Optimizing Process Development for Microbial Fermentation

Biopharma processes must be developed in alignment with quality guidelines, such as those established by FDA and the International Council for Harmonisation, according to Paul Mugford, director, Biologics Process Development at BIOVECTRA. Process development often utilizes a quality-by-design approach to ensure quality and understand process parameters and critical quality attributes.

“Understanding the design space is important for all process steps, and typically, we would use a design of experiments to map out that design space and understand the relationships between parameters and the quality of the product produced,” Mugford says. “[There are a] few considerations when designing a fermentation [process] and optimizing it. The first decisions are around plasmid selection and strain or cell line.”

“For microbial systems that we work with, there are several options, options in strain selection for E. coli [Escherichia coli], depending on whether or not you're making a recombinant protein or a plasmid DNA. So engineered E. coli strains are necessary for optimal performance, and we have partnerships with different organizations, [such as] the National Research Council in Canada, for particular strains,” says Mugford. “So, considerations in strain selection include the protein solubility, whether or not you get correct folding, the expression location, [and whether] it's going to be in the periplasm or cytoplasm. And there's also modified strains that allow [correction] for any codon bias or disulfide bond formation. So, selecting the appropriate strain is important up front, and then there [are many] considerations around the plasmin design for optimal protein selection.”

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About the speaker

Paul Mugford is director, Biologics Process Development at BIOVECTRA.