Evaluation of the In-Use Stability of Monoclonal Antibody IV Admixtures Prepared from Drug Products Containing Polysorbate 20 Degraded by Host-Cell Lipases

Host-cell lipases can be present in monoclonal antibody drug products and can degrade polysorbates present in the formulations as stabilizers. We hypothesized that the in-use stability of the IV admixture prepared from such a drug product might be impacted by decreasing levels of polysorbate 20. Host-cell lipase activity has, in fact, been observed during development of one of our therapeutic monoclonal antibody drug products. Throughout the course of the product shelf life, polysorbate 20 levels decreased but no other quality attributes of the drug product were impacted. An experimental approach was developed to simulate how the prepared IV admixture in-use stability is affected as polysorbate 20 concentration in the drug product decreased over the shelf life, and from that a minimum level of polysorbate 20 required in the drug product was determined to estimate the in-use stability of the IV admixture as the polysorbate 20 in the drug product degrades. The results indicate that although the observed degradation of polysorbate 20 does not affect quality attributes of this drug product, in-use stability of the IV admixture as a function of polysorbate degradation can be impacted and should be assessed to ensure sufficient quality. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

The activity of host-cell lipases in monoclonal antibody drug products can lead to degradation of polysorbate 20, a stabilizer in the formulations. This study investigates the impact of decreasing levels of polysorbate 20 on the in-use stability of an intravenous admixture prepared from such a drug product. Experimental approaches were used to determine the minimum level of polysorbate 20 required in the drug product and evaluate the in-use stability of the admixture as polysorbate 20 degrades. The results suggest that although the degradation of polysorbate 20 does not affect the quality attributes of the drug product, the in-use stability of the admixture can be impacted.