Overview of the nonclinical quality and toxicology testing for recombinant biopharmaceuticals produced in mammalian cells.

Biopharmaceuticals represent significant advances in therapeutic approaches for unmet medical needs, and increasingly, traditional pharmaceutical firms have been incorporating biotechnology capabilities into their product portfolios. There are some differences in the overall safety testing paradigms for small molecules and biopharmaceuticals, this safety testing including both quality and toxicology aspects. These differences are associated with both the manufacturing processes involved and the molecules themselves. For example, for biopharmaceuticals, living cells represent the factories for synthesizing complex molecular entities. As a result of this, safety testing for this class of drugs includes adventitious agent testing (e.g. viral, mycoplasma, transmissible spongiform encephalopathy agents) not normally needed for small molecules. Also, strategies for nonclinical toxicology testing of biopharmaceuticals differ from the paradigms used for small molecules and often need to be defined on a case-by-case basis, primarily taking into consideration species cross-reactivity attributes of the molecule of interest. Certain studies required for small molecules are not applicable to most biopharmaceuticals (i.e. genotoxicity testing, testing for interactions with the hERG channel). This manuscript provides an overview of both the quality and nonclinical toxicology testing for these mammalian-cell-derived products, two elements pivotal to the overall nonclinical assessment of the safety of these biopharmaceutical products.