Molecular Development 21st Century Pharmaceuticals

1
Molecular Development21st Century Pharmaceuticals

• Joseph M. Palma, MD, MPH, CPE
• Institute of Defense Analyses
• March 29, 2007

571-437-7948 josephpalma_at_cox.net jpalma_at_ida.org
2
(No Transcript)
3
Networks
4
Global Regulators And Their Regulated Operons And
Functions In The Regulatory Network Of E. Coli
Radu Dorbin et al, BMC Bioinformatics. 2004 5
199
5
E-ColiTranscription Regulatory Network
Radu Dorbin, et al, BMC Bioinformatics. 2004 5
199
6
E-ColiTranscription Regulatory Network
BMC Bioinformatics. 2004 5 199
7
Outline

• Background
• Status
• Strategy
• Challenges
• System Issues
• Insights
• Considerations

8
Background

• Broad Spectrum Countermeasures against Emerging
  and Bioengineered Agents

9
Status

• Development System
• Traditionally One-BugOne Drug
• New Strategic Directioin
• Network Based Pharmaceuticals
• One DrugMultiple Bugs
• Strategy Alignment
• Resources and Needs

10
Relevant Competencies

• Research and Technology Centers of Excellence
• World Class Laboratories
• Research and Technology Centers of Excellence
• Advanced Product Development
• Pharmaceutical and FDA Regulatory Depth
  Expertise
• Human and Animal Protection
• Long-Standing FDA Regulatory Interface
• Technical Expertise and Depth
• Logistics
• Extensive Legal, Acquisition Procurement
  Expertise
• Information, Informatics and Bioinformatics
• Innovation

11
Strategy

• Components
• Characterization of the host-pathogen interaction
• Diagnostics and Therapeutics
• Preventive Measures
• Information Systems and Bioinformatics
• Challenges
• Innovation
• Technical
• Pharmaceutical
• Industrial
• Oversight

12
Orchestrating
Information
The Strategy
Reporting
Orchestration
Execution
Technology, Bioinformatics, Knowledge Development
Management
Timelines
Metrics
Trends
Documentation
Accountability
13
Challenges

• Pharmaceutical Development Challenges
• Radiological, Biological, Chemical Network
  Similarities
• Human Disease States Likely Share Networks
• Portfolios Current vs Orthogonal
• Technology Development
• Knowledge Development and Integration
• Information and Bioinformatics
• Product Development
• Competencies
• Integration of Network Development

14
Current Process
Portfolios
15
A Snapshot of the Industry Pharmaceutical Process
Portfolios
Candidates
M E T R I C S
DECISIONS
TPP Target Product Profile DP Decision Point
16
Current Industry View
Portfolios
Pharmaceutical Process
NDA
Clinical Data Analysis
Registration
Rework Optimize
Full Development
Candidate Medicine Tested in 3-10,000 Patients
(Phase III)
Extensive Safety Studies
Large Amounts of Candidate Medicine Synthesized
Rework Optimize
Studies in Healthy Volunteers (Phase I)
Candidates
Formulations Developed
Candidate Development
Exploratory Development
Early Safety Studies
Synthesis of Compounds
Screening
START
Project Team and Plans
Discovery
Rework Optimize
Adapted from information provided by Pfizer
Pharmaceuticals, Inc
17
Network Development
Portfolios
Very Dynamic
Points
1 2 3 4 5 6
Milestone C
Phase III (File NDA)
Milestone B
Phase I Small Human Test
Phase II
Approved
Post Launch Reviews
Candidates Optimized
Candidates Selected
Optimize
Approaches
E-IND
Multiple Approaches are Matured Multiple Drug
Candidates Manufactured
Requirements
IND Milestone A
Optimize
Several Genomic Candidates
Technologies
Develop one or More Network-Specific Countermeasur
es and Determine on Integration into a Cocktail
Validate Targets and Test Various Approaches
Several Proteomic Candidates
Technologies
Define KEY Network Components
Tes KEY t Network Components
Select the Best /or Integrate multicomponent
Select Candidates Approaches
Human Test All Candidates
Several Small Molecule Candidates
Technologies
Several Metabolic Candidates
Technologies
One Product or Multi-component Cocktails
Optimize
Orthogonal
Current
18
Orthogonal Reviews
Portfolios
Phase I
2 3
E-IND
Pre-Clinical
IND
Genomics
MEDS
Proteomics
Immunologic
Metabolomics
Development Decisions
19
Summary of Differences
Portfolios
20
I n t e g r a t i n g D e c i s i o n sfor the
Multiple Network Projects
Portfolios
Operations and Support
Concept Development
Production and Deployment
Technology Development 4 years
System Development Demonstration 3-4 years
2 Animal Rule/Surrogates To INDA
E-IND
Network CANDIDATES
FDA Review
IND
EUA
Discovery
Phase II III
Phase I
Discovery Early Development
Production
Process Scale-up
Idea
Confirmation of Profiles
Network Discovery
Continued FDA
Market
Ongoing Reviews
Proposal
Req for Dev
NDA
Leads
FORMULATIONS
MANUFACTURING
Integrating Oversight

• Academia
• Industry

Industry Partner
Thrust Area Leader
Thrust Area Leader
Disc. PTL
Development PTL
Discovery Lead
Development Lead
Industry Partner PTL
21
System Issues
22
Technology

• Knowledge
• Network Knowledge-Base Development
• Skills in Innovation, Research, Clinical
  Research, Network Formulations, Development,
  Manufacture, FDA, Quality Assurance, Oversight of
  Integrated Effort
• Polyvalent Technologies Knowledge Enhancement
• Associated Skills
• Animal Models and Surrogate Development
• GLP/cGMP/Pilot Lot Production Capabilities
• Expertise in FULL SPECTRUM Pharma Development
• Expertise in FULL-SCALE Manufacturing
• Strategic Business Development Industry,
  Academia, Orchestrated International Integration

23
Knowledge and Information

• Integrating Knowledge and Information
• Bioinformatics
• Dynamic Understanding of Networks
• Knowledge Development and Application to
  Development
• Multiscience and Multidiscipline
• Valuation of Orthogonal Analyses of Multiple
  Projects
• Detailed Analysis of Scientific Endeavors
• Status and Maturity of Each Technology
• Project Stage of Development
• Judgments on Manufacturing and Production
• Process and Programmatic Reviews
• Business, Legal and IP, Contracting with Partners

24
Product Development

• Scale-up
• Network-Based Pharmaceuticals
• Broad Spectrum
• Evaluation for non-Biodefense Applications
• Production Platforms
• Genomics, Proteomics, Immunologics, Metabolomics
• Cells, Plants, Animals, eggs, Protein
  Scaffolds, Alternatives
• Oversight of Projects Integration Across
  Projects
• Internal Cognitive Excellence vs
• Reliance on External Experience

25
Competencies

• Comprehensive Development
• Research through Development to Licensure and
  Patient
• Pharmaceutical Process in detail
• Multiple Scientific Pathways
• Multicomponent Pharmaceuticals
• Robust Post-Licensure Studies
• Broad Spectrum Endeavors
• Infectious Diseases Common Networks
• Network Commonalities
• Biological, Chemical, Radiological
• Human Disease States
• Knowledge Development and Information Management
• FDA Critical Paths, 2 Animal Rule, Licensure of
  Network Pharmaceuticals

26
Insights

• Need Broad Spectrum Development Enterprise
• Grounded in Science, Medicine and Pharmaceutical
  Development
• Broad Spectrum Testing to other Infectious
  Diseases
• May Require Multicomponent Pharmaceutical
  Initiative
• Core Competencies Resident in the Organization
  Do they Align?
• Cross-Cutting Integration of Information Systems
• Knowledge Development Bioinformatics
  Information and Knowledge Management
• Pharmaceutical Requirements Not Focused on
  Network Development
• Implement Orthogonal Development Strategy
• Develop Detailed Expertise in The Science under
  Development
• In Detail at the bench and all the way to
  the bottle and patient
• Integrate Other Government, Industry, Academia,
  International Partners
• Decision Processes Not Necessarily Positioned to
  Adapt to Network Development
• Infuse Milestone Decision Process with
  Scientific, Medical and Pharmaceutical Judgment
• Recognize Multiple Technical Challenges
• Identify Required Intellectual and Institutional
  (Scientific, Medical, Pharmaceutical and
  Programmatic Review Infrastructure) Capital
• Structural Challenges Exist
• Integration of Expertise
• Establish Scientific Oversight of Network
  Development

27
Considerations
28
Strategic

• Integrated Strategic Oversight
• Integrate Science into Network Decision Making
• Process Management Control
• Orthogonal Reviews
• Scientific gt Pharmaceutical gt Medical gt
  Programmatic
• Tiered Metrics Drive Funding Decisions
• Technical Review and Judgment Body Senior Body
• Funding Plans for Integration of Insights
  Solutions
• Collaborations
• National, Intl, Govt/Industry/Academia, Consortia
  Opportunities
• Inject Innovation Throughout

29
System

• Broad Spectrum Pharmaceutical Enterprise
• Network Biology
• Knowledge Information Development Management
  Activity
• Develop /or Recruit Necessary Competencies
• Orthogonal Pharmaceutical Process Decisions
• ScientificgtPharmaceuticalgtMedicalgtProgrammatic
• Scientific and Process Network Metrics
• Chem, Biol, PK/PD, Safety, Toxicity, Biomarkers,
  Formulation
• FDA Innovation Critical Path, 2-Animal Rule,
  e-IND PAT
• Infrastructure Partnerships
• National, Government, International, Academia,
  Capital
• Quantify Infrastructure Requirements

30
Process

• Link Milestones to Scientific Evolution
• Infuse Scientific, Medical and Pharmaceutical
  Judgment Throughout
• Will Likely be Different for Each Project
• Network Characterization Key Characteristics
  (KC)
• Based on Understanding of Key Network
  Components
• Structure KCs to Link to Clinical Outcomes at
  Earliest Opportunity
• Orthogonal Development
• Establish Cross-Cutting Technically Competent
  Project Teams
• Discovery, Optimization and Development
• Metrics
• Establish Scientific Through Programmatic Metrics
  Tied to pre-Clinical Decision Points, and to Key
  Decisions in Clinical Development
• Establish Process Analytical Technologies Program
  with Metrics
• Establish Expert Oversight Capability
• Internal or Consultant
• Approach 1. Various Scientific Endeavors
• 2. Multiple
  Candidates Under Development
• 3. FDA Critical Path
  Discussions
• E-IND Tests in Humans
• IND and Milestone A Dynamic

31
Organizational Considerations

• Pharmaceutical Incorporate Network Development
• Bioinformatics for Network Development
• Orthogonal Portfolio Review
• Decision Process - Base on Scientific Validation
  at
• 1. Implementation of E-IND
• 2. Development After E-IND
• 3 Decisive Development post IND
• 4 Pre-Licensure
• 5 Process Analytical Technologies Metrics
• Quantify Institutional and Intellectual
  Requirements
• Establish Manufacturing Capability At Least for
  Network Enterprise
• Organize Competencies Innovation Organization
  Network Expertise Network Animal/Surrogate
  Studies, Biodefense Campus Integration

32
QUESTIONS?