TY - JOUR
T1 - Correlating multidimensional short-term empirical protein properties to long-term protein physical stability data via empirical phase diagrams
AU - Klijn, Marieke E.
AU - Hubbuch, Jürgen
PY - 2019
Y1 - 2019
N2 - Identification of long-term stable biopharmaceutical formulations is essential for biopharmaceutical product development. Reduction of the number of long-term storage experiments and a well-defined formulation search space requires knowledge-based formulation screenings and a detailed protein phase behavior understanding. To achieve this, short-term analytical techniques can serve as predictors for long-term protein phase behavior. Protein phase behavior studies that investigate this concept commonly display shortcomings such as limited and small datasets, sample adjustments, or simplistic data analysis. To overcome these shortcomings, 150 unique lysozyme solutions were analyzed using six different short-term analytical techniques. Lysozyme's structural properties, conformational stability, colloidal stability, surface charge, and surface hydrophobicity were obtained directly after formulation preparation. Employing the empirical phase diagram method, this short-term data was correlated to long-term physical stability data obtained during 40 days of storage. Short-term protein properties showed partial correlation to long-term phase behavior. Structural differences, changing surface properties, colloidal stability, and conformation stability as a function of formulation conditions were observed. This study contributes to long-term protein phase behavior research by presenting a systematic, data-dependent, and multidimensional data evaluation workflow to create a comprehensive overview of short-term protein analytics in relation to long-term protein phase behavior.
AB - Identification of long-term stable biopharmaceutical formulations is essential for biopharmaceutical product development. Reduction of the number of long-term storage experiments and a well-defined formulation search space requires knowledge-based formulation screenings and a detailed protein phase behavior understanding. To achieve this, short-term analytical techniques can serve as predictors for long-term protein phase behavior. Protein phase behavior studies that investigate this concept commonly display shortcomings such as limited and small datasets, sample adjustments, or simplistic data analysis. To overcome these shortcomings, 150 unique lysozyme solutions were analyzed using six different short-term analytical techniques. Lysozyme's structural properties, conformational stability, colloidal stability, surface charge, and surface hydrophobicity were obtained directly after formulation preparation. Employing the empirical phase diagram method, this short-term data was correlated to long-term physical stability data obtained during 40 days of storage. Short-term protein properties showed partial correlation to long-term phase behavior. Structural differences, changing surface properties, colloidal stability, and conformation stability as a function of formulation conditions were observed. This study contributes to long-term protein phase behavior research by presenting a systematic, data-dependent, and multidimensional data evaluation workflow to create a comprehensive overview of short-term protein analytics in relation to long-term protein phase behavior.
KW - Empirical phase diagrams
KW - Long-term stability
KW - Lysozyme
KW - Microbatch experiments
KW - Multidimensional data analysis
KW - Protein phase behavior
UR - http://www.scopus.com/inward/record.url?scp=85061657680&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.02.006
DO - 10.1016/j.ijpharm.2019.02.006
M3 - Article
C2 - 30769132
AN - SCOPUS:85061657680
SN - 0378-5173
VL - 560
SP - 166
EP - 174
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
ER -