1 integrated development pharmaceutical advisors llc july 2005
TRANSCRIPT
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Integrated DevelopmentIntegrated Development
Pharmaceutical Advisors LLCJuly 2005
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Integrated Development StrategiesIntegrated Development Strategies
• Required Between:– Discovery & Development Organizations– Within Development Organization– Between Development Organization and
Commercial Organization– With RSOs/Suppliers
• Acceleration/Compression Requires Timeline:– Forward from nomination and…..– Backwards from projected NDA filing date
and approval/launch target
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Start No Later Than…Start No Later Than…
• Candidate Nomination– Transition from Discovery to Development– Candidate Nomination Guidelines
• Agreed Criteria Which Need to be Met to Nominate new Drug Candidate
• Drives Discovery Strategies from Lead Identification/Optimization to Candidate Nomination
– Ensures candidate selection process is driven by agreed targets/goals across portfolio of candidates
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Must Be Forward Looking and…Must Be Forward Looking and…
• Candidate Nomination– Candidate Nomination Document
• Summary of Data/Rational for Progression of Candidate to Development
– What are Positive Features of Candidate?– What are Issues/Flaws
• For Management Review and Approval• Approval Formally Triggers activities to Progress
Candidate to Phase I– integrated planning required to ensure efficient
transition– need to define process for managing this transition
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Work Back From Commercial GoalsWork Back From Commercial Goals
• Candidate Nomination Document (CND) Template– Table of Contents
• Biological Profile• Market Positioning/Rationale• Competitive Situation• Pharmacokinetics/Pharmacodynamic Summary/Issues
(ADME)• Safety Information/Issues• Drug Substance Technology/Issues• Physical Pharmacy/Dosage Form Issues• Bulk Supply Status/Issues• Intellectual Property Status/Issues
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Approved Indicated Products
UnapprovedProducts
Target Product Profile
ParameterLong ActingAnti-XXXXX
Long ActingXX Agonist
XXXInhibitor
Minimum Desired
ClassExample
XXXXX XXXXX XXXX
EFFICACY
ΔFEV1(vs baseline)
XXX-XXX ml(28-31%)
XXXml(20%)
XXX ml(500 mcg dose)
XXX ml(X%)
>XX%
Quality of Life Indicators #
Improvement Improvement Improvement XXX XXX
Development of Tolerance
no no no (?) XXX XXX
DiseaseModification ##
no no ? XXX XXX
# Post dose exercise challenge## Reduction in the rate of XXXXXX
Considering a Target Product ProfileConsidering a Target Product Profile
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Approved Indicated Products
UnapprovedProducts
Target Product Profile
ParameterLong Acting
Anti-XXXLong ActingXX Agonist
XX InhibitorMinimum Desired
SAFETY
Safe to Use in Combination
yes yes ? XXX XXX
Anti-XXXX X yes - - XXX- XXX-
XXX Stimulation XX - yes - XXX XXX-
GI Disturbances(nausea, vomiting)
- -?
(at elevated doses)
XXX XXX
SpecialPopulations
X X ? XXX XXX
PHARMACOKINETICS
Dosing XX mcg OD XXmcg BID XXX mcg OD XX XX
Delivery XXXXX XXX PO XX XX
OTHER
Annual Cost of Rx (Direct)
$XXX $XXX $X $X
Reduction in Indirect Costs
Considering a Target Product ProfileConsidering a Target Product Profile
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Link to Development PlanningLink to Development Planning
• Early Development Plan (EDP)– Developed After Approval of CND– Integrated Plan for all Key Activities Leading
to IND• To be updated as required by significant changes
in strategies/issues• Provides overview of ongoing development
activities, issues, timing • Requires Matrix Team to Manage
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Early Development PlanEarly Development Plan
• Early Development Plan Template– Table of Contents
• Clinical Plan/Strategy• Drug Safety Evaluation Plan• ADME Evaluation/Plan• DS/DP Strategy/Issues• IP Overview/Strategy/Issues• Other
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Making the TransitionMaking the Transition
Early Development Plan• Clinical Plan/Strategy• Drug Safety Evaluation Plan• ADME Evaluation/Plan• DS/DP Strategy/Issues• IP Overview / Strategy/
Issues• Financial
Integrated Development• Executive Summary• Marketing Strategy• Regulatory Strategy• Pre-Clinical Strategy• Clinical Strategy• Chemical Development• Manufacturing• Supply Chain • Financial
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Integrated Plan Contents IIntegrated Plan Contents I
Executive Summary • Key Objectives (can include a draft package insert)• Major Milestones & Decision Points• Risk Management Strategy• Financial Overview (project P&L, costs, resources, outsource requirements, etc)
Marketing Strategy• Key Indications • Global Market Forecast (regions, revenues, longevity, etc)• Product/Brand Image (size, color, dose, formulation, packaging, etc)• Trademark & Patent issues• Competitive Environment
Regulatory Strategy• Country/Regional issues (NDA, MAA, JNDA, PAI timelines, acceleration)• Regulatory Environment (pertinent guidelines, regional differences, etc)• Safety & Efficacy Targets
Pre-Clinical Development Strategy• PK studies required (protocol descriptions, pivotal vs. non-pivotal)• Toxicology/Pathology (protocol descriptions, pivotal vs. non-pivotal)• Clinical Development Strategy• Studies required (protocol descriptions, pivotal vs. non-pivotal)
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Integrated Plan Contents IIIntegrated Plan Contents II
Clinical Development Strategy• Studies required (protocol descriptions, pivotal vs. non-pivotal)
Chemical Manufacturing & Control (CMC) Development• Primary API batches• Route & filing strategy• Salt selection strategy• Stability batches• Technology transfer & scale-up• Manufacturing• Dosage form manufacturing site requirements• Delivery systems requirements• Storage & transport requirements• Analytical method development• Process & technology transfer requirements
Supply Chain • Volumes (typically units and kgs per year)• Sourcing• Distribution
Financial• Capital required• P&L, ROI etc
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Why All This Planning So Early?Why All This Planning So Early?
– Formalizes product development across the business– Provides a common, consistent planning framework across
diverse business segments/therapeutic areas– Ensures alignment with business objectives/high-level
strategies– Provides management with a high-level overview of a
complex project– Provides multi-disciplinary project teams with a clear intent
and roadmap– Holds key decision data for review, approval, “go/no go”
etc– Provides a basis for monitoring/managing the progress of
the project– Achieves consistency across projects– Guides planning at lower levels of detail
The Integrated Development Strategy is the guide to developing a drug candidate
and the business case for continued project funding.
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Common QuestionCommon Question
• Why all this planning? Our strategy is to license out in Phase II…– Ok if future milestone payments from
partner are not needed!– What if partner relationship changes?! – Often more is done than needed because of
lack of understanding about phase-appropriate development and quality!
– When is GMP material needed?– When do you start collecting NDA
documentation?
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The Development Strategy ProcessThe Development Strategy ProcessThere are usually three levels of strategy and planning There are usually three levels of strategy and planning
documents maintained throughout the lifetime of the product documents maintained throughout the lifetime of the product development effortdevelopment effort
Integrated Development Strategy (IDS)
Integrated Development Strategy (IDS)
Integrated Development PlanIntegrated Development Plan
Prepared by:Project TeamApproved by: Senior ManagementUpdated/Reviewed: QuarterlyAccountable: Project Team Leader
Prepared by:Project TeamApproved by: Senior ManagementUpdated/Reviewed: MonthlyAccountable: Project Team Leader
Pre-Clinical Development PlanPre-Clinical Development Plan
Clinical Development PlanClinical Development Plan
Regulatory Development PlanRegulatory Development Plan
Marketing Development PlanMarketing Development Plan
Prepared by:Sub-Team LeadersApproved by: Project Team LeaderUpdated/Reviewed: WeeklyAccountable: Sub-Team Leaders
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Timeline Compression Timeline Compression
• Presents Significant Challenges to Technology Development– Requires earlier investment of resources
• API can activities lead the way when compressing clinical timelines
• Invest in time critical activities early– Technology– Materials
– Better integration of activities with partners essential • Internal • External
• Integration of Activities Dictate that During Phase II:– Critical technology must be:
• Developed• Demonstrated at scale• Used to support preparation of:
– Phase III clinical supplies– ICH stability supplies
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Timeline Compression ImpactTimeline Compression Impact
CMC Investments then Precede Clinical Phase Preclinical I II III Review
API/DP Enabling TechnologyPhase I API/DP Supplies
API/DP TechnologyPhase II API/DP Supplies
Commercial TechnologyPhase III API/DP Supplies
Nomination PhI PhII PhIII NDA/MAA Approval
LaunchAPI/DPEnabling Technology &Supply Manufacturer
API/DPTechnology/Supplies
RM API DP
PhIII Supplies
RM API DPLaunchPlanning
RM DP DP StabilityAPI PAIn Planning
RM API DP ICH Stability ICH DP StabilityPlanning
DP Technology
API Technology
Raw Materials API Activities DP Activities Enabling
Phase II Becomes The BattlegroundPhase II Becomes The Battleground
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The Phase II BattlegroundThe Phase II Battleground
• Often under-considered by both out-licensing and commercially integrated firms– Resource limitations– Poor integration– Emphasis on clinical
• Integration of drug development activities – Balancing risk of investments against speed– Risk of CMC investments
• versus unknown clinical outcomes– Speed
• Delayed CMC investments put CMC activities on critical path to filing
• Huge potential impact on time, cost and clinical flexibility that directly impacts value
For Out licensing and Integrated companies alike
The Phase II BattlegroundThe Phase II Battleground
Nomination PhI PhII PhIII NDA/MAA Launch
APIForm
DP
API
CommercialTechnology
Window
CHANGE
PotentiallyImpacts
Filing Date
Clinical Efficacy Determination
The Phase II BattlegroundThe Phase II Battleground
Nomination PhI PhII PhIII NDA/MAA Launch
APIForm
DP
API
CommercialTechnology
Window
CHANGE
PotentiallyImpacts
Filing Date
Clinical Efficacy Determination
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Are You Ready Now?Are You Ready Now?
Will You Be Ready?