Typically, early fermentation process development (PD) is performed using univariate and designed experiments without clearly defined targets for process performance.  Not only is this approach time consuming but also puts huge demands on scarce resources. Here we present an alternative approach, which is based on quality risk assessment and design space concepts, to optimize an early phase fermentation growth medium and induction conditions for expressing a recombinant protein.  To direct the PD effort, input parameters were analyzed based on their potential impact (severity) on process performance (protein expression, specific protein productivity, and product purity).  Using a risk scoring matrix, input parameters identified as high risk were evaluated using a combination of multivariate and univariate designed experiments.  With this systematic approach, the optimized fermentation production process achieved 166 and 100% increase in recombinant protein expression and specific protein productivity, respectively, in comparison to the performance in the non-optimized fermentation medium while maintaining the product purity, in a much shorter development time.

Application of quality risk assessment and design space concepts to early phase production fermentation of recombinant protein

241st National Meeting (2011)

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