Some process control/design considerations in the development of a microgravity mammalian cell bioreactor

The purpose is to review some of the physical/metabolic factors which must be considered in the development of an operating strategy for a mammalian cell bioreactor. Emphasis is placed on the dissolved oxygen and carbon dioxide requirements of growing mammalian epithelial cells. Literature reviews concerning oxygen and carbon dioxide requirements are discussed. A preliminary, dynamic model which encompasses the current features of the NASA bioreactor is presented. The implications of the literature survey and modeling effort on the design and operation of the NASA bioreactor are discussed

Managing and Mitigating Risk in Biologics Process Transfer

processes into clinical and commercial production facilities. However, the application of the full set of tactics for every process transfer is often not warranted. Product quality and process performance must fulfil expectations in every process transfer, but the tactics to achieve these goals are typically product/project-dependent. Two important factors to consider when allocating tactics (and the associated resources) to a particular process transfer are the probability of an initial process transfer delay, and the impact to patients and the company of such a delay. The probability of an initial process implementation problem is heighted under a number of circumstances: for example, when the transfer is to an unfamiliar plant, when the process is non-platformed in some aspect, or when there has been a change of equipment or automation software in the plant. The impact to patients and financial impact to the company of a process start-up delay is also project specific. Janssen Pharmaceuticals transfers bulk biologics processes to a variety of internal and external, clinical and commercial production facilities around the world. In this presentation, we will discuss our menu of process transfer tactics, and our business process for allocating tactics and resources to each process transfer. The presentation will be illustrated by examples from recent clinical and commercial process transfers

The stress response system of proteins: Implications for bioreactor scaleup

Animal cells face a variety of environmental stresses in large scale bioreactors, including periodic variations in shear stress and dissolved oxygen concentration. Diagnostic techniques were developed for identifying the particular sources of environmental stresses for animal cells in a given bioreactor configuration. The mechanisms by which cells cope with such stresses was examined. The individual concentrations and synthesis rates of hundreds of intracellular proteins are affected by the extracellular environment (medium composition, dissolved oxygen concentration, ph, and level of surface shear stress). Techniques are currently being developed for quantifying the synthesis rates and concentrations of the intracellular proteins which are most sensitive to environmental stress. Previous research has demonstrated that a particular set of stress response proteins are synthesized by mammalian cells in response to temperature fluctuations, dissolved oxygen deprivation, and glucose deprivation. Recently, it was demonstrated that exposure of human kidney cells to high shear stress results in expression of a completely distinct set of intracellular proteins

The effect of oligosaccharides on glycoprotein stability

A series of experiments aimed at determining the sites of glycosylation of Staphylococcal nuclease (SNase) were conducted

A regional metabolic contrast method for the study of brain pathology

The use of 2-deoxyglucose for the measurement of regional cerebral glucose utilization in both animals and humans has gained widespread application. An attractive aspect of regional brain glucose metabolism is its apparent correlation with functional activity in neurons. Animal experiments suggest that this relationship is altered in brain lesions and that barbiturate anesthesia may be employed in the detection of brain regions where uncoupling of metabolism and neuronal function has occurred. A functional metabolic contrast technique is described that will permit determination of regional metabolism that is specifically attributable to neuronal activity. Areas of potential clinical application are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50307/1/410150717_ftp.pd