Fundamentals Of Viral Clearance Studies Part 4: Considerations For Evaluating Viral Clearance By Chromatography Steps
By Kathryn Martin Remington, Ph.D., Principal Scientist for Clearance Services, BioReliance
Chromatography steps are typically the backbone of the purification process for a biopharmaceutical product, and are usually included in the evaluation of the viral reduction capacity of a manufacturing process. In viral clearance studies of chromatography steps, the capacity of the chromatography resin to provide physical separation of the spiked virus from the product fraction is determined. Viral reduction by chromatography steps is considered less robust than by other less complex steps, such as inactivation steps. This is because chromatography can be more difficult to accurately scale down and also because a number of operating parameters may influence the viral reduction that is achieved.
When scaling down a chromatography step for a viral clearance study, operating parameters such as pH, ionic strength, protein concentration, temperature, resin bed height and linear flow rate must be equivalent to the manufacturing scale (1). The process step output measurements, should also match the manufacturing scale. This may include elution profiles, product yield, impurity removal and specific activity. Any measures used to demonstrate the successful performance of the large scale process should be considered for evaluation of the comparability of the small scale model to the large scale process step. The viral clearance data are only valid if the small scale model of the chromatography step accurately mimics the large scale process step.