Maximizing Processing Efficiency in Bioprocessing: Strategies for Cost-Effective Scale-Up

In the fast-evolving world of bioprocessing, optimizing each step of the downstream process is crucial for achieving maximum productivity and cost-effectiveness. As laboratories strive to enhance yield while minimizing expenses, the importance of processing eluates as they emerge has become paramount. This blog explores the nuances of processing efficiency, shedding light on potential bottlenecks—such as quality control steps and prolonged downstream processes—that can hinder overall progress. 

In this discussion, Field Application Specialists Jon Baker and William Bowen navigate these critical topics, offering expert analysis on how bioprocessing professionals can leverage these strategies for enhanced productivity and substantial savings across multiple batches. 

We will also examine how bed height impacts various types of chromatography resins, revealing insights on how adopting shorter bed heights can lead to significant cost savings and improved throughput. While this approach can transform workflows, it's essential to balance factors like flow rates and binding dynamics, especially for exceptions such as size exclusion resins. 

When Not to Target Reduced Bed Height 

While, in theory, extremely low bed heights are possible, chromatography performance can become hardware-limited. A certain level of back pressure is essential for effective column operation. If the liquid entering the column doesn't have adequate pressure, it may flow preferentially through the center of the packed bed, resulting in lower resolution. Typically, a bed height of less than five centimeters would be pushing the limits. Some chromatography systems require specific back pressure to function efficiently, which is more commonly seen at lab scale than at process scale. 

Estimating Potential Savings 

The potential savings from adjusting bed height vary significantly based on what you're benchmarking. For instance, if you're using a 20-centimeter bed height and drop to a 10-centimeter bed height, you could achieve up to 50% cost reduction. If you're working with a larger bead resin that has a lower binding capacity (e.g., 50 grams per liter instead of 70), the results may differ. Depending on the size of the columns and whether you're dealing with toxicity or preclinical batches, you could save several hundred thousand dollars. When applied across multiple molecules, these savings can compound considerably. 

Scaling Up Bed Height for Commercial Use 

Scaling up while increasing bed height is straightforward. Generally, the goal is to maintain both the bed height and linear flow rate during scaling. Instead, focus on column volumes per hour, applicable regardless of bed height. This strategy ensures consistent capacity and binding dynamics. Just be cautious; if you’re operating close to pressure limits at a low bed height, monitor closely to avoid exceeding specifications when transitioning to a higher bed height. Using column volumes per hour is a practical way to measure flow rate when changing bed height.