Approach of design for air mass balance in an aseptic processing area for cell-based products.

Introduction: The manufacture of cell-based products requires assuring sterility through all processes, with aseptic processing in a cleanroom. The environment consists of a critical processing zone (CPZ) that can ensure a level of cleanliness that allows cell culture containers to be opened, and a support zone (SZ) adjacent to it and accessed by an operator. In this study, an environment for cell manufacturing was proposed by designing an air mass balance in an aseptic processing area (APA). Methods: We considered the distribution of particle concentration related to the airflow of clean air passing through a high efficiency particulate air (HEPA) filter and the location of the particle emission sources and set up a model dividing the SZ into two zones vertically: the upper and lower zones in a cleanroom, considering three cases practically. Both the air inlet and outlet were located outside the cleanroom and were connected to the CPZ directly by air ducts (Case 1). The inlets of the CPZ were located in the lower or upper zones of the SZ inside the cleanroom, and the outlets were located in the upper zone (Case 2 or Case 3, respectively). We analyzed how the cleanliness of the APA was affected by different locations of the inlet and outlet of the CPZ by varying the particle emission rate or air change rate. Results: In Case 1, changes in the particle emission rate or air change rate within the SZ did not affect the particle concentration in the CPZ. In Case 2, an increase in the particle emission rate led to an increase in the particle concentration of the CPZ. In Case 3, the particle concentration of the CPZ was not affected by the particle emission rate. Cases 2 and 3 showed differences in particle concentrations between the CPZ and SZ, indicating that the location of the air inlet of the CPZ had an impact on the cleanliness of both zones. The partial circulation of air between the SZ and CPZ exhibited an additional air cleaning effect, leading to a reduction in the particle concentration in the SZ in Cases 2 and 3. Conclusions: These results suggest that the appropriate location of the air inlet and outlet can construct the cleanliness of the APA, which reduces the risk of microbial contamination. In addition, we consider that this approach can realize an APA design policy, which eliminates the need for air ducts between the outside of the cleanroom and the equipment for the CPZ, reduces the requirements for gowning, thereby reducing the required air change rate.