Blog

Each sample was analyzed using the LC-MS method summarized above. therapeutic molecules. The MAM represents an optimized analytical solution to focus on the attributes of the therapeutic molecule essential for function and implement QbD principles across Proglumide process development, manufacturing and drug disposition. Keywords:monoclonal antibody, multi-attribute method (MAM), peptide map, product quality attributes, quality by design == Abbreviations == immunoglobulin G2 antibody isotype post-translational modifications critical quality attributes Quality by Design reverse phase, high performance liquid chromatography mass spectrometry tandem MS or MS/MS multi-attribute method reduced capillary electrophoresis sodium dodecyl sulfate non-glycosylated heavy chain asialo-, bi-galactosylated bi-antennary, core substituted with fucose asialo-, agalacto-, mono-antennary oligomannose 5 asialo-, agalacto-, mono-antennary, core substituted with fucose asialo-, agalacto-, bi-antennary oligomannose 6 asialo-, mono-galactosylated mono-antennary, core substituted with fucose asialo-, agalacto-, bi-antennary, core substituted with fucose asialo-, mono-galactosylated bi-antennary oligomannose 7 asialo-, mono-galactosylated bi-antennary, core substituted with fucose asialo-, bi-galactosylated bi-antennary oligomannose 8 oligomannose 9 == Introduction == The demand for new therapies, loss of revenue from patent expirations and growth of emerging markets have Proglumide placed increasing pressure on Proglumide manufacturing networks to be cost effective and highly productive.1,2New processes, control strategies and quality systems that allow efficient product disposition are needed to enable optimal changeover Proglumide of manufacturing batches. In addition, regulatory expectations have shifted to a quality by design (QbD) approach to specifications, filings and product understanding to better ensure patient safety and benefits when bringing new drugs to market.3-9These QbD guidelines include development of a quality target product profile (QTPP) that identifies critical quality attributes (CQAs) and implementation of a control strategy to ensure the QTPP.10The need for increased efficiencies in manufacturing with higher regulatory expectations for QbD require technological advancements that optimize product disposition speed while providing better product knowledge. Application of highly resolving mass spectrometry (MS) techniques have resulted in better understanding at the molecular level of the attributes that are crucial for safety and efficacy of complex bio-therapeutic molecules, as well as elucidation of the mechanisms associated with degradation.11-14A logical next step for the biopharmaceutical companies that have embraced QbD and CQA during process development would be the applications of these concepts for data-directed manufacturing and quality control associated with drug disposition. To achieve the premises of QbD, analytics that focus on Proglumide product quality attributes are clearly needed.15,16Ideally, such analytical tools would be universally applied to provide quantitative information and optimize the successive stages in the lifecycle of a protein drug, from clone selection and process development to quality control and drug disposition. Complex glycoproteins, specifically monoclonal antibodies, are currently the most prevalent type of bio-therapeutic in development.17,18Monoclonal Rabbit Polyclonal to EDG4 antibodies, which offer high specificity and low side effects, are used to treat many types of cancer, autoimmunity/inflammatory diseases, infections, and metabolic disorders, yielding their impressive success as human medicines.18,19In-depth characterization of these bio-therapeutics is essential before they can be used in clinical trials.11A panel of separation techniques such as capillary electrophoresis (CE), ion exchange chromatography, reversed-phase high performance liquid chromatography (RP-HPLC), Size-exclusion chromatography (SEC) or hydrophobic-interaction chromatography (HIC) can be typically utilized on intact molecules to monitor consistency of the process and identify product variants and impurities.13,20,21These electrophoretic and chromatographic methods, although classically used in quality control of biologics as release tests, 22are not directly able to monitor PQAs at the molecular level. Characterization and quantification of product attributes of glycoproteins is typically done during analytical development at the peptide or glycan level using successive steps of enzymatic digestion, chemical labeling, electrophoretic or chromatographic separation. When combined at the characterization stage to increasingly powerful mass.