Federal Register / Vol. 82, No. 189 / Monday, October 2, 2017 / Notices 45863 

IV. Paperwork Reduction Act of 1995 

This guidance refers to previously 

approved collections of information 

found in FDA regulations. These 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520). The collections of information in 

21 CFR parts 1002, 1010, and 1040 are 

approved under OMB control number 

0910–0025. 

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. 

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 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 

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/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. 

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 


sradovich on DSK3GMQ082PROD with NOTICES
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: 

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 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 

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 45865 

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. 

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 

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. 

SUMMARY: 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. 

ADDRESSES: 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 


sradovich on DSK3GMQ082PROD with NOTICES