
[Federal Register Volume 81, Number 44 (Monday, March 7, 2016)]
[Notices]
[Pages 11804-11806]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-04965]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-N-0668]


Mechanistic Oral Absorption Modeling and Simulation for 
Formulation Development and Bioequivalence Evaluation; Public Workshop; 
Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is

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announcing a public workshop entitled ``Mechanistic Oral Absorption 
Modeling and Simulation for Formulation Development and Bioequivalence 
Evaluation.'' The purposes of the workshop are to share current FDA 
experiences on the application of mechanism-based absorption modeling 
and simulation in regulatory activities; discuss current and future 
utility of mechanism-based absorption modeling and simulation in the 
development of bioequivalent oral drug products and regulatory reviews; 
obtain input from various stakeholders on when, where, and how to 
conduct mechanism-based absorption modeling and simulations in the 
context of bioequivalent product development; and request comments on 
these topics.

DATES: The public workshop will be held on May 19, 2016, from 8:30 a.m. 
to 4:30 p.m. Individuals who wish to attend the workshop must register 
by April 19, 2016. The deadline for submitting either electronic or 
written comments on this workshop is June 20, 2016. See the 
SUPPLEMENTARY INFORMATION section for registration date and 
information.

ADDRESSES: The public workshop will be held at FDA White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room 
(Rm. 1503A), Silver Spring, MD 20993-0002. 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 http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Since 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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2016-N-0668 for ``Mechanistic Oral Absorption Modeling and 
Simulation for Formulation Development and Bioequivalence Evaluation; 
Public Workshop; Request for Comments.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at http://www.regulations.gov or at 
the Division of Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Xinyuan Zhang, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4612, Silver Spring, MD 20993, 240-402-
7971, email: Xinyuan.Zhang@fda.hhs.gov; or Liang Zhao, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4606, Silver Spring, MD 20993, 240-402-
4468, email: Liang.Zhao@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In July 2012, Congress passed the Generic Drug User Fee Amendments 
(GDUFA) (Title III of the Food and Drug Administration Safety and 
Innovation Act (Pub. L. 112-144)). GDUFA is designed to enhance public 
access to safe, high-quality generic drugs and reduce costs to 
industry. To support this goal, FDA agreed in the GDUFA commitment 
letter to work with industry and interested stakeholders on identifying 
regulatory science research priorities specific to generic drugs for 
each fiscal year covered by GDUFA. The commitment letter outlines FDA's 
performance goals and procedures under the GDUFA program for the years 
2012 to 2017. The commitment letter can be found at http://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM282505.pdf.
    In the Regulatory Science section of the GDUFA Commitment Letter, 
FDA outlined its plans to advance regulatory science, including with 
respect to modeling and simulation. To enhance communication of recent 
advances in modeling and simulation, including those supported by GDUFA 
funds, FDA plans to hold a public workshop on

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mechanistic oral absorption modeling and simulation. Mechanism-based 
absorption modeling and simulation is a computational tool that 
integrates drug substance information, drug product information, drug 
product in vitro performance, and physiological properties of the human 
body to predict drug product pharmacokinetics in vivo. Modeling 
simulation studies may also, in principle, be used as a tool to 
elucidate dissolution boundaries that have high likelihood of remaining 
bioequivalence, and those boundaries can be used to inform clinically 
relevant dissolution specifications. Models developed in a mechanistic 
manner integrating all available knowledge relevant to the absorption 
process lend great value for development of bioequivalent oral drug 
products and regulatory evaluation because the main differences between 
the reference drug products and the bioequivalent products (e.g., the 
difference in formulation factors) are taken into account in the model.

II. Purpose and Scope of the Workshop

    The purpose of the workshop is to:
    1. Share FDA's current experiences on the application of mechanism-
based absorption modeling and simulation in regulatory activities;
    2. Discuss the current and future utility of mechanism-based 
absorption modeling and simulation in development of bioequivalent oral 
drug products and regulatory reviews; and
    3. Obtain input from the public on when, where, and how mechanism-
based absorption modeling and simulation should be applied in 
development of bioequivalent oral drug products and review of 
bioequivalence.
    The scope of the workshop covers the current status of mechanism-
based absorption modeling and simulation from academia, industry, and 
regulatory perspectives.
    The majority of drug products on the market are administered 
orally. Predicting oral bioavailability is always of great interest for 
pharmaceutical scientists. It has been a long journey for scientists to 
develop mechanistic absorption models for oral bioavailability 
prediction to reduce drug development time and cost, and to inform 
regulatory decisions. From simpler models to more complex ones, 
mechanism-based absorption models have been advanced substantially and 
their applications have been increasingly found in scientific 
literature and regulatory reports.
    The high value of leveraging mechanistic absorption models in the 
development and evaluation of bioequivalent drug products can be 
attributed to their incorporation of formulation factors. The focus of 
this public workshop is on the application of mechanistic absorption 
modeling and simulation for development of bioequivalent oral drug 
products and evaluation of bioequivalence, including discussing the 
areas in which mechanistic oral absorption models can contribute 
significantly, how the mechanistic absorption modeling and simulation 
should be conducted and evaluated, and inherent scientific challenges.
    Public input will improve FDA's current understanding of using 
mechanism-based absorption modeling and simulation in bioequivalence 
evaluation. The knowledge gained from, and consensus reached, through 
this workshop will be summarized and disseminated to the scientific 
community by publication(s).

III. Scope of Public Input Requested

    FDA seeks input from the public on when, where, and how to utilize 
mechanism-based absorption modeling and simulation in the context of 
development of bioequivalent oral drug products and regulatory 
evaluation of bioequivalence. Specific topics to be addressed include:
    1. Identifying the areas in which mechanistic oral absorption 
models can contribute significantly during development of bioequivalent 
oral drug products and regulatory evaluation of bioequivalence;
    2. How mechanistic absorption modeling and simulation should be 
conducted and evaluated; and
    3. The scientific challenges in mechanistic oral absorption and 
simulation.
    Registration and Requests for Attendee Participation: 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 (either in person or by Webcast (see Streaming 
Webcast of the Public Workshop)) must register on or before April 19, 
2016, by sending a request to CDER-OGD-OfficeofResearchandStandardsAnnouncement@fda.hhs.gov with their 
complete contact information (i.e., name, title, affiliation, address, 
email address, and telephone number).
    There is no registration fee for the public workshop. Early 
registration is recommended because seating is limited. Registration on 
the day of the public workshop will be provided on a space available 
basis beginning at 8 a.m.
    If you need special accommodations due to a disability, please 
contact Xinyuan Zhang (see FOR FURTHER INFORMATION CONTACT) at least 7 
days in advance.
    The workshop agenda and other background materials will be 
available approximately 2 weeks before the workshop at http://www.fda.gov/Drugs/NewsEvents/ucm488178.htm. The agenda will include 
time for questions and answers throughout the day and for general 
comments and questions from the audience following panel discussions.
    In this document, FDA has included specific issues that will be 
addressed by the panel. If you wish to address one or more of these 
issues, please submit your comments via the Docket or speak during the 
public comments session at the workshop. If you wish to speak during 
the public comments session at the workshop, please indicate it at the 
time you register so that FDA can consider that in planning the agenda. 
FDA will do its best to accommodate requests to speak.
    Streaming Webcast of the Public Workshop: A live Webcast of this 
workshop will be viewable at https://collaboration.fda.gov/r6gjahu3ejv 
on the day of the workshop. The live Webcast will be in a listening 
only mode.
    Transcripts: Transcripts of the workshop will be available for 
review at http://www.fda.gov/Drugs/NewsEvents/ucm488178.htm at the 
Division of Dockets Management (see ADDRESSES), and at http://www.regulations.gov approximately 30 days after the workshop. A 
transcript will also be available, in either hardcopy or on CD-ROM, 
after submission of a Freedom of Information request. The Freedom of 
Information office address is available on the Agency's Web site at 
http://www.fda.gov.

    Dated: March 1, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-04965 Filed 3-4-16; 8:45 am]
BILLING CODE 4164-01-P


