Critical Path Opportunities for Critical Path Opportunities for Biologics ProductsBiologics Products

Jesse L. Goodman, M.D. M.P.H.Jesse L. Goodman, M.D. M.P.H.

DirectorDirector

Kathryn M. Carbone, M.D. Kathryn M. Carbone, M.D.

Associate Director for ResearchAssociate Director for Research

Center for Biologics Evaluation and ResearchCenter for Biologics Evaluation and Research

Vision for CBER

INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH

Protect and improve public and individual health in the US and, where feasible, globally

Facilitate the development, approval and access to safe and effective products and promising new technologies

Strengthen CBER as a preeminentregulatory organization for biologics

Innovations in the Science of Innovations in the Science of Biologics Product DevelopmentBiologics Product Development

Get more innovative biological products to patients

Achieve robust biological product development pathways that are efficient and predictable.– Many promising biologics products have no

established development pathways, e.g., gene and cell therapies—a true opportunity

How?– Communicate and work closely with stakeholders – Develop and evaluate new scientific toolkits that

bring scientific advances into the product development process.

CBER Proactively Improving the Product Development Process

Working with stakeholders to develop and prioritize needs for scientific tools and knowledge for product development

CBER staff coordinating and collaborating with academic and industry scientists to respond to these needs– Communicating with stakeholders, e.g., workshops &

guidances Applying new science to chart a more predictable

and efficient path for new biologics product evaluation

Assessing progress and revising priorities in collaboration with stakeholders on a routine basis

Why CBER? Unique Role of the Center Why CBER? Unique Role of the Center vis-a-vis Science of Biologics Product vis-a-vis Science of Biologics Product EvaluationEvaluation

CBER guidance based on science can foster innovation and improve chances of success of entire field of biological products

CBER scientists are part of the review process during product development—they directly see the successes, failures, and missed opportunities due to lack of science

CBER can play both a direct role as well as a convening and coordinating role for scientific needs across sponsors

CBER Critical Path Grand CBER Critical Path Grand OpportunitiesOpportunities

New vaccine delivery systems, rapid use vectors, New vaccine delivery systems, rapid use vectors, adjuvants, including vaccines for BT, EIDadjuvants, including vaccines for BT, EID

Develop and make available well characterized cell banks Develop and make available well characterized cell banks (and related methods to assay for safety/adventitious (and related methods to assay for safety/adventitious agents) useful for vaccine and other biologics production agents) useful for vaccine and other biologics production

Characterize cell therapies & link this information to Characterize cell therapies & link this information to standardized outcomes (e.g. stem cells) standardized outcomes (e.g. stem cells)

Development and evaluation of methods for:Development and evaluation of methods for:– Multipathogen, rapid detection of microbial contamination of Multipathogen, rapid detection of microbial contamination of

biologics including blood and tissue productsbiologics including blood and tissue products

– Pathogen inactivation for blood, plasma, tissues and other Pathogen inactivation for blood, plasma, tissues and other productsproducts

Improving longevity/storage of blood and tissuesImproving longevity/storage of blood and tissues

CBER Workshop 10-04CBER Workshop 10-04http:www.fda.gov/cber/summaries.htmhttp:www.fda.gov/cber/summaries.htm

CBER recently held an open, public workshop to CBER recently held an open, public workshop to discuss scientific opportunities to support discuss scientific opportunities to support evaluations of biologics product efficacy and evaluations of biologics product efficacy and safetysafety

Morning presentation by CBER Offices of Morning presentation by CBER Offices of Vaccines, Blood, Cell-Tissue-Gene Therapy and Vaccines, Blood, Cell-Tissue-Gene Therapy and Compliance & Biologics QualityCompliance & Biologics Quality

Afternoon Breakout Discussions with members of Afternoon Breakout Discussions with members of academia, industry, patient advocacy groups and academia, industry, patient advocacy groups and non-FDA government scientists and attendeesnon-FDA government scientists and attendees

Summaries of Breakout Sessions completed and Summaries of Breakout Sessions completed and manuscripts are being prepared for publicationmanuscripts are being prepared for publication

Critical Path: Critical Path: Improving the Improving the Predictability of Clinical StudiesPredictability of Clinical Studies

Study design & statistical analysisStudy design & statistical analysis– Missing data, data mining, standardized outcomes, data Missing data, data mining, standardized outcomes, data

bridging (animal-human; pediatric-adult), Risk Mgmt, bridging (animal-human; pediatric-adult), Risk Mgmt, multiple endpointsmultiple endpoints

Preclinical safety assays Preclinical safety assays – Gene/CellGene/Cell

» Predicting cancer risksPredicting cancer risks

» Animal models: Adenovirus-associated respiratory distress Animal models: Adenovirus-associated respiratory distress model in liver disease (rat), Bioterrorism vaccinesmodel in liver disease (rat), Bioterrorism vaccines

– VaccineVaccine» Neurotoxicity models: Smallpox vaccine, Influenza vaccine, Neurotoxicity models: Smallpox vaccine, Influenza vaccine,

Polio vaccine, Mumps vaccine; HIV, WNV, SARSPolio vaccine, Mumps vaccine; HIV, WNV, SARS

Critical Path: Improving the Critical Path: Improving the Predictability of Clinical StudiesPredictability of Clinical Studies

Biomarkers & surrogate endpoints for efficacyBiomarkers & surrogate endpoints for efficacy– Vaccines for Bioterrorism, EID, Hep C, HIVVaccines for Bioterrorism, EID, Hep C, HIV

» Animal models (Smallpox, anthrax, ebola)Animal models (Smallpox, anthrax, ebola)» Immune surrogates: Rotavirus, HIV, pneumococcusImmune surrogates: Rotavirus, HIV, pneumococcus» Assays to distinguish immune response from natural, persistent Assays to distinguish immune response from natural, persistent

infection vs. vaccination (HIV)infection vs. vaccination (HIV)

– Gene and cell therapiesGene and cell therapies» Noninvasive imaging techniques (w/CDRH)Noninvasive imaging techniques (w/CDRH)

Correlation of product characteristics with clinical Correlation of product characteristics with clinical outcomes & subject biomarkers: Stem cells, outcomes & subject biomarkers: Stem cells, vaccinesvaccines

Postmarketing surveillance: Particularly important Postmarketing surveillance: Particularly important when surrogate endpoints are usedwhen surrogate endpoints are used

Manufacturing: Better techniques Manufacturing: Better techniques and resources for product qualityand resources for product quality

Product microbial assaysProduct microbial assays» TSE, Microarray for Mycoplasma, Spiroplasma, Ureaplasma, TSE, Microarray for Mycoplasma, Spiroplasma, Ureaplasma,

Xenotransplantation: PERV, bacteria in blood productsXenotransplantation: PERV, bacteria in blood products

Potency assays: Faster, easier, more quantitativePotency assays: Faster, easier, more quantitative– Smallpox vaccine/VIG assay, blood product assaySmallpox vaccine/VIG assay, blood product assay

Cell substrates: Developing the assays and qualified Cell substrates: Developing the assays and qualified cell bankscell banks– Along with assays for tumorigenicity, contamination with Along with assays for tumorigenicity, contamination with

infectious agents, including TSEinfectious agents, including TSE References, Standards, Statistical ApproachesReferences, Standards, Statistical Approaches

– Influenza vaccine, standard and pandemicInfluenza vaccine, standard and pandemic– Adenovirus & Retrovirus gene vectorsAdenovirus & Retrovirus gene vectors

Continuing the collaborative process Continuing the collaborative process of Critical Path discovery and applicationof Critical Path discovery and application

Continue open discussions of Biologics CP issues– To develop CBER science future priorities and agenda– Seek outside scientists for consultation, collaborative

projects or to inspire for independent projects Transparency and accountability:

– CBER science organization, priorities and outcomes to be presented and reviewed in public Advisory Committee meetings in 2005

– Continue regular formal external reviews of CBER science programs to seek evaluation of quality and to update priorities

Critical Path Scientific advances to be communicated in guidances, policy and publications to support product development