Industry perspective on the validation of column-based separation processes for the purification of proteins. Parenteral Drug Association.

Validation of column-based separations is necessary to ensure the quality and safety of protein and peptide products produced by rDNA, peptide synthesis, and hybridoma technologies. Process validation for column-based separations includes qualification of raw materials, equipment, and the purification process. Combined with in-process control and quality control of the final product, column validation ensures that a uniform product is produced consistently from batch to batch. In the best case, validation is designed into the process. During process design, techniques are selected which can remove impurities and contaminants. Equipment and chromatographic media which can perform reproducibly are selected. Column performance standards, cleaning and regeneration routines, and column life should be considered as early as possible. Clearance studies should be planned and implemented to ensure that a product is produced with the requisite purity. There are no explicit rules for process validation of column-based separation processes. This document is intended to serve as a starting point for those needing to validate column-based separation processes.