Predicting Airborne Volatile Organic Compound Transport in Highly Sensitive In Vitro Processes and Biopharmaceutical Manufacturing Facilities with Kinetic Models

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Introduction: Volatile organic compounds (VOCs) are ubiquitous in indoor air spaces, including the most sensitive medical environments. In assisted reproductive technology facilities, VOCs are known to greatly decrease embryo implantation rates and may impact embryo growth rate as well as miscarriage rates. There is reason to believe that the observed impacts of VOCs translate into parallel industries as well, such as the emerging cell and gene therapy industry. Previous modeling efforts on VOC transport into cell culture media components have provided estimates on the expected equilibrium concentrations from airborne VOC exposure. However, a fundamental knowledge gap remains regarding the rate of VOC partitioning into cell cultures. Materials and Methods: In this work, we present an enhanced modeling approach to quantify the partitioning kinetics of selected VOCs in cell cultures consisting of a multiphase system with an oil overlay and a water-based culture media, as well as a water-based media without overlay. Results: Preliminary results from eight prevalent and cytotoxic VOCs indicate rapid equilibration into the system with equilibrium achieved within a timescale of seconds to minutes. Discussion: These results suggest that practitioners must take steps to maintain VOC-free air for the protection of cell cultures to avoid adverse outcomes, as open-air processes may be compromised even during brief exposure to VOCs. Conclusion: VOCs have been modeled to rapidly equilibrate into cell cultrue systems, potentially disrupting normal cellular development.