Process intensification originated in the chemical and food processing industries and is commonly used as a framework to maximize manufacturing productivity and output. Purolite customers apply process intensification to downstream processing in order to accelerate processing times, decrease energy use and waste generation, and control manufacturing costs.
In downstream processing, studies have shown that up to 80 percent of purification costs occur during downstream processing, with the protein A chromatography step accounting for a large portion of downstream costs. Purolite is continually developing new process intensification strategies – focused on cost, sustainability, and productivity – that our customers can adopt with minimal disruption.
In this Question-and-Answer session, Purolite Field Application Specialist, William Bowen, PhD, reviews various process intensification strategies, including SMART Cycling and Purolite’s patented Jetting technology.
What are the benefits of Purolite’s SMART Cycling compared to continuous chromatography?
A key differentiator between continuous chromatography and Purolite SMART Cycling is the ability to work within existing limitations or with existing equipment. To deploy continuous chromatography, significant changes may be required. For example, you may need to redesign your facility or invest in new equipment – both of which can be quite expensive.
SMART Cycling essentially allows you to create cost savings and productivity improvements without having to change your facility and while using your current hardware.
Which manufacturers should elect to implement SMART Cycling versus continuous chromatography?
This decision is up to the discretion of the facility, based on various factors or limitations. For example, if you don’t have access to continuous chromatography, but you have pre-existing hardware related to traditional pack-bed chromatography or standard chromatography, then it would make more sense to stick with that process for the moment and explore process intensification strategies that complement your procedures.
However, if you have the capacity to invest in continuous chromatography – you can afford new equipment or the facility downtime – then transitioning to continuous chromatography can certainly be done.
As I mentioned during the webinar, Purolite’s Praesto® A50 resins have been used in a variety of continued chromatography applications, so that is an option for Purolite customers.
Are there any concerns when reducing bed height as a means of process intensification? For example, is there any impact on the maximum column diameter that can be used in this case?
Not particularly, no. Particularly with modern columns, and at lower bed heights, you can achieve a very efficient and consistent pack. For instance, with our partners at Repligen, we’ve had customers pack down to five-centimeter column bed heights without any issues. Obviously, the outcome will depend on your hardware, but it’s important to note these challenges are frequently overcome.
When aiming to scale operations, what outcomes can be expected by implementing Purolite’s SMART Cycling as a process intensification strategy?
The outcomes of SMART Cycling depend heavily on the strategy or scenario applied. Aligned with process intensification strategies, a key goal here is to increase resin utility by reducing the volume of resin used, such that excess capacity does not go unused–something which often occurs at pre-commercial scale. As I mentioned during the webinar, there are various scenarios in which to deploy SMART Cycling. For example, a reduction in bed height is the most simplistic option with values as low as 10-centimeters being used. In addition to lowering resin costs, a further benefit would be to increase productivity and save time.
While we’re on the subject of bed height, I want to clarify that while 10-centimeters was used as the example for optimal bed height during the webinar, it is not a requirement. Purolite has customers, both those operating clinical applications and several commercial customers as well that use 12, 15, or even 17-centimeter bed height. This range in application is what allows SMART Cycling to be such a scalable process.
Regarding Purolite’s Praesto A50 resin, have Purolite’s jetted beads been used in continuous applications?
Yes, absolutely. Several publications have been presented at conferences and in literature highlighting the rapid mass transfer benefits due to Jetting technology or more uniform bead size. The higher mass transfer at lower bead sizes enables higher dynamic binding capacities at lower residence times.
Finally, regarding sodium hydroxide and stability in terms mole size, are Purolite’s Praesto A50 resins stable up to 0.5 moles?
Purolite typically recommends using 0.1 molar sodium hydroxide. With the cap process, we do have some customers using 0.5 molar caustic or sodium hydroxide every fifth or tenth cycle, with either 0.1 molar sodium hydroxide for cycles 1-4 or with cycles 1-9. It balances out quite well in that use case, but generally we wouldn't recommend 0.5 molar caustic to every cycle.
If you have more questions, we encourage you to reach out to a member of our team or you can explore solutions on your own using Purolite’s productivity and throughput calculator.
