Industrial Purification of Pharmaceutical Antibodies: Development, Operation, and Validation of Chromatography Processes

Recombinant monoclonal antibodies are becoming a great success for the biotechnology industry. They are currently being studied in many clinical trials for treating a variety of diseases, and recently several have been approved for treating cancer (Carter et al., 1992; Anderson et al., 1996; Baselga et al~, 1996; Bodey et al., 1996; Longo~ 1996). Although there are several types of antibodies produced in different types ofcel1lines, the most clinically significant antibodies are full-length humanized IgG. produced in CHO cells. This review describes the methods used to purify these antibodies at industrial scale, focusing on chromatography processes~ and with particular reference to recent work at Genentech. Routine laboratory purification ofantibodies has been well described (for example see Scott et aL, 1987), but the considerations for large-scale production of pharmaceutical-grade antibodies are much different than those for laboratory scale. There are extreme purity requirements for pharmaceutical antibodies~ and routine large-scale production requires high yield and process reliability. To gain regulatory approval, the process must be completely validated to run consistently within specified limits, so the process should be designed to facilitate validation, Large-scale production of antibodies as pharmaceutical products is a complex