During the manufacturing process, the drug product often undergoes a hold step for several days. The standard practice is to perform these holds under positive pressure and low temperature to minimize the risk of microbial growth during hold. During filling step, the product comes back to atmospheric pressure and ambient temperature, triggering degassing of the solution. Time pressure filling is observed to be sensitive to degassing due to bubble formation in the tubing. A conditioning step can be implemented as a mitigation prior to filling. The duration of the conditioning step, however, is dependent on the duration and conditions of hold. As a result, there is a need to better understand the degassing phenomenon and to determine the duration of the conditioning step required to achieve equilibration.<br/><br/>A numerical model based on first principles and the finite element method has been implemented to predict the impact of pressure and temperature conditions on drug product degassing. The model solves for the conservation of mass, momentum and energy in tanks and provides the distribution of dissolved O2 and N2 in the product as a function of time.<br/><br/>The model is validated with respect to experimental measurements using water as a drug product. The numerical and experimental results show a great match at batch sizes ranging from 5L to 30L.

Mechanistic understanding of the degassing phenomenon of drug products

255th National Meeting (2018)

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