mAb Process Optimization

Process intensification in mAb production refers to optimizing mAb process steps across upstream and downstream operations to enhance efficiency while supporting cost-effective manufacturing. By refining media and feed strategies, applying perfusion modes, and streamlining purification steps, development teams can increase productivity and yield, improve process robustness, and enable greater flexibility in scaling. These advances can help reduce manufacturing costs per kilo of mAb, shorten timelines, and support consistent product quality, ultimately making the production process more efficient and adaptable to changing demands. Learn more about mAb process intensification strategies.

Typical upstream process bottlenecks include low titers, nutrient limitations that affect cell health, raw material quality or supply issues, process instability, and contamination risks. Scaling from benchtop to production can introduce additional variability. These challenges can be mitigated by using CHO cell lines, optimized media and feeds, and bioreactors, such as the DynaDrive Single-Use Bioreactor, to enable stable and efficient production.

Upstream optimization improves yield and consistency by refining media composition to enable optimal nutrients, implementing precise feeding strategies to maintain cell health and productivity, and enhancing process control to allow stable environmental conditions. These measures lead to more efficient cell growth and protein expression, resulting in higher and more consistent yields of the desired product.

Intensified upstream strategies are appropriate when higher productivity is needed without major changes to the manufacturing plant. Using an intensified fed-batch instead of a standard fed-batch can help meet increased mAb demand, while implementing perfusion in the N-1 seed train facilitates reduced seed train time and high cell densities for production inoculum. Gibco HIP CHO Medium and the DynaDrive Bioreactor support high cell densities, and the high turndown ratio of DynaDrive Bioreactor further enables upstream intensification.

Downstream purification can be optimized by selecting the appropriate mode, such as affinity, ion exchange, or hydrophobic interaction chromatography, and using high-performance resins that support efficient impurity reduction. Implementing effective buffer strategies helps maintain optimal separation conditions. Flow-through elution can enhance efficiency while reducing process liquid volumes, manufacturing footprints, and costs.

Effective ways to scale monoclonal antibody production include applying fed-batch, intensified fed-batch, or perfusion processes with single-use bioreactors to support a smooth transition from development to larger volumes. Fed-batch strategies enable controlled nutrient delivery to strengthen yield, while perfusion maintains continuous nutrient supply and waste removal. Single-use bioreactors, controllers, and automation solutions offer flexibility and simplify scale-up, helping teams advance efficiently toward clinical and commercial production.

Thermo Fisher offers tailored solutions, advanced technologies, and collaborative guidance to strengthen efficiency and productivity across antibody-optimization workflows. Support includes upstream and downstream process development, analytical testing resources, and regulatory experience to help teams optimize, scale, and maintain robust manufacturing performance.