The Use of Physiologically Based Pharmacokinetic Analyses-Biopharmaceutics Applications for Oral Drug Product Development, Manufacturing Changes, and Controls; Draft Guidance for Industry; Availability, 61953-61955 [2020-21652]
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61953
Federal Register / Vol. 85, No. 191 / Thursday, October 1, 2020 / Notices
ESTIMATED ANNUALIZED BURDEN HOURS
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respondents
Total burden
(in hours)
Form name
Law enforcement officers ..................
60
1
30/60
30
60
60
60
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60
60
1
2
2
2
1
42
1
1
15/60
5/60
1/60
2/60
2/60
2/60
150/60
5/60
15
10
2
4
2
84
150
5
Law enforcement officers ..................
Law enforcement officers ..................
phone call for recruitment & informed consent.
Initial meeting ...................................
Knowledge survey ............................
Epworth Sleepiness Scale ...............
Pittsburgh Sleep Quality Index ........
Demographics and work experience
Sleep diary .......................................
Online training ..................................
Feedback about Training, Barriers,
and Influential People.
Changes in Behaviors after Training
Actigraph fitting and return ...............
60
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10/60
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334
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enforcement
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enforcement
enforcement
officers
officers
officers
officers
officers
officers
officers
officers
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Jeffrey M. Zirger,
Lead, Information Collection Review Office,
Office of Scientific Integrity, Office of Science,
Centers for Disease Control and Prevention.
[FR Doc. 2020–21731 Filed 9–30–20; 8:45 am]
BILLING CODE 4163–18–P
and corrected in this correcting
document. The provision in this
correction document is effective as if it
had been included in the document
published September 28, 2020.
Accordingly, the correction is effective
September 28, 2020.
II. Summary of Error
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Medicare & Medicaid
Services
[CMS–3386–CN]
Medicare Program; Approval of
Application by The Compliance Team
for Initial CMS-Approval of its Home
Infusion Therapy Accreditation
Program; Correction
Centers for Medicare &
Medicaid Services (CMS), HHS.
ACTION: Final notice; correction.
AGENCY:
This document corrects a
technical error that appeared in the final
notice published in the Federal Register
on September 28, 2020 entitled
‘‘Medicare Program; Approval of
Application by The Compliance Team
for Initial CMS-Approval of Its Home
Infusion Therapy Accreditation
Program.’’
SUMMARY:
On page 60799, in the DATES section
of the notice, the phrase ‘‘takes effect
October 1, 2020 through October 1,
2024’’ should be replaced with the
phrase ‘‘September 28, 2020-September
28, 2024.’’
The Use of Physiologically Based
Pharmacokinetic Analyses—
Biopharmaceutics Applications for
Oral Drug Product Development,
Manufacturing Changes, and Controls;
Draft Guidance for Industry;
Availability
AGENCY:
Food and Drug Administration,
HHS.
SUMMARY:
Dated: September 28, 2020.
Wilma M. Robinson,
Deputy Executive Secretary to the
Department, Department of Health and
Human Services.
[FR Doc. 2020–21766 Filed 9–28–20; 4:15 pm]
BILLING CODE 4120–01–P
Christina Mister-Ward, (410) 786–2441.
Shannon Freeland, (410) 786–4348.
Lillian Williams, (410) 786–8636.
SUPPLEMENTARY INFORMATION:
I. Background
In FR Doc. 2020–21260 of September
28, 2020 (85 FR 60799–60800), there
was a technical error that is identified
Jkt 253001
[Docket No. FDA–2020–D–1517]
In the Federal Register of September
28, 2020, in FR Doc. 2020–21260, on
page 60799, in the 2nd column, in the
DATES section, the phrase ‘‘takes effect
October 1, 2020 through October 1,
2024’’ is corrected to read ‘‘September
28, 2020-September 28, 2024.’’
FOR FURTHER INFORMATION CONTACT:
22:13 Sep 30, 2020
Food and Drug Administration
ACTION:
This correction is effective
September 28, 2020.
VerDate Sep<11>2014
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
III. Correction of Error
DATES:
jbell on DSKJLSW7X2PROD with NOTICES
Average
burden per
response
(in hours)
Number of
responses per
respondent
Type of respondents
PO 00000
Frm 00035
Fmt 4703
Sfmt 4703
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a draft
guidance for industry entitled ‘‘The Use
of Physiologically Based
Pharmacokinetic Analyses—
Biopharmaceutics Applications for Oral
Drug Product Development,
Manufacturing Changes, and Controls.’’
This guidance provides general
recommendations regarding the
development, evaluation, and use of
physiologically based pharmacokinetic
(PBPK) analyses for biopharmaceutics
applications employed by sponsors of
investigational new drug applications,
new drug applications, or abbreviated
new drug applications, and
supplements to these applications, for
oral drug product development,
manufacturing changes, and controls.
The guidance covers how to develop,
evaluate, and apply PBPK models for
biopharmaceutics-related uses, such as
establishing clinically relevant
dissolution specifications and quality
risk assessment for postapproval
manufacturing changes.
E:\FR\FM\01OCN1.SGM
01OCN1
61954
Federal Register / Vol. 85, No. 191 / Thursday, October 1, 2020 / Notices
Submit either electronic or
written comments on the draft guidance
by November 30, 2020 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:
DATES:
jbell on DSKJLSW7X2PROD with NOTICES
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–
2020–D–1517] for ‘‘The Use of
Physiologically Based Pharmacokinetic
Analyses—Biopharmaceutics
Applications for Oral Drug Product
Development, Manufacturing Changes,
and Controls.’’ 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
VerDate Sep<11>2014
22:13 Sep 30, 2020
Jkt 253001
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-201509-18/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: Paul
Seo, Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
PO 00000
Frm 00036
Fmt 4703
Sfmt 4703
Ave., Bldg. 21, Rm. 1628, Silver Spring,
MD 20993–0002, 301–796–4874.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘The Use of Physiologically Based
Pharmacokinetic Analyses—
Biopharmaceutics Applications for Oral
Drug Product Development,
Manufacturing Changes, and Controls.’’
This draft guidance provides general
recommendations regarding the
development, evaluation, and use of
PBPK analyses for biopharmaceutics
applications employed by sponsors of
investigational new drug applications,
new drug applications, or abbreviated
new drug applications, and
supplements to these applications, for
oral drug product development,
manufacturing changes, and controls.
PBPK analyses use models and
simulations that combine physiology,
population, and drug characteristics to
mechanistically describe the
pharmacokinetic and/or
pharmacodynamic behaviors of a drug
product.
Submission of these analyses to FDA
is discussed in the guidance for industry
entitled ‘‘Physiologically Based
Pharmacokinetic Analyses—Format and
Content’’ (available at https://
www.fda.gov/media/101469/download).
However, the application of PBPK
modeling in support of drug product
development is an evolving field. FDA
recognizes this challenge and
encourages the development and use of
new tools and approaches for linking
pharmaceutical quality to clinical
performance.
Advances in modeling and simulation
have enabled the integration of factors
such as the physicochemical properties
of the active pharmaceutical ingredient,
dissolution data, and the physiology of
the gastrointestinal tract into the
development of PBPK models. As such,
PBPK modeling has become a promising
tool in predicting systemic drug
exposure of oral drug products.
PBPK analyses for biopharmaceutics
applications combine dissolution
modeling, biopredictive dissolution
profiles, or other in vitro testing inputs
with PBPK modeling strategies to
quantitatively describe the differential
and potential interactions of
formulation variants with the body and
their effect on drug exposure.
This guidance describes
recommended PBPK model structure,
which provides a mechanistic
framework of drug oral absorption by
representing the in vivo drug absorption
process and accounting for the relevant
E:\FR\FM\01OCN1.SGM
01OCN1
Federal Register / Vol. 85, No. 191 / Thursday, October 1, 2020 / Notices
product quality attributes that affect
drug dissolution and absorption, and
discusses how to capture and present
model assumptions and parameters.
Model validation and refinement are
also discussed.
In addition, the guidance discusses
the major regulatory uses of PBPK
modeling for biopharmaceutics
applications with respect to supporting
product quality. Factors regarding the
development of clinically relevant
dissolution specifications to aid in
biopredictive dissolution method
development and to support clinically
relevant dissolution acceptance criteria
are presented, as well as considerations
for conducting virtual bioequivalence
studies.
PBPK modeling for biopharmaceutics
applications also can be used to
establish clinically relevant drug
product quality specifications other
than dissolution, which can be used to
ensure bioequivalence of batches within
the specification limits, to the pivotal
clinical/bioavailability batches, or to the
reference listed drug for generic drugs.
Finally, the guidance discusses the use
of PBPK analyses for biopharmaceutics
applications as an advanced tool for
quality risk assessment and
management in both the pre- and
postapproval stages.
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 ‘‘The Use of Physiologically Based
Pharmacokinetic Analyses—
Biopharmaceutics Applications for Oral
Drug Product Development,
Manufacturing Changes, and Controls.’’
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.
jbell on DSKJLSW7X2PROD with NOTICES
II. Paperwork Reduction Act of 1995
This draft guidance refers to
previously approved FDA collections of
information. 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. 3501–3521). The
collections of information in 21 CFR
part 314 have been approved under
OMB control number 0910–0001.
III. Electronic Access
Persons with access to the internet
may obtain the draft guidance at either
https://www.fda.gov/drugs/guidancecompliance-regulatory-information/
VerDate Sep<11>2014
22:13 Sep 30, 2020
Jkt 253001
guidances-drugs or https://
www.regulations.gov.
Dated: September 23, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020–21652 Filed 9–30–20; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2019–D–5743]
Importation of Certain Food and Drug
Administration-Approved Human
Prescription Drugs, Including
Biological Products, and Combination
Products Under Section 801(d)(1)(B) of
the Federal Food, Drug, and Cosmetic
Act; Guidance for Industry; Availability
Food and Drug Administration,
Health and Human Services (HHS).
ACTION: Notice of availability.
AGENCY:
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a final
guidance for industry entitled
‘‘Importation of Certain FDA-Approved
Human Prescription Drugs, Including
Biological Products, and Combination
Products under Section 801(d)(1)(B) of
the Federal Food, Drug, and Cosmetic
Act.’’ This guidance describes
recommended procedures to obtain a
National Drug Code (NDC) for certain
FDA-approved prescription drugs that
are imported into the United States in
compliance with the Federal Food,
Drug, and Cosmetic Act (FD&C Act),
which would provide an additional
avenue through which these drugs
could be sold at a lower cost in the U.S.
market. This guidance is intended to
address certain challenges in the private
market faced by manufacturers seeking
to sell their drugs at lower costs. This
guidance finalizes the draft guidance
issued on December 23, 2019.
DATES: The announcement of the
guidance is published in the Federal
Register on October 1, 2020.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
SUMMARY:
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://
PO 00000
Frm 00037
Fmt 4703
Sfmt 4703
61955
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–
2019–D–5743 for ‘‘Importation of
Certain FDA-Approved Human
Prescription Drugs, Including Biological
Products, and Combination Products
under Section 801(d)(1)(B) of the
Federal Food, Drug, and Cosmetic Act.’’
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
E:\FR\FM\01OCN1.SGM
01OCN1
]]>Agencies
[Federal Register Volume 85, Number 191 (Thursday, October 1, 2020)]
[Notices]
[Pages 61953-61955]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-21652]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1517]
The Use of Physiologically Based Pharmacokinetic Analyses--
Biopharmaceutics Applications for Oral Drug Product Development,
Manufacturing Changes, and Controls; Draft Guidance for Industry;
Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a draft guidance for industry entitled ``The Use of
Physiologically Based Pharmacokinetic Analyses--Biopharmaceutics
Applications for Oral Drug Product Development, Manufacturing Changes,
and Controls.'' This guidance provides general recommendations
regarding the development, evaluation, and use of physiologically based
pharmacokinetic (PBPK) analyses for biopharmaceutics applications
employed by sponsors of investigational new drug applications, new drug
applications, or abbreviated new drug applications, and supplements to
these applications, for oral drug product development, manufacturing
changes, and controls. The guidance covers how to develop, evaluate,
and apply PBPK models for biopharmaceutics-related uses, such as
establishing clinically relevant dissolution specifications and quality
risk assessment for postapproval manufacturing changes.
[[Page 61954]]
DATES: Submit either electronic or written comments on the draft
guidance by November 30, 2020 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-2020-D-1517] for ``The Use of Physiologically Based Pharmacokinetic
Analyses--Biopharmaceutics Applications for Oral Drug Product
Development, Manufacturing Changes, and Controls.'' 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 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: Paul Seo, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 21, Rm. 1628, Silver Spring, MD 20993-0002, 301-796-4874.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``The Use of Physiologically Based Pharmacokinetic Analyses--
Biopharmaceutics Applications for Oral Drug Product Development,
Manufacturing Changes, and Controls.'' This draft guidance provides
general recommendations regarding the development, evaluation, and use
of PBPK analyses for biopharmaceutics applications employed by sponsors
of investigational new drug applications, new drug applications, or
abbreviated new drug applications, and supplements to these
applications, for oral drug product development, manufacturing changes,
and controls. PBPK analyses use models and simulations that combine
physiology, population, and drug characteristics to mechanistically
describe the pharmacokinetic and/or pharmacodynamic behaviors of a drug
product.
Submission of these analyses to FDA is discussed in the guidance
for industry entitled ``Physiologically Based Pharmacokinetic
Analyses--Format and Content'' (available at https://www.fda.gov/media/101469/download). However, the application of PBPK modeling in support
of drug product development is an evolving field. FDA recognizes this
challenge and encourages the development and use of new tools and
approaches for linking pharmaceutical quality to clinical performance.
Advances in modeling and simulation have enabled the integration of
factors such as the physicochemical properties of the active
pharmaceutical ingredient, dissolution data, and the physiology of the
gastrointestinal tract into the development of PBPK models. As such,
PBPK modeling has become a promising tool in predicting systemic drug
exposure of oral drug products.
PBPK analyses for biopharmaceutics applications combine dissolution
modeling, biopredictive dissolution profiles, or other in vitro testing
inputs with PBPK modeling strategies to quantitatively describe the
differential and potential interactions of formulation variants with
the body and their effect on drug exposure.
This guidance describes recommended PBPK model structure, which
provides a mechanistic framework of drug oral absorption by
representing the in vivo drug absorption process and accounting for the
relevant
[[Page 61955]]
product quality attributes that affect drug dissolution and absorption,
and discusses how to capture and present model assumptions and
parameters. Model validation and refinement are also discussed.
In addition, the guidance discusses the major regulatory uses of
PBPK modeling for biopharmaceutics applications with respect to
supporting product quality. Factors regarding the development of
clinically relevant dissolution specifications to aid in biopredictive
dissolution method development and to support clinically relevant
dissolution acceptance criteria are presented, as well as
considerations for conducting virtual bioequivalence studies.
PBPK modeling for biopharmaceutics applications also can be used to
establish clinically relevant drug product quality specifications other
than dissolution, which can be used to ensure bioequivalence of batches
within the specification limits, to the pivotal clinical/
bioavailability batches, or to the reference listed drug for generic
drugs. Finally, the guidance discusses the use of PBPK analyses for
biopharmaceutics applications as an advanced tool for quality risk
assessment and management in both the pre- and postapproval stages.
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 ``The Use of
Physiologically Based Pharmacokinetic Analyses-- Biopharmaceutics
Applications for Oral Drug Product Development, Manufacturing Changes,
and Controls.'' 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
This draft guidance refers to previously approved FDA collections
of information. 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. 3501-3521). The collections of
information in 21 CFR part 314 have been approved under OMB control
number 0910-0001.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.
Dated: September 23, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020-21652 Filed 9-30-20; 8:45 am]
BILLING CODE 4164-01-P
