Building a Cell Culture Process with Stable Foundations: Searching for Certainty in an Uncertain World

摘要: Considerable effort is expended during the mammalian cell line construction process to find a stably-transfected clone capable of supporting large-scale manufacture recombinant therapeutic protein. Such must synthesise sufficient volumetric concentration product with correct biochemical characteristics (glycosylation, structural integrity, etc.). Furthermore, this performance be maintained over extended time period required support manufacturing campaign in 20,000 L bioreactors. However, significant proportion clonal lines show production instability long-term sub-culture, where yield and/or quality are not maintained. This can potentially extend development timelines and affect ability meet market demand. In worse-case scenario it also jeopardise patient safety if impaired. order prevent this, industrial processes include stability studies several candidate lead clones serially sub-cultured monitored for signs before selecting final line. The roots varied, but epigenetic silencing transgenes at sites host chromosome integration, direct mutation or loss prominent molecular causes. research has been conducted by both industry academic groups into mechanisms underpinning instability, an emphasis on uncovering early predictive markers incipient as well preventing its occurrence. article we present detailed overview experience impact therapeutics. We discuss our current understanding causes how used mitigate phenomenon through novel vector redesigns screening.