Optimized Upstream Process Development For Production of A Leunase (L-Asparaginase) Biosimilar

Asparaginase is an enzyme that catalyzes the hydrolysis of l-asparagine to l-aspartic acid and ammonia which is one of the most significant oncologic drugs for the treatment of leukemia# therefore, process developments for pharmaceutical-grade production of l-asparaginase biosimilars is being pursued worldwide# in this research, cell culture process for production of an l-asparaginase biosimilar candidate, amidohydrolase type ii expressed in e#coli host, was developed regarding the quality-by-design (qbd) principles# also design of experiments, based on risk assessment of the production process, was carried out to control the critical process parameters (cpps) which could significantly affect the final product quality# based on the results of cell culture process optimization, feeding of glucose %50, µset = 0#13 h-1 and iptg as the inducer for expression of the protein product, were selected# sds-page results showed an appropriate amount of protein expression after cell culture induction with iptg# also, the enzyme activity assays demonstrated that enzymatic activity of the biosimilar product sample was within acceptable range with ~106% of activity relative to that of the reference standard drug samples#