ABSTRACT
In this chapter, a case study is presented that describes validation of a puriŒcation process for a therapeutic monoclonal antibody. Zevalin® is a radiolabeled monoclonal antibody for the treatment of several types of non-Hodgkin’s lymphoma. The monoclonal antibody is expressed and secreted by Chinese hamster ovary (CHO) cells. The treatment dosage is substantially lower than that of unlabeled antibody treatments because only a small amount of radiolabeled antibody is needed to irradiate and destroy tumor cells. Since Zevalin is such a low-dosage drug, only a few production lots were required to satisfy product needs for phase I/II and phase III clinical trials. This posed substantial challenges for process validation due to the fact that only very few data points from manufacturing-scale campaigns were available to design a process validation. The intention of this chapter is to describe an approach to deal with the challenge of setting acceptance criteria for process validation based on limited manufacturing-scale experience. In this regard, the scenario outlined subsequently may be considered a typical one for low-dosage biopharmaceuticals.
