caa a22 4500 445313927 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-011-0385-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0385-x The Degradation of Polysorbates 20 and 80 and its Potential Impact on the Stability of Biotherapeutics [Elektronische Daten] [Ravuri Kishore, Sylvia Kiese, Stefan Fischer, Astrid Pappenberger, Ulla Grauschopf, Hanns-Christian Mahler] ABSTRACT: Purpose: To study the potential impact of the degradation of Polysorbates (PS) 20 and 80 on the stability of therapeutic proteins in parenteral formulations. Method: First, degradation products of PS20 and 80 were identified. Subsequently, the effect of degraded polysorbate on physical characteristics and long-term stability of protein formulations was assessed. Further, the impact of polysorbate degradation on protein stability was evaluated via shaking stress studies on formulations spiked with artificially degraded polysorbate or degradants like fatty acids. Additionally, aged formulations with reduced polysorbate content were shaken. Results: The degradation of polysorbate leads to a buildup of various molecules, some of which are poorly soluble, including fatty acids and polyoxyethylene (POE) esters of fatty acids. Spiking studies showed that the insoluble degradants could potentially impact protein stability and that the presence of sufficient intact polysorbate was crucial to prevent this. End-of-shelf-life shaking of protein formulations showed that the stability of various monoclonal antibodies was, however, not affected. Conclusions: Although some degradants can potentially influence the stability of the protein (as discerned from spiking studies), degradation of polysorbates did not impact the stability of the different proteins tested in pharmaceutically relevant temperature and storage conditions. Springer Science+Business Media, LLC, 2011 auto-oxidation nationallicence degradation nationallicence hydrolysis nationallicence polysorbate nationallicence protein formulations nationallicence surfactant nationallicence Kishore Ravuri Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut Kiese Sylvia Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut Fischer Stefan Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut Pappenberger Astrid Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut Grauschopf Ulla Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut Mahler Hanns-Christian Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1194-1210 0724-8741 28:5<1194 2011 28 11095 https://doi.org/10.1007/s11095-011-0385-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0385-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kishore Ravuri Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Kiese Sylvia Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Fischer Stefan Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Pappenberger Astrid Formulation Research, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Grauschopf Ulla Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Mahler Hanns-Christian Pharmaceutical & Device Development, Pharma Technical Development, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Bldg 9/666, CH-4070, Basel, Switzerland aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1194-1210 0724-8741 28:5<1194 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer