Safety aspects in the quality control of recombinant products from mammalian cell culture.

The recent approval of the recombinant DNA-derived biological, human tissue-type plasminogen activator (rt-PA), obtained from large scale mammalian cell culture, addressed a number of issues concerning the safety of recombinant products. The assurance of the safety of such highly complex proteins requires that the following topics be investigated: the characterisation of the recombinant production organism; control of large scale cell culture production conditions; design of the purification process and consistency of manufacture; the purity, safety, and stability testing of the final product; and clinical studies. Each of the topics described above is discussed with respect to those key quality control issues that ensure the safety of the product. The use of analytical techniques such as peptide mapping and multiantigen ELISA assays to guarantee both the genetic stability and the purity of the final product is also discussed.