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Table 2 Cell culture platform evolution from conventional to intensified fed-batch production

From: Development of an intensified fed-batch production platform with doubled titers using N-1 perfusion seed for cell culture manufacturing

CategoryParameterProcess AProcess BProcess C
MediaSeed expansionB1 + MSXB1 + MSXB1 + MSX
Production basalB1B1 or B1 enrichedB2 or B2 enriched
FeedF11.3 × F1 or 1.3 × F1 enrichedF2 or F2 enriched
Process modeN-2 seedBatchBatchPerfusion or batch
N-1 seedBatchEnriched batch or fed-batchPerfusion
Production (N)Conventional fed-batchIntensified fed-batch with non-perfusion N-1Intensified fed-batch with perfusion N-1
Production process parametersInoculation density (× 106 cells/mL)0.3–1.53.0–6.010–20
Feeding strategyFixed at 3.6% of initial volume from Day 3VariableVariable
Temperature shiftNoVariableVariable
HarvestDayDay 14Day 10–14Day 10–14
Process yieldFinal normalized titer0.1–0.3~ 0.5~ 1.0
  1. The Process C final titer was normalized as 1 for each of mAb1, mAb3 and mAb4, while the Process C titer on Day 10 was normalized as 1 for mAb2