Quality Control of rDNA-Derived Human Tissue-Type Plasminogen Activator
The uniqueness of biotechnology is based on the use of genetically altered living organisms for the manufacture of commercial and human health care products. Although it traces its origins to the fermentation industry, biotechnology is best represented by the recombinant DNA (rDNA) and monoclonal antibody industries. These industries have succeeded in developing a number of products that profoundly affect the quality of human life. An example of a product derived from rDNA technology is the recently approved thrombolytic therapy drug, human tissue-type plasminogen activator (rt-PA). The development of rt-PA required the codevelopment of quality control systems capable of ensuring the lot-to-lot consistency of a glycosylated biomolecule of approximately 64,000 daltons manufactured from large-scale mammalian cell culture. In this chapter, rt-PA is used to illustrate some of the strategies and analytical methods for the control of recombinant cell culture products. The rationale and limitations of the use of these methods are also discussed.