Protein loss during membrane processes in biopharmaceutical manufacturing.

Maximizing product yield in biopharmaceutical manufacturing processes is a critical factor in determining the overall cost of goods, especially given the high value of these biological products. However, there has been relatively limited research on the quantitative analysis of protein losses due to adsorption and fouling during the different membrane filtration processes employed in typical downstream operations. This study aims to provide a comprehensive analysis of protein loss in the range of membrane systems used in downstream processing including clarification, virus removal filtration, ultrafiltration/diafiltration for formulation, and final sterile filtration, all using commercially available membranes with three model proteins (bovine serum albumin, human serum albumin, and immunoglobulin G). The correlation between protein loss and various parameters (i.e., protein type, protein concentration, throughput, membrane morphology, and protein removal mechanism) was also investigated. This study provides important insights into the nature of protein loss during membrane processes as well as a methodology for quantifying protein yield loss in bioprocesses.

Mental Health and Quality of Life for Disaster Service Workers in a Province under COVID-19.

Objective: Healthcare workers and disaster service workers have been reported to be vulnerable to mental health problems during outbreaks of infectious diseases such as the COVID-19 pandemic. This study aimed to investigate the psychosocial characteristics of disaster service workers in charge of COVID-19-related work and also identify the factors affecting their quality of life. Methods: From June 2020 to June 2021, a survey was conducted of 526 disaster service workers in charge of COVID-19-related work. This included those working in public health care centers (PHC), 119 rescue and emergency medical services (119 REMS), public servants of city hall (PS), and police officers. The Korean version of the Fear of COVID-19 Scale, Patient Health Questionnaire-15, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Connor−Davidson Resilience Scale, and World Health Organization quality of life assessment instrument brief form were used. A one-way ANOVA was conducted, and a stepwise regression analysis was carried out to determine the factors affecting quality of life. Results: Regarding quality of life, 119 REMS (180.64 ± 26.20) scored significantly higher than PHC (165.76 ± 23.73) and PS (163.90 ± 23.60), while police officers (176.87 ± 23.17) scored significantly higher than PS (163.90 ± 23.60) (F = 12.373, p < 0.001). Resilience (ß = 0.897, p < 0.01) was the most significant explanatory variable, and together with insomnia (ß = 0.154, p < 0.01), depression (ß = −0.152, p < 0.01), and COVID-19 anxiety (ß = −0.057, p < 0.01) accounted for 91.8% of the explanatory variance with regard to quality of life. Discussion: Quality of life was found to be negatively correlated with insomnia, depression, and COVID-19 anxiety while being positively correlated with resilience. Therefore, active interventions are needed to improve the resilience of disaster service workers.

Effects of Impurities from Sugar Excipient on Filtrate Flux during Ultrafiltration and Diafiltration Process.

Sugar excipients such as sucrose and maltose are widely used for biopharmaceutical formulation to improve protein stability and to ensure isotonicity for administration. However, according to recent literature, pharmaceutical-grade sucrose contained nanoparticulate impurities (NPIs) that result in protein aggregation and degradation. The objective of this study was to evaluate the filtrate flux behavior of sugar solution during ultrafiltration (UF) and diafiltration (DF). Filtrate flux data were obtained using either a tangential flow filtration (TFF) system for DF experiments or a normal flow filtration system for UF experiments. In diafiltration experiments, which were performed using 7 g/L of human immunoglobulin G in a 20 mM histidine buffer with the 100 mM sucrose or maltose, the filtrate flux with sucrose solution decreased significantly. In contrast, the one with maltose solution was in good correspondence with the calculated filtrate flux accounting for the effects of solution viscosity. This large decline in the flux was also observed during UF experiments, in which the presence of NPIs was identified by dynamic light scattering analysis and by capturing an SEM image of the membrane surface after filtration. In addition, highly purified sucrose resulted in a much lower flux decline in TFF in the absence of NPIs. These results provide important insights into the factors governing the optimization of the UF/DF process using appropriate excipients for biopharmaceutical formulation.