(586v) An Effective and Facility Compatible Cleaning in Place (CIP) Procedure for Affinity Resin in Monoclonal Antibody (Mab) Purification

Cleaning-in-place (CIP) for column chromatography plays an important role in therapeutic protein production. A robust and efficient CIP procedure improves column life time and increase cost effectiveness of the purification processes, particularly for those using highly expensive affinity resins. Cleaning efficiency, resin compatibility, and facility compatibility are the three major aspects to consider in CIP process design. Cleaning affinity resin with sodium hydroxide along with high concentration of salt is one of the most popular cleaning procedures used in biopharmaceutical industries. However, high concentration sodium chloride could cause corrosion in the stainless steel containers used in large scale manufacture. Therefore, it is challenging to apply this cleaning procedure into commercial scale purification due to facility compatibility. Here we introduce an effective and environmental-friendly cleaning procedure which is suitable for large scale affinity chromatography. A high throughput screening method was developed in 96-well plate format for selection of the most effective cleaning reagent from ten candidate solutions which meet facility compatibility. Resin compatibility of selected cleaning reagents was also evaluated. The optimized cleaning strategy was comprehensively investigated in resin life cycle study. The new cleaning regime is able to prolong resin life time and consistently deliver high purity drug products.