mAb Downstream Processing

Intensifying mAb polishing with single-pass TFF and anion exchange chromatography

While it is common for mAb downstream purification processes to use a flow-through anion exchange (AEX) resin as a final impurity adsorption step, this conventional polishing step can lead to process bottlenecks due to large columns with long processing times. A growing number of manufacturers are taking advantage of a new solution: pre-concentrating the mAb feed before the AEX column by connecting inline single-pass tangential flow filtration (SPTFF) with AEX chromatography. This approach improves the AEX resin’s capacity for HCP impurities and minimizes the bottleneck at the AEX polishing step.

Increasing purification efficiency using chromatography membrane

Conventional purification technologies generally require trade-offs in process design. For example, resin-based chromatography columns are often oversized due to throughput limitations and are less compatible with flexible manufacturing. Conventional membrane adsorbers offer faster throughput, but their low binding capacity may not provide sufficient process robustness.

To overcome these limitations, a new generation of high-capacity, high-throughput AEX chromatography membrane has been developed, combining high binding capacity and flow rates in a single-use plug-and-play format. This new option for purification offers the potential of  more productive, flexible, and robust process design.

Handling high-viscosity feeds associated with increasing concentration

Converting infusion-based treatments to subcutaneous injections can increase patient comfort and satisfaction. The challenges to development of these solutions include:

• Delivering a much higher concentration drug
• Designing an efficient ultrafiltration process, using high-quality formulation buffers
• Overcoming viscosity limitations with some TFF systems

TFF cassettes designed for high-viscosity operation enable drugs to be concentrated without modifying current systems or replacing pumps. Excipient combinations to decrease viscosity of highly concentrated protein solutions can be used to improve process economics during TFF. This can ultimately enable a higher final protein concentration in formulation still administrable with standard syringes.

Optimizing reuse and storage of TFF cassettes

Qualification of TFF cassette reuse, lifetime, and storage is important during optimization and qualification of any manufacturing process. Understanding the requirements and risks of TFF cassette storage and reuse is essential to developing a comprehensive validation plan and mitigating potential risks of product recalls or plant shutdowns.

Optimizing cleaning for extended chromatography resin lifetime

Chromatography resins are a major contributor to monoclonal antibody production costs. To improve process economics and maximize resin lifetime, resins should be effectively cleaned before reuse to remove fouling species.

Optimization of resin cleaning procedures over multiple cycles through traditional lab-scale experiments is time-consuming and requires a significant amount of feed material. However, miniaturized, high-throughput screening tools can be used to optimize resin cleaning procedures. Studies at miniaturized scale accelerate the time to results, while minimizing the volume of feed material and buffers required.