Accelerate Scale-Up with Sartobind^® Rapid A

When it comes to scaling up a mAb purification process, aligning process development (PD) and manufacturing with easy to scale technologies is key. But it is also important to minimize validation efforts and avoid low value operations (time lost on cleaning protocols, consumables change-over, maintenances or column packing) to maximize productivity and speed to market.

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In this article, we are going to focus on how to enhance productivity in a scalable manner. If productive PD processes can be reliably transitioned to manufacture, then outputs increase, and costs go down. It can also reduce the time for production runs, meaning a plant can produce a more diverse portfolio of mAbs in any given timeframe. This helps to meet the ever-increasing demand for smaller production runs of many different mAbs and allows production facilities to deliver the flexibility for multiple products. In turn, this then increases revenue streams for a production plant, helping it to amortize more quickly.

Increasing Productivity with an Alternative to Columns

Columns have always been the workhorse for mAb purification, and they work extremely well. However, when speed and productivity count, sometimes columns are the cause of delays and bottlenecks. Packing, storing, and cleaning columns takes a lot of time and space. Additionally, the routine use of columns opens them up to problems like cracking and bioburden, which can result in a production run grinding to a halt. 

Even though changing to a new technology can seem risky and difficult, membranes have become a real alternative to columns from PD to manufacture. One of the big reasons for this is the productivity benefits they allow over all scales. 

One of the best ways to optimize efficiency of a plant during scale up is to reduce the hands-on time needed for manufacture. Every time there is a hands-on intervention, production will be affected and will likely have to stop, so decreasing the number of these interventions decreases downtime and increases productivity.

Membrane chromatography can help to reduce the number of interventions. The fact that membrane products like Sartobind^® Rapid A  are provided in ready-to-use formats require fewer interventions. They are designed in line with the current trend: most plants leverage the benefits of single use consumables to enable agile manufacturing. Sartobind^® Rapid A can be cycled many times but discarded after the processing of the batch, using a 1-batch 1-membrane approach. These plants come very close to eliminating downtime which increases the productivity of the plant and reduces costs at the same time.

In general, implementing membrane chromatography is a simple process, especially when compared to columns. With simplicity in mind, when you compare membranes to columns, it’s interesting to see what steps are essential for column use but are not required for membranes. Eliminating steps (especially if they include manual interventions) can really help to improve the productivity of mAb manufacture. 

The following steps are eliminated when using membranes:

1. Slurry preparation
2. Column packing
3. Column unpacking
4. Column maintenance
5. Cleaning in place
6. HETP release testing

Removing these steps allows a plant to manufacture more of the same mAb per shift or add more batches. The simplicity also makes procurement much easier. This may seem like a trivial factor but if you’ve ever had a production run delayed while waiting for raw materials, you’ll know how important this is. This is one of the areas expanded upon in our free whitepaper “A Disruptive, Scalable, and Robust Capture Solution with Sartobind^® Rapid A”.

Membrane chromatography devices can also accept higher flow rates than columns. This means that more mAbs can be captured in a shorter period. The residence time for membranes can be decreased by 15 to 20X when compared to columns, meaning that more products can be purified in a shorter amount of time. It enables to use smaller consumables which reduces the costs for clinical manufacturing and the footprint of the production plant. 

The increasing demands on mAb production mean that scaling to full scale manufacturing volumes needs to become simpler and more productive. For an in-depth view of how membrane chromatography can deliver easier scale up, while maintaining productivity, read our new white paper “A Disruptive, Scalable, and Robust Capture Solution with Sartobind^® Rapid A”. In this white paper you will find more detailed analysis and a case study showing how to speed up preparation for manufacture by reducing lifetime studies.