83 FR 4660 - Best Practices in Modeling and Simulation for Oncology Products; Public Workshop

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 22 (February 1, 2018)

Page Range		4660-4661
FR Document		2018-01992

The Food and Drug Administration's (FDA, the Agency, or we) Center for Drug Evaluation and Research (CDER), in co-sponsorship with the International Society of Pharmacometrics (ISoP), is announcing a public workshop entitled ``Best Practices in Modeling and Simulation for Oncology Products.'' The purpose of the meeting is to discuss ``best practices'' in integrating pharmacokinetic, pharmacodynamic, efficacy, and safety data into models to best inform oncology drug development, evaluate disease- and mechanism-specific early endpoints to predict long-term efficacy, and discuss potential regulatory implications of model-informed decisions in drug development. This workshop is also being conducted to satisfy one of FDA's performance goals included in the sixth reauthorization of the Prescription Drug User Fee Act (PDUFA VI), part of the FDA Reauthorization Act of 2017 (FDARA), to hold a series of workshops related to model-informed drug development (MIDD).

Federal Register, Volume 83 Issue 22 (Thursday, February 1, 2018)

[Federal Register Volume 83, Number 22 (Thursday, February 1, 2018)]
[Notices]
[Pages 4660-4661]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2018-01992]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-0001]


Best Practices in Modeling and Simulation for Oncology Products; 
Public Workshop

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration's (FDA, the Agency, or we) 
Center for Drug Evaluation and Research (CDER), in co-sponsorship with 
the International Society of Pharmacometrics (ISoP), is announcing a 
public workshop entitled ``Best Practices in Modeling and Simulation 
for Oncology Products.'' The purpose of the meeting is to discuss 
``best practices'' in integrating pharmacokinetic, pharmacodynamic, 
efficacy, and safety data into models to best inform oncology drug 
development, evaluate disease- and mechanism-specific early endpoints 
to predict long-term efficacy, and discuss potential regulatory 
implications of model-informed decisions in drug development. This 
workshop is also being conducted to satisfy one of FDA's performance 
goals included in the sixth reauthorization of the Prescription Drug 
User Fee Act (PDUFA VI), part of the FDA Reauthorization Act of 2017 
(FDARA), to hold a series of workshops related to model-informed drug 
development (MIDD).

DATES: The public workshop will be held on February 1, 2018, from 8 
a.m. to 5 p.m., Eastern Time. See the SUPPLEMENTARY INFORMATION section 
for registration date and information.

ADDRESSES: The public workshop will be held at the FDA White Oak 
Campus, 10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great 
Room (Rm. 1503, B and C), Silver Spring, MD 20993-0002. Entrance for 
public workshop participants (non-FDA employees) is through Building 1 
where routine security procedures will be performed. For parking and 
security information, please refer to: http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.

FOR FURTHER INFORMATION CONTACT: Jeannette Dinin, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2108, Silver Spring, MD 20993-0002, 240-
402-4978, email: [email protected]; or Yvonne Knight, Center 
for Drug Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 51, Rm. 2142, Silver Spring, MD 20993-0002, 
301-796-2133, email: [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Under FDARA, FDA agreed, in accordance with section I of the PDUFA 
VI Performance Goals, Ensuring the Effectiveness of the Human Drug 
Review, part J, Enhancing Regulatory Decision Tools to Support Drug 
Development and Review, to convene a series of workshops to identify 
best practices for MIDD (https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf). FDA is conducting this 
workshop as part of the MIDD workshop series.
    Over the past few decades, there has been extensive investment in 
oncology drug discovery and development. Despite greater understanding 
of disease biology and drug mechanisms of action, further progress in 
model-informed strategies is needed to continue advancements in 
oncology drug development. Innovations in clinical trial design 
utilizing more informative endpoints could help bring more effective 
treatment options to cancer patients faster by accelerating development 
of effective new drugs and reducing failure rates in expensive late-
phase development.
    As more effective and complex combination strategies and novel 
targets for cancer treatment evolve, exploring more informative and 
predictive endpoints to assess treatment response

[[Page 4661]]

(e.g., response evaluation criteria in solid tumors-based endpoints 
(RECIST)) has become an active area of research. Alternative metrics 
that require shorter periods of observation or provide more precise 
assessment of treatment effects could lead to more rapid completion of 
clinical trials and require fewer patients. Promising among these 
alternative metrics are model-based metrics, such as those based on 
longitudinal continuous tumor size measurements. Additionally, model-
informed approaches can help satisfy a need to optimize dosing regimens 
for patients. Investigations to refine dosing regimens often occur 
after new drug approval and/or are driven by pharmacometric modeling 
approaches. There is growing interest in using model-informed 
approaches to help balance the risks and benefits of oncology products 
by identifying optimal dosing regimens, and broad stakeholder 
engagement and discussion around this topic can be beneficial.

II. Objectives

    The objectives of the workshop are to:
    1. Discuss ``best practices'' in integrating human pharmacokinetic, 
pharmacodynamic, efficacy, and safety data into models that best inform 
oncology drug development.
    2. Describe novel imaging techniques and diagnostic and predictive 
biomarkers that may be utilized in oncology drug development.
    3. Describe disease- and mechanism-specific early endpoints to 
predict long-term efficacy.
    4. Evaluate the potential to shift from traditional RECIST-based 
endpoints such as Overall Response Rate (ORR) and Progression Free 
Survival (PFS) to modified RECIST approaches (e.g., imRECIST for 
immunotherapies) as well as to other (model-based) tumor kinetic 
metrics to support early decision making in Phase 1/2 as well as in 
confirmatory trials.
    5. Discuss potential regulatory implications of model-informed 
decisions in drug development, including, model-based target 
identification, dose/exposure justification based on preclinical 
evidence, dose selection for first-in-human trials, quality by design, 
early clinical study design, dose finding/titration, confirmatory 
trials, product labeling, and post-marketing studies.
    A detailed agenda will be posted on the following website in 
advance of the workshop: https://www.fda.gov/downloads/Drugs/NewsEvents/UCM589458.pdf.

III. Registration and Accommodations

    Registration: Persons interested in attending this public workshop 
must register online by January 31, 2018, at https://fdaoce.formstack.com/forms/isop. Please provide complete contact 
information for each attendee, including name, title, affiliation, 
address, email, and telephone number.
    Registration is free and based on space availability, with priority 
given to early registrants. Early registration is recommended because 
seating is limited; therefore, FDA may limit the number of participants 
from each organization. Registrants will receive confirmation when they 
have been accepted. If time and space permit, onsite registration on 
the day of the public workshop will be provided beginning at 8 a.m.
    If you need special accommodations due to a disability, please 
contact Yvonne Knight (see FOR FURTHER INFORMATION CONTACT) no later 
than January 24, 2018.
    Streaming Webcast of the Public Workshop: The meeting will also be 
webcast. A live webcast of this workshop will be available at https://collaboration.fda.gov/fdaisop/ 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 website 
addresses in this document, as of the date this document publishes in 
the Federal Register, but websites 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://
FDAOCE.formstack.com/forms/isop. It may be viewed at the Dockets 
Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

    Dated: January 29, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-01992 Filed 1-31-18; 8:45 am]
 BILLING CODE 4164-01-P

4660 Federal Register / Vol. 83, No. 22 / Thursday, February 1, 2018 / Notices

2. Question #7 has been revised to Estimated Annualized Burden Hours The total estimated burden is 4,345
change wording to ‘‘Name of program hours per year. ACL/AoA estimates the
offered.’’ The proposed Falls Prevention Data burden of this collection of information
Collection Tools can be found at ACL’s as 288 hours for project staff, 1,435
Website at: https://www.acl.gov/about- hours for local agency staff, and 2,622
acl/public-input. hours for individuals.

Average time Total burden
Estimated number of Number of responses
Type of respondent Form name per response hours
respondents per respondent (in hours) (annual)

Project staff ..................... Semi-annual Perform- 18 ................................... Twice a year ................... 8 288
ance Report.
Local agency leaders ...... Program Information 700 leaders .................... Twice a year (one set .50 700
Cover Sheet/Partici- per program).
pant Information Form/
Attendance Log/Post
Program Survey.
Local data entry staff ...... 36 data entry staff .......... Once per program × .50 700
1,400 programs.
Local organization staff Host Organization Data 700 staff ......................... 1 ..................................... .05 35
and local database Form.
entry staff.
Program participants ....... Participant Information 16,390 ............................ 1 ..................................... .10 1,639
Form.
Program participants ....... Post Program Survey ..... 9,834 .............................. 1 ..................................... .10 983

Total Burden Hours .. ......................................... ......................................... ......................................... .......................... 4,345

Dated: January 26, 2018. being conducted to satisfy one of FDA’s 796–2133, email: Yvonne.Knight@
Mary Lazare, performance goals included in the sixth fda.hhs.gov.
Principal Deputy Administrator. reauthorization of the Prescription Drug SUPPLEMENTARY INFORMATION:
[FR Doc. 2018–02000 Filed 1–31–18; 8:45 am] User Fee Act (PDUFA VI), part of the
BILLING CODE 4154–01–P FDA Reauthorization Act of 2017 I. Background
(FDARA), to hold a series of workshops Under FDARA, FDA agreed, in
related to model-informed drug accordance with section I of the PDUFA
DEPARTMENT OF HEALTH AND development (MIDD). VI Performance Goals, Ensuring the
HUMAN SERVICES DATES: The public workshop will be Effectiveness of the Human Drug
held on February 1, 2018, from 8 a.m. Review, part J, Enhancing Regulatory
Food and Drug Administration to 5 p.m., Eastern Time. See the Decision Tools to Support Drug
[Docket No. FDA–2018–N–0001] SUPPLEMENTARY INFORMATION section for Development and Review, to convene a
registration date and information. series of workshops to identify best
Best Practices in Modeling and ADDRESSES: The public workshop will practices for MIDD (https://
Simulation for Oncology Products; be held at the FDA White Oak Campus, www.fda.gov/downloads/ForIndustry/
Public Workshop 10903 New Hampshire Ave., Bldg. 31 UserFees/PrescriptionDrugUserFee/
Conference Center, the Great Room (Rm. UCM511438.pdf). FDA is conducting
AGENCY: Food and Drug Administration,
1503, B and C), Silver Spring, MD this workshop as part of the MIDD
HHS.
20993–0002. Entrance for public workshop series.
ACTION: Notice of public workshop. workshop participants (non-FDA Over the past few decades, there has
SUMMARY: The Food and Drug employees) is through Building 1 where been extensive investment in oncology
Administration’s (FDA, the Agency, or routine security procedures will be drug discovery and development.
we) Center for Drug Evaluation and performed. For parking and security Despite greater understanding of disease
Research (CDER), in co-sponsorship information, please refer to: http:// biology and drug mechanisms of action,
with the International Society of www.fda.gov/AboutFDA/ further progress in model-informed
Pharmacometrics (ISoP), is announcing WorkingatFDA/BuildingsandFacilities/ strategies is needed to continue
a public workshop entitled ‘‘Best WhiteOakCampusInformation/ advancements in oncology drug
Practices in Modeling and Simulation ucm241740.htm. development. Innovations in clinical
for Oncology Products.’’ The purpose of FOR FURTHER INFORMATION CONTACT: trial design utilizing more informative
the meeting is to discuss ‘‘best Jeannette Dinin, Center for Drug endpoints could help bring more
practices’’ in integrating Evaluation and Research, Food and effective treatment options to cancer
pharmacokinetic, pharmacodynamic, Drug Administration, 10903 New patients faster by accelerating
efficacy, and safety data into models to Hampshire Ave., Bldg. 22, Rm. 2108, development of effective new drugs and
sradovich on DSK3GMQ082PROD with NOTICES

best inform oncology drug development, Silver Spring, MD 20993–0002, 240– reducing failure rates in expensive late-
evaluate disease- and mechanism- 402–4978, email: Jeannette.Dinin@ phase development.
specific early endpoints to predict long- fda.hhs.gov; or Yvonne Knight, Center As more effective and complex
term efficacy, and discuss potential for Drug Evaluation and Research, Food combination strategies and novel targets
regulatory implications of model- and Drug Administration, 10903 New for cancer treatment evolve, exploring
informed decisions in drug Hampshire Ave., Bldg. 51, Rm. 2142, more informative and predictive
development. This workshop is also Silver Spring, MD 20993–0002, 301– endpoints to assess treatment response

VerDate Sep<11>2014 19:34 Jan 31, 2018 Jkt 244001 PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 E:\FR\FM\01FEN1.SGM 01FEN1

Federal Register / Vol. 83, No. 22 / Thursday, February 1, 2018 / Notices 4661

(e.g., response evaluation criteria in III. Registration and Accommodations DEPARTMENT OF HEALTH AND
solid tumors-based endpoints (RECIST)) HUMAN SERVICES
has become an active area of research. Registration: Persons interested in
Alternative metrics that require shorter attending this public workshop must Food and Drug Administration
periods of observation or provide more register online by January 31, 2018, at
https://fdaoce.formstack.com/forms/ [Docket Nos. FDA–2016–E–1234 and FDA–
precise assessment of treatment effects 2016–E–1257]
could lead to more rapid completion of isop. Please provide complete contact
clinical trials and require fewer patients. information for each attendee, including Determination of Regulatory Review
Promising among these alternative name, title, affiliation, address, email, Period for Purposes of Patent
metrics are model-based metrics, such and telephone number. Extension; CORLANOR
as those based on longitudinal Registration is free and based on
continuous tumor size measurements. AGENCY: Food and Drug Administration,
space availability, with priority given to HHS.
Additionally, model-informed early registrants. Early registration is
approaches can help satisfy a need to ACTION: Notice.
recommended because seating is
optimize dosing regimens for patients.
limited; therefore, FDA may limit the SUMMARY: The Food and Drug
Investigations to refine dosing regimens
number of participants from each Administration (FDA or the Agency) has
often occur after new drug approval
and/or are driven by pharmacometric organization. Registrants will receive determined the regulatory review period
modeling approaches. There is growing confirmation when they have been for CORLANOR and is publishing this
interest in using model-informed accepted. If time and space permit, notice of that determination as required
approaches to help balance the risks and onsite registration on the day of the by law. FDA has made the
benefits of oncology products by public workshop will be provided determination because of the
identifying optimal dosing regimens, beginning at 8 a.m. submission of applications to the
and broad stakeholder engagement and If you need special accommodations Director of the U.S. Patent and
discussion around this topic can be due to a disability, please contact Trademark Office (USPTO), Department
beneficial. of Commerce, for the extension of a
Yvonne Knight (see FOR FURTHER
patent which claims that human drug
II. Objectives INFORMATION CONTACT) no later than
product.
January 24, 2018.
The objectives of the workshop are to: DATES: Anyone with knowledge that any
Streaming Webcast of the Public
1. Discuss ‘‘best practices’’ in of the dates as published (in the
Workshop: The meeting will also be
integrating human pharmacokinetic, SUPPLEMENTARY INFORMATION section) are
webcast. A live webcast of this
pharmacodynamic, efficacy, and safety incorrect may submit either electronic
workshop will be available at https:// or written comments and ask for a
data into models that best inform collaboration.fda.gov/fdaisop/ on the
oncology drug development. redetermination by April 2, 2018.
day of the workshop. If you have never Furthermore, any interested person may
2. Describe novel imaging techniques attended a Connect Pro event before,
and diagnostic and predictive petition FDA for a determination
test your connection at https:// regarding whether the applicant for
biomarkers that may be utilized in collaboration.fda.gov/common/help/en/
oncology drug development. extension acted with due diligence
support/meeting_test.htm. To get a during the regulatory review period by
3. Describe disease- and mechanism- quick overview of the Connect Pro July 31, 2018. See ‘‘Petitions’’ in the
specific early endpoints to predict long- program, visit https://www.adobe.com/ SUPPLEMENTARY INFORMATION section for
term efficacy. go/connectpro_overview. FDA has more information.
4. Evaluate the potential to shift from verified the website addresses in this ADDRESSES: You may submit comments
traditional RECIST-based endpoints document, as of the date this document as follows. Please note that late,
such as Overall Response Rate (ORR) publishes in the Federal Register, but untimely filed comments will not be
and Progression Free Survival (PFS) to websites are subject to change over time. considered. Electronic comments must
modified RECIST approaches (e.g.,
Transcripts: Please be advised that as be submitted on or before April 2, 2018.
imRECIST for immunotherapies) as well
soon as a transcript of the public The https://www.regulations.gov
as to other (model-based) tumor kinetic
workshop is available, it will be electronic filing system will accept
metrics to support early decision
accessible at https:// comments until midnight Eastern Time
making in Phase 1/2 as well as in
FDAOCE.formstack.com/forms/isop. It at the end of April 2, 2018. Comments
confirmatory trials.
may be viewed at the Dockets received by mail/hand delivery/courier
5. Discuss potential regulatory (for written/paper submissions) will be
implications of model-informed Management Staff (HFA–305), Food and
considered timely if they are
decisions in drug development, Drug Administration, 5630 Fishers
postmarked or the delivery service
including, model-based target Lane, Rm. 1061, Rockville, MD 20852. acceptance receipt is on or before that
identification, dose/exposure Dated: January 29, 2018. date.
justification based on preclinical Leslie Kux,
evidence, dose selection for first-in- Electronic Submissions
Associate Commissioner for Policy.
human trials, quality by design, early Submit electronic comments in the
clinical study design, dose finding/ [FR Doc. 2018–01992 Filed 1–31–18; 8:45 am]
following way:
sradovich on DSK3GMQ082PROD with NOTICES

titration, confirmatory trials, product BILLING CODE 4164–01–P
• Federal eRulemaking Portal:
labeling, and post-marketing studies. https://www.regulations.gov. Follow the
A detailed agenda will be posted on instructions for submitting comments.
the following website in advance of the Comments submitted electronically,
workshop: https://www.fda.gov/ including attachments, to https://
downloads/Drugs/NewsEvents/ www.regulations.gov will be posted to
UCM589458.pdf. the docket unchanged. Because your

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Document Created: 2018-10-26 13:47:27
Document Modified: 2018-10-26 13:47:27

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of public workshop.
Dates		The public workshop will be held on February 1, 2018, from 8 a.m. to 5 p.m., Eastern Time. See the SUPPLEMENTARY INFORMATION section for registration date and information.
Contact		Jeannette Dinin, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2108, Silver Spring, MD 20993-0002, 240- 402-4978, email: [email protected]; or Yvonne Knight, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2142, Silver Spring, MD 20993-0002, 301-796-2133, email: [email protected]
FR Citation		83 FR 4660

83 FR 4660 - Best Practices in Modeling and Simulation for Oncology Products; Public Workshop

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 22 (February 1, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration