[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Notices]
[Pages 106510-106512]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31261]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-5016]


Protocol Deviations for Clinical Investigations of Drugs, 
Biological Products, and Devices; Draft Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Protocol 
Deviations for Clinical Investigations of Drugs, Biological Products, 
and Devices.'' This draft guidance provides recommendations to assist 
sponsors, clinical investigators, and institutional review boards 
(IRBs) in defining, identifying, and reporting protocol deviations. The 
guidance provides definitions for protocol deviations and important 
protocol deviations. In addition, the guidance provides a recommended 
classification system for sponsors to report protocol deviations to FDA 
in clinical study reports for drugs, biological products, and devices; 
for investigators to report protocol deviations to sponsors and to 
IRBs; and for IRBs to evaluate protocol deviations.

DATES: Submit either electronic or written comments on the draft 
guidance by February 28, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2023-D-5016 for ``Protocol Deviations for Clinical Investigations 
of Drugs, Biological Products, and Devices.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at

[[Page 106511]]

https://www.regulations.gov or at the Dockets Management Staff between 
9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or 
the Office of Policy, Guidance and Policy Development, Center for 
Devices and Radiological Health, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002. 
Send one self-addressed adhesive label to assist that office in 
processing your requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Dat Doan, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 3334, Silver Spring, MD 20993, 240-402-8926; or James 
Myers, Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver 
Spring, MD 20993-0002, 240-402-7911; or Soma Kalb, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. G318, Silver Spring, MD 20993-0002, 301-
796-6359.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Protocol Deviations for Clinical Investigations of Drugs, 
Biological Products, and Devices.'' Protocols document the study 
design, objectives, population, planned procedures, investigational 
product management, method(s) of data capture, monitoring and oversight 
plans, and statistical analysis plans either directly or by reference 
to associated investigational plans. In the conduct of a clinical 
investigation, some deviations from the specifics outlined in the 
protocol may occur.
    This guidance provides recommendations to assist sponsors, clinical 
investigators, and IRBs in defining, identifying, and reporting 
protocol deviations. FDA regulations do not include a definition of the 
term protocol deviation or provide a system for classifying the various 
types of deviations that may occur during the conduct of a clinical 
investigation. A system that applies consistent classification, 
reporting, and documentation standards is important to assure the most 
interpretable and useful information emerges from the reporting of 
protocol deviations. To address these considerations, this guidance 
includes (1) definitions for protocol deviations and important protocol 
deviations, (2) recommendations on the types of protocol deviations 
that sponsors should report to FDA in clinical study reports, (3) 
recommendations on the types of protocol deviations that investigators 
should report to sponsors and to IRBs, and (4) recommendations for IRBs 
in their evaluation of protocol deviations.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Protocol 
Deviations for Clinical Investigations of Drugs, Biological Products, 
and Devices.'' 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.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information 
in 21 CFR part 56 have been approved under OMB control number 0910-
0130; the collections of information in 21 CFR part 312 have been 
approved under OMB control number 0910-0014; the collections of 
information in 21 CFR part 314 have been approved under OMB control 
number 0910-0001; the collections of information in 21 CFR part 320 
have been approved under OMB control number 0910-0291; the collections 
of information in 21 CFR part 601 have been approved under OMB control 
number 0910-0338; the collections of information in 21 CFR part 812 
have been approved under OMB control number 0910-0078; and the 
collections of information in 21 CFR part 814 have been approved under 
OMB control number 0910-0231.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products, or https://www.regulations.gov.


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    Dated: December 17, 2024.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2024-31261 Filed 12-27-24; 8:45 am]
BILLING CODE 4164-01-P