The Impact of Protein A Resin on Ensuring an Efficient and Reliable Continuous Downstream Process in mAb Purification

Introduction

Many manufacturers have been exploring alternatives to batch processing for the purification of monoclonal antibodies in order to reduce costs and improve productivity. Monoclonal antibodies are making up a large proportion of pharmaceutical company pipelines with more than 100 being licensed over the last 30 years. Yet there are still industry-wide issues in providing affordable, timely and sustainable access to mAb products. With protein A resins being a significant cost in the manufacture of these mAb products, we review the true impact of protein A resin on ensuring an efficient and reliable continuous downstream process in mAb purification.

Continuous chromatography

Continuous chromatography is emerging as an alternative manufacturing method to batch chromatography. The aim is to create a continuous process that utilizes the same resin and buffer systems as existing traditional methods but instead split the one large column into a series of smaller columns, operating over a higher number of cycles. While product is being loaded into two of the columns, the others will be going through the wash, elution and regeneration phases creating a succinct and efficient process. The aim is to continuously load the columns using the maximum capacity. This method demonstrates improved productivity and increased resin capacity utilization in comparison to batch operations. Traditional chromatography requires more time and resin, leading to bottlenecks in the downstream process, a common issue within the industry. Whilst the same resin and buffer systems are used in both manufacturing methods, the continuous process does this within a smaller footprint with less resin and buffer consumption.

The main advantages of using a continuous chromatography process include:

• Reduced equipment footprint
• Reduced capital cost
• Higher productivity
• Greater flexibility to increase capacity
• Significant savings in buffer and resin volumes

Why is continuous chromatography important in mAb purification?

Since it’s adoption into downstream processing, many companies are finding that this approach in antibody capture allows them to better optimize the use of expensive protein A resin. A continuous process allows for improved resin capacity utilization through the continuous loading of the column which in turn results in increased process efficiency. It is good for sensitive biomolecules that need to be rapidly separated from the other components.

Another important aspect of mAb purification for clinical manufacturers is the efficient use of the resin lifetime. Continuous chromatography allows you to cycle as much as possible using shorter residence times in order to use less resin. The most noticeable benefits however are greater productivity and improved process economics due to the reduction in resin requirements and buffer usage.

Protein A resins for mAb purification
The cost of protein A resins makes up a substantial share of the cost of monoclonal antibody purification. The antibody industry is now working with titers of up to 10g/L so productivity maximization has become even more essential.

Our Praesto® range of chromatography resins for mAb purification have been purposely manufactured to withstand the demands of modern continuous chromatography processes. With hydrophilic base matrices and very high capacity these chromatography resins are designed to maximize the productivity of your continuous operations. With recent innovations in resin manufacture, we can now create agarose-based chromatographic resins that are commercially available with uniform-sized beads (such as Praesto® Jetted A50). This uniformity results in faster mass transfer effects, reducing overall cycle time when compared to traditionally manufactured resins.

One of the most important parameters that affect productivity during continuous chromatography is the capacity at higher flow rates.

The Praesto® Jetted A50 resin utilizes the Repligen® NGL-Impact™ A ligand resulting in high-purity recovery demonstrating a dynamic binding capacity of ~50g/L at just 2 minutes residence time. 

Making a change to your continuous chromatography process

In order to make your continuous chromatography process for mAb purification more beneficial, it is important to create the most productive conditions. The best way to achieve this is by using the best protein A resin.

Learn more about the Praesto® range of agarose-based chromatography resins for monoclonal antibody purification here.

Alternatively, discover SMART cycling. SMART cycling combines our protein A resin technology with minor changes to implement in your process to achieve the best mAb purification results possible. View the process model for attaining better productivity here.