Furomitsu Shunpei, Mizutani Manabu, Kino-Oka Masahiro
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Research Institute for Bioscience Products & Fine Chemicals, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-8681, Japan.
Regen Ther. 2024 Nov 28;28:20-29. doi: 10.1016/j.reth.2024.11.009. eCollection 2025 Mar.
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).
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.
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.
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.
基于细胞的产品制造需要在所有流程中确保无菌，在洁净室内进行无菌处理。该环境包括一个关键处理区（CPZ），可确保达到一定的清洁水平，使细胞培养容器能够打开，以及与之相邻且供操作人员进入的支持区（SZ）。在本研究中，通过设计无菌处理区域（APA）内的空气质量平衡，提出了一种细胞制造环境。
我们考虑了与通过高效空气过滤器（HEPA）的洁净空气气流相关的颗粒浓度分布以及颗粒排放源的位置，并建立了一个模型，将SZ垂直划分为洁净室内的上下两个区域，实际考虑了三种情况。空气进出口均位于洁净室外，并通过风道直接连接到CPZ（情况1）。CPZ的入口位于洁净室内SZ的下部或上部区域，出口位于上部区域（分别为情况2或情况3）。我们通过改变颗粒排放率或换气率，分析了CPZ进出口不同位置对APA清洁度的影响。
在情况1中，SZ内颗粒排放率或换气率的变化不会影响CPZ内的颗粒浓度。在情况2中，颗粒排放率的增加导致CPZ内颗粒浓度增加。在情况3中，CPZ内的颗粒浓度不受颗粒排放率的影响。情况2和情况3显示CPZ和SZ之间的颗粒浓度存在差异，表明CPZ进气口的位置对两个区域的清洁度都有影响。SZ和CPZ之间的部分空气循环表现出额外的空气清洁效果，导致情况2和情况3中SZ内的颗粒浓度降低。
这些结果表明，空气进出口的合适位置可以构建APA的清洁度，从而降低微生物污染风险。此外，我们认为这种方法可以实现APA设计策略，即无需在洁净室外与CPZ设备之间设置风道，减少了着装要求，从而降低了所需的换气率。
