Understanding the formation and behaviors of droplets toward consideration of changeover during cell manufacturing

Abstract

Preventing the contamination of processed cells is required for achieving reproducible manufacturing. A droplet is one of the potential causes contamination in cell manufacturing. The present study elucidates the formation mechanism and characteristics of droplets based on the observation and detection of droplets on the base surface of the biological safety cabinet (BSC) where cell processing is conducted under unidirectional airflow. Pouring fluorescent solution into the vessel using a measuring pipette was conducted to visualize the formation of droplets by videos as well as visual detection by blacklight irradiation on the base surface of the BSC. The experiments revealed that airborne and non-airborne droplets emerged from bursting bubbles, which formed when the entire solution was pushed out of the measuring pipette. Therefore, the improving procedure of pouring technique when entire solution was not pushed out of the pipette realized no formation of the droplets due to the prevention of emergence of bubble. In addition, an alternative procedure in which the entire solution was poured into the deep point of the test tube prevented the flying of non-airborne droplets outside the tube, while airborne droplets that escaped the tube rode the airflow of BSC. These results suggested a method for the prevention of the droplet formation, as well as the deposit control of droplets onto the surface in BSC, leading to cleanup area in the BSC for changeover with environment continuity.

Approach of resource expenditure estimation toward mechanization in the manufacturing of cell-based products

“…As a technical example, rapid loading methods employing a new decontamination technology permit operations in which the CPZ is continuously aseptic or maintained aseptic by cleaning without decontamination is assumed [ 29 , 30 ]. Furthermore, omitting the intervention of human operators with such methods is also profitable due to reduce the resource expenditure.…”

Cross-contamination risk and decontamination during changeover after cell-product processing

“…Cell-processing facilities are known to harbor risks, including environmental bacteria [ 1 ], which may contaminate biosafety cabinets during processing [ 2 ]. During autologous cell-product processing, cross-contamination can occur during changeover.…”

Stress and motivation of cell processing operators: A pilot study of an online questionnaire survey

“…While technological development of mechanization and automation is progressing in cell processing for regenerative therapy, flexibility is often required and, in many cases, cell processing is carried out manually by operators [ 1 , 2 ]. In particular, cell culture is a delicate process that relies heavily on the manual skills of the operators [ 3 , 4 ], and cell processing operators (CPOs) play an important role in ensuring the processing of cell products that maintain safety and quality.…”