Cleaning validation of different cleaning procedures for monoclonal antibodies on stainless steel

Abstract Introduction: Despite their growing importance in tumor treatment, monoclonal antibodies (mAbs) are still underrepresented in investigations on the efficiency of cleaning procedures. Effective cleaning routines are essential for pharmacies to minimize occupational exposure as well as proteinaceous surface contamination which otherwise can result in microbial growth. This study focused on the efficiency of different cleaning agents (alkaline, alcohol) and procedures (single pass, multipass) to remove various mAbs from stainless steel. Methods: Stainless steel surfaces were contaminated with known concentrations of various mAbs. Specifically, this study involved the use of bevacizumab, cetuximab, daratumumab, omalizumab, rituximab, and trastuzumab. Then, different standardized cleaning procedures were applied. This was followed by wipe sampling, enzymatic digestion of the wipe extracts, and analysis of the digested wipe extracts by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to investigate the cleaning efficiency of the different cleaning procedures. Results and Discussion: The cleaning performance of the alkaline cleaning solutions investigated was significantly higher than of 70% isopropyl alcohol (70% IPA) in the removal of various mAbs from stainless steel. Isopropyl alcohol has a low cleaning efficiency for the removal of mAbs on stainless steel. The cleaning procedures evaluated in this study are contextualized within a cleaning protocol recommended by the European Society of Oncology Pharmacy and the contamination control strategy outlined in EU GMP Annex 1. Conclusion and Outlook: In this study, the cleaning efficiency of different solutions and procedures for removing monoclonal antibodies from stainless steel was evaluated for the first time to our knowledge. Wipe sampling and analysis of monoclonal antibodies on stainless steel surfaces could be successfully implemented. It was demonstrated that multipass cleaning three-cycle two-agent procedure with an alkaline cleaner followed by alcohol cleaner results in complete removal of the applied monoclonal antibodies on stainless steel. Future studies could focus on assessing further cleaning agents and substrates such as glass.