Therapeutic proteins are used to successfully treat hemophilia, Crohn's Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous work at the University of Denver demonstrated that fluid cavitation can generate a large number of sub-visible protein particles in ultra clean formulations, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and vial drop conditions were performed. The impact of geometry, fluid properties and operating conditions were varied to establish thresholds and mitigation strategies. The results of this research show that reducing the turbulence in a fluid system will cause the fluid to be less likely to cavitate. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.
","abstract_html":"<p>Therapeutic proteins are used to successfully treat hemophilia, Crohn's Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous work at the University of Denver demonstrated that fluid cavitation can generate a large number of sub-visible protein particles in ultra clean formulations, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and vial drop conditions were performed. The impact of geometry, fluid properties and operating conditions were varied to establish thresholds and mitigation strategies. The results of this research show that reducing the turbulence in a fluid system will cause the fluid to be less likely to cavitate. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.</p>","abstract_has_math":false,"creators":["Sederstrom, Donn"],"institution":null,"degree_name":"M.S.","degree_level":"Masters Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Corinne S. Lengsfeld, Ph.D.","Peter Laz","Breigh Roszelle","Alvaro Arias"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-01T08:00:00Z","date_published":"2013-01-01T08:00:00Z","updated_at":"2026-07-24T02:03:35Z","subjects":["Cavitation","Computation fluid dynamics","CFD","Critical pressure","Fluid solid interaction","FSI","Pharmaceutical","Proteins","Biomechanical Engineering","Engineering","Mechanical Engineering"],"languages":["en"],"rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.du.edu/etd/586","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Corinne S. Lengsfeld, Ph.D.","Peter Laz","Breigh Roszelle","Alvaro Arias"]},{"key":"dc:creator","label":"Author","values":["Sederstrom, Donn"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2001-01-01T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cavitation","Computation fluid dynamics","CFD","Critical pressure","Fluid solid interaction","FSI","Pharmaceutical","Proteins","Biomechanical Engineering","Engineering","Mechanical Engineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author. User is responsible for all copyright compliance.
"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.du.edu/etd/586"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Therapeutic proteins are used to successfully treat hemophilia, Crohn's Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous work at the University of Denver demonstrated that fluid cavitation can generate a large number of sub-visible protein particles in ultra clean formulations, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and vial drop conditions were performed. The impact of geometry, fluid properties and operating conditions were varied to establish thresholds and mitigation strategies. The results of this research show that reducing the turbulence in a fluid system will cause the fluid to be less likely to cavitate. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.
"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Cavitation in Pharmaceutical Manufacturing and Shipping"]}]}],"canonical_facts":{"dc:contributor":["Corinne S. Lengsfeld, Ph.D.","Peter Laz","Breigh Roszelle","Alvaro Arias"],"dc:creator":["Sederstrom, Donn"],"dc:date.available":["2001-01-01T08:00:00Z"],"dc:description.abstract":["Therapeutic proteins are used to successfully treat hemophilia, Crohn's Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous work at the University of Denver demonstrated that fluid cavitation can generate a large number of sub-visible protein particles in ultra clean formulations, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and vial drop conditions were performed. The impact of geometry, fluid properties and operating conditions were varied to establish thresholds and mitigation strategies. The results of this research show that reducing the turbulence in a fluid system will cause the fluid to be less likely to cavitate. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.
"],"dc:format":["application/pdf"],"dc:identifier":["https://digitalcommons.du.edu/etd/586"],"dc:language":["en"],"dc:rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"dc:subject":["Cavitation","Computation fluid dynamics","CFD","Critical pressure","Fluid solid interaction","FSI","Pharmaceutical","Proteins","Biomechanical Engineering","Engineering","Mechanical Engineering"],"dc:title":["Cavitation in Pharmaceutical Manufacturing and Shipping"],"thesis:degree_level":["Masters Thesis"],"thesis:degree_name":["M.S."]},"updated_at":"2026-07-24T02:03:35Z"}