Abstract
A major limitation of biological therapeutics is their propensity for degradation particularly in aqueous solutions hence resulting in their short shelf-life. In this study, the stability of trastuzumab (Herceptin®) intravenous (i.v.) solutions, an IgG1 monoclonal antibody (mAb), indicated for the treatment of HER2 positive breast cancer, stored under refrigerated conditions, was evaluated over 28 days. No change in visual appearance or average particle size was observed. The pH values of the trastuzumab i.v. solutions remained stable over time. Interestingly, no change in trastuzumab monomer concentration was observed throughout the 28-day study, as determined by SEC-HPLC. SDSPAGE showed only a monomer band corresponding to the molecular weight of trastuzumab. Circular dichroism spectra obtained following 28-day storage demonstrated integrity of the secondary structural conformation of trastuzumab. Results from this study show that trastuzumab i.v. solutions remain physically and structurally stable on storage at 2-8°C for 28 days. These findings suggest that trastuzumab in solution may not be as sensitive to degradation as expected for a mAb and therefore may have important implications in extending trastuzumab shelf life for clinical use and reducing associated healthcare cost.
Keywords: Trastuzumab, stability, protein aggregation, SEC, particle size, SDS-PAGE, Circular dichroism
Current Pharmaceutical Biotechnology
Title:Physical and Structural Stability of the Monoclonal Antibody, Trastuzumab (Herceptin®), Intravenous Solutions
Volume: 14 Issue: 2
Author(s): Ritesh M. Pabari, Benedict Ryan, Wazir Ahmad and Zebunnissa Ramtoola
Affiliation:
Keywords: Trastuzumab, stability, protein aggregation, SEC, particle size, SDS-PAGE, Circular dichroism
Abstract: A major limitation of biological therapeutics is their propensity for degradation particularly in aqueous solutions hence resulting in their short shelf-life. In this study, the stability of trastuzumab (Herceptin®) intravenous (i.v.) solutions, an IgG1 monoclonal antibody (mAb), indicated for the treatment of HER2 positive breast cancer, stored under refrigerated conditions, was evaluated over 28 days. No change in visual appearance or average particle size was observed. The pH values of the trastuzumab i.v. solutions remained stable over time. Interestingly, no change in trastuzumab monomer concentration was observed throughout the 28-day study, as determined by SEC-HPLC. SDSPAGE showed only a monomer band corresponding to the molecular weight of trastuzumab. Circular dichroism spectra obtained following 28-day storage demonstrated integrity of the secondary structural conformation of trastuzumab. Results from this study show that trastuzumab i.v. solutions remain physically and structurally stable on storage at 2-8°C for 28 days. These findings suggest that trastuzumab in solution may not be as sensitive to degradation as expected for a mAb and therefore may have important implications in extending trastuzumab shelf life for clinical use and reducing associated healthcare cost.
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Cite this article as:
M. Pabari Ritesh, Ryan Benedict, Ahmad Wazir and Ramtoola Zebunnissa, Physical and Structural Stability of the Monoclonal Antibody, Trastuzumab (Herceptin®), Intravenous Solutions, Current Pharmaceutical Biotechnology 2013; 14 (2) . https://dx.doi.org/10.2174/1389201011314020012
DOI https://dx.doi.org/10.2174/1389201011314020012 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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