No abstract

Presented is a novel antibody production platform based on the fed-batch culture of recombinant, NS0-derived cell lines. A standardized fed-batch cell culture process was developed for five non-GS NS0 cell lines using enriched and optimized protein-free, cholesterol-free, and chemically defined basal and feed media. The process performed reproducibly and scaled faithfully from the 2-L to the 100-L bioreactor scale achieving a volumetric productivity of > 120 mg/L per day. Fed-batch cultures for all five cell lines exhibited significant lactate consumption when the cells entered the stationary or death phase. Peak and final lactate concentrations were low relative to a previously developed fed-batch process (FBP). Such low lactate production and high lactate consumption rates were unanticipated considering the fed-batch culture basal medium has an unconventionally high initial glucose concentration of 15 g/L, and an overall glucose consumption in excess of 17 g/L. The potential of this process platform was further demonstrated through additional media optimization, which has resulted in a final antibody concentration of 2.64 +/- 0.19 g/L and volumetric productivity of > 200 mg/L per day in a 13-day FBP for one of the five production cell lines. Use of this standardized protein-free, cholesterol-free NS0 FBP platform enables consistency in development time and cost effectiveness for manufacturing of therapeutic antibodies.

Superplasticisers improve the flow properties of fresh cement and offer undoubted benefits to the construction sector. There is concern in the nuclear industry, however, that the presence of a superplasticiser in grout or backfill cement may increase the solubility of radionuclides in the cementitious pore water and/or reduce their adsorption from solution. This paper describes the effect of a commercial, polycarboxylated, polyether comb type superplasticiser on the behaviour of selected metals in blended cements through a series of batch and monolith leach experiments.Results of batch experiments show that the presence of free superplasticiser in solution reduces uptake of nickel ( 63 Ni) and europium ( 152 Eu) by both blast-furnace-slag-and pulverised-fly-ash-modified ordinary Portland cement.Further, metal bound in the presence of free superplasticiser is readily remobilised on exposure to fresh cement solution. Conversely, metal uptake is almost complete and appears irreversible when exposed to hardened cements prepared with superplasticiser as part of the original mix. Monolithic slag cement samples prepared with superplasticiser suffer from bleed, with the surplus water containing a significant proportion of the metals added, including uranium and thorium. Digital autoradiography reveals heterogeneous distribution of radioactivity in the monoliths and demonstrates that the dissolved metals have not been effectively immobilised throughout the specimen. The mobility of thorium may indicate similar behaviour by other tetravalent actinide species, notably Pu(IV) and Np(IV).