Biotech 98: From Promise to Reality North Carolina Biotechnology Center Insight into the New FDA

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Biotech 98 From Promise to RealityNorth
Carolina Biotechnology CenterInsight into the
New FDA

• Kathryn C. Zoon, Ph.D.
• Director, CBER
• April 22, 1998

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BIOLOGICAL PRODUCTSREGULATED BY CBER
Vaccines
Allergenic Extracts
Blood Derivatives
Monoclonal Antibodies
BloodComponents
Biotech DerivedTherapeutics
Whole Blood
SomaticCell GeneTherapy
Tissues
Xenotransplantation
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Regulation of Biological Products
Review
Research
Enforcement
Policy
Compliance
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Regulation of Biological Products
Review
Research
Enforcement
Policy
Compliance
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Regulation of Biological Products
Review
Research
Enforcement
Policy
Compliance
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FY98Major Biotechnology Initiatives, Action
Plans and Challenges

• CBER Strategic Plan 2004
• FDA Modernization Act 1997
• Prescription Drug User Fee Act II (1997)
• Xenotransplantation
• Tissue
• International Conference on Harmonization
• Human Cloning

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CBER Strategic Goals2004

• A managed and seamless regulatory process which
  is seamless from discovery through post marketing
• A high quality research program which contributes
  directly to the regulatory mission
• A high quality and diverse work force
• Interactive information systems that are integral
  to all CBER activities
• Leveraged resources

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Project Plan

• Develop a business model of CBERs regulatory
  process - DONE
• Identify weaknesses/bottlenecks in the current
  regulatory process - DONE
• Propose and evaluate solutions to overcome these
  weaknesses/bottlenecks - DONE
• Design a new, streamlined Managed Review Process
  (MRP) - DONE
• Identify performance goals in order to expand the
  MRP (in Progress)

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Impact of Research
Pre-IND
Phase 1,2
Phase 3
Phase 4
Safety/Toxicity Pharmacology
Manufacturing Reviewer Expertise
Safety/Toxicity Pharmacology
Manufacturing Test methods
Manufacturing Test methods Clinical
Research Lot Release/Stds
Manufacturing Test methods Clinical
Research Lot Release/Stds
Categories
Program Output
Policy Statements Risk Assessment Consensus
Policy
Policy Statements Testing Recommendations
Consensus Development Risk Assessment
Change in Policy Labeling Changes Methods
Change in Policy Standards Methods
Predicted or Demonstrated Benefit for Industry
Outcome Measures
Clinical Holds Time for OS Review Impact of
Phase 1 Education
Decreased Testing Enhanced Safety Decreased
Time Clinical Holds Economic Cost
Cost of Changes Relief of Testing Review of
Supplements Economic Cost
New products Decreased time Economic cost
Predicted or Demonstrated Benefit for the Public
Health

• Reduction/Elimination of specific diseases

• Increased margin of safety of products

• Reduced cost to consumers of products

• More rapid availability of products

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Investigational New Drug (IND)
Ensure safety of xenotransplantation clinical
trials

• Research Category
• Test methods for detection of porcine endogenous
  retrovirus
• Safety of porcine xenografts and other porcine
  products
• Research Program Output
• Provide methodology for detection of porcine
  endogenous retrovirus (PERV)
• Provide preclinical in vitro data on infectivity
  of PERV
• Develop guidance to industry on testing for PERV
  in xenograft products and in patients who receive
  this treatment

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Investigational New Drug (IND)
Ensure safety of xenotransplantation clinical
trials

• Outcome Measure for Industry and Public Health
• Decreased time in development of methods for
  detection of PERV
• Enhanced safety of porcine xenografts by
  accumulating data on activation and infectivity
  of PERV
• Identification of a public safety issue related
  to the presence of retroviruses

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Significant Accomplishments in Information
Technology

• Desktop Standardization
• Electronic Submissions - BLAs, INDs
• Document Management Technology
• Regulatory Management System
• Electronic Lot Release (note 26 reduction in
  Review Days)

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FDA Modernization Actof 1997(FDAMA)

• Signed into law November 21, 1997
• Amends the Food, Drug Cosmetic Act
• Amends the Public Health Service Act
• Renews the Prescription Drug User Fee Program
  with amendments (PDUFA 2)
• Effective 90 days after enactment unless
  otherwise specified

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FDA MODERNIZATION ACTDRUG PROVISIONS

• Fast Track Products
• Manufacturing Changes
• Biologics Modernization
• Postmarketing Studies Reporting
• Clinical Investigations

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FDA MODERNIZATION ACTDRUG PROVISIONS

• Streamlining Clinical Research
• Data Requirements
• Content and Review of Applications
• Scientific Advisory Panels
• Radiopharmaceuticals

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FDA MODERNIZATION ACTGENERAL PROVISIONS

• Dissemination of Information
• Expanded Access to Investigational therapies
• Supplemental Applications
• Dispute Resolution
• Informal Agency Statements
• Interstate Commerce
• Intramural Research Training Authority

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FAST TRACK PRODUCTS

• Basically puts Accelerated Approval regulation
  into the statute
• Expedite development and review
• Product request for designation
• Serious and life threatening
• Potential to address unmet need
• Rolling review
• Expedited withdrawal

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CBER LEAD IN FDAMA REGULATION/GUIDANCE INITIATIVES

• RADIOPHARMACEUTICALS - New requirements for
  review of Radiopharmaceuticals (122) PR - May 20,
  1998, FR - May 20, 1999
• POSTMARKETING STUDIES - revise 314 and 601 to
  require annual progress reports (130)
• BIOLOGICS MODERNIZATION - regulations for BLAs
  (123)
• FAST TRACK - policies and procedures on fast
  track products (112) Nov. 21, 1998

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CBER LEAD IN OTHER FDAMA ACTIVITIES

• Postmarketing Studies-Publish Status Annually
  (130)
• Fast Track disseminate to physicians and others
  a description of the provisions applicable to
  fast track products (112)
• Modernization of regulation MAPP/SOP to
  minimize differences between CDER and CBER review
  and approval (123)
• PDUFA II Implementation CBER/CDER co-lead

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IMPLEMENTATION OF PDUFA II

• Review Performance
• Discipline Reviews/Informational Request Letters
• Two Level Resubmissions Class 1 and 2
• Meeting Management
• Clinical Hold Responses
• Major Dispute Resolution
• Special Protocol Agreements
• Electronic Submissions

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Xenotransplantation Action Plan

• Develop a comprehensive Public Health Policy
  Tools
• Emerging Infectious Diseases
• Notification and Look-back
• FDA Response to Emergencies
• Ensuring Compliance
• International Collaboration
• Workshops and Public Education's

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Tissue Action Plan

• Issuing Guidance Documents
• Promulgating Tissue Regulations
• Inspections and Compliance
• Coordinating Scientific and Regulatory Policy

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International HarmonizationPriorities

• ICH
• WHO
• NIBSC

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CBERs Biotech Leadership

• Q5A - Quality of Biotechnological Products Viral
  Safety Evaluation of Biotechnology Products
  Derived from Cell Lines of Human or Animal Origin
  - Final March, 1997
• Q5B - Analysis of the Expression Construct in
  Cells Used for Production of r-DNA Derived
  Protein Products - Final November, 1995
• Q5C - Quality of Biotechnological Products
  Stability Testing of Biotechnological/Biological
  Products - Final November, 1995

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CBERs Biotech Leadership

• Q5D - Derivation and Characterization of Cell
  Substrates Used for Production of
  Biotechnological/ Biological Products - Final
  July, 1997
• Q6B - Specifications Test Procedures and
  Acceptance Criteria for Biotechnological/
  Biological Products - Draft February 1998
• S6 - Preclinical Safety Evaluation of
  Biotechnology-Derived Pharmaceuticals - Final
  July, 1997

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ICH FUTURE DIRECTIONS

• CTD INCLUDING BIOTECH/
• BIOLOGICAL PRODUCTS
• GMPs for APIs
• PEDIATRICS

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Human Cloning

• National Bioethics Advisory Commission
• FDA Jurisdiction
• Public Discussion
• Federal Legislation

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HOW TO GET INFORMATION FROM CBER

• Visit CBERs home page
• www.fda.gov/cber/
• Send e-mail to
• CBER_INFO_at_A1.CBER.FDA.GOV
• For a list of documents
• DOC_LIST_at_A1.CBER.FDA.GOV
• FAX Information System
• 1-888-CBER-FAX [phone] outside of U.S.)
• Telephone
• 1-800-835-4709 (301-827-1800 outside of U.S.)