Application of Physiologically-Based Pharmacokinetic Modeling To Support Dose Selection; Notice of Public Workshop; Request for Comments, 8192-8194 [2014-02883]
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Federal Register / Vol. 79, No. 28 / Tuesday, February 11, 2014 / Notices
Control and Prevention, 1600 Clifton Road
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pertaining to announcements of meetings and
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both the Centers for Disease Control and
Prevention and the Agency for Toxic
Substances and Disease Registry.
Elaine L. Baker,
Director, Management Analysis and Services
Office, Centers for Disease Control and
Prevention (CDC).
[FR Doc. 2014–02859 Filed 2–10–14; 8:45 am]
BILLING CODE 4163–18–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Disease Control and
Prevention
Clinical Laboratory Improvement
Advisory Committee
tkelley on DSK3SPTVN1PROD with NOTICES
In accordance with section 10(a)(2) of
the Federal Advisory Committee Act
(Pub L. 92–463), the Centers for Disease
Control and Prevention (CDC)
announces the following meeting of the
aforementioned committee:
Times and Dates:
8:30 a.m.–4:30 p.m., March 5, 2014
8:30 a.m.–12:00 p.m., March 6, 2014
Place: CDC, 1600 Clifton Road NE., Tom
Harkin Global Communications Center,
Building 19, Auditorium B, Atlanta, Georgia
30333. This meeting will also be Webcast,
please see information below.
Status: Open to the public, limited only by
the space available. The meeting room
accommodates approximately 100 people.
Purpose: This Committee is charged with
providing scientific and technical advice and
guidance to the Secretary of Health and
Human Services (HHS); the Assistant
Secretary for Health; the Director, Centers for
Disease Control and Prevention; the
Commissioner, Food and Drug
Administration (FDA); and the
Administrator, Centers for Medicare and
Medicaid Services (CMS). The advice and
guidance pertain to general issues related to
improvement in clinical laboratory quality
and laboratory medicine practice and specific
questions related to possible revision of the
Clinical Laboratory Improvement
Amendment (CLIA) standards. Examples
include providing guidance on studies
designed to improve safety, effectiveness,
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laboratories are regulated; the impact of
proposed revisions to the standards on
medical and laboratory practice; and the
modification of the standards and provision
of non-regulatory guidelines to accommodate
technological advances, such as new test
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methods and the electronic transmission of
laboratory information.
Matters To Be Discussed: The agenda will
include agency updates from CDC, CMS, and
FDA. Presentations and discussions will
include the CMS implementation of
Individualized Quality Control Plan (IQCP)
as a new CLIA quality control option based
on risk management for laboratories
performing nonwaived testing; CDC’s
strategic priority for strengthening public
health and health care collaborations; and
quality improvement tools for managing
laboratory testing in ambulatory settings.
Agenda items are subject to change as
priorities dictate.
Webcast: The meeting will also be
Webcast. Persons interested in viewing the
Webcast can access information at: https://
wwwn.cdc.gov/cliac/default.aspx.
Online Registration Required: All people
attending the CLIAC meeting in-person are
required to register for the meeting online at
least 5 business days in advance for U.S.
citizens and at least 10 business days in
advance for international registrants. Register
at https://wwwn.cdc.gov/cliac/default.aspx by
scrolling down and clicking the appropriate
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Registration) and completing all forms
according to the instructions given. Please
complete all the required fields before
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Providing Oral or Written Comments: It is
the policy of CLIAC to accept written public
comments and provide a brief period for oral
public comments whenever possible. Oral
Comments: In general, each individual or
group requesting to make oral comments will
be limited to a total time of five minutes
(unless otherwise indicated). Speakers must
also submit their comments in writing for
inclusion in the meeting’s Summary Report.
To assure adequate time is scheduled for
public comments, speakers should notify the
contact person below at least one week prior
to the meeting date. Written Comments: For
individuals or groups unable to attend the
meeting, CLIAC accepts written comments
until the date of the meeting (unless
otherwise stated). However, it is requested
that comments be submitted at least one
week prior to the meeting date so that the
comments may be made available to the
Committee for their consideration and public
distribution. Written comments, one hard
copy with original signature, should be
provided to the contact person below, and
will be included in the meeting’s Summary
Report.
Availability of Meeting Materials: To
support the green initiatives of the federal
government, the CLIAC meeting materials
will be made available to the Committee and
the public in electronic format (PDF) on the
internet instead of by printed copy. Check
the CLIAC Web site on the day of the meeting
for materials. Note: If using a mobile device
to access the materials, please verify that the
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from the CDC’s Web site before the meeting.
https://wwwn.cdc.gov/cliac/
PO 00000
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cliac_meeting_all_documents.aspx
Alternatively, the files can be downloaded to
a computer and then emailed to the portable
device. An internet connection, power source
and limited hard copies may be available at
the meeting location, but cannot be
guaranteed.
Contact Person for Additional Information:
Nancy Anderson, Chief, Laboratory Practice
Standards Branch, Division of Laboratory
Programs, Standards, and Services, Center for
Surveillance, Epidemiology and Laboratory
Services, Office of Public Health Scientific
Services, Centers for Disease Control and
Prevention, 1600 Clifton Road NE., Mailstop
F–11, Atlanta, Georgia 30329–4018;
telephone (404) 498–2741; or via email at
NAnderson@cdc.gov.
The Director, Management Analysis and
Services Office, has been delegated the
authority to sign Federal Register Notices
pertaining to announcements of meetings and
other committee management activities, for
CDC and the Agency for Toxic Substances
and Disease Registry.
Elaine L. Baker,
Director, Management Analysis and Services
Office, Centers for Disease Control and
Prevention.
[FR Doc. 2014–02858 Filed 2–10–14; 8:45 am]
BILLING CODE 4163–18–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–N–0129]
Application of Physiologically-Based
Pharmacokinetic Modeling To Support
Dose Selection; Notice of Public
Workshop; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice of public workshop;
request for comments.
ACTION:
The Food and Drug
Administration (FDA or the Agency) is
announcing a public workshop entitled
‘‘Application of Physiologically-Based
Pharmacokinetic (PBPK) Modeling to
Support Dose Selection.’’ The purpose
of the workshop is to obtain input on
scientific approaches for the conduct
and assessment of physiologically-based
pharmacokinetic (PBPK) modeling
within the framework of drug
development and regulatory
decisionmaking. The input from the
workshop may be used to refine FDA’s
thinking on the various applications of
PBPK. Preliminary elements of a draft
concept paper will be presented to
facilitate discussion at this public
workshop.
DATES: The workshop will be held on
March 10, 2014, from 8:30 a.m. to 4:30
p.m. Individuals who wish to attend the
SUMMARY:
E:\FR\FM\11FEN1.SGM
11FEN1
Federal Register / Vol. 79, No. 28 / Tuesday, February 11, 2014 / Notices
tkelley on DSK3SPTVN1PROD with NOTICES
workshop must register by February 24,
2014. Please submit either electronic or
written comments by April 10, 2014, to
receive consideration.
ADDRESSES: The public workshop will
be held at FDA’s White Oak Campus,
10903 New Hampshire Ave., Bldg. 2,
Rm. 2047, Silver Spring, MD 20993.
Participants must enter through
Building 1 and undergo security
screening. For parking and security
information, please visit https://
www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/
WhiteOakCampusInformation/
ucm241740.htm.
Please submit electronic comments to
https://www.regulations.gov. Submit
written comments to the Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
Identify all comments with the
corresponding docket number found in
brackets in the heading of this notice. A
transcript of the workshop will be
available for review at the Division of
Dockets Management and at https://
www.regulations.gov approximately 30
days after the public workshop (see
section VI of SUPPLEMENTARY
INFORMATION).
FOR FURTHER INFORMATION CONTACT: Ping
Zhao, Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 3182, Silver Spring,
MD 20993, 301–796–3774, FAX: 301–
847–8720, email: ping.zhao@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
On July 9, 2012, the President signed
into law the Food and Drug
Administration Safety and Innovation
Act (FDASIA) (Pub. L. 112–144). Title I
of FDASIA reauthorizes the Prescription
Drug User Fee Act (PDUFA) and
provides FDA with the user fee
resources necessary to maintain an
efficient review process for human drug
and biological products. The
reauthorization of PDUFA includes
performance goals and procedures for
the Agency that represent FDA’s
commitments during fiscal years 2013–
2017. These commitments are fully
described in the document entitled
‘‘PDUFA Reauthorization Performance
Goals and Procedures Fiscal Years 2013
through 2017’’ (‘‘PDUFA Goals Letter’’),
which is available at https://
www.fda.gov/downloads/ForIndustry/
UserFees/PrescriptionDrugUserFee/
UCM270412.pdf. Section IX of the
PDUFA Goals Letter, entitled
‘‘Enhancing Regulatory Science and
VerDate Mar<15>2010
17:58 Feb 10, 2014
Jkt 232001
Expediting Drug Development,’’
includes provisions to promote
innovation through enhanced
communication between FDA and
sponsors during drug development. As
part of this enhanced communication,
FDA made a commitment to hold a
public workshop to: (1) Engage
stakeholders in a discussion of current
and emerging scientific approaches and
applications for the conduct of PBPK
modeling and simulations and (2) to
facilitate stakeholder input regarding
the utility of PBPK during drug
development and regulatory review. The
public workshop announced by this
document will fulfill this commitment.
PBPK modeling is a mathematical
modeling technique for predicting drug
behavior in humans. A PBPK model
takes information about a drug’s
physical, chemical, and other
properties, as well as information about
processes in the body, and turns them
into mathematical equations to predict
what will happen when a patient takes
the medication. Consequently, PBPK
models may be a useful platform in risk
assessment during drug development.
II. Purpose and Scope of the Workshop
The objectives of the workshop are to:
1. Share and discuss best practices in
the use of PBPK to inform dose selection
in specific patient populations, such as
patients with renal or hepatic
impairment, pediatric patients, elderly
patients, and patients with genetic
variation,
2. Discuss the current state of
knowledge and share current FDA
experience regarding important criteria
for evaluating the adequacy of PBPK
models for intended uses, as well as
criteria for considering modeling results
when making regulatory decisions,
3. Obtain input on specific issues
identified by FDA on the conduct of
PBPK analysis.
Since the 1970s PBPK modeling and
simulation has been routinely used in
toxicology to assess the risk of
environmental toxins that cannot be
safely studied in humans. In the past
decade, PBPK models have increasingly
been applied to complex drug
development issues that cannot be
evaluated in a clinical trial or to issues
that can be reliably assessed in silico,
thereby minimizing the need for costly
clinical trials. These types of
applications of PBPK are submitted to
FDA for regulatory review. As a result,
FDA is looking to adopt a rigorous
approach to the review of PBPK
submissions and the conduct of de novo
PBPK analysis to support regulatory
review. FDA also wishes to be
transparent regarding its evidentiary
PO 00000
Frm 00043
Fmt 4703
Sfmt 4703
8193
standards and how it weighs the
evidence of a PBPK simulation in
arriving at a decision or regulatory
action.
The public workshop will focus on
the use of PBPK models for assessing
the effect of various intrinsic and
extrinsic factors in order to inform dose
optimization. FDA acknowledges,
however, that PBPK can be used to
support decision making through the
entire life cycle of drug development,
including preclinical and clinical
evaluations.
The input from the workshop may be
used to refine FDA’s thinking on use of
PBPK in determining proper dosage and
may lead to the development of a draft
guidance for industry. There is currently
no FDA guidance on this topic.
Specifically, this guidance would
describe FDA’s view of criteria
considered important when evaluating
the strength and quality of evidence
provided by a PBPK analysis.
FDA will also be preparing a concept
paper that will propose best practices
and principles for the use of PBPK
modeling in drug development and
regulatory review. Preliminary elements
of this document will be presented at
the public workshop by FDA to elicit
comments and facilitate discussion. The
paper will incorporate the workshop
outcomes, then the public will be
invited to comment through a public
docket.
III. Scope of Public Input Requested
FDA seeks input on a range of topics
related to the conduct of PBPK
modeling and simulation by
pharmaceutical industries and by FDA
and on the interpretation and use of
simulations when evaluating risk in the
regulation of pharmaceutical products.
These include:
1. Predictive performance of PBPK
models for a specific aim
2. Identification of knowledge gaps in
the specific application of PBPK
simulation to replace a clinical trial:
a. Criteria for the adequacy of a PBPK
model for a specific aim
b. Biological plausibility and predictive
performance
c. Model validation and statistical
considerations
3. Presentation of simulations in
approved product labeling (labeling):
a. When should PBPK simulations be
included in drug labeling?
b. What is the best format for
presenting PBPK simulations in
different sections of the labeling?
c. How should uncertainty in
simulations be presented in the
labeling?
E:\FR\FM\11FEN1.SGM
11FEN1
8194
Federal Register / Vol. 79, No. 28 / Tuesday, February 11, 2014 / Notices
tkelley on DSK3SPTVN1PROD with NOTICES
IV. Attendance and Registration
The FDA Conference Center at the
White Oak Campus is a Federal facility
with security screening and limited
seating. Individuals who wish to attend
the public workshop must register on or
before February 24, 2014, by visiting
https://www.surveymonkey.com/s/
MW5WZDW and contacting Ping Zhao
(see FOR FURTHER INFORMATION CONTACT).
Early registration is recommended.
Registration is free and will be on a firstcome, first-served basis. However, FDA
may limit the number of participants
from each organization based on space
limitations. Onsite registration on the
day of the workshop will be based on
space availability.
During the workshop, time will be
designated for questions and answers
throughout the day and for general
comments and questions from the
audience following the panel
discussions.
In this Federal Register document,
FDA has included specific issues that
will be addressed by the panel. If you
wish to address one or more of these
issues in your presentation, please
indicate this at the time you register so
that FDA can consider that in organizing
the presentations. FDA will do its best
to accommodate requests to speak and
will determine the amount of time
allotted to each presenter and the
approximate time that each oral
presentation is scheduled to begin. An
agenda will be available approximately
2 weeks before the workshop at https://
www.fda.gov/Drugs/NewsEvents/
ucm132703.htm (select this workshop
meeting from the events list).
If you need special accommodations
because of a disability, please contact
Ping Zhao (see FOR FURTHER
INFORMATION CONTACT) at least 7 days
before the workshop.
A live webcast of this workshop will
be viewable at https://
collaboration.fda.gov/pbpk/ on the day
of the workshop. A video record of the
workshop will be available at the same
web address for 1 year.
V. Comments
Regardless of attendance at the public
workshop, interested persons may
submit written or electronic comments
to the Division of Dockets Management
(see ADDRESSES). It is only necessary to
send one set of comments. Identify
comments with the docket number
found in brackets in the heading of this
notice. Received comments may be seen
in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday, and will be posted to
the docket at https://
www.regulations.gov.
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17:58 Feb 10, 2014
Jkt 232001
VI. Transcripts
Transcripts of the workshop will be
available for review at the Division of
Dockets Management (see ADDRESSES)
and at https://www.regulations.gov
approximately 30 days after the
workshop. A transcript will also be
made available in either hard copy or on
CD–ROM upon submission of a
Freedom of Information request. Send
requests to Division of Freedom of
Information (ELEM–1029), Food and
Drug Administration, 12420 Parklawn
Dr., Element Bldg., Rockville, MD
20857.
Dated: February 5, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014–02883 Filed 2–10–14; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
Agency Information Collection
Activities: Proposed Collection: Public
Comment Request
Health Resources and Services
Administration, HHS.
ACTION: Notice.
AGENCY:
In compliance with the
requirement for opportunity for public
comment on proposed data collection
projects (Section 3506(c)(2)(A) of the
Paperwork Reduction Act of 1995), the
Health Resources and Services
Administration (HRSA) announces
plans to submit an Information
Collection Request (ICR), described
below, to the Office of Management and
Budget (OMB). Prior to submitting the
ICR to OMB, HRSA seeks comments
from the public regarding the burden
estimate, below, or any other aspect of
the ICR.
DATES: Comments on this Information
Collection Request must be received
within 60 days of this notice.
ADDRESSES: Submit your comments to
paperwork@hrsa.gov or mail the HRSA
Information Collection Clearance
Officer, Room 10–29, Parklawn
Building, 5600 Fishers Lane, Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: To
request more information on the
proposed project or to obtain a copy of
the data collection plans and draft
instruments, email paperwork@hrsa.gov
or call the HRSA Information Collection
Clearance Officer at (301) 443–1984.
SUMMARY:
PO 00000
Frm 00044
Fmt 4703
When
submitting comments or requesting
information, please include the
information request collection title for
reference.
Information Collection Request Title:
Children’s Hospitals Graduate Medical
Education Payment Program. OMB No.
0915–0247 Revision.
Abstract: The Children’s Hospitals
Graduate Medical Education (CHGME)
Payment Program was enacted by Public
Law 106–129 and reauthorized by
Public Law 109–307 to provide federal
support for graduate medical education
(GME) to freestanding children’s
hospitals. This legislation attempts to
provide support for GME comparable to
the level of Medicare GME support
received by other, non-children’s
hospitals. The legislation indicates that
eligible children’s hospitals will receive
payments for both direct and indirect
medical education. Direct payments are
designed to offset the expenses
associated with operating approved
graduate medical residency training
programs, and indirect payments are
designed to compensate hospitals for
expenses associated with the treatment
of more severely ill patients and the
additional costs relating to teaching
residents in such programs.
The Centers for Medicare and
Medicaid Services (CMS) issued a final
rule in the Federal Register regarding
Sections 5503, 5504, 5505, and 5506 of
the Affordable Care Act of 2010, Public
Law 111–148 on Wednesday, November
24, 2010. This final rule included policy
changes on counting resident time in
non-provider settings, counting resident
time for didactic training, and the redistribution of resident caps. It required
modification of the data collection
forms within the CHGME Payment
Program application. The necessary
modifications were made and received
OMB clearance on June 30, 2012.
On September 30, 2013, CMS
published revised forms on their Web
site, requiring additional modifications
of the data collection forms in the
CHGME Payment Program application.
The CHGME Payment Program
application forms have been adjusted to
accommodate the most recent CMS
policy changes. These changes require
OMB approval.
Need and Proposed Use of the
Information: Data are collected on the
number of full-time equivalent residents
in applicant children’s hospitals’
training programs to determine the
amount of direct and indirect medical
education payments to be distributed to
participating children’s hospitals.
Indirect medical education payments
will also be derived from a formula that
SUPPLEMENTARY INFORMATION:
Sfmt 4703
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]]>Agencies
[Federal Register Volume 79, Number 28 (Tuesday, February 11, 2014)]
[Notices]
[Pages 8192-8194]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-02883]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2014-N-0129]
Application of Physiologically-Based Pharmacokinetic Modeling To
Support Dose Selection; Notice of Public Workshop; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public workshop; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing a public workshop entitled ``Application of Physiologically-
Based Pharmacokinetic (PBPK) Modeling to Support Dose Selection.'' The
purpose of the workshop is to obtain input on scientific approaches for
the conduct and assessment of physiologically-based pharmacokinetic
(PBPK) modeling within the framework of drug development and regulatory
decisionmaking. The input from the workshop may be used to refine FDA's
thinking on the various applications of PBPK. Preliminary elements of a
draft concept paper will be presented to facilitate discussion at this
public workshop.
DATES: The workshop will be held on March 10, 2014, from 8:30 a.m. to
4:30 p.m. Individuals who wish to attend the
[[Page 8193]]
workshop must register by February 24, 2014. Please submit either
electronic or written comments by April 10, 2014, to receive
consideration.
ADDRESSES: The public workshop will be held at FDA's White Oak Campus,
10903 New Hampshire Ave., Bldg. 2, Rm. 2047, Silver Spring, MD 20993.
Participants must enter through Building 1 and undergo security
screening. For parking and security information, please visit https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
Please submit electronic comments to https://www.regulations.gov.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. Identify all comments with the corresponding
docket number found in brackets in the heading of this notice. A
transcript of the workshop will be available for review at the Division
of Dockets Management and at https://www.regulations.gov approximately
30 days after the public workshop (see section VI of SUPPLEMENTARY
INFORMATION).
FOR FURTHER INFORMATION CONTACT: Ping Zhao, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 3182, Silver Spring, MD 20993, 301-796-3774, FAX: 301-
847-8720, email: ping.zhao@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
On July 9, 2012, the President signed into law the Food and Drug
Administration Safety and Innovation Act (FDASIA) (Pub. L. 112-144).
Title I of FDASIA reauthorizes the Prescription Drug User Fee Act
(PDUFA) and provides FDA with the user fee resources necessary to
maintain an efficient review process for human drug and biological
products. The reauthorization of PDUFA includes performance goals and
procedures for the Agency that represent FDA's commitments during
fiscal years 2013-2017. These commitments are fully described in the
document entitled ``PDUFA Reauthorization Performance Goals and
Procedures Fiscal Years 2013 through 2017'' (``PDUFA Goals Letter''),
which is available at https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM270412.pdf. Section IX of the PDUFA
Goals Letter, entitled ``Enhancing Regulatory Science and Expediting
Drug Development,'' includes provisions to promote innovation through
enhanced communication between FDA and sponsors during drug
development. As part of this enhanced communication, FDA made a
commitment to hold a public workshop to: (1) Engage stakeholders in a
discussion of current and emerging scientific approaches and
applications for the conduct of PBPK modeling and simulations and (2)
to facilitate stakeholder input regarding the utility of PBPK during
drug development and regulatory review. The public workshop announced
by this document will fulfill this commitment.
PBPK modeling is a mathematical modeling technique for predicting
drug behavior in humans. A PBPK model takes information about a drug's
physical, chemical, and other properties, as well as information about
processes in the body, and turns them into mathematical equations to
predict what will happen when a patient takes the medication.
Consequently, PBPK models may be a useful platform in risk assessment
during drug development.
II. Purpose and Scope of the Workshop
The objectives of the workshop are to:
1. Share and discuss best practices in the use of PBPK to inform
dose selection in specific patient populations, such as patients with
renal or hepatic impairment, pediatric patients, elderly patients, and
patients with genetic variation,
2. Discuss the current state of knowledge and share current FDA
experience regarding important criteria for evaluating the adequacy of
PBPK models for intended uses, as well as criteria for considering
modeling results when making regulatory decisions,
3. Obtain input on specific issues identified by FDA on the conduct
of PBPK analysis.
Since the 1970s PBPK modeling and simulation has been routinely
used in toxicology to assess the risk of environmental toxins that
cannot be safely studied in humans. In the past decade, PBPK models
have increasingly been applied to complex drug development issues that
cannot be evaluated in a clinical trial or to issues that can be
reliably assessed in silico, thereby minimizing the need for costly
clinical trials. These types of applications of PBPK are submitted to
FDA for regulatory review. As a result, FDA is looking to adopt a
rigorous approach to the review of PBPK submissions and the conduct of
de novo PBPK analysis to support regulatory review. FDA also wishes to
be transparent regarding its evidentiary standards and how it weighs
the evidence of a PBPK simulation in arriving at a decision or
regulatory action.
The public workshop will focus on the use of PBPK models for
assessing the effect of various intrinsic and extrinsic factors in
order to inform dose optimization. FDA acknowledges, however, that PBPK
can be used to support decision making through the entire life cycle of
drug development, including preclinical and clinical evaluations.
The input from the workshop may be used to refine FDA's thinking on
use of PBPK in determining proper dosage and may lead to the
development of a draft guidance for industry. There is currently no FDA
guidance on this topic. Specifically, this guidance would describe
FDA's view of criteria considered important when evaluating the
strength and quality of evidence provided by a PBPK analysis.
FDA will also be preparing a concept paper that will propose best
practices and principles for the use of PBPK modeling in drug
development and regulatory review. Preliminary elements of this
document will be presented at the public workshop by FDA to elicit
comments and facilitate discussion. The paper will incorporate the
workshop outcomes, then the public will be invited to comment through a
public docket.
III. Scope of Public Input Requested
FDA seeks input on a range of topics related to the conduct of PBPK
modeling and simulation by pharmaceutical industries and by FDA and on
the interpretation and use of simulations when evaluating risk in the
regulation of pharmaceutical products. These include:
1. Predictive performance of PBPK models for a specific aim
2. Identification of knowledge gaps in the specific application of
PBPK simulation to replace a clinical trial:
a. Criteria for the adequacy of a PBPK model for a specific aim
b. Biological plausibility and predictive performance
c. Model validation and statistical considerations
3. Presentation of simulations in approved product labeling
(labeling):
a. When should PBPK simulations be included in drug labeling?
b. What is the best format for presenting PBPK simulations in
different sections of the labeling?
c. How should uncertainty in simulations be presented in the
labeling?
[[Page 8194]]
IV. Attendance and Registration
The FDA Conference Center at the White Oak Campus is a Federal
facility with security screening and limited seating. Individuals who
wish to attend the public workshop must register on or before February
24, 2014, by visiting https://www.surveymonkey.com/s/MW5WZDW and
contacting Ping Zhao (see FOR FURTHER INFORMATION CONTACT). Early
registration is recommended. Registration is free and will be on a
first-come, first-served basis. However, FDA may limit the number of
participants from each organization based on space limitations. Onsite
registration on the day of the workshop will be based on space
availability.
During the workshop, time will be designated for questions and
answers throughout the day and for general comments and questions from
the audience following the panel discussions.
In this Federal Register document, FDA has included specific issues
that will be addressed by the panel. If you wish to address one or more
of these issues in your presentation, please indicate this at the time
you register so that FDA can consider that in organizing the
presentations. FDA will do its best to accommodate requests to speak
and will determine the amount of time allotted to each presenter and
the approximate time that each oral presentation is scheduled to begin.
An agenda will be available approximately 2 weeks before the workshop
at https://www.fda.gov/Drugs/NewsEvents/ucm132703.htm (select this
workshop meeting from the events list).
If you need special accommodations because of a disability, please
contact Ping Zhao (see FOR FURTHER INFORMATION CONTACT) at least 7 days
before the workshop.
A live webcast of this workshop will be viewable at https://collaboration.fda.gov/pbpk/ on the day of the workshop. A video record
of the workshop will be available at the same web address for 1 year.
V. Comments
Regardless of attendance at the public workshop, interested persons
may submit written or electronic comments to the Division of Dockets
Management (see ADDRESSES). It is only necessary to send one set of
comments. Identify comments with the docket number found in brackets in
the heading of this notice. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday, and will be posted to the docket at https://www.regulations.gov.
VI. Transcripts
Transcripts of the workshop will be available for review at the
Division of Dockets Management (see ADDRESSES) and at https://www.regulations.gov approximately 30 days after the workshop. A
transcript will also be made available in either hard copy or on CD-ROM
upon submission of a Freedom of Information request. Send requests to
Division of Freedom of Information (ELEM-1029), Food and Drug
Administration, 12420 Parklawn Dr., Element Bldg., Rockville, MD 20857.
Dated: February 5, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-02883 Filed 2-10-14; 8:45 am]
BILLING CODE 4160-01-P
