In a concerted effort to investigate the implementation of a process analytical technology (PAT), we have evaluated the applicability of off-gas mass spectrometry (MS) analysis in mammalian cell culture based on the inlet and outlet gases from bioreactors. The limitations of the system & potential applications are also discussed.<br/><br/>Compared to other invasive methods that require physical probes inserted directly into the culture, the MS only requires gas going in and out of the cell culture which means it has minimal impact on the culture itself. With the Prima BT magnetic sector MS (Thermo Fisher Scientific), multiple gas streams can be analyzed. Distance between bioreactors and the MS is also not an issue given a high enough gas flow and a long enough gas tubing connection to the MS. Our data showed that changes in the gas traces on the MS, down to 0.001% mol, can be captured during various events throughout a typical cell culture. The MS data from two replicate 5L benchtop glass bioreactor runs are very comparable, as is the offline data between them; this indicates that the MS data can be used reliably to identify process deviations during bioreactor runs and be used as a convenient way to evaluate batch to batch variation, within predefined specifications, for robust manufacturing. We have also demonstrated that the same MS setup in the benchtop experiments, with minor modifications, can be applied in a 50L single-use bioreactor (SUB). We would also report that there are technical considerations with respect to the feasibility of integrating this system to the various cell culture platforms.<br/><br/>In conclusion, we believe that our work presented here will be of significant relevance to the cell culture community who are keen adopters of PAT and its practical implementation.

Rapid process monitoring & control in mammalian cell culture using off-gas mass spectrometry analysis

255th National Meeting (2018)

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