March 07, 2018

Full single-use downstream process? Not any time soon.

By Madhu Raghunathan, Product Strategy Leader at GE Healthcare Life Sciences

Single-use technologies (SUTs) are here to stay. But where we see full single-use upstream processes, downstream is often a hybrid solution. Here’s why SUTs will not completely replace reuse systems in the near future.


Marrying single-use upstream and hybrid downstream simply works

Why is there a greater adoption of SUTs in upstream compared to downstream processing? One reason is the more complex clean-in-place (CIP) and sterilization-in-place (SIP) requirements in upstream. The growth environment, high processing volume, and high presence of in-process impurities increase the risk of bioburden.

As you move downstream, bioburden risk and volumes decrease. But the value of the biologic drug and the burden of demonstrating its purity increase exponentially. Consequently, sensors used to secure quality need to have great accuracy and sensitivity. However, most single-use sensors used today have limitations in this aspect.

All in all, a hybrid approach to unit operations downstream often makes good business and process sense. So, I believe that hybrid solutions are here to stay...At least until technical advances allows a full single-use downstream process.

More single-use technologies will be introduced to downstream processes

Some advances in SUTs for downstream are already here. More accurate single-use sensors are continuously being developed. New single-use chromatography systems for manufacturing scale meet capacity demands from single-use upstream processes of 2000 L high-titer feeds, which used to be a limiting factor.

There are also smarter solutions for increasing productivity using reuse systems. For instance, new inventions like SNAP connectors for chromatography systems speed up cleaning procedures.

Manufacturing-scale single-use ÄKTA ready chromatography system

…but we can’t disregard the proven value of reuse systems

On the flipside, there are many scenarios where clean- and reuse systems still make practical sense. For instance, when you are performing large-scale manufacturing of a product with repetitive batches, then a workflow based on fixed flow-paths wins out over single-use equipment from an economic standpoint.

However, even the cost of single-use consumables can be minimized through adoption of best practices such as forecasting and supply agreements. In Figure 1 you see an indicative example of how operating costs is affected by the manufacturing approach.

Operating expenditures for single-use consumables under different biomanufacturing scenarios

Fig 1. Operating expenditures for single-use consumables under different scenarios.

Choosing a column—the deciding factors

The choice between prepacked or conventional chromatography columns depends on your specific processing goals. Many factors drive this decision, such as your annual production volume, anticipated manufacturing frequency and internal column-packing expertise.

You should also consider the nature of the manufacturing operations; is it clinical or commercial, multi- or single-product? And, of course, weigh your business objectives, what are your capital and operating expenditures? All of these questions may decide which type of column you use.

Here’s an example: when your intention is to get through a pipeline of molecules quickly for clinical trials, using prepacked columns is an efficient approach. This is because it minimizes time spent on changeover between molecules. On the other hand, if you intend to continuously manufacture a single molecule, conventional columns can unlock greater cost efficiency.

How hybrid will you go? The answer lies in your unique process

For the near future, I believe that hybrid downstream solutions are here to stay. Several drivers affect choice of facility design and choice of processing tools for unit operations. And there is no universally accepted template that will work across the board irrespective of business objectives, process outcomes, and resource/knowledge footprint.

The choice of processing tools needs to be consultative with selective and targeted application of tools that can sustainably deliver desired results.

What can hybrid solutions bring to your process? You’ll find more insights on the topic in three blog posts discussing how hybrid bioprocessing helps achieve cost-effectiveness, how to intensify large-scale buffer management, and why combining batch and continuous processing could be the best solution.