Investigating the Degradation Behaviors of a Therapeutic Monoclonal Antibody Associated with pH and Buffer Species

AAPS PharmSciTech
Songyan ZhengRajesh Gandhi

Abstract

This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study il...Continue Reading

References

Oct 7, 2004·Biophysical Journal·Shixin YeJ Kent Blasie
Apr 29, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hongcheng LiuJoanne Sun
Jul 15, 2006·Advanced Drug Delivery Reviews·Ann L Daugherty, Randall J Mrsny
Sep 26, 2006·Journal of Pharmaceutical Sciences·Wei WangSandeep Nema
Oct 10, 2006·The AAPS Journal·Amy S Rosenberg
Aug 28, 2007·Journal of Pharmaceutical Sciences·Roxana M IonescuMarc Kirchmeier
May 14, 2008·Pharmaceutical Research·Georgeen Gaza-Bulseco, Hongcheng Liu
Dec 17, 2008·Biochimica Et Biophysica Acta·Aimee M MorrisRichard G Finke
Dec 30, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Lawrence W DickKuang-Chuan Cheng
Apr 17, 2009·Biotechnology and Bioengineering·Jared S BeeTheodore W Randolph
Jun 23, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Andrea HaweWim Jiskoot
Jan 22, 2010·Journal of Pharmaceutical Sciences·Branden A SalinasTheodore W Randolph
Apr 23, 2014·Biotechnology Journal·Varsha JoshiAnurag Rathore

❮ Previous
Next ❯

Citations

May 16, 2018·Pharmaceutical Research·Sahithi RavuluriAnurag S Rathore
Dec 13, 2016·AAPS PharmSciTech·Javier O Morales
Nov 19, 2020·Journal of Pharmaceutical Sciences·Cindy D RenNitin Rathore
Oct 16, 2020·Journal of Pharmaceutical Sciences·M Laura DarribaKarina A Pasquevich
Apr 24, 2018·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Anthony EhkirchSarah Cianférani
May 31, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Marieke E Klijn, Jürgen Hubbuch
Jun 20, 2021·Biomolecular Concepts·Rohit BansalNiraj Kumar Jha

❮ Previous
Next ❯

Methods Mentioned

BETA
dynamic light scattering
size-exclusion
electrophoresis
light scattering
size-exclusion chromatography

Software Mentioned

Origin
MicroCal
Empower

Related Concepts

Related Feeds