A5050047819- Viral Infectious Diseases and Gene Expression in Insects
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- Biomedical and Engineering Education
- Chromatography in Natural Products
- Carbohydrate Chemistry and Synthesis
- Membrane Separation Technologies
- Mineral Processing and Grinding
- Spectroscopy and Chemometric Analyses
- Lattice Boltzmann Simulation Studies
- Aerosol Filtration and Electrostatic Precipitation
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Business Process Modeling and Analysis
- Genomics and Phylogenetic Studies
- Microbial Natural Products and Biosynthesis
- Asymmetric Hydrogenation and Catalysis
- Fluid Dynamics and Mixing
- Biochemical Acid Research Studies
- Biotechnology and Related Fields
- Virus-based gene therapy research
- Spectroscopy Techniques in Biomedical and Chemical Research
- Analytical Chemistry and Chromatography
- Enzyme Catalysis and Immobilization
Merck & Co., Inc., Rahway, NJ, USA (United States)
2007-2023
Merck (Japan)
2015
Combining process analytical technology (PAT) with continuous production provides a powerful tool to observe and control monoclonal antibody (mAb) fermentation purification processes. This work demonstrates on-line liquid chromatography (on-line LC) as PAT for monitoring biologics forced degradation studies. Specifically, this focused on ion exchange (IEX), which is critical separation technique detect charge variants. Product-related impurities, including variants, that impact function are...
Protein A chromatography is widely employed for the capture and purification of monoclonal antibodies (mAbs). Because high cost protein resins, there a significant economic driving force to seek new downstream processing strategies. Membrane has emerged as promising alternative conventional resin based column chromatography. However, date, application been limited mostly ion exchange flow through (FT) mode. Recently, advances in Natrix hydrogel membrane resulted increased dynamic binding...
Over the past few years, capacity bottleneck in biomanufacturing has shifted from upstream process to purification process. In particular, capture chromatography steps have become a limiting factor facility throughput. This is direct result of discrepancy between expression levels, which increased by ten, and biochromatography media, at best doubled. Continuous countercurrent multicolumn promising approach deal with bottleneck, particularly if designed single-use format. BioSMB™ technology...
For many protein therapeutics including monoclonal antibodies, aggregate removal process can be complex and challenging. We evaluated two different analytical technology (PAT) applications that couple a purification unit performing preparative hydrophobic interaction chromatography (HIC) to multi-angle light scattering (MALS) system. Using first principle measurements, the MALS detector calculates weight-average molar mass, Mw control levels in purification. The application uses an in-line...
Abstract Bioprocess intensification can be achieved through high cell density perfusion culture with continuous protein capture integration. Protein passage and retention are commonly accomplished using tangential flow filtration systems consisting of microporous membranes. Significant challenges, including low efficiency decaying product sieving over time, observed in these devices. Here, we demonstrate that a macroporous membrane overcomes the challenges when comparing to several other...
Abstract An 8 ton per year manufacturing facility is described based on the framework for integrated and continuous bioprocessing (ICB) common to all known biopharmaceutical implementations. While output of this plant rivals some largest fed‐batch plants in world, equipment inside relatively small: consists four 2000 L single‐use bioreactors has a maximum flow rate 13 L/min. The ICB sufficient detail allow companies, vendors, contract manufacturers build or buy their own systems. design will...
The concise synthesis of a potent thrombin inhibitor was accomplished by mild lactone aminolysis between an orthogonally protected bis-benzylic amine and diastereomerically pure lactone. synthesized the condensation l-proline methyl ester with enantiomerically hydroxy acid, which in turn highly stereoselective (>500:1 er) productive (100,000:1, S/C) enzymatic reduction alpha-ketoester. In addition, second route to diastereoselective ketoamide reduction.
Continuous countercurrent tangential chromatography (CCTC) enables steady-state continuous bioprocessing with low-pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest postcapture polishing mAb; however, these studies were performed commercial resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20-25 µm) lower cross-linking was...
Although several compelling benefits for bioprocess intensification have been reported, the need a streamlined integration of perfusion cultures with capture chromatography still remains unmet. Here, robust solution is established by conducting tangential flow filtration-based wide-surface pore microfiltration membrane. The resulting integrated continuous demonstrated negligible retention antibody, DNA, and host cell proteins in bioreactor average sieving coefficients 98 ± 1%, 124 28%, 109...
Raman spectroscopy is an analytical technology for the simultaneous measurement of important process parameters, such as concentrations nutrients, metabolites, and product titer in mammalian cell culture. The majority published studies have concentrated on using technique monitoring control bioreactors at pilot manufacturing scales. This research presents a novel approach to generating models high-throughput 250 mL mini bioreactor system with following two integrated analysis modules:...
Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there growing need move protein quantitation off-line in-line analysis. One solution fulfill this process analytical technology index of refraction (IoR) sensor measure in real time. Here performance IoR evaluated through series experiments assess linear response, buffer matrix...
Virus filtration (VF) is an important unit operation in the manufacture of biotherapeutics that provides robust removal potential virus contaminants. Small can be impacted by low operating pressures and depressurization events are often associated with continuous operations where increased operational flexibility for higher loading at flux pressure required. In this study, we evaluated impact (7 LMH) interruptions on minute mice (MVM) removal. We used long-term filtrations conducted to a...