Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations.

Autor: Pegues MA; Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Szczepanek K; Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Sheikh F; Division of Biotechnology Research and Review II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Thacker SG; Laboratory of Immunology, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Aryal B; Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Ghorab MK; Policy Development and Evaluation Branch 1, Division of Regulations, Guidance and Standards, Office of Policy for Pharmaceutical Quality, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Wolfgang S; Cosmetics Regulatory Activities Branch, Cosmetics Division, Office of Cosmetics and Colors, Center for Food Safety and Applied Nutrition, College Park, MD, 20740, USA., Donnelly RP; Division of Biotechnology Research and Review II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Verthelyi D; Laboratory of Immunology, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA., Rao VA; Laboratory of Applied Biochemistry, Division of Biotechnology Research and Review III, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administrations, Silver Spring, MD, 20993, USA. ashutosh.rao@fda.hhs.gov.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2021 Nov; Vol. 38 (11), pp. 1961-1975. Date of Electronic Publication: 2021 Nov 29.
DOI: 10.1007/s11095-021-03125-6
Abstrakt: Purpose: Polysorbate excipients are commonly used as surfactants to stabilize therapeutic proteins in formulations. Degradation of polysorbates could lead to particle formation and instability of the drug formulation. We investigated how the fatty acid composition of polysorbate 80 impacts the degradation profile, particle formation, and product stability under stress conditions.
Methods: Two polysorbate 80-containing therapeutic protein formulations were reformulated with either Polysorbate 80 NF synthesized from a fatty acid mixture that contains mainly oleic acid (≥58%) or a version of polysorbate 80 synthesized with high oleic acid (>98%). Stress conditions, including high temperature and esterase spiking, were applied and changes to both the polysorbate and the therapeutic protein product were investigated for stability, purity, innate immune response and biological activity.
Results: The addition of esterase and storage at 37°C led to significant hydrolysis of the polysorbate and increases in sub-visible particle formation for both polysorbates tested. The fatty acid composition of polysorbate 80 did not directly alter the stability profile of either therapeutic protein as measured by size exclusion chromatography, or significantly impact innate immune response or biological activity. However, formulations with Polysorbate 80 NF showed greater propensity for sub-visible particle formation under stress conditions.
Conclusions: These results suggest that composition of fatty acids in polysorbate 80 may be a promoter for sub-visible particulate formation under the stress conditions tested but may not impact protein aggregation or biological activity.
(© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021.)
Databáze: MEDLINE
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