{"id":{"repo_id":"cork","oai_identifier":"oai:cora.ucc.ie:10468/9969"},"canonical_url":"https://search.dev.ndltd.org/etd/cork/oai:cora.ucc.ie:10468/9969","repository":{"repo_id":"cork","name":"University College Cork","base_url":"https://cora.ucc.ie/server/oai/request"},"display":{"title":"The impact of variation in freezing and thawing process parameters on the critical quality attributes of a monoclonal antibody","abstract":"Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS).","abstract_html":"Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS).","abstract_has_math":false,"creators":["Day, Neil"],"institution":"University College Cork","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Crean, Abina","Vucen, Sonja"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-09-23","date_published":"2019-09-23","updated_at":"2026-07-24T01:47:31Z","subjects":["Monoclonal antibody","Plank equation","Cryo-concentration","Freezing","Thawing"],"languages":["en"],"rights":["© 2019, Neil Day."],"rights_urls":["https://creativecommons.org/licenses/by-nc-nd/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10468/9969","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Crean, Abina","Vucen, Sonja"]},{"key":"dc:creator","label":"Author","values":["Day, Neil"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2020-05-18T09:38:15Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2020-05-18T09:38:15Z"]},{"key":"dc:date.issued","label":"Date","values":["2019-09-23"]},{"key":"dc:publisher","label":"Institution","values":["University College Cork"]},{"key":"dc:type","label":"Dc Type","values":["Masters thesis (Research)"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["MRes - Master of Research"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Monoclonal antibody","Plank equation","Cryo-concentration","Freezing","Thawing"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["© 2019, Neil Day."]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://creativecommons.org/licenses/by-nc-nd/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10468/9969"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS)."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The impact of variation in freezing and thawing process parameters on the critical quality attributes of a monoclonal antibody"]}]}],"canonical_facts":{"dc:contributor.advisor":["Crean, Abina","Vucen, Sonja"],"dc:creator":["Day, Neil"],"dc:date.accessioned":["2020-05-18T09:38:15Z"],"dc:date.available":["2020-05-18T09:38:15Z"],"dc:date.issued":["2019-09-23"],"dc:description.abstract":["Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS)."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/10468/9969"],"dc:language.iso":["en"],"dc:publisher":["University College Cork"],"dc:rights":["© 2019, Neil Day."],"dc:rights.uri":["https://creativecommons.org/licenses/by-nc-nd/4.0/"],"dc:subject":["Monoclonal antibody","Plank equation","Cryo-concentration","Freezing","Thawing"],"dc:title":["The impact of variation in freezing and thawing process parameters on the critical quality attributes of a monoclonal antibody"],"dc:type":["Masters thesis (Research)"],"dc:type.qualificationlevel":["Masters"],"dc:type.qualificationname":["MRes - Master of Research"]},"updated_at":"2026-07-24T01:47:31Z"}