Are continuous cell lines safe as substrates for human drugs and biologics? A case study with human growth hormone.

The development of a genetically engineered human growth hormone (hGH) preparation is described. The cell line used to produce hGH is a C127 mouse cell transformed with a bovine papilloma virus (BPV) vector. Master, Extended Production, and Working Cell Banks were established. Product is produced by culturing in growth medium, and purified using a series of chromatography and ultrafiltration steps. Extensive testing of cell banks, and bulk and finished product reveals that the cells used to produce hGH are phenotypically and genotypically stable and are free from contamination with adventitious agents. Levels of residual host cell DNA are well below accepted guidelines. Clinical data gathered in multicenter trials confirm the efficacy and safety of the product in the treatment of classic growth hormone deficiency. The regulatory history of human growth hormone in the U.S. is reviewed.