Protein-based drugs have widespread roles in prevention and treatment of disease. Among these, monoclonal antibodies, vaccines, and recombinant proteins have been shown to be effective in combating various cancers and immune diseases, and make up a growing cross-section of drugs gaining approval for the treatment of a variety of these clinically significant diseases. Careful characterization of the molecules in question is critical to ensure safety and efficacy. CE technology plays a key role in the characterization process as it lends its strengths to the determination of protein purity, heterogeneity, and identity prior to their use in the clinic.
SCIEX Separations offers an automated high resolution protein characterization platform to determine the purity of therapeutics in development and also any impurities that may be present in the development process. Additionally, critical biochemical characteristics of these therapeutics can be determined.
Monoclonal antibody therapeutics, or MAbs, are becoming more widely approved for treatment of clinically significant disease. Approximately twenty monoclonal antibodies have been approved to date by the FDA for use in treatment of a variety of diseases. Twenty times that are in development.
Breakdown in antibody production processes or in the end-product itself can lead to unwanted effects impacting both patient safety and drug function. Therefore, biocomparability studies to assess antibody purity, heterogeneity and identity from development through final lot manufacturing are essential to conserve therapeutic efficacy.
Commonly addressed Issues in Antibody Development:
Cell line development
Molecular size characterization
Molecular charge characterization
Common Problems encountered in Antibody Production:
Capillary Electrophoresis has proven useful in characterization studies for therapeutic biologics. As a replacement assay for SDS-PAGE technology, (SDS-MW, IgG Purity Analysis) can provide quantitative high resolution information pertaining to the molecular weight of proteins, their stability, and the presence of any impurities that may be present in a preparation. Differences in protein charge can be assessed and compared using Capillary Isoelectric focusing, or cIEF, which separates protein isoforms on the principles of isoelectric focusing. This assay allows for automated and quantitative protein analysis. As many proteins exist as glycosylated species, analysis of the nature of this glycosylation is also important. Using a Carbohydrate Labeling and Analysis strategy allows for quantitative, high resolution separation of N-linked oligosaccharides associated with many glycoproteins. This assay is able to resolve positional isomers like G1 and G1', found on monoclonal antibodies from one another.
SCIEX Separations provides a complete solution, the PA 800 Plus Pharmaceutical Analysis, which addresses the need for the determination of altered end-product due to changes during development and/or production. This solution simplifies therapeutic characterization and answers questions regarding the purity, heterogeneity, and identity of MAbs.