: These monitor the product during manufacturing to detect deviations early.
The final stage is implementing a to ensure the process remains within the design space. This combines traditional testing with modern approaches like Process Analytical Technology (PAT) for real-time monitoring.
Modern approaches rely on . The spokesperson from Boehringer Ingelheim notes that the best approach to ensuring scalability is to use a standardized platform rather than developing a unique process for every molecule. Established platform processes, such as those using single-use bioreactors from Thermo Fisher, are engineered to maintain comparable performance across a wide volume range, which helps to manage risk and speed up development timelines significantly. A Mab A Case Study In Bioprocess Development
Programmed automated feeding to maintain glucose levels between 2.0 and 4.0 g/L, preventing osmotic shock and minimizing toxic byproduct accumulation.
A mAb: A Case Study in Bioprocess Development Monoclonal antibodies (mAbs) represent the backbone of modern biotherapeutics. Developing a robust, scalable, and cost-effective bioprocess for a new mAb is a complex journey that bridges molecular biology, chemical engineering, and regulatory science. : These monitor the product during manufacturing to
This scaling knowledge is applied in projects like the one conducted by Enzene Biosciences for a customer facing an upstream bottleneck: their human-engineered mAb was not viable in culture for more than . Enzene methodically screened clones and media in 2L batch cultures for proof of concept before finalizing the process. The process was then transferred to a 50L reactor, with all necessary qualifications completed in just 10 days . In only five months , they scaled the entire manufacturing process from 250 mL to 50L , producing 55 grams of drug substance and overcoming the critical bottleneck.
Even after Protein A, impurities remain. We implemented a two-step polishing phase: Modern approaches rely on
| Step | Primary Goal | Key Technologies | Typical Outcome | | :--- | :--- | :--- | :--- | | | Isolate and concentrate the mAb from clarified harvest | Protein A affinity chromatography | High concentration mAb with significant impurities removed | | Intermediate Purification | Remove major impurities: HCPs, DNA, some aggregates | Ion exchange (AEX, CEX), hydrophobic interaction (HIC) | Improved purity with most process-related contaminants cleared | | Polishing | Remove remaining trace impurities and product variants | Mixed-mode chromatography, AEX, CEX in flow-through mode | Final high-purity mAb with minimal aggregates and fragments |
Moving from a 2L benchtop bioreactor to a 2,000L production scale is where physics fights biology.
Operated in bind-elute mode. This step served as the final resolution mechanism to separate monomeric mAb from high-molecular-weight aggregates and charge variants. Elution was achieved via a linear salt gradient. Viral Filtration and Ultrafiltration/Diafiltration (UF/DF)