1. CBER Executive Staff Briefing
Status and Priorities
October 26, 2010
Robert Yetter, PhD Associate Director for Review Management Center for Biologics Evaluation and Research Food and Drug Administration

2. Innovative Technology Advancing
CBER Our Vision
Innovative Technology Advancing
Public Health
Protect and improve public and individual health in the US and globally
Facilitate development, approval, and access to safe and effective products and promising new technologies
Strengthen CBER as a pre-eminent regulatory organization for biologics

3. CBER Our 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; and help to defend the public against the threats of emerging infectious diseases and bioterrorism

4. CBER Organization OFFICE OF THE CENTER DIRECTOR
Director: Karen Midthun, MD Associate Director for Policy: Diane Maloney, JD
Associate Director for Review Management: Robert Yetter, PhD
Associate Director for Research: Carolyn Wilson, PhD
Associate Director for Quality Assurance: Sheryl Lard-Whiteford, PhD
Office of Vaccines Research and Review Director: Norman Baylor, PhD Deputy: Marion Gruber, PhD
Office of Blood Research and Review Director: Jay Epstein, MD Deputy: Ginette Michaud, MD
Office of Cellular, Tissue and Gene Therapies Director: Celia Witten, MD, PhD Deputy: Stephanie Simek, PhD
Office of Compliance and Biologics Quality Director: Mary Malarkey Deputy (Acting): Jalena Specht, JD
Office of Biostatistics and Epidemiology Director: Robert Ball, MD, MPH Deputy: Steven Anderson, PhD
Office of Communication, Outreach and Development Director: Lorrie McNeill Deputy: Joanne Binkley
Office of Management Director: James Sigg Deputy: Deirdre Hussey
Divisions
Manufacturers Assistance
Leslie Wheelock
Disclosure and Ovresight Mgt
Susan Frantz-Bohn
Communication & Consumer Affairs
Diane Bartell
Epidemiology: Rickey Wilson
Biostatistics: Henry Hsu
Case Management: Robert Sausville Manufacturing & Product Quality: John Eltermann
Inspections & Surveillance: Gilliam Conley
Cell & Gene Therapy: Raj Puri
Clin. Eval. & Pharm./Tox.: Wilson Bryan/Mercedes Serabian
Human Tissues: Ellen Lazarus
Blood Applications: Richard Davey
Hematology:
Basil Golding
Emerging & Transfusion-Transmitted Dis.: Hira Nakhasi
Bacterial, Parasitic & Allergenic Products: Milan Blake
Viral Products: Jerry Weir
Vaccines & Related Product Applications: Wellington Sun
Product Quality: William McCormick
Planning, Eval & Budget
Karen O’Brien
Program Services
David Leffler
Scientific Advisors & Consultants
William Freas
Veterinary Services
Philip Snoy

5. Our Products Blood Derivatives Whole Blood Blood Components
Selected Devices
Human Tissues
Vaccines (preventive and therapeutic)
Allergenic Products
Cell & Gene Therapies
Xenotransplantation products

6. CBER Strategic Priorities
Enhance the nation’s public health preparedness
Protect and promote public health globally
Keep patients and products safe
Improve the quality and safety of biological products
Bring innovative products to patients
Strengthen our human resources and performance

7. CBER’s 2010 Actions to Address Key Agency Initiatives
Safety
Transparency
National and Global Public Health
Regulatory Science
Enhanced Regulatory Processes

8. Focus on 2011 Priorities: Safety is Key

9. CBER’s Integrated Safety Teams: Pooling our Expertise
3 Product-based teams
Tissue Safety Team
Blood Safety Team
Vaccine Safety Team
With multi-disciplinary collaborations within CBER
Product office (blood, tissue or vaccines)
Office of Biostatistics & Epidemiology
Office of Compliance & Biologics Quality
Office of Communication, Outreach & Development
Office of the Center Director

10. CBER Safety Teams (2)
Multi-disciplinary teams (epidemiologists, clinical/product reviewers, compliance/manufacturing experts, communications) to improve acquisition, analysis, and communication of safety information
Encompass entire product life cycle
Use data - evaluate emerging safety issues
Coordinate FDA response to issues with others
Enhance collaboration with other gov’ts., WHO, etc.
Proactive: contribute to research, policy, outreach

11. FDAAA Safety Activities
Center Activities:
Cross-Office Center group
Part of Cross-Center Agency group
Focus on:
Safety Labeling Changes
REMS Considerations
Post-marketing Requirements

12. CBER Post-Marketing Safety Collaborations
Vaccine Adverse Event Reporting System (with CDC)
Centers for Medicaid & Medicare Services (CMS): 45 million enrollees
Department of Defense
Vaccine Safety Database (managed by CDC)
Department of Veterans Affairs
Indian Health Service
Post-Licensure Rapid Immunization Safety Monitoring (linking state immunization registries with health care database medical records)
International collaborations (e.g., WHO and many regulatory and public health agencies worldwide)

13. 2011 Priorities: Transparency
2011 Priorities: Transparency *Overarching Agency Initiative to Enhance Communications in All Areas *CBER Continues to Facilitate the Development of Safe and Effective Biological Products

14. Communication to Facilitate Product Development
Guidance
Workshops
Advisory Committees

15. RECENT CBER GUIDANCES Pathways for Developing Innovative Cell & Gene Therapy Products
Final:
Minimally manipulated, unrelated allogeneic placental/ umbilical cord blood intended for hematopoietic reconstitution for specified indications (10/09)
How to pursue licensure
Considerations for Allogeneic Pancreatic Islet Cell Products (9/09)
Draft:
Investigational New Drug Applications (INDs) for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications (10/09)
Patient access to life-saving products
Clinical Considerations for Therapeutic Cancer Vaccines (9/09)
Somatic Cell Therapy for Cardiac Disease (3/09)

16. Workshops on Cellular Products
Public Workshop on Cell and Gene Therapy Clinical Trials in Pediatric Populations -upcoming Nov 2, 2010
Cord Blood Licensure: A Workshop – March 8-9, 2010
FDA/NCI Workshop: Therapeutic Cancer Vaccines; Considerations for Early Phase Clinical Trials Based on Lessons Learned from Phase III - October 27, 2009

17. Blood Safety Guidances Addressing Agents of Emerging Infectious Diseases
Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor Deferral and Reentry (May 2010)
Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products (May 2010)
Draft Guidance for Industry: Recommendations for the Assessment of Blood Donor Suitability, Blood Product Safety, & Preservation of the Blood Supply in Response to Pandemic (H1N1) 2009 Virus (11/13/2009)
Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Donors of Whole Blood and Blood Components Intended for Transfusion (11/6/2009)

18. Blood and Tissue Safety
Workshops Addressing Emerging Infectious Diseases
& Blood Safety
Public Workshops:
Quantitative Risk Assessment: Blood Safety and Availability Public Workshop -May 13, 2010
Emerging Infectious Diseases: Evaluation to Implementation for Transfusion and Transplantation Safety –May , 2010
Emerging Arboviruses: Evaluating the Threat to Transfusion and Transplantation Safety – December 14-15, 2009

19. Vaccines: Guidance/ Advisory Committee Meetings
Public Meeting on Animal Models—Essential Elements to Address Efficacy Under the Animal Rule; and Reopening of Comment Period (Docket No. FDA–2009–D–0007)-upcoming November 5, 2010
Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications-March 2010
Vaccines and Related Biological Products Advisory Committee (VRBPAC)-May 7, 2010 :
majority of the advisory committee members expressed support for the continued use of Rotarix and RotaTeq and stated that the vaccine’s benefits far outweigh the theoretical risks posed by PCV.

20. 2011 Priorities: Global Collaboration to Improve Public Health
Emerging infectious diseases
Worldwide collaboration on emerging pubic health threats
Countermeasures against bioterrorism
Worldwide collaboration to address product quality, safety, and availability

21. Challenge: H1N1 Pandemic
H1N1 response central to CBER’s international activities
CBER agreed to be Reference NRA for WHO vaccine prequalification for multiple H1N1 vaccines
CBER provides technical assistance to developing countries via WHO
FDA continues to work with international authorities so that data from other countries can inform US decision-making

22. CBER’s WHO Engagements
CBER serves as reference NRA [National Regulatory Authority] for a number of WHO prequalified vaccines
Collaborating Center (CC) for Biological Standardization since 1998
Large Spectrum of Activities as CC, e.g.:
Expert Committee on Biological Standards
Global Advisory Committee on Vaccine Safety
Advisory Committee on HIV Vaccines
Blood Regulators Network
PAHO Training on post-marketing surveillance
Work with WHO developing countries’ networks

23. Regulatory Dialogue
Confidentiality arrangements with a number of regulatory agencies
European Medicines Agency (EMA)
Product “clusters” reflecting routine, on-going dialogue; newest cluster = Blood Products (Feb 2010)
Parallel scientific advice
Staff exchanges in areas of vaccines and cell, tissue & gene therapies
Health Canada
Sharing regulatory information on ad hoc basis
Mutual learning on training of staff

24. Harmonization Efforts
ICH (USA, Europe, Japan) 2009/10 highlights
1st ICH guideline on gene therapy taken up
Progress on interface between ICH and Standards Development Organizations
Expansion of Global Cooperation Group to additional individual countries
Global Harmonization Task Force (GHTF)
Efforts to harmonize medical device regulatory requirements & terminology
Asia-Pacific Economic Cooperation
Life Sciences Innovation Forum, regulatory harmonization efforts launched in 2009
Pharmaceutical Inspection Cooperation Scheme

25. Improve Product Safety
Regulatory Science Priorities: Using Science and Regulation to Advance Product Development and
Improve Product Safety

26. The CBER Model
CBER research contributes to regulatory policy, risk assessments, new methods & standards, and changes to product labeling
CBER researchers are fully integrated into review process
Together with others contribute to policy documents
Meet with sponsors and advisory committees
Evaluate adverse drug reactions and do risk assessment

27. Influenza Program: CBER’s Role
Develops new high-growth influenza virus reference strains for vaccines
Evaluates manufacturers’ influenza seed viruses before vaccine production
Prepares influenza virus reagents to determine potency of influenza vaccines
Expanded post-market ongoing safety assessment
Photo: Wikimedia Commons

28. Examples: CBER Research–Based Activities to Facilitate Product Development
Rapid influenza hemagglutinin (HA) antibody reagent produced by recombinant techniques (no need to grow whole virus, then purify HA to assess vaccine potency)
Expedited influenza vaccine reagent calibration process and development of back-up procedures to ensure availability
New technologies to determine vaccine potency without using antibodies – for influenza vaccines (e.g., cell culture-derived, adjuvanted, DNA, recombinant protein-based, virus-like particles)

29. Meeting Challenges to Advance and Enhance Regulatory Processes
Some Challenges: new & on-going
New laws/regulations (e.g., FDAAA, PREA, Patient Protection and Affordable Care Act
Biologics Price Competition and Innovation Act of 2009-“Biosimiliars” Sections of the Patient Protection and Affordable Care Act (Public Law No ) 
PDUFA V- Reauthorization; Legislative authority expires Sept 2012
Adoption/implementation of new standards (e.g., SPL, CDISC/SDTM and other computer standards)
Regulatory processes for innovative new products (especially for treatment of serious and/or rare conditions)

30. Meeting Challenges to Advance and Enhance Regulatory Processes
Some Responses
Workgroups to address new laws, regulations
Enhanced reviewer training
Public Workshops and Guidance development
Approval Pathway for Biosimilar and Interchangeable Biological Products Public Meeting (upcoming Nov 2-3, 2010)
Safety Reporting Rule (9/28/10) Final Rule: Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalance Studies in Humans
Standards development

31. A Few Notable 2010 CBER Approvals
Menveo (meningococcal conjugate vaccine) to prevent invasive meningococcal disease
Prevnar 13 vaccine against more pneumococcal types a broadened vaccine to prevent invasive pneumococcal disease in infants and young children
Prism automated blood screening antibody assay for automated detection of Chagas Disease
Provenge - autologous cellular immunotherapy for treatment of hormone refractory prostate cancer

32. Acknowledgments Karen Midthun David Cho Joan Wilmarth Blair
Mary Pat Leary

33. Thank You for Your Attention – Questions?

34. Resources/Contact
Consumer Questions about Products - Please direct all consumer questions about biological products to
Manufacturers Assistance - Please direct all manufacturers' assistance questions to