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

Cellular Products Cellular Products for Cardiac Diseasesfor Cardiac Diseases

Dwaine Rieves, MDDwaine Rieves, MDCenter for Biologics Evaluation and Center for Biologics Evaluation and

ResearchResearch

FDA Perspective on:FDA Perspective on:

Cellular Products Cellular Products OverviewOverview

Topics Purpose Regulatory background Questions

Cellular Products Cellular Products PurposePurpose

A scientific discussion of

– Manufacturing

– Preclinical testing

– Pilot clinical studies


Cellular Products– Blood or bone marrow-derived cells

– Skeletal muscle-derived cells

– Predominantly autologous


Early Stage of Evolving Field

– Little precedent

– Limited data

– Hypothetical considerations


A Scientific Focus

– All insights tentative

– No definitive assessment of data

– No specific product assessment

Cellular Products Cellular Products Regulatory Regulatory

A Scientific Focus

Research Regulatory

Cellular Products

Cellular Products Cellular Products RegulatoryRegulatory

Regulatory Mission

Promote & Protect Public Health by:

– Pre-marketing product development

– Post-marketing product monitoring


Cellular Products for Cardiac Diseases

Biologic/drug/device regulations IND Early clinical development:

– Safety and bioactivity


Safety Concerns Manufacturing Sufficient preclinical testing Sufficient clinical study design


Manufacturing--Product Safety Cell source & reagents Procedures

– aseptic collection, processing, cell selection, storage, tracking & labeling

Testing– sterility, endotoxin, viability, enumeration


Manufacturing—Product Characterization

Identification of cell populations Purity (non-cellular) Potency


Pre-clinical Testing Evolving paradigm Generally c/w biological products Catheters

– novel use of marketed

– non-marketed


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


Clinical Study Design

Adverse event detection– evaluation plan

duration, frequency, extent

– safety monitoring sequential enrollment, stopping rules


Clinical Study Design Adverse event analysis—

--Txt-related vs natural history– randomization

– controls (placebo vs other)

– masking

– other?

Cellular Products Cellular Products SummarySummary

Topics Purpose Regulatory background Questions

Cellular Products Cellular Products QuestionsQuestions

Questions Manufacturing

– extent of testing & characterization

Pre-clinical and catheter – extent and nature of testing

Clinical study – adverse event detection & analysis


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)

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

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