460619 Metal-Catalyzed Fragmentation of a Mab: a Case Study
Michael Grooms, Jennifer Fetter, T. Bruce Vickroy, Rianna Gallo Collier, Myrna Monck, George Alkire, Matthew Henry, Jennifer Dally, Robert G. Luo, Kent E. Göklen
King of Prussia, PA, USA
The level of metals in pharmaceuticals has come under scrutiny lately due to recent regulatory guidance requiring a clearer understanding and better controls of these impurities. This is motivated primarily by concerns of metal toxicity, but of equal concern for the producers of biopharmaceuticals is metal-catalyzed fragmentation of their product. In this case study, a mAb product is found to unexpectedly suffer fragmentation during accelerated stability experiments, where none had been seen earlier in the program. The investigation that led to an understanding of the phenomenon and the change that caused it will be presented. In addition, spiking studies to understand the impurity levels and their clearance during the downstream process, along with approaches to control the problem will also be presented.