CBER Executive Staff Briefing

Status and PrioritiesOctober 26, 2010

Robert Yetter, PhD Robert Yetter, PhD Associate Director for Review Management Associate Director for Review Management Center for Biologics Evaluation and ResearchCenter for Biologics Evaluation and Research

Food and Drug AdministrationFood and Drug Administration

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

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

CBER Organization

Planning, Eval & BudgetPlanning, Eval & BudgetKaren O’BrienKaren O’Brien

Program ServicesProgram ServicesDavid LefflerDavid Leffler

Scientific Advisors & Scientific Advisors & ConsultantsConsultants

William FreasWilliam FreasVeterinary ServicesVeterinary Services

Philip SnoyPhilip Snoy

OFFICE OF THE CENTER DIRECTOROFFICE OF THE CENTER DIRECTOR Director: Karen Midthun, MDDirector: Karen Midthun, MD

Associate Director for Policy: Diane Maloney, JDAssociate Director for Policy: Diane Maloney, JDAssociate Director for Review Management: Robert Yetter, PhD Associate Director for Review Management: Robert Yetter, PhD

Associate Director for Research: Carolyn Wilson, PhDAssociate Director for Research: Carolyn Wilson, PhDAssociate Director for Quality Assurance: Sheryl Lard-Whiteford, PhDAssociate Director for Quality Assurance: Sheryl Lard-Whiteford, PhD

Office of Vaccines ResearchOffice of Vaccines Researchand Review and Review

Director: Norman Baylor, Director: Norman Baylor, PhDPhD

Deputy: Deputy: Marion Gruber, PhD

Office of Blood ResearchOffice of Blood Researchand Review and Review

Director: Jay Epstein, MDDirector: Jay Epstein, MDDeputy: Deputy: Ginette Michaud,

MD

Office of Cellular, TissueOffice of Cellular, Tissueand Gene Therapies and Gene Therapies

Director: Celia Witten, MD, Director: Celia Witten, MD, PhDPhD

Deputy: Deputy: Stephanie Simek, PhD

Office of ComplianceOffice of Complianceand Biologics Qualityand Biologics Quality

Director: Mary MalarkeyDirector: Mary MalarkeyDeputy Deputy (Acting(Acting)): : Jalena

Specht, JD

Office of Biostatistics and Office of Biostatistics and EpidemiologyEpidemiology

Director: Robert Ball, MD, Director: Robert Ball, MD, MPHMPH

Deputy: Deputy: Steven Anderson, PhD

Office of Office of Communication, Communication,

Outreach and Outreach and DevelopmentDevelopment

Director: Lorrie McNeillDirector: Lorrie McNeillDeputy: Deputy: Joanne Binkley

Office of ManagementOffice of ManagementDirector: James SiggDirector: James Sigg

Deputy: Deputy: Deirdre Hussey

DivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisionsDivisions

Manufacturers AssistanceManufacturers Assistance

Leslie WheelockLeslie Wheelock

Disclosure and Ovresight MgtDisclosure and Ovresight Mgt

Susan Frantz-BohnSusan Frantz-Bohn

Communication & Consumer Communication & Consumer AffairsAffairs

Diane BartellDiane Bartell

Epidemiology: Epidemiology: Rickey WilsonRickey Wilson

Biostatistics: Biostatistics: Henry HsuHenry Hsu

Case Management: Case Management: Robert SausvilleRobert Sausville

Manufacturing & Product Manufacturing & Product Quality: Quality:

John EltermannJohn Eltermann

Inspections & Surveillance: Inspections & Surveillance: Gilliam ConleyGilliam Conley

Cell & Gene Therapy: Cell & Gene Therapy: Raj PuriRaj Puri

Clin. Eval. & Pharm./Tox.: Clin. Eval. & Pharm./Tox.: Wilson Bryan/Mercedes Wilson Bryan/Mercedes

SerabianSerabian

Human Tissues: Human Tissues: Ellen LazarusEllen Lazarus

Blood Applications: Blood Applications: Richard DaveyRichard Davey

Hematology: Hematology:

Basil GoldingBasil Golding

Emerging & Transfusion-Transmitted Emerging & Transfusion-Transmitted Dis.: Hira NakhasiDis.: Hira Nakhasi

Bacterial, Parasitic & Allergenic Bacterial, Parasitic & Allergenic Products: Products:

Milan BlakeMilan Blake

Viral Products:Viral Products:Jerry WeirJerry Weir

Vaccines & Related Product Vaccines & Related Product Applications:Applications:

Wellington SunWellington Sun

Product Quality: Product Quality: William McCormickWilliam McCormick

Our Products

• Blood Derivatives• Whole Blood• Blood Components• Selected Devices• Human Tissues• Vaccines (preventive and therapeutic)• Allergenic

Products• Cell &

Gene Therapies• Xenotransplantation products

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

CBER’s 2010 Actions to Address Key Agency Initiatives

Safety

Transparency

National and Global Public Health

Regulatory Science

Enhanced Regulatory Processes

Focus on 2011

Priorities:

Safety is Key

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

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

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

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)

2011 Priorities:

Transparency

*Overarching Agency Initiative to

Enhance Communications in All Areas

*CBER Continues to Facilitate the

Development of Safe and Effective

Biological Products

Communication to Facilitate Product Development

• GuidanceGuidance

• WorkshopsWorkshops

• Advisory CommitteesAdvisory Committees

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)

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

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)

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 11 -12, 2010

• Emerging Arboviruses: Evaluating the Threat to Transfusion

and Transplantation Safety – December 14-15, 2009

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.

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

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

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

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

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

Regulatory Science

2011 Priorities:Using Science and Regulation to Advance Product Development

and

Improve Product Safety

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

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

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)

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 7001-7003 of the Patient Protection and Affordable Care Act (Public Law No. 111-148) 

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)

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)

http://www.fda.gov/Drugs/NewsEvents/ucm221688.htm

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

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

Acknowledgments

• Karen Midthun

• David Cho

• Joan Wilmarth Blair

• Mary Pat Leary

Thank You for Your Attention – Questions?

Resources/Contact

• Consumer Questions about Products - Please direct all consumer questions about biological products to ocod@fda.hhs.gov

• Manufacturers Assistance - Please direct all manufacturers' assistance questions to matt@fda.hhs.gov