Retavase is a recombinant plasminogen activator. It is expressed in an inactive form in E.coli. Consequently, the resulting question for large scale production is the same as in academic research: how to get to the correctly folded active state. The answer for  the folding processes of Retavase is given with respect to principal process steps and design of large scale equipment. The native Retavase molecule contains 9 disulfide bridges which bear the risk of wrong crosslink formation during refolding resulting in a low yield of correctly folded protein. Important milestones in process development of the Retavase folding process are addressed.

Data from more than 10 years of large scale routine production experience are shown and examples of production problems which occurred during this time period are discussed. Additionally, the experience from a process transfer for this product to an US company is presented.