Viral infection of cell-culture processes represents a significant risk in biopharmaceutical processing using mammalian cells. Treatment of media with ultraviolet light is an effective means for inactivation of a broad set of adventitious virus. Owing to the high optical absorbance of media, delivery of a uniform dose of light is a significant challenge with this treatment. Use of thin-film optical reactors is one approach for over-coming this challenge but the heterogeneity of the resulting dose can hamper process design, scale-up, technology transfer and process qualification.<br/><br/>Mechanistic modeling can be used to quantify the dose received by particles flowing through different regions of the photo-reactor and provide the means to link laboratory results utilizing virus with production-scale conditions. Further, use of photo-sensitive beads as photon detectors provides means for ensuring models are fit-for-purpose in process design and qualification. This paper describes the development and use of mechanistic stochastic models which enable quantification of the dose distribution received by particles transgressing thin-film photoreactors. Models were qualified using NIST-traceable standards and applied to different reactor types and media composition. Viral inactivation was assured using viral propagation and PCR methods.

Modeling light transmission and chemistry in production-scale ultraviolet thin-film reactors

255th National Meeting (2018)

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