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This paper provides an overview of the fundamentals of viral inactivation and clearance studies required for mammalian cell culture-derived biotechnological products. Strategies and considerations for evaluating the potential of purification processes to inactivate or remove adventitious or endogenous viruses are also discussed. The principles are illustrated by presenting data derived from the evaluation of clinical manufacturing processes for recombinant human interferon-beta and recombinant soluble CD4.

A model for validation of viral clearances in Biopharmaceutical processes is developed from an analysis of validation of terminal sterilization processes. The model develops the role for small-scale experiments in the validation of large-scale production processes. The steps for process validation are: identify or discover the basic general physical, chemical, or biological laws governing the process; identify the critical process control parameters for the specific application under investigation; and demonstrate the ability of the production equipment to maintain critical parameters with specified limits. For concurrent validation, this final step is seen as equivalent to demonstrating that a scaled-down model experiment is an appropriate representation of the production process.