High-density perfusion cultivation of mammalian cells can result in elevated bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2) exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH control. Recognizing the limitations to the practicality of gas sparging for CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the source was investigated. The NaHCO(3) in the medium was replaced with a MOPS-Histidine buffer, while Na(2)CO(3) replaced NaHCO(3) for pH control. These changes resulted in 63-70% pCO(2) reductions in multiple 15 L perfusion bioreactors, and were reproducible at the manufacturing-scale. Bioreactor pCO(2) values after these modifications were in the 68-85 mm Hg range, pCO(2) reductions consistent with those theoretically expected. Low bioreactor pCO(2) was accompanied by both 68-123% increased growth rates and 58-92% increased specific productivity. Bioreactor pCO(2) reduction and the resulting positive implications for cell growth and productivity were brought about by process changes that were readily implemented and robust. This philosophy of pCO(2) reduction at the source through medium and base modification should be readily applicable to large-scale fed-batch cultivation of mammalian cells.
This paper will discuss how to reduce (IDM) Indirect Material consumption for derailing process by eliminating the manual derailing method as part of cost saving project. It involves the removal of cutter blade used for derail.Cost improvement was one of organizational goals of the company for 2019. This drive can be supported by analyzing Indirect Material spending and process simplification at assembly plant. At assembly End-Of-Line processes, derail cutter blade was one of the top Indirect Material spending at singulation and there is an opportunity to reduce if not eliminated the cost consumption of derail cutter blades through process simplification. Increasing volume in Quad-Flat-No lead (QFN) packages and new banner products being develop by New Product Integration NPI, Q1’20 means increase in IDM consumption per process. The challenge is to drive a process simplification that will reduce IDM to save cost by start of Q2’20. DMAIC methodology was used to improve the process of derailing process.
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