PROCESS SCALE-UP CRITERIA IN PRODUCTION OF RECOMBINANT PROTEINS IN E. COLI: A SYSTEMATIC REVIEW

Abstract

This systematic review provides an overview of the scale-up of recombinant protein production. A systematic search was conducted using pre-established terms in four electronic databases (PubMed, Europe PMC, Science Direct, and Scopus), and included journal articles published between 1999 to 14 November 2019. Studies that met the inclusion and exclusion criteria specified were included. Initially, 665 abstracts were screened, of which 595 were excluded. A further 58 articles were excluded after full-text review and 14 articles underwent quality assessment. Finally, only eight (8) eligible articles were identified and included in this review. Oxygen transfer, shear, and production costs were identified as the main factor that affected the choice and success of a scale-up strategy. The comparison of different fermentation systems revealed that maintaining kLa constant was found to be effective in all included studies which employed it, and superior in the two studies that compared it to other criteria. Risk of bias assessment revealed that publication bias and reporting bias are significant issues to be considered in scale-up. Overall, these findings provide insight that can assist researchers to improve the scaling up of fermentation processes and achieve a successful scale-up of recombinant protein production using E. coli as the host.