@article {Siavashpouri461, author = {Mahsa Siavashpouri and Christina M. Bailey-Hytholt and Jean-Rene Authelin and Sanket Patke}, title = {Quantification and Stability Impact Assessment of Drop Stresses in Biologic Drug Products}, volume = {76}, number = {6}, pages = {461--473}, year = {2022}, doi = {10.5731/pdajpst.2021.012722}, publisher = {Parenteral Drug Association (PDA)}, abstract = {Product can experience a combination of cavitation and agitation stresses as a result of dropping post-manufacture. We optimized terephthalic acid (TA) dosimetry, hydroxyphenyl fluorescein fluorimetry, and p-nitrophenol calorimetry as tools to detect and quantify the levels of hydroxyl radicals generated in solution. Using TA dosimetry, we determined the level of hydroxyl radicals generated from a vial drop and found that it is a function of drop height and fill volume and that protein and excipients may serve to mitigate but not completely quench the radicals. Additionally, we optimized sonication and friability as scale-down models to simulate dropping stresses and applied them to assess the impact on the stability of biologics. Our results suggest that chemical degradation dominates when a protein is subjected to cavitation stress alone, and that physical degradation induced by air{\textendash}liquid and solid{\textendash}liquid interfaces is the dominant degradation mode when there is a combination of cavitation and agitation stress. Taken together, this work provides a quick and simplistic approach that can be applied during drug product process development to evaluate the impact of drop stresses on the stability of biologic drug product.}, issn = {1079-7440}, URL = {https://journal.pda.org/content/76/6/461}, eprint = {https://journal.pda.org/content/76/6/461.full.pdf}, journal = {PDA Journal of Pharmaceutical Science and Technology} }