[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]


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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.

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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: [email protected]; 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: [email protected].

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 http://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