{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79960"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79960","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Challenges Facing the Subcutaneous Administration of Therapeutic Monoclonal Antibodies","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Turner, Michael"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Balu-Iyer, Sathy","Pharmaceutical Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-30T15:11:25Z","date_published":"2019-07-30T15:11:25Z","updated_at":"2026-07-27T19:05:21Z","subjects":["pharmaceutical sciences","physiology","immunology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79960","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Balu-Iyer, Sathy","Pharmaceutical Sciences"]},{"key":"dc:creator","label":"Author","values":["Turner, Michael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:11:25Z","2019","2019-05-15 19:26:46"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmaceutical sciences","physiology","immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79960"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","As an ever increasing number of therapeutic antibodies are being formulated and designed for subcutaneous (SC) dosing, it is an ever growing importance to understand the complexities of this route of administration. The requirement of large, often highly concentrated dosage forms sometimes introduce stability problems to protein formulations, and this can impact both the pharmacokinetics (PK) and immunogenicity of monoclonal antibodies (mAbs). Quality control testing and biophysical stability analysis are only pieces to the puzzle, as the implications to SC absorption span into monitoring the effects of PK as well as the development of anti-drug antibodies (ADAs). Current formulation testing does not take into account this holistic approach; however, it is important to factor all of these avenues in when selecting ideal drug candidates. Since the SC route is quickly becoming a preferred route of administration, the advantages in testing and comparing data from each of these critical components are paramount. Research into the impact of physical properties such as protein charge, formulation variables, dosing strategies, SC absorption analysis, and monitoring of ADA development have each illustrated particular problems, and this research seeks to address these as interdependent to better understand the problems facing SC administration of mAbs. The primary focus in our laboratory has been the prevention or reversal of immunogenicity and the improvement to protein-based drug therapy. Recently we have begun to explore the SC space and seek to better understand the underlying processes of SC absorption. Several protein-specific factors have come to light in our pursuit of this goal, such as the influence of protein stability on not only residence and absorption out of the extracellular matrix (ECM) but also immunogenic potential. Additionally, formulation factors such as degree of osmolarity, volume of administration, and excipient co-administration have provided insight into the mechanisms of protein uptake and sometimes provide improvements to PK. Tonicity agents including lipid nanoparticles such as O-Phospho-L-Serine (OPLS), bulky constituents such as Mannitol, and increased concentrations of sodium chloride (NaCl) have illustrated improved SC absorption through fluid driving forces within the ECM and lymphatic network. Volume of administration as well as site of administration have revealed additional complexities to absorption rates and often extent. The works of this lab as well as our partner lab for this research, Dr. Mager’s group, have provided incredible insights into this still evolving understanding of the SC space and protein administration."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Challenges Facing the Subcutaneous Administration of Therapeutic Monoclonal Antibodies"]}]}],"canonical_facts":{"dc:contributor":["Balu-Iyer, Sathy","Pharmaceutical Sciences"],"dc:creator":["Turner, Michael"],"dc:date":["2019-07-30T15:11:25Z","2019","2019-05-15 19:26:46"],"dc:description":["Ph.D.","As an ever increasing number of therapeutic antibodies are being formulated and designed for subcutaneous (SC) dosing, it is an ever growing importance to understand the complexities of this route of administration. The requirement of large, often highly concentrated dosage forms sometimes introduce stability problems to protein formulations, and this can impact both the pharmacokinetics (PK) and immunogenicity of monoclonal antibodies (mAbs). Quality control testing and biophysical stability analysis are only pieces to the puzzle, as the implications to SC absorption span into monitoring the effects of PK as well as the development of anti-drug antibodies (ADAs). Current formulation testing does not take into account this holistic approach; however, it is important to factor all of these avenues in when selecting ideal drug candidates. Since the SC route is quickly becoming a preferred route of administration, the advantages in testing and comparing data from each of these critical components are paramount. Research into the impact of physical properties such as protein charge, formulation variables, dosing strategies, SC absorption analysis, and monitoring of ADA development have each illustrated particular problems, and this research seeks to address these as interdependent to better understand the problems facing SC administration of mAbs. The primary focus in our laboratory has been the prevention or reversal of immunogenicity and the improvement to protein-based drug therapy. Recently we have begun to explore the SC space and seek to better understand the underlying processes of SC absorption. Several protein-specific factors have come to light in our pursuit of this goal, such as the influence of protein stability on not only residence and absorption out of the extracellular matrix (ECM) but also immunogenic potential. Additionally, formulation factors such as degree of osmolarity, volume of administration, and excipient co-administration have provided insight into the mechanisms of protein uptake and sometimes provide improvements to PK. Tonicity agents including lipid nanoparticles such as O-Phospho-L-Serine (OPLS), bulky constituents such as Mannitol, and increased concentrations of sodium chloride (NaCl) have illustrated improved SC absorption through fluid driving forces within the ECM and lymphatic network. Volume of administration as well as site of administration have revealed additional complexities to absorption rates and often extent. The works of this lab as well as our partner lab for this research, Dr. Mager’s group, have provided incredible insights into this still evolving understanding of the SC space and protein administration."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79960"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmaceutical sciences","physiology","immunology"],"dc:title":["Challenges Facing the Subcutaneous Administration of Therapeutic Monoclonal Antibodies"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:21Z"}