 Requirements on FDA-regulated clinical investigations. 
 
III.  INFORMED CONSENT 
 
The 2018 Requirements contain several new informed consent requirements, including changes 
relating to the content, organization, and presentation of information included in the consent 
form and process to facilitate a prospective subjects decision about whether to participate in 
research as well as changes to the basic and additional elements of consent. FDA has received 
questions from stakeholders as to whether these provisions could be incorporated into consent 
forms and the consent process for FDA-regulated clinical investigations or if it would be 
necessary to develop two separate informed consent forms, one for federally-conducted/-
supported research and another for research regulated by FDA.   
 
In response to stakeholder inquiries, we are clarifying that the provisions of the 2018 
Requirements related to the content, organization, and presentation of information included in 
the consent form and process as well as the basic and additional elements of informed consent 
are not inconsistent with FDAs current policies and guidances.  This may avoid the need for 
sponsors or investigators to develop, and IRBs to review, two separate informed consent forms. 
See Appendix for a subset of the new informed consent provisions from the 2018 Requirements. 
 
IV.  EXPEDITED REVIEW PROCEDURES AND LIST 
 
FDAs regulation at 21 CFR 56.110 sets forth expedited IRB review procedures for certain kinds 
of research involving no more than minimal risk.   Section 56.110(a) describes a list of categories 
of research that may be reviewed by an IRB through an expedited review procedure that may be 
established through a Federal Register Notice. FDA established and published this list in the 
Federal Register on November 9, 1998 (the 1998 list).8  Section 56.110(b) makes clear that, as 
appropriate, IRB reviewer(s) must find that the research on the list involves no more than 
minimal risk in order for the IRB to use the expedited review procedure.    
 
FDA recognizes that under the 2018 Requirements at 45 CFR 46.110(b), an IRB may use the 
expedited procedures for research appearing on the expedited review list, unless the IRB 
reviewer determines that the study involves more than minimal risk.  Because FDA has not 
revised its regulations, IRBs must continue to comply with FDAs regulation at 21 CFR 
56.110(b) and use the 1998 list for FDA-regulated clinical investigations, including those that are 
subject to both HHS and FDA regulations.      
                                                 
8 63 FR 60353, November 9, 1998; https://www.gpo.gov/fdsys/pkg/FR-1998-11-09/pdf/98-29748.pdf. 
 
 
3    Contains Nonbinding Recommendations 
 
 
V.  IRB CONTINUING REVIEW 
 
The 2018 Requirements eliminated the requirement to conduct continuing review in certain 
circumstances (see 45 CFR 46.109(f)(1)).  Under 45 CFR 46.109(f)(1)(i) and (iii), continuing 
review will not be required for research that is either eligible for expedited review in accordance 
with 45 CFR 46.110, or for research that has progressed to the point that the only remaining 
activities are data analysis, and/or accessing follow-up clinical data from procedures that subjects 
would undergo as part of clinical care, unless the IRB determines otherwise.  
 
Because FDA has not revised its regulations, IRBs must continue to comply with our current 
requirements for IRB continuing review at 21 CFR 56.109(f), including for clinical 
investigations that are subject to both HHS and FDA jurisdiction.  IRBs are required to conduct 
continuing review of research at intervals appropriate to the degree of risk, but not less than once 
per year (21 CFR 56.109(f)).9 
 
VI.   FURTHER CLARIFICATION 
 
FDA is actively working to harmonize its human subject protection regulations consistent with 
the Cures Act.  We recognize there may be questions regarding the application of other 
provisions of the 2018 Requirements to FDA-regulated clinical investigations during this interim 
period.  Questions and/or comments requesting further clarification may be submitted at any time 
to the public docket for this guidance, and FDA will consider issuing additional guidance, if 
necessary, to address other provisions. 
 
 
   
                                                 
9 For further information, see FDAs Guidance for IRBs, Clinical Investigators, and Sponsors; IRB Continuing 
Review after Clinical Investigation Approval, (February 2012), 
(https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm294558.pdf).   
4    Contains Nonbinding Recommendations 
 
 
APPENDIX: SELECTED INFORMED CONSENT PROVISIONS FROM THE 2018 
REQUIREMENTS 
 
 
A.  General Requirements for Informed Consent 
 
The 2018 Requirements contain new general requirements for informed consent related to the 
content, organization, and presentation of information in the consent form and process to 
facilitate a prospective subjects decision about whether to participate in the research.   
 
The provisions which are new or include new information are as follows:   
 
46.116(a)(4) The prospective subject or the legally authorized representative must be 
provided with the information that a reasonable person would want to have in order to 
make an informed decision about whether to participate, and an opportunity to discuss 
that information.    
 
46.116(a)(5)(i) Informed consent must begin with a concise and focused presentation of 
the key information that is most likely to assist a prospective subject or legally authorized 
representative in understanding the reasons why one might or might not want to 
participate in the research. This part of the informed consent must be organized and 
presented in a way that facilitates comprehension.  
 
46.116(a)(5)(ii) Informed consent as a whole must present information in sufficient detail 
relating to the research, and must be organized and presented in a way that does not 
merely provide lists of isolated facts, but rather facilitates the prospective subject's or 
legally authorized representative's understanding of the reasons why one might or might 
not want to participate. 
 
46.117(b)(2) A short form written informed consent form stating that the required 
elements of informed consent required by 45 CFR 46.116 have been presented orally to 
the subject or the subject's legally authorized representative and that the key information 
required by 45 CFR 46.116(a)(5)(i) was presented first to the subject, before other 
information, if any, was provided. 
 
B.  Basic and Additional Elements of Informed Consent  
 
The 2018 Requirements contain a new basic element and three additional elements of 
informed consent, as follows:  
 
 
 
 
 
 
5    Contains Nonbinding Recommendations 
 
New Basic Element at 45 CFR 46.116(b)(9)  
 
One of the following statements about any research that involves the collection of 
identifiable private information or identifiable biospecimens:10 
(i) A statement that identifiers might be removed from the identifiable private 
information or identifiable biospecimens and that, after such removal, the information or 
biospecimens could be used for future research studies or distributed to another 
investigator for future research studies without additional informed consent from the 
subject or the legally authorized representative, if this might be a possibility; or 
(ii) A statement that the subjects information or biospecimens collected as part of the 
research, even if identifiers are removed, will not be used or distributed for future 
research studies. 
New Additional Elements at 45 CFR 46.116(c)(7) - (9)  
 
46.116(c)(7) A statement that the subjects biospecimens (even if identifiers are removed) 
may be used for commercial profit and whether the subject will or will not share in this 
commercial profit;  
46.116(c)(8) A statement regarding whether clinically relevant research results, including 
individual research results, will be disclosed to subjects, and if so, under what conditions; 
and 
46.116(c)(9) For research involving biospecimens, whether the research will (if known) 
or might include whole genome sequencing (i.e., sequencing of a human germline or 
somatic specimen with the intent to generate the genome or exome sequence of that 
specimen).   
 
                                                 
10 Private information includes information about behavior that occurs in a context in which an individual can 
reasonably expect that no observation or recording is taking place, and information that has been provided for 
specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., a 
medical record). (45 CFR 46.102(e)(4)). 
 
Identifiable private information is private information for which the identity of the subject is or may readily be 
ascertained by the investigator or associated with the information.  (45 CFR 46.102(e)(5)). 
 
An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained 
by the investigator or associated with the biospecimen. (45 CFR 46.102(e)(6)). 
 
6