Biosafety Testing of Biologicals for Mycoplasma Contamination Comparison of Current US, European, and Japanese Regulations

摘要

Mycoplasma contamination of cell culture (both of primary and continuous eukaryotic cell lines) is common and represents a significant issue of importance in the basic research, development, and production of biologicals. Contamination can alter virtually every physical and chemical property of cells (depending on the contaminating species and the cell type), potentially leading to unreliable results and perhaps unsafe biologicals, biopharmaceutical drugs, or viral vaccines. In fact, contamination may be present with no obvious change in the host culture, even when the concentration of Mycoplasma exceeds that of the host cells by 10- to 100-fold. Thus, testing for Mycoplasma contamination during development and manufacturing is a requirement by theworldwide regulatory authorities in the United States, Europe, and Japan. Key regulations are defined under European Pharmacopoeia (EP) section 2.6.7 (1), Japanese Pharmacopoeia (JP) section 9 (2), FDA Points to Consider (PTC) documents in 1993 (3) and 1997 (4); 21 CFR 610.30 (5), and the recently announced United States Pharmacopoeia <63> (USP) monograph that will become effective in October 2010 (6).