Cellular Products for Cardiac Diseases Dwaine Rieves, MD Center for Biologics Evaluation and Research

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Cellular Products for Cardiac DiseasesDwaine
Rieves, MDCenter for Biologics Evaluation and
Research
FDA Perspective on
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Cellular Products Overview

• Topics
• Purpose
• Regulatory background
• Questions

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Cellular Products Purpose

• A scientific discussion of
• Manufacturing
• Preclinical testing
• Pilot clinical studies

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Cellular Products Purpose

• Cellular Products
• Blood or bone marrow-derived cells
• Skeletal muscle-derived cells
• Predominantly autologous

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Cellular Products Purpose

• Early Stage of Evolving Field
• Little precedent
• Limited data
• Hypothetical considerations

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Cellular Products Purpose

• A Scientific Focus
• All insights tentative
• No definitive assessment of data
• No specific product assessment

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Cellular Products Regulatory
Research
Regulatory

• A Scientific Focus

Cellular Products
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Cellular Products Regulatory

• Regulatory Mission
• Promote Protect Public Health by
• Pre-marketing product development
• Post-marketing product monitoring

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Cellular Products Regulatory

• Cellular Products
• for Cardiac Diseases
• Biologic/drug/device regulations
• IND
• Early clinical development
• Safety and bioactivity

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Cellular Products Regulatory

• Safety Concerns
• Manufacturing
• Sufficient preclinical testing
• Sufficient clinical study design

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Cellular Products Regulatory

• Manufacturing--Product Safety
• Cell source reagents
• Procedures
• aseptic collection, processing, cell selection,
• storage, tracking labeling
• Testing
• sterility, endotoxin, viability, enumeration

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Cellular Products Regulatory

• ManufacturingProduct Characterization
• Identification of cell populations
• Purity (non-cellular)
• Potency

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Cellular Products Regulatory

• Pre-clinical Testing
• Evolving paradigm
• Generally c/w biological products
• Catheters
• novel use of marketed
• non-marketed

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Cellular Products Regulatory

• Pre-clinical Testing
• Relevant species
• Disease model
• Administration (catheter)

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Cellular Products Regulatory

• Clinical Study Design
• Adverse event detection
• evaluation plan
• duration, frequency, extent
• safety monitoring
• sequential enrollment, stopping rules

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Cellular Products Regulatory

• Clinical Study Design
• Adverse event analysis
• --Txt-related vs natural history
• randomization
• controls (placebo vs other)
• masking
• other?

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Cellular Products Summary

• Topics
• Purpose
• Regulatory background
• Questions

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Cellular Products Questions

• Questions
• Manufacturing
• extent of testing characterization
• Pre-clinical and catheter
• extent and nature of testing
• Clinical study
• adverse event detection analysis

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Cellular Products Regulatory

• References (www.FDA.gov/cber)
• Draft Guidance for CMC Reviewers Human Somatic
  Cell Therapy Investigational New Drug
  Applications
• ICH Guideline Preclinical Safety Evaluation of
  Biotechnology-derived pharmaceuticals (S6)
• ICH Guideline Good Clinical Practice (E6)