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

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Agenda Tom Hiltke 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

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

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

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Preclinical Services to Support Product Development DiagnosticsVaccinesTherapeutics Basic Research Preclinical Development Discovery IDE- and IND- Enabling Activities Clinical Evaluation Hypothesis Development and Testing 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 Product Development Pathway

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

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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

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

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

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Preclinical Services

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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 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 Resource Center 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 Research Materials Past Present Therapeutic and Interventional Product Development Services (Under Development)

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

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

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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

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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

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

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

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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

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Preclinical Services Standard Criteria 1.Proposed studies within DMID/NIAID mission 2.Proposed studies within scope of and/or technology provided by awarded contracts 3.Sufficient quality and/or quantity of product available 4.Proposed studies in compliance with animal welfare regulations 5.Proposed work not supported by/available from other funding sources 6.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

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Preclinical Services Standard Criteria (Contd) 7.Preliminary data adequate to support the request to advance the product to the next step in the product development pipeline 8.Likelihood that services will contribute significantly to the eventual development and/or evaluation of a product of high quality 9.Purported public health impact 10.Improvements in health benefits offered beyond current measure(s) 11.Availability of a plan for advancing the product beyond completion of the services requested 12.Rank of requested studies among competing priorities 20

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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

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Clinical Services

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Broad 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)

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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

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

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

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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

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

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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

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

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Making Information Available

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DMID Resources for Researchers Funding Opportunities Services for Researchers Research tools and technologies Preclinical and clinical services to facilitate product development http://www.niaid.nih.gov/LabsAndResources/resources/dmid/

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