Center for Biologics Evaluation and Research

FDAOverview Site Visit

Carolyn A. Wilson, Ph.D.Associate Director for Research

CBER’s Mission

To ensure the safety, purity, potency, and effectiveness of biological products, including vaccines, blood and blood products, and cells, tissues and gene therapies for the prevention, diagnosis, and treatment of human diseases, conditions or injury.

CBER Regulates Complex Products

CBER Organization

CBER Strategic Goals

Increase national preparedness to address threats from bioterrorism, pandemic and EIDs

Improve global public health through international collaboration

Enhance ability of science and technology to facilitate development of safe and effective biological products

Ensure safety of biological products Advance regulatory science and research Advance regulatory science and research Manage for organizational excellence

CBER Strategic Plan FY2012-2016:

http://www.fda.gov/downloads/aboutfda/centersoffices/cber/ucm266867.pdf

CBER Strategic Plan for Research

and Regulatory Science

Regulatory Science:Regulatory Science: Development and use of the scientific

knowledge, tools, standards, and approaches necessary for the assessment of medical product

safety, efficacy, quality, potency, and performance. CBER intends to participate fully in

this initiative as it develops

http://www.fda.gov/downloads/BiologicsBloodVaccines/ScienceResearch/UCM303542.pdf

CBER Vision for Regulatory Science and Research

• Proactive and anticipatory of regulatory and public health issues

• Responsive to emerging public health and regulatory issues

• Collaborative, highest quality and relevance, and integral to our regulatory mission and public health portfolio

• Provide CBER with scientific expertise, tools, and data to support science-based decision-making and policy development

CBER Mission: Role of Research

Regulatory Regulatory ChallengeChallengePublic HealthPublic Health

Novel ProductNovel Product

CBERCBERResearchResearch

DiscoveryDiscoveryNew ToolsNew ToolsRegulatoryRegulatory

Policy/DecisionPolicy/Decision

Licensed Licensed ProductProduct

Improved Improved Data – Data – Benefit/RiskBenefit/Risk

+

CBER researcher =“Researcher-Regulator”

~20% CBER Staff

Integration of research and review ensures

Relevance, Expertise, Timeliness, and Usability

CBER Research Facilities• Biotechnology Core Facility

– Oligonucleotide, siRNA, PNA, and peptide synthesis– Peptide and DNA sequencing (Illumina, soon!)– Taqman Probe synthesis– HPLC; Capillary electrophoresis– Mass Spectrometry/Proteomics– Amino acid analysis

• Core support for – Flow Cytometry: Sorting/Analytic– Confocal microscopy– Microarray

• Vivarium with procedure rooms– Rodents, NHP, BSL-2 capacity for infectious agents

• BSL-3 and ABSL-3 laboratories

Scientific Expertise

• Novel technologies: NMR, mass spec, flow cytometry, microarray, high throughput sequencing

• Microbiology: parasitology, bacteriology, virology

• Immunology• Biochemistry and molecular biology• Cell and developmental biology• Epidemiology, meta-analyses of large

healthcare databases• Biostatistics

CBER Advances Regulatory Science through External Collaborations

Data from FY11 CBER ResearchData from FY11 CBER Research

Reporting DatabaseReporting Database

Annual Review of Research

Cyclic Peer Review of Every PI Every 4 Years

• Internal – Promotion, Conversion, Evaluation Committee

• External – peer review by scientific experts, Site Visits

Research Career Paths

PCESenior Staff Fellow(Visiting Scientist)Senior Staff Fellow(Visiting Scientist) Site Visit

7 years Senior InvestigatorSenior Investigator

PCEStaff Fellow

(Visiting Associate) Site Visit4+3 years

ORISE FellowPre and Post-Doctoral

Up to 5 years

ORISE FellowPre and Post-Doctoral

Up to 5 years

Temporary Permanent

Staff ScientistStaff Scientist

PCE: Promotion, Conversion and Evaluation Committee

Independent ScientistIndependent Scientist

Support ScientistSupport Scientist

Site-Visit Report, ContentFor each investigator reviewed, • Evaluation of the relevance and quality of

science• New research directions and approaches to be

considered• Needed laboratory expertise• Changes in laboratory organization• New collaborations• Specific comments on Laboratory Program and

Management issues• Specific comments on Personnel issues

– Conversion Potential– Promotion Potential/Cyclical Review for Progress

Site-Visit Report• Draft report is distributed to full Advisory

Committee• Final report is approved by full Advisory

Committee • Final report used in many ways:

– Internal peer review of research/PI by Promotion, Conversion, Evaluation Committee (PCE) for personnel actions

– By PIs for improving research program– By management, resource allocation

decisions may be impacted by report (pending resource availability)

OCTGT MissionFacilitate development of, approval of, and

access to safe and effective CTGT products

OCTGT Mission

• Evaluate investigational new drug, device, biological license; pre-market applications for OCTGT products

• Protect subjects from infectious disease transmission from tissue transplantation.

• Strongly committed to partnership between FDA, government agencies, industry, patient advocates, scientists, and the public to promote and develop new therapies for the 21st Century, while protecting human subjects and maximizing biological product safety

• Plan and conduct FDA’s Mission relevant research to support development of cutting edge medical products

Products Regulated by OCTGT

Cellular therapies Tumor vaccines and immunotherapy Gene therapies Tissue and tissue-based products Xenotransplantation products Combination products Devices used for cells/tissues Cord blood Donor screening tests for use with cadaveric blood

samples

CBER Office of Cellular, Tissue, and Gene Therapies

Office of the Director

Celia M.Witten, Ph.D., M.D., Director

Stephanie Simek, Ph.D. Deputy Director

Suzanne Epstein, Ph.D. Associate Director of Research

Richard McFarland, M.D., Ph.D., Associate Director of Policy

Division of Cellular and Gene Therapies

Raj Puri, M.D., Ph.D., Director

Kimberly Benton, Ph.D., Deputy Director

Division of Human Tissues

Ellen Lazarus, M.D., Director

Division of Clinical Evaluation and Pharmacology/Toxicology

Wilson Bryan, M.D., Director

Mercedes Serabian, MS., Pharm/Tox Branch Chief

OCTGT regulatory portfolio and activities

Over 1325 active INDs and IDEs, over 5000 INDamendments in 2012, plus consult reviews

Seven licensed products, a growing number of IND products in advanced development

Devices: 510ks, PMAs, HDEs

Tissue regulations

Pre-INDs, pre-pre-IND advice

Policy and guidance, advisory committee meetings

Inspections, regulatory site visits

Enforcement actions, international activities

Guidance Examples Potency testing for cell and gene therapies

Therapeutic cancer vaccines

Allogeneic pancreatic islet cell products

Cell therapy for cardiac disease

Products to repair or replace knee cartilage

Cord Blood

Good Tissue Practices

International Harmonization on Genomic Biomarkers

Additional DCGT regulatory portfolio and activities

• Partnerships: National Toxicology Program, NIH, CDC, NCI/IOTF program, NIH stem cell task force, NIST, MATES, TERMIS, ASTM

• Participation in ICH (international conference on harmonization), WHO

• Outreach talks at conferences, academic institutions, consumer and patient advocacy group meetings

• Liaison activities with professional groups• Publication of manuscripts on regulatory topics• OCTGT Learn webinar series on product

manufacturing and testing, clinical, and preclinical topics.

See http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

OCTGT research: Stay ahead of the curve as products and technologies

evolve For this wide spectrum,

cannot have research related to each product.

If research addressed only the products and assays of today, we would already be obsolete. We must guide pre-IND work, prepare the way for anticipated products.

OCTGT Research StrategyOCTGT products are diverse and rapidly evolving. They use

new regulatory paradigms, developing rather than established

Fill scientific gaps, deal with barriers

Perform studies relevant to entire product classes (sponsors study individual products)

Make results public, and thus accessible to all sponsors, to advance the entire field

Perform horizon scanning to choose priorities

Scientific areas emphasized will be covered in the Division Director summary

2012 OCTGT Research Priorities

1. Chemistry, manufacturing, controls: Development and evaluation of methods and standards for improved product characterization and lot release testing, including definition of product markers predictive of safe, effective, and consistent product performance.

2. Pharmacology, toxicology, product rationale: Development and evaluation of preclinical/nonclinical in vitro and in vivo methods and studies informative about the safety and efficacy of OCTGT products.

3. Participation in CBER-, FDA-, and DHHS-wide initiatives including risk assessment, clinical trial design and monitoring, development of biomarkers identification of characteristics predictive of product performance, counterterrorism, pandemic influenza preparedness, and HIV/AIDS programs, nanotechnology, and efforts to reduce, refine, and replace the use of animals (3Rs), as well as OCTGT-specific initiatives in these areas.

4. Improvement of the microbial safety of human tissue products by development and evaluation of methods for better processing conditions, pathogen inactivation, and/or pathogen detection.

2012 OCTGT Research Priorities1. Chemistry, manufacturing, controls: Development and evaluation of methods and

standards for improved product characterization and lot release testing, including definition of product markers predictive of safe, effective, and consistent product performance.

2. Pharmacology, toxicology, product rationale: Development and evaluation of preclinical/nonclinical in vitro and in vivo methods and studies informative about the safety and efficacy of OCTGT products.

3. Participation in CBER-, FDA-, and DHHS-wide initiatives including risk assessment, clinical trial design and monitoring, development of biomarkers identification of characteristics predictive of product performance, counterterrorism, pandemic influenza preparedness, and HIV/AIDS programs, nanotechnology, and efforts to reduce, refine, and replace the use of animals (3Rs), as well as OCTGT-specific initiatives in these areas.

4. Improvement of the microbial safety of human tissue products by development and evaluation of methods for better processing conditions, pathogen inactivation, and/or pathogen detection.

Thank you to the site visitors

for reviewing CBER research programs

and providing your insights.

Thank you!

To the Site Visit reviewers and Advisory Committee

Your input improves CBER’s research programs

External review is critical to fulfilling our regulatory mission!