Designing a Strategy for pH Control to Improve CHO Cell Productivity inBioreactor

Background: drastic ph drop is a common consequence of scaling up a mammaliancell culture process, where it may affect the final performance of cell culture. althoughco2 sparging and base addition are used as common approaches for ph control,these strategies are not necessarily successful in large scale bioreactors due to theireffect on osmolality and cell viability. accordingly, a series of experiments were conductedusing an igg1 producing chinese hamster ovary (cho-s) cell culture in 30 lbioreactor to assess the efficiency of an alternative strategy in controlling culture ph.methods: factors inducing partial pressure of co2 and lactate accumulation (as themain factors altering culture ph) were assessed by plackett-burman design to identifythe significant ones. as culture ph directly influences process productivity, proteintiter was measured as the response variable. subsequently, central composite design(ccd) was employed to obtain a model for product titer prediction as a function ofindividual and interaction effects of significant variables.results: the results indicated that the major factor affecting ph is non-efficient co2removal. co2 accumulation was found to be affected by an interaction between agitationspeed and overlay air flow rate. accordingly, after increasing the agitationspeed and headspace aeration, the culture ph was successfully maintained in therange of 6.95-7.1, resulting in 51% increase in final product titer. similar results wereobtained during 250 l scale bioreactor culture, indicating the scalability of the approach.conclusion: the obtained results showed that ph fluctuations could be effectivelycontrolled by optimizing co2 stripping.