In general,quality control systems for biotechnology-derived products are very similar to those quality control systems routinely employed for traditional pharmaceutical products in such areas as raw material testing and release,manufacturing and process control documentation,and aseptic processing.Quality control systems of biotechnology-derived products incorporate some of the same philosophies applied to the analysis of low molecular weight pharmaceutical products.These include the use of chemical reference standards and validated methods to evaluate a broad spectrum of known and/or potential product impurities and potential breakdown products.The quality control systems for biotechnology-derived products are generally analogous to those established for traditional biologicals with respect to determining product sterility,product safety in experimental animals,and product potency.For example,refer to Injections á1ñ,pHá791ñ,Particulate Matter in Injections á788ñ,Bacterial Endotoxins Test á85ñ,and Impurities in Official Articles á1086ñ.
The fundamental difference between quality control systems for biotechnology-derived products and traditional pharmaceuticals is in the types of methods that are used to determine product identity,consistency,purity,and impurity profiling.Furthermore,in biotechnology quality control,it is frequently necessary to use a combination of final product and validated in-process testing and process validation to ensure the removal of undesired real or potential impurities to the levels suggested by regulatory agencies.Biotechnology-derived products generally require a detailed characterization of the production organism (cell),a complete assessment of the means of cell growth/propagation,and explicit analysis of the final product recovery process.
The complexity of the quality control systems for biotechnology-derived products is related to both the size and structural characteristics of the product and manufacturing process.In general,the quality control systems required for products produced in prokaryotic cells are less complex than the systems required for products produced in eukaryotic cells.The quality control systems for prokaryotic production organisms usually entail documentation of the origin of the producer strain and encompass traditional testing for adventitious organisms,karyology,phenotyping,and antibiotic resistance.In addition,newer techniques such as DNArestriction mapping,DNAsequence analysis,and routine monitoring that may include measurement of mRNAand/or plasmid DNAlevels may be useful.The quality control of the master cell bank and working cell bank for eukaryotic production organisms generally includes testing for adventitious organisms,karyology,identity,and stability monitoring.All eukaryotic cell lines (except yeast)are generally tested for the presence of retroviruses,retroviral activity markers,and tumorigenicity,although many of these tests may be of limited value.