Leveraging Quantitative Methods and Modeling To Modernize Generic Drug Development and Review; Public Workshop; Request for Comments, 45863-45865 [2017-21017]
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Federal Register / Vol. 82, No. 189 / Monday, October 2, 2017 / Notices
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This guidance refers to previously
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collections of information are subject to
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Dated: September 22, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–21079 Filed 9–29–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2017–N–5442]
Leveraging Quantitative Methods and
Modeling To Modernize Generic Drug
Development and Review; Public
Workshop; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice of public workshop;
request for comments.
ACTION:
sradovich on DSK3GMQ082PROD with NOTICES
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The public workshop will
be held at FDA’s White Oak Campus,
10903 New Hampshire Ave., Bldg. 31,
Great Room, Silver Spring, MD 20993.
Entrance for the public workshop
participants (non-FDA employees) is
through Building 1 where routine
security check procedures will be
performed. For parking and security
information, please refer to https://www.
fda.gov/AboutFDA/WorkingatFDA/
BuildingsandFacilities/WhiteOak
CampusInformation/ucm241740.htm.
You may submit comments as
follows. Please note that late, untimely
filed comments will not be considered.
Electronic comments must be submitted
on or before November 3, 2017. The
https://www.regulations.gov electronic
filing system will accept comments
until midnight Eastern Time at the end
of November 3, 2017. Comments
received by mail/hand delivery/courier
(for written/paper submissions) will be
considered timely if they are
postmarked or the delivery service
acceptance receipt is on or before that
date.
ADDRESSES:
Electronic Submissions
The Food and Drug
Administration (FDA, the Agency, or
we) is announcing the following public
workshop entitled ‘‘Leveraging
Quantitative Methods and Modeling to
Modernize Generic Drug Development
and Review.’’ The purpose of the public
workshop is to engage stakeholders in a
discussion of current and emerging
scientific approaches and applications
for the conduct of quantitative modeling
and simulations in generic drug
development, especially for complex
and locally acting products, and to gain
input regarding opportunities and
knowledge gaps related to the use of
quantitative modeling and simulation to
inform regulatory decision making
through the product lifecycle. FDA will
use the information gained through the
workshop to support product-specific
guidance development, improve preabbreviated new drug applications
(ANDA) interactions with applicants,
increase the quality and efficiency of
regulatory reviews, and identify a next
generation modeling and simulation
toolset for complex and locally acting
products.
DATES: The public workshop will be
held on October 2 and 3, 2017, from
8:30 a.m. to 4:30 p.m. Submit either
electronic or written comments on this
SUMMARY:
public workshop by November 3, 2017.
See the SUPPLEMENTARY INFORMATION
section for registration date and
information.
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:
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45863
• 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–
2017–N–5442 for ‘‘Leveraging
Quantitative Methods and Modeling to
Modernize Generic Drug Development
and Review.’’ Received comments, those
filed in a timely manner (see
ADDRESSES), 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.
• 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/
fdsys/pkg/FR-2015-09-18/pdf/201523389.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
E:\FR\FM\02OCN1.SGM
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45864
Federal Register / Vol. 82, No. 189 / Monday, October 2, 2017 / Notices
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Lanyan (Lucy) Fang, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 4686,
Silver Spring, MD 20993, 301–796–
5005, email: Lanyan.fang@fda.hhs.gov;
or Liang Zhao, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 4702,
Silver Spring, MD 20993, 240–402–
4468, email: Liang.zhao@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
sradovich on DSK3GMQ082PROD with NOTICES
I. Background
To enhance dialogue regarding
modeling and simulation and
communication of recent advances in
modeling and simulation, including
those supported by the Generic Drug
User Fee Amendments regulatory
science research program, FDA plans to
hold a public workshop to (1) engage
stakeholders in a discussion of current
and emerging scientific approaches and
applications for the conduct of
quantitative modeling and simulations
in generic drug development, especially
for complex and locally acting products,
and (2) gain input regarding
opportunities and knowledge gaps
related to the use of quantitative
modeling and simulation to inform
regulatory decision making through the
product lifecycle.
Modeling and simulation has been
increasingly used in drug development,
providing a framework for synthesizing
information and extrapolating beyond
what has been studied. Model-informed
drug development (MIDD) approaches
can be applied to brand drug products
approved pursuant to a new drug
application (NDA), and generic drug
products approved pursuant to an
ANDA. MIDD holds particular promise
in key opportunity areas including
pharmacokinetic/pharmacodynamics
(PK/PD) models, physiologically based
pharmacokinetic (PBPK) or absorption
models, systems pharmacology,
quantitative risk modeling, and
emergent machine learning tools. These
application areas can leverage the large
pharmaceutical data sets (big data)
available to FDA and other
organizations. Quantitative approaches
have been used to address significant
scientific and regulatory issues in all
phases of the product lifecycle: from
pre-investigational new drug
applications through NDAs, ANDAs,
and post-approval evaluation of new
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and generic drugs. Given the broad
applications of modeling and simulation
through the entire lifecycle of a product,
there is a need to identify best practices
to improve the routine use and
acceptance of modeling and simulation
for regulatory decision making.
The purposes of the workshop are to:
(1) Engage global stakeholders and
share experience and vision on using
quantitative approaches in regulatory
decision making for generic drug
development and product lifecycle
management;
(2) Identify and prioritize potential
areas for global harmonization for tools
to inform regulatory decision making;
(3) Share the current state of
knowledge and practice in utilizing
quantitative methods and modeling for
generic drug development and review
by case demonstrations and by
integrating experience and lessons
learned from new drug product
development and reviews;
(4) Identify opportunities for complex
and locally acting product development
and discuss approaches and principles
in using quantitative methods and
modeling to aid product-specific
guidance development, pre-ANDA
interactions between FDA and
prospective applicants, ANDA reviews,
and postmarket performance
monitoring; and
(5) Discuss next generation
quantitative method and modeling
toolsets, future directions, and
application areas beyond currently
available tools.
There is a paradigm shift to a riskbased product-specific regulatory
approach for generic drugs. Examples of
this transition include
recommendations for partial AUC (area
under the concentration-time curve) for
some modified release drugs and
replicate study bioequivalence (BE)
recommendations for narrow
therapeutic index (NTI) drugs. These
product-specific guidances are driven
by the therapeutic significance of either
the exposure-response relationships for
safety and efficacy (NTI drugs) or the
difference in the shape of PK profiles.
Modeling and simulation toolsets direct
the design and evaluation of PK or
comparative clinical endpoint BE
studies, help evaluate clinical endpoint
sensitivity and feasibility, and enable
the assessment of alternative BE
approaches. Overall, quantitative
methods and modeling support better
and faster decisions during the generic
drug development and review process
because they integrate knowledge
accumulated during and after new drug
product development, including in vitro
in vivo correlation for formulation
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design, absorption, distribution,
metabolism, and excretion properties,
population PK, and exposure-response
relationships for efficacy and safety.
There is also a growing recognition
that analysis of large datasets helps
organizations and individuals make
better decisions. Emerging
methodologies that enable the Agency to
take advantage of big data will impact
how generic drugs are developed,
reviewed, and monitored. Knowledge
extracted from large datasets can
provide FDA the opportunity to
improve the focus of regulatory review,
modernize BE assessment criteria, and
efficiently manage workload by
predicting future ANDA applications.
Further, such knowledge will support
industry’s efforts to optimize their
generic drug portfolios to meet
upcoming patient and market needs.
The public workshop will focus on the
use and advance of quantitative
methods and modeling in modernizing
generic drug development, regulatory
review, and product lifecycle
management.
II. Scope of Public Input Requested
FDA seeks input on a range of topics
related to the conduct of modeling and
simulation by pharmaceutical industries
and by FDA and on the interpretation
and use of simulations for risk-based
regulatory assessment. They include:
(1) Opportunity areas for modelinformed generic drug development and
review
(2) Risk-based BE standard for
complex and locally acting products:
a. Under what circumstances would
alternative approaches to the productspecific BE guidances be encouraged?
b. What can serve as evidentiary data
when proposing alternative BE
approaches?
c. What are the scientific and
regulatory challenges in using a modelbased BE approach?
(3) Emerging quantitative methods
and modeling in assisting regulatory
decision making for drug development
and product life cycle management:
a. What are the areas (e.g., excipient
selection, molecular target/mechanism
of action-safety profile association,
universal exposure response models for
drugs with the same target) that can
benefit most in the big data era and
what will be the regulatory impact and
implications?
b. What are the potential new
methods, including but not limited to,
machine learning and their application
areas in assisting drug development and
review?
(4) Post-approval evaluation of the
substitutability of generic products for
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Federal Register / Vol. 82, No. 189 / Monday, October 2, 2017 / Notices
sradovich on DSK3GMQ082PROD with NOTICES
the corresponding reference listed drugs
or reference standards:
a. How to effectively integrate systems
pharmacology, PBPK, and the exposureclinical response relationship to
evaluate product risk and assist BE
evaluation?
b. What will be the next generation
methodologies in postmarket signal
detection to evaluate product
substitution or compare product
performance using the Sentinel database
or complementary toolsets?
III. Participating in the Public
Workshop
Registration: Persons interested in
attending this public workshop must
register online at https://survey.co1.
qualtrics.com/jfe/form/SV_3eiJOCsnr
PdTZU9. Please provide complete
contact information for each attendee,
including name, title, affiliation,
address, email, and telephone.
Registration is free and based on
space availability, with priority given to
early registrants. Persons interested in
attending this public workshop must
register by September 25, 2017,
midnight, Eastern Standard Time. Early
registration is recommended because
seating is limited; therefore, FDA may
limit the number of participants from
each organization.
If you need special accommodations
due to a disability, please contact
Lanyan (Lucy) Fang (see FOR FURTHER
INFORMATION CONTACT) no later than 7
days before the workshop.
Requests for Oral Presentations:
During online registration you may
indicate if you wish to present during a
public comment session, and which
topic(s) you wish to address. We will do
our best to accommodate requests to
make public comments. Individuals and
organizations with common interests are
urged to consolidate or coordinate their
presentations, and to request time for a
joint presentation, or to submit requests
for designated representatives to
participate in the focused sessions.
Following the close of registration, we
will determine the amount of time
allotted to each presenter and the
approximate time each oral presentation
is to begin, and will select and notify
participants by September 27, 2017. All
requests to make oral presentations
must be received by the close of
registration on September 25, 2017. If
selected for presentation, any
presentation materials must be emailed
to Lanyan (Lucy) Fang (see FOR FURTHER
INFORMATION CONTACT) no later than
September 28, 2017. No commercial or
promotional material will be permitted
to be presented or distributed at the
public workshop.
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Streaming Webcast of the Public
Workshop: This public workshop will
also be webcast. A live webcast of this
workshop will be viewable at https://
collaboration.fda.gov/dqmm1017/on the
day of the workshop.
If you have never attended a Connect
Pro event before, test your connection at
https://collaboration.fda.gov/common/
help/en/support/meeting_test.htm. To
get a quick overview of the Connect Pro
program, visit https://www.adobe.com/
go/connectpro_overview. FDA has
verified the Web site addresses in this
document, as of the date this document
publishes in the Federal Register, but
Web sites are subject to change over
time.
Transcripts: Please be advised that as
soon as a transcript of the public
workshop is available, it will be
accessible at https://
www.regulations.gov. It may be viewed
at the Dockets Management Staff (see
ADDRESSES). A link to the transcript will
also be available on the internet at
https://www.fda.gov/Drugs/NewsEvents/
ucm554182.htm.
Dated: September 26, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning,
Legislation, and Analysis.
[FR Doc. 2017–21017 Filed 9–29–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Prospective Modification of Exclusive
Patent License Potent and Selective
Analogues of: Monamine Transporters;
Methods of Making; and Uses Thereof
AGENCY:
National Institutes of Health,
HHS.
ACTION:
Notice.
The National Institute of Drug
Abuse, an institute of the National
Institutes of Health, Department of
Health and Human Services is
contemplating the modification of grant
of an Exclusive Patent License to
EncepHeal Therapeutics, Inc., located in
Winston-Salem, North Carolina, to
practice the inventions embodied in the
patent applications listed in the
Supplementary Information section of
this notice.
DATES: Only written comments and/or
applications for a license which are
received by the National Institute on
Drug Abuse’s Technology Transfer
Office on or before October 17, 2017
will be considered.
SUMMARY:
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Requests for copies of the
patent application, inquiries, and
comments relating to the contemplated
modification of the Exclusive Patent
License should be directed to Martha
Lubet, Ph.D., Technology Transfer
Manager, NCI TTC, 9609 Medical Center
Drive, Room IE350, MSC 9702,
Rockville, MD 20850. Telephone: 240
276–5508. Facsimile: 240 276–5505.
Email: lubetm@mail.nih.gov.
SUPPLEMENTARY INFORMATION: The
following represents the intellectual
property to be licensed under the
prospective agreement:
U.S. provisional application 61/
774,878, filed March 8, 2013 entitled
‘‘Potent and Selective Inhibitors of
Monamine Transporters; Methods of
Making; and Uses Thereof’’ [HHS Ref.
No. E–073–2013/0–US–01];
PCT application PCT/US2014/021514,
filed March 7, 2014 entitled ‘‘Potent and
Selective Analogues of: Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–PCT–02];
U.S. application 14/772,486, filed
September 3, 2015 entitled ‘‘Potent and
Selective Analogues of Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–US–06];
EPO application 14714043.8, filed
September 1, 2015 entitled ‘‘Potent and
Selective Analogues of Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–EP–05];
Australian application 2014225550,
filed September 8, 2015 entitled ‘‘Potent
and Selective Analogues of Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–AU–03];
Australian application 2017202849,
filed April 28, 2017 entitled Potent and
Selective Analogues of Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–AU–07];
Canadian application 2903746, filed
September 2, 2015 entitled ‘‘Potent and
Selective Analogues of Monamine
Transporters; Methods of Making; and
Uses Thereof’’ [HHS Ref. No. E–073–
2013/0–CA–04];
The patent rights to these inventions
have been assigned to and/or
exclusively licensed to the Government
of the United States of America.
The Government previously
announced its intention to grant an
exclusive license to EncepHeal at FR
80:245 (December 22, 2015), pp. 79595–
79596.
The Notice of Intent to Grant (NOITG)
specified a Field of Use as ‘‘Use of
ADDRESSES:
E:\FR\FM\02OCN1.SGM
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]]>Agencies
[Federal Register Volume 82, Number 189 (Monday, October 2, 2017)]
[Notices]
[Pages 45863-45865]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-21017]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2017-N-5442]
Leveraging Quantitative Methods and Modeling To Modernize Generic
Drug Development and Review; 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, the Agency, or we) is
announcing the following public workshop entitled ``Leveraging
Quantitative Methods and Modeling to Modernize Generic Drug Development
and Review.'' The purpose of the public workshop is to engage
stakeholders in a discussion of current and emerging scientific
approaches and applications for the conduct of quantitative modeling
and simulations in generic drug development, especially for complex and
locally acting products, and to gain input regarding opportunities and
knowledge gaps related to the use of quantitative modeling and
simulation to inform regulatory decision making through the product
lifecycle. FDA will use the information gained through the workshop to
support product-specific guidance development, improve pre-abbreviated
new drug applications (ANDA) interactions with applicants, increase the
quality and efficiency of regulatory reviews, and identify a next
generation modeling and simulation toolset for complex and locally
acting products.
DATES: The public workshop will be held on October 2 and 3, 2017, from
8:30 a.m. to 4:30 p.m. Submit either electronic or written comments on
this public workshop by November 3, 2017. See the SUPPLEMENTARY
INFORMATION section for registration date and information.
ADDRESSES: The public workshop will be held at FDA's White Oak Campus,
10903 New Hampshire Ave., Bldg. 31, Great Room, Silver Spring, MD
20993. Entrance for the public workshop participants (non-FDA
employees) is through Building 1 where routine security check
procedures will be performed. For parking and security information,
please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
You may submit comments as follows. Please note that late, untimely
filed comments will not be considered. Electronic comments must be
submitted on or before November 3, 2017. The https://www.regulations.gov electronic filing system will accept comments until
midnight Eastern Time at the end of November 3, 2017. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are postmarked or the delivery service
acceptance receipt is on or before that date.
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-2017-N-5442 for ``Leveraging Quantitative Methods and Modeling to
Modernize Generic Drug Development and Review.'' Received comments,
those filed in a timely manner (see ADDRESSES), 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.
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/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
[[Page 45864]]
``Search'' box and follow the prompts and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Lanyan (Lucy) Fang, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 4686, Silver Spring, MD 20993, 301-796-
5005, email: Lanyan.fang@fda.hhs.gov; or Liang Zhao, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 4702, Silver Spring, MD 20993, 240-402-
4468, email: Liang.zhao@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
To enhance dialogue regarding modeling and simulation and
communication of recent advances in modeling and simulation, including
those supported by the Generic Drug User Fee Amendments regulatory
science research program, FDA plans to hold a public workshop to (1)
engage stakeholders in a discussion of current and emerging scientific
approaches and applications for the conduct of quantitative modeling
and simulations in generic drug development, especially for complex and
locally acting products, and (2) gain input regarding opportunities and
knowledge gaps related to the use of quantitative modeling and
simulation to inform regulatory decision making through the product
lifecycle.
Modeling and simulation has been increasingly used in drug
development, providing a framework for synthesizing information and
extrapolating beyond what has been studied. Model-informed drug
development (MIDD) approaches can be applied to brand drug products
approved pursuant to a new drug application (NDA), and generic drug
products approved pursuant to an ANDA. MIDD holds particular promise in
key opportunity areas including pharmacokinetic/pharmacodynamics (PK/
PD) models, physiologically based pharmacokinetic (PBPK) or absorption
models, systems pharmacology, quantitative risk modeling, and emergent
machine learning tools. These application areas can leverage the large
pharmaceutical data sets (big data) available to FDA and other
organizations. Quantitative approaches have been used to address
significant scientific and regulatory issues in all phases of the
product lifecycle: from pre-investigational new drug applications
through NDAs, ANDAs, and post-approval evaluation of new and generic
drugs. Given the broad applications of modeling and simulation through
the entire lifecycle of a product, there is a need to identify best
practices to improve the routine use and acceptance of modeling and
simulation for regulatory decision making.
The purposes of the workshop are to:
(1) Engage global stakeholders and share experience and vision on
using quantitative approaches in regulatory decision making for generic
drug development and product lifecycle management;
(2) Identify and prioritize potential areas for global
harmonization for tools to inform regulatory decision making;
(3) Share the current state of knowledge and practice in utilizing
quantitative methods and modeling for generic drug development and
review by case demonstrations and by integrating experience and lessons
learned from new drug product development and reviews;
(4) Identify opportunities for complex and locally acting product
development and discuss approaches and principles in using quantitative
methods and modeling to aid product-specific guidance development, pre-
ANDA interactions between FDA and prospective applicants, ANDA reviews,
and postmarket performance monitoring; and
(5) Discuss next generation quantitative method and modeling
toolsets, future directions, and application areas beyond currently
available tools.
There is a paradigm shift to a risk-based product-specific
regulatory approach for generic drugs. Examples of this transition
include recommendations for partial AUC (area under the concentration-
time curve) for some modified release drugs and replicate study
bioequivalence (BE) recommendations for narrow therapeutic index (NTI)
drugs. These product-specific guidances are driven by the therapeutic
significance of either the exposure-response relationships for safety
and efficacy (NTI drugs) or the difference in the shape of PK profiles.
Modeling and simulation toolsets direct the design and evaluation of PK
or comparative clinical endpoint BE studies, help evaluate clinical
endpoint sensitivity and feasibility, and enable the assessment of
alternative BE approaches. Overall, quantitative methods and modeling
support better and faster decisions during the generic drug development
and review process because they integrate knowledge accumulated during
and after new drug product development, including in vitro in vivo
correlation for formulation design, absorption, distribution,
metabolism, and excretion properties, population PK, and exposure-
response relationships for efficacy and safety.
There is also a growing recognition that analysis of large datasets
helps organizations and individuals make better decisions. Emerging
methodologies that enable the Agency to take advantage of big data will
impact how generic drugs are developed, reviewed, and monitored.
Knowledge extracted from large datasets can provide FDA the opportunity
to improve the focus of regulatory review, modernize BE assessment
criteria, and efficiently manage workload by predicting future ANDA
applications. Further, such knowledge will support industry's efforts
to optimize their generic drug portfolios to meet upcoming patient and
market needs. The public workshop will focus on the use and advance of
quantitative methods and modeling in modernizing generic drug
development, regulatory review, and product lifecycle management.
II. Scope of Public Input Requested
FDA seeks input on a range of topics related to the conduct of
modeling and simulation by pharmaceutical industries and by FDA and on
the interpretation and use of simulations for risk-based regulatory
assessment. They include:
(1) Opportunity areas for model-informed generic drug development
and review
(2) Risk-based BE standard for complex and locally acting products:
a. Under what circumstances would alternative approaches to the
product-specific BE guidances be encouraged?
b. What can serve as evidentiary data when proposing alternative BE
approaches?
c. What are the scientific and regulatory challenges in using a
model-based BE approach?
(3) Emerging quantitative methods and modeling in assisting
regulatory decision making for drug development and product life cycle
management:
a. What are the areas (e.g., excipient selection, molecular target/
mechanism of action-safety profile association, universal exposure
response models for drugs with the same target) that can benefit most
in the big data era and what will be the regulatory impact and
implications?
b. What are the potential new methods, including but not limited
to, machine learning and their application areas in assisting drug
development and review?
(4) Post-approval evaluation of the substitutability of generic
products for
[[Page 45865]]
the corresponding reference listed drugs or reference standards:
a. How to effectively integrate systems pharmacology, PBPK, and the
exposure-clinical response relationship to evaluate product risk and
assist BE evaluation?
b. What will be the next generation methodologies in postmarket
signal detection to evaluate product substitution or compare product
performance using the Sentinel database or complementary toolsets?
III. Participating in the Public Workshop
Registration: Persons interested in attending this public workshop
must register online at https://survey.co1.qualtrics.com/jfe/form/SV_3eiJOCsnrPdTZU9. Please provide complete contact information for
each attendee, including name, title, affiliation, address, email, and
telephone.
Registration is free and based on space availability, with priority
given to early registrants. Persons interested in attending this public
workshop must register by September 25, 2017, midnight, Eastern
Standard Time. Early registration is recommended because seating is
limited; therefore, FDA may limit the number of participants from each
organization.
If you need special accommodations due to a disability, please
contact Lanyan (Lucy) Fang (see FOR FURTHER INFORMATION CONTACT) no
later than 7 days before the workshop.
Requests for Oral Presentations: During online registration you may
indicate if you wish to present during a public comment session, and
which topic(s) you wish to address. We will do our best to accommodate
requests to make public comments. Individuals and organizations with
common interests are urged to consolidate or coordinate their
presentations, and to request time for a joint presentation, or to
submit requests for designated representatives to participate in the
focused sessions. Following the close of registration, we will
determine the amount of time allotted to each presenter and the
approximate time each oral presentation is to begin, and will select
and notify participants by September 27, 2017. All requests to make
oral presentations must be received by the close of registration on
September 25, 2017. If selected for presentation, any presentation
materials must be emailed to Lanyan (Lucy) Fang (see FOR FURTHER
INFORMATION CONTACT) no later than September 28, 2017. No commercial or
promotional material will be permitted to be presented or distributed
at the public workshop.
Streaming Webcast of the Public Workshop: This public workshop will
also be webcast. A live webcast of this workshop will be viewable at
https://collaboration.fda.gov/dqmm1017/on the day of the workshop.
If you have never attended a Connect Pro event before, test your
connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. To get a quick overview of the Connect Pro program,
visit https://www.adobe.com/go/connectpro_overview. FDA has verified
the Web site addresses in this document, as of the date this document
publishes in the Federal Register, but Web sites are subject to change
over time.
Transcripts: Please be advised that as soon as a transcript of the
public workshop is available, it will be accessible at https://www.regulations.gov. It may be viewed at the Dockets Management Staff
(see ADDRESSES). A link to the transcript will also be available on the
internet at https://www.fda.gov/Drugs/NewsEvents/ucm554182.htm.
Dated: September 26, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-21017 Filed 9-29-17; 8:45 am]
BILLING CODE 4164-01-P
