[Federal Register Volume 89, Number 65 (Wednesday, April 3, 2024)]
[Notices]
[Pages 23020-23021]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-07080]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-1245]


Data Integrity for In Vivo Bioavailability and Bioequivalence 
Studies; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Data 
Integrity for In Vivo Bioavailability and Bioequivalence Studies.'' The 
purpose of this guidance is to provide recommendations to applicants 
and testing site management on achieving and maintaining data integrity 
for the clinical and bioanalytical portions of bioavailability (BA) and 
bioequivalence (BE) studies submitted in support of investigational new 
drug applications (INDs), new drug applications (NDAs), abbreviated new 
drug applications (ANDAs), and the bioanalytical portion of clinical 
pharmacologic studies supporting Center for Drug Evaluation and 
Research-regulated biologic license applications (BLAs) as well as 
amendments and supplements to these applications. In addition, the 
recommendations in this guidance apply to the bioanalytical portion of 
nonclinical studies. FDA also encourages applicants and testing sites 
to consider these recommendations when conducting other studies, 
including in vitro and pharmacology and toxicology studies.

DATES: Submit either electronic or written comments on the draft 
guidance by June 3, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2024-D-1245 for ``Data Integrity for Bioavailability and 
Bioequivalence Studies at Testing Sites.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at 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

[[Page 23021]]

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. 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: David Coppersmith, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Silver Spring, MD 20993, 301-796-9193.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Data Integrity for In Vivo Bioavailability and 
Bioequivalence Studies.''
    Requirements for submitting BA and BE data in INDs, NDAs, ANDAs, 
and amendments and supplements to these applications, the definitions 
of BA and BE, and the types of in vitro and in vivo studies that are 
appropriate to measure BA and establish BE are set forth in parts 312, 
314, and 320 (21 CFR parts 312, 314, and 320). Requirements for BLAs 
and amendments and supplements to these applications are included in 
part 601 (21 CFR part 601). FDA expects that all data submitted to the 
Agency, including data from BA and BE studies submitted in support of 
INDs, NDAs, and ANDAs and clinical pharmacologic studies submitted in 
support of BLAs, are accurate, complete, and reliable, and that 
industry maintain data integrity throughout the data lifecycle of the 
product(s) or biologic therapeutic(s). In recent years, however, FDA 
has observed data integrity concerns during the inspection of testing 
sites, clinical testing sites, and analytical testing sites, and during 
the assessment of the BA and BE study data submitted in support of 
applications. Data integrity concerns can impact application acceptance 
for filing, assessment, regulatory actions, and approval as well as 
post-approval actions, such as therapeutic equivalence ratings.
    This guidance provides recommendations to achieve and maintain data 
integrity with respect to (1) applicants, (2) testing site management, 
and (3) implementation and management of a quality management system. 
This guidance does not include a comprehensive list of all best 
practices that applicants and testing sites should use to achieve and 
maintain data integrity. It is each applicant's responsibility to 
achieve and maintain data integrity for their studies, which includes 
identifying and implementing the most effective and efficient risk-
based controls. FDA encourages applicants and testing site management 
to review FDA regulations and all applicable guidance for industry to 
understand FDA's current thinking on a topic.
    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 ``Data 
Integrity for In Vivo Bioavailability and Bioequivalence Studies.'' 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 part 312 for investigational new drug applications have been 
approved under OMB control number 0910-0014. The collections of 
information in part 314 for new drug applications and abbreviated new 
drug applications have been approved under OMB control number 0910-
0001. The collections of information in part 601 for biologics license 
applications have been approved under OMB control number 0910-0338. The 
collections of information found in 21 CFR part 11 pertaining to 
electronic records and electronic signatures have been approved under 
OMB control number 0910-0303. The collections of information found in 
21 CFR parts 50 and 56 pertaining to protection of human subjects, 
institutional review boards and informed consent have been approved 
under OMB control number 0910-0130. The collections of information in 
21 CFR part 58 for good laboratory practices for have been approved 
under OMB control number 0910-0119. The collections of information 
found in 21 CFR parts 210 and 211 pertaining to current good 
manufacturing practice (CGMP) and the recordkeeping requirement for 
CGMP sample retention have been approved under OMB control number 0910-
0139.

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, or https://www.regulations.gov.

    Dated: March 29, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-07080 Filed 4-2-24; 8:45 am]
BILLING CODE 4164-01-P