[Federal Register Volume 83, Number 171 (Tuesday, September 4, 2018)]
[Notices]
[Pages 44883-44884]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-19065]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-3969]


Physiologically Based Pharmacokinetic Analyses--Format and 
Content; 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 final guidance for industry entitled 
``Physiologically Based Pharmacokinetic Analyses--Format and Content.'' 
This guidance outlines the recommended format and content for a sponsor 
or applicant to submit physiologically based pharmacokinetic (PBPK) 
analyses to FDA to support applications including, but not limited to, 
investigational new drug applications (INDs), new drug applications 
(NDAs), biologics license applications (BLAs), or abbreviated new drug 
applications (ANDAs). This guidance does not address methodological 
considerations and best practices for the conduct of PBPK modeling and 
simulation or the appropriateness of PBPK analyses for a particular 
drug or a drug product.

DATES: The announcement of the guidance is published in the Federal 
Register on September 4, 2018.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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-2016-D-3969 for ``Physiologically Based Pharmacokinetic Analyses--
Format and Content.'' 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.
    <bullet> 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.gpo.gov/

[[Page 44884]]

fdsys/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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Xinyuan Zhang, Office of Clinical 
Pharmacology, Office of Translational Sciences, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 2128, Silver Spring, MD 20993-0002, 240-
402-7971.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Physiologically Based Pharmacokinetic Analyses--Format and 
Content.'' A PBPK analysis uses models and simulations that combine 
physiology, population, and drug characteristics to mechanistically 
describe the pharmacokinetic behaviors of a drug or drug product. 
Throughout a drug's life cycle, PBPK model predictions can be used to 
support decisions on whether, when, and how to conduct certain clinical 
pharmacology studies, and to support dosing recommendations in product 
labeling. Because of the lack of regulatory guidance, the format and 
content of PBPK analysis reports that are submitted to FDA vary 
significantly. The goal of this guidance is to standardize the content 
and format of these reports to facilitate FDA's efficient assessment, 
consistent application, and timely decision making during regulatory 
review.
    This guidance outlines the recommended format and content for a 
sponsor or applicant to submit PBPK analyses to FDA to support 
applications including, but not limited to, INDs, NDAs, BLAs, and 
ANDAs. This guidance does not address methodological considerations and 
best practices for the conduct of PBPK modeling and simulation or the 
appropriateness of PBPK analyses for a particular drug or a drug 
product.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Physiologically Based Pharmacokinetic 
Analyses--Format and Content.'' 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. This guidance is not subject to Executive 
Order 12866.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collection of information in 21 CFR 314.50(d) has been approved under 
OMB control number 0910-0001.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: August 27, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-19065 Filed 8-31-18; 8:45 am]
 BILLING CODE 4164-01-P