Process Optimization and Characterization

• Progenipoietin
• Dual agonist of G-CSF and fetal liver
tyrosine kinase 3 receptors
• Stimulate dendritic-cell proliferation
• E. coli inclusion body
 Process Optimization
• Optimize operating parameters

• Identify key process parameter

 Critical Process Parameter
• Acceptable range (AR)
– The range in which the process parameter
(pH) can vary without having an unacceptable
impact on performance
• Operating range (OR)
– The range in which the process parameter
varies from lot to lot (ie batch record)
• Critical process parameter
– AR< 2 X OR
 Process Characterization
• Create scale-down model for process
characterization
• Establish acceptable ranges for all “key”
process parameters
• Generate list of critical process
parameters for use during process
validation
 Anion Exchange Resin
• Pharmacia Q FF, Pharmacia Q HP,
Pharmacia DEAE FF, Whatman QA52,
Whatman Q, Whatman DE53, Bio-Rad
High Q, Bio-Rad DEAE, and TosoHaas
Q650M
 Comparison of Performance
• Product recovery
– Product peak area in pooled fractions
• Pool purity
– Purity of total pool (with fractions meeting
purity criteria
 Parameter Evaluation
• Buffer pH
• Conductivity
• Protein loading
• Flow velocity
• Temperature
• Bed height
• Gradient slope