Use of Liquid Medium Concentrates to Enhance Biological Productivity.

Abstract

Liquid medium concentrates (LMC) were initially developed in response to industrial customer demand for improved efficiency and productivity of mammalian cell bioreactors. The resultant technology, which is undergoing its second generation of improvement, exploits biochemical properties intrinsic to the constituent nutrients to improve solubility, stability, and biological performance. Customer-perceived benefits, relative to liquid media produced by conventional technologies, include both enhanced biological productivity and improved manufacturing efficiency. The key concept which drives superior performance is that in concentrate technology all nutrient components of a complex biochemical formulation are fully pre-solubilized as a minimal number (generally three) of 50X LMC sub-groupings precedent to complete admixture. Under conventional procedures, critical nutrient potencies may be reduced relative to theoretical values due to poor solubilization and partial removal by precipitation and filtration. Use of LMC intermediates for the formulation of liquid media produces superior initial correlation with theoretical nutrient potency and may result in superior performance stability. Delivery of the full complement of nutrients to the biomass may be limiting to culture survival, attainment of maximal cell density, optimization of the specific cellular productivity, and prolongation of the bioreactor production cycle. The advantages of LMC become increasingly apparent with serum reduction or elimination, augmented cell densities, enhanced medium residence time and increasing development of balanced nutrient formulations. Complex nutrient media, formulated as LMC, are stable for up to one year in many cases, are compatible with various hulk containers, and exhibit superior biochemical potency and biological performance relative to conventionally-prepared culture media.