1. Advanced Vaccine Development: the Challenge is in the Details
3/18/2011
Chlamydia Basic Research Society
Redondo Beach, CA

2. Agenda Tom Hiltke Michael Roy, Ph.D. Sharon Frey, M.D.
NIAID
Introduction and Summary of NIAID support and services
Michael Roy, Ph.D.
Science Applications International Corporation (SAIC)
“Planning for Success: Biotechnology Product Development”
Sharon Frey, M.D.
Saint Louis University School of Medicine
“Herpevac Trial for Women as a Model for Vaccine Efficacy Trials Against STD”
Scott Stibitz, Ph.D.
U.S. Food and Drug Administration
“FDA Regulation of Bacterial Vaccines”

3. Resources for Researchers
Product Development Pathway
Basic Research
Preclinical Development
Clinical Evaluation
Diagnostics
Vaccines
Therapeutics
Hypothesis Development and Testing
Discovery
IDE- and IND-Enabling Activities
Trials
Research Tools and Technologies
►Funding opportunities
►Research tools and technologies
►Preclinical and clinical services
to facilitate product development

4. Research Tools and Technologies
Product Development Pathway
Basic Research
Preclinical Development
Clinical Evaluation
Diagnostics
Vaccines
Therapeutics
Hypothesis Development and Testing
Discovery
IDE- and IND-Enabling Activities
Trials
Research Tools and Technologies
Biological resources repository
Sequencing, genotyping, and protein biomarker discovery
Data, databases, and bioinformatics tools
Biocontainment facilities and core services

5. Preclinical Services to Support Product Development
Product Development Pathway
Basic Research
Preclinical Development
Clinical Evaluation
Diagnostics
Vaccines
Therapeutics
Hypothesis Development and Testing
Discovery
IDE- and IND-Enabling Activities
Trials
Research Tools and Technologies
In vitro testing
In vivo testing
Lead identification and development
Chemistry and manufacturing
Synthesis and optimization
Preclinical development, planning, and evaluation

6. Clinical Services to Support Product Development
Product Development Pathway
Basic Research
Preclinical Development
Clinical Evaluation
Diagnostics
Vaccines
Therapeutics
Hypothesis Development and Testing
Discovery
IDE- and IND-Enabling Activities
Trials
Research Tools and Technologies
Clinical trials
Support for clinical
programs

7. What Can the Resources Provide?
Expertise/capability
Data to support/address:
Research/knowledge gaps
New/continued funding
Go/no-go decisions
Investigational New Drug (IND)Applications
Lifting of FDA clinical hold

8. Research Tools and Technologies
Biological resources repository
Sequencing, genotyping, and protein biomarker discovery
Data, databases, and bioinformatics tools
Biocontainment facilities and core services 8

9. Microbiology and Infectious
Programs Contributing to the Microbiology and Infectious Diseases Biological Resource Repository (MID-BRR)
Human
Microbiome
Project
(NIH Roadmap)
Proteomics
Research
Centers
(PRC)
Microbiology and Infectious
Diseases BEI
Resources Repository
Regional Centers
Of Excellence
(RCE)
Pathogen
Functional
Genomics
Research Centers
(PFGRC)
Animal
Models of
Infectious
Diseases
Centers of
Excellence for
Influenza
Research and
Surveillance
(CEIRS)
Other
Research
Programs 9

10. Preclinical Services

11. Resources for Researchers Integration & Evolution
Network on Antimicrobial Resistance in S. aureus (NARSA)
Biodefense and
Emerging Infectious
Diseases Research
Resources Program
Respiratory
Pathogens Reference
Laboratory Support
World Reference
Center for
Arboviruses
Filariasis
Research
Resource Center
New Animal
Models for Post
Genomics (TB & IA)
Schistosomiasis
Research Reagent
Leprosy/Armadillo
Support and
Maintenance
Animal Models of
Human Viral Infection
for Evaluation of
Experimental Therapeutics
In Vitro Antiviral
Screening Program
In Vitro and Animal
Models for EID and
Biodefense
Animal Models for
Prevention and
Treatment of
Hepatitis B & C
Malaria Research & Reference Reagent Resource Center
Shiga Toxin-Producing E. coli Center
Services for Preclinical Development of Therapeutic Agents
TB Vaccine
Testing and
Materials
Microbiology and Infectious
Diseases BEI Resources
Repository
Vaccine and Other
Biologics
Development Services
(Under Development)
Animal Models of
Infectious Diseases
In Vitro Assessment for
Antimicrobial Activity
Therapeutic and
Interventional Product
Development Services
(Under Development)
Past
Present 11 11

12. In vitro Assessment for Antimicrobial Activity
Screen for in vitro antimicrobial activity
Develop and perform or provide in vitro assays

13. Animal Models of Infectious Diseases
Development/refinement of animal models
In vivo screening
Toxicology and immunogenicity testing of vaccines and therapeutics
Efficacy testing

14. New Programs Development of Vaccines and Other Biologics
Additional vaccine development services
Preclinical planning and program evaluation
Process development and manufacturing
Formulation, stability, and fill/finish
Assay development
Sample testing
In vivo immunogenicity
Efficacy testing
Safety/toxicity
Capacity to develop other biologics 14

15. Preclinical Services Access
Available through application
Resources are limited
To provide critical information needed to move a product forward
Not intended as the sole source of development
Preliminary data required to proceed through each stage of development

16. Preclinical Services Eligibility Criteria
Investigators in academia, not-for-profit organizations, industry, and government
National/international
Don’t need to be funded by NIH

17. Preclinical Services Assurances Provided
Confidentiality
Materials Transfer Agreement (MTA)
Non-Clinical Evaluation Agreement (NCEA)
Clinical Trial Agreement (CTA)

18. Preclinical Services Application and Approval Process
Program Officer and Requestor explore request informally
Branch/Office Review*
Program Officer invites Requestor with promising proposal to submit formal request for approval
Senior Leadership Review*
Studies/protocols are carried out under contract
*Based on standard criteria 18

19. Preclinical Services Standard Criteria
Proposed studies within DMID/NIAID mission
Proposed studies within scope of and/or technology provided by awarded contracts
Sufficient quality and/or quantity of product available
Proposed studies in compliance with animal welfare regulations
Proposed work not supported by/available from other funding sources
Previous use of DMID resources for assessment of the same or similar product (Repeat use of DMID resources may be undertaken with strong justification.) 19

20. Preclinical Services Standard Criteria (Cont’d)
Preliminary data adequate to support the request to advance the product to the next step in the product development pipeline
Likelihood that services will contribute significantly to the eventual development and/or evaluation of a product of high quality
Purported public health impact
Improvements in health benefits offered beyond current measure(s)
Availability of a plan for advancing the product beyond completion of the services requested
Rank of requested studies among competing priorities 20

21. Preclinical Services Requirements for Users
Requirements may include:
Shipping and handling charges
Acknowledging the contribution of NIAID contract support in publications and presentations
Submitting manuscripts, abstracts and presentations for NIAID review

22. Clinical Services

23. Clinical Services Broad programs Specific programs
Phase I Clinical Trial Units
Vaccine and Therapeutic Evaluation Units (VTEUs)
Specific programs
Sexually Transmitted Infections Clinical Trials Group (STI CTG)
Tuberculosis Clinical Diagnostics Research Consortium (CDRC)

24. Support for Clinical Evaluation
Clinical Agents and Specimen Repository
Clinical Research and Operations Management Support (CROMS)
Regulatory Affairs Support
Statistics and Data Coordinating Center for Clinical Research (SDCC)
Clinical Research Policies and Procedures

25. Vaccine and Treatment Evaluation Units and Phase I Clinical Trial Units
VTEUs

26. Clinical Services Eligibility Criteria
Concept proposals may be submitted by
Investigational site Principal Investigators
DMID staff
Outside collaborators

27. Clinical Services Assurances Provided
Materials Transfer Agreement (MTA)
Clinical Trial Agreement (CTA)
Safety oversight, clinical monitoring, data management and regulatory management, as needed
Retention of publication rights

28. Clinical Services Application Process
Submit concept proposal to the Project Officer, outlining:
Study objectives and rationale
Recruitment
Protocol timeline
Budget

29. Clinical Services Approval Process
Step 1 - Branch approval
Step 2 - Prioritized by DMID VTEU and Phase I Clinical Trials Oversight Committee based on:
Public health significance
Appropriateness and feasibility of study design
Capacity of proposed clinical sites
Proposed personnel
Protocols must be implemented within 12 months of concept approval in order to secure funding

30. Clinical Services Requirements for Users
Acknowledge the contribution of NIAID contract support in publications and presentations
Submit manuscripts, abstracts and presentations for NIAID review

31. Making Information Available

32. DMID Resources for Researchers
Funding Opportunities
Services for Researchers
Research tools and technologies
Preclinical and clinical services to facilitate product development