Validation of Biopharmaceutical Chromatography Systems

Abstract

The importance of validation of biopharmaceutical systems is introduced in the previous chapter. The key elements of validation are summarised by Bala (1) whilst the general areas of validation are detailed by the PDA (2). More specifically the importance of validating the biopharmaceutical chromatographic system becomes apparent when one realises that the system is being used for product purification purposes. The quality and product failures of the past, combined with public protection issues, led the US Food and Drug Administration (FDA) to publish the current Good Manufacturing Practices (cGMPs) in the Code of Federal Regulations (CFR) in 1979. The principal of validation was introduced by the FDA almost immediately thereafter to demonstrate that a process truly functions as intended with supporting documentation.

This tenet applies equally to chromatographic systems, where the aim of the validation is to show that purification has functioned as intended during standard process conditions and to provide the supporting documentation to prove this.

The difficulty arises in that the FDA has never really identified the manner in which validation is to be carried out and so industry has led the way in defining methods to satisfy the validation requirement.

This chapter is an overview of those methods with specific reference to chromatographic systems.