Process parameters Buffer pH Inlet and transfilter pressure (shear stress) Pore size Flux

Affected product quality attributes Aggregation, deamination, disulfide variants HCP and DNA release (influence on membrane), yield and clarification efficiency Clarification efficiency Product recovery

Process parameters
Buffer pH Inlet and transfilter pressure (shear stress) Pore size Flux % composition of ionic charged resin binder in filter Operating temperature

% composition of ionic charged resin HCP and DNA removal binder in filter Operating temperature Fragmentatio n, aggregates, deamination Severity(1-10) Detectability Occurrence RPN (1-125) deamination, fragmentation Holding time Aggregation, (1-5) (1-5)
10 6 2 2 6 8 2 2 3 2 3 2 2 2 2 3 1 2 40 24 12 12 18 32

Product Quality Impact Uncertainty Attribute 12 5 Aggregate Deamidated 4 2 variants Figure 1: The existing (a) and the proposed (b) production line DNA 2 3 12 3 HCP Leaches 2 2 (Diatomaceous) 12 7 Disulfide variants Fragmented 4 2 variants

Risk Score 60 8 6 36 4 84 8