Pre-Investigational New Drug Meetings with the FDA
Evaluation of Meeting Content and Characteristics of Applications
for New Drug and Biologic Products
National Organization of Rare Diseases (NORD)
Rare Diseases and Orphan Products Breakthrough Summit
October 21, 2014
Hong H. Vu, PharmD, MSc
Office of New Drugs, CDER
U.S. Food and Drug Administration
Disclaimer
• This presentation reflects the views of the presenter and
should not be construed to represent FDA’s view or
policies
• I have no conflicts of interest relevant to this activity
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Outline
• Background for evaluation of pre-Investigational New Drug
(pre-IND) Meetings with the FDA
• Analysis of marketing applications submitted to FDA CDER
in Fiscal Years (FY) 2008-2012
– Objectives
– Method
– Results
• Key points
• Who to contact
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Background
• Clinical development time (CDT)* for marketing applications
(NME and new biologic products) that received an approval
action from FDA CDER during FY 2008-2012.
pre-IND meeting
(n= 49 approved applications)
NO pre-IND meeting
(n= 83 approved applications)
Mean
6.6 yrs
9.7 yrs
Median
6.4 yrs
8.3 yrs
Range
1.6 - 12.3
1.6-43.8
CDT (years)
*CDT= defined as the time from receipt by FDA of the key IND through to the day of marketing application approval
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Analysis of Marketing Applications
Submitted to FDA CDER (FY 2008-2012)
• Objectives:
– To identify topics appropriate to the phase of drug development to
assist sponsors in holding efficient and productive pre-IND meetings
with FDA.
– To assess factors relating to application characteristics that can affect a
drug development program, such as company size, in order to identify
applications that may benefit the most from early interactions with
FDA.
• Methods:
– Retrospective analysis of New Molecular Entities (NME) and original
biological product marketing applications [NDAs and BLAs,
respectively]* for which an action was taken by FDA CDER from
October 1, 2007 to September 30, 2012.
*NDA=New Drug Application; BLA=Biologic License Application
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Methods (continued)
DOMAIN
SUBDOMAIN
CMC
NON-CLINICAL
CLINICAL
REGULATORY
Safety
Proof of concept
(efficacy)
Clinical Pharmacology
Clinical
Toxicology
Pharmacodynamic
Pharmcodynamic
Efficacy
Pediatrics
Toxicokinetic
Biomarker
Pharmacokinetic
Safety (premarketing)
Special
population
Carcinogenicity
Disease
model/nonclinical
outcome/endpoint
Pharmacogenomics
Study population
Inspection
Reprotoxicity
Indication
Labeling &
packaging
Genotoxicity
Endpoint
Format &
documentation
Study design
REMS or
postmarketing
CONTENT
Statistical
analysis plan
Abbreviation: CMC = Chemistry, Manufacturing and Controls; REMS = Risk Evaluation and Mitigation Strategy
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Results
• 200 marketing applications were identified
• 73 (36%) held a pre-IND meeting
• Pre-IND meeting content by domain
A. Questions posed by sponsors and responses
provided by FDA at pre-IND meetings by domain
B. Additional advice provided by
FDA at pre-IND meetings by domain
Occurence of topics by domain (73 drug applications)
32 (44%) applications with additional FDA comments ONLY
100%
Percentage of Occurrences
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
CMC
Non-Clinical
Clinical
Regulatory
Domain
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Results (2)
• Pre-IND meeting content at subdomain level
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Results (3)
• Application characteristics by company size*
*Company
size defined as small (< 150 employees), medium (150-14,999 employees) or large (≥ 15,000 employees)
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Results (4)
• Approval rate by whether a pre-IND meeting was held and the
true phase of drug development at which the sponsor submitted
the IND to FDA.
100%
90%
Percentage of approval
80%
70%
60%
True phase
50%
Phase 1
40%
Phase 2
30%
Phase 3
20%
10%
0%
PIND meetings
(n=48)
No PIND meetings
(n=84)
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Results: Summary of Major Findings
•
The data suggests that even though holding a pre-IND meeting does not appear to
affect approval rate, it may have a positive effect on a program’s overall
development time.
•
Topics frequently discussed in pre-IND meeting minutes tended to reflect topics
appropriate to an early phase of drug development, such as non-clinical toxicology,
clinical pharmacology, and clinical safety.
•
Notable trends observed for company size* (small, medium and large):
– Small companies had lower approval rates and longer clinical development time
compared with larger companies.
– Small companies also had less regulatory experience than larger companies, tended
to open INDs at later phases of development, and were more likely to submit
applications for rare disease indications.
*Company
size defined as small (< 150 employees), medium (150-14,999 employees) or large (≥ 15,000 employees)
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Key Points
• Meeting the challenges of product development for RDs requires
a destination-focused strategy.
– Opportunity for study and replication will be limited.
– “Getting it right” from the start is critical.
– Careful planning, frequent and quality communication (esp. early
communication) with FDA is strongly recommended.
• Small companies with limited regulatory and drug development
experience, particularly those developing new drugs for rare
diseases, may benefit from early and frequent communications
with the FDA.
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Contact Us…..
•
Within CDER:
– OND Enhanced Communication Team
• For general questions or which review division to contact
• Email [email protected] or call 301-796-0319
– OND Rare Diseases Program
• General questions relating to drug development for RDs
• Website at:
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm221248.htm
– Office of Communications, Division of Drug Information
• CDER’s focal point for public inquiries regarding human drug products
• Email [email protected] or call 301-796-3400
•
Within Office of Special Medical Programs:
– Office of Orphan Products Development
• General questions relating to drug development for RDs, especially Orphan designation
• Email [email protected] or call 301-796-8660
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Thank You
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