Navigating Bioprocessing for Biosimilar Development

This Question-and-Answer excerpt taken from BioSpectrum Asia’s Webinar, Navigating Downstream Bioprocessing for Biosimilar Development, reviews the challenges and opportunities to expanding biosimilar production, including regulatory hurdles and cost-effective manufacturing.  

The webinar was hosted by Ecolab Field Applications Scientist, Jake Jo, and Ecolab Director of Product Management, Mats Ramberg. 

Between Purolite Praesto Jetted A50 and Purolite Praesto AP+80, which resin is better for developing the actual process for production? 

Jake Jo: The two resins have different characteristics. Purolite Praesto Jetted A50 uses high kinetics properties to induce sufficient dynamic binding capacity (DBC) at a high flow rate. A 10-13 centimeter column is recommended for this purpose. This minimizes resin consumption, and the increase in the number of cycles run is compensated for by a faster flow rate.  

On the other hand, Purolite Praesto AP+80 is a resin that can be used in most process conditions. If you need to minimize resin consumption, I recommend Purolite Praesto Jetted A50. However, if you need to use popular process conditions such as 20 centimeter packing height and 4-6 minute residence time, I recommend Purolite Praesto AP+80.  

What are the primary differences in developing a biosimilar versus the originator drug? 

Mats Ramberg: The major difference is that because you have the originator drug as a reference, you need to prove the similarity between the originator drug and the biosimilar drug by conducting a lot of analytical characterization experiments. 

When you have done that, you have proven that you have a very equivalent molecule, and that means that you can actually reduce the number of clinical trials required for approval, and that’s a significant difference.  

You can actually shorten the time to market from the 10 to 15 years it takes for a newly originated drug down to 6 to 8 years for a biosimilar drug.  

Of course, that also leads to a much lower risk of failure in clinical trials because you know what molecule you actually have. That’s the major difference from the perspective of a pharmaceutical company. 

What are the differences between jetted and emulsified technology? 

MR: As said in the talk, Ecolab’s Purolite resins are manufactured using Jetting technology, which is the standard for all new resin developments that we conduct. 
 
The driver for this has been reducing the carbon footprint because much less solvents and water are used in the production of Jetting beads than in the classical emulsified beads. It’s a big saving on sustainability and saving the planet.  

The other technical benefit is that you get a more uniform bead because you actually spray the beads through a membrane, and you get almost exactly the same diameter for every bead. So, it will be a very narrow particle size distribution, as compared to the emulsified technology where you actually have a stir that controls the bead size and the resulting distribution of the beads. That will get you a much broader particle size distribution. 

More narrow distribution [of resin beads] also leads to better chromatographic performance when you are striving for high resolution processes. [Uniform beads] could also ultimately lead to better packing performance because you have less risk of clogging. 

What types of services are available to support resin substitution? 

JJ: This question is what I get from customers always, actually. Ecolab regulatory support is available beginning at the clinical phase – from the preliminary documentation through each phase of the necessary steps.  

Professional [regulatory support] consists of Ecolab employees who have experience in resin substitution. Ecolab will guide [customers] by announcing what kind of documents and experiments should be prepared and detailed. [If you’re developing a biosimilar], please contact us, we can help you. 

Specifically for biosimilar development and manufacturing, what are the benefits of Ecolab’s jetted resin bead?  

MR: An obvious benefit is that, since we are using agarose chemistry and the majority of the originator processes are agarose-based technologies, you have a much smoother and less risky transition from the originated drug to our resin. Ultimately, you can sort of predict the outcome since the chemistries are very similar. It should also lead to less time spent on the lab bench doing verification experiments and related activities.  

That’s on the development side.  

If you also think about the commercial side of things – when you ultimately reach the commercial scale – security of supply is a key element in this industry. The commitment to deliver resins of the same quality over decades. This is a commitment that we have at Ecolab, [where we are] building out capacities and working a lot on supply security and related topics.  

Those two elements, predictability in the PD scale and security of supply at the commercial scale, I would say, are the two main benefits. 

Several Purolite™ Resins were mentioned during the presentation, but it can be difficult to know the use case for each, could you simplify the purpose of Purolite Praesto Jetted A50, Purolite Praesto AP+80, Purolite Praesto Jetted A50 HipH, and Purolite Praesto 70 CH1? 

JJ: Thank you, this is a good chance to introduce many of the platforms we have. The description of Purolite Praesto Jetted A50 and Purolite Praesto AP+80 has been made earlier.  

I will first explain Purolite DurA Cycle A50, which is durable enough to withstand processes using up to 0.5 M of sodium hydroxide. Therefore, it is preferred for target process development where protection and CIP and SIP for bioburden are required.  

As you know, the elution of protein A resin is usually done at a pH lower than 4. However, there are target molecules whose yield is reduced by this condition. So, Purolite Praesto Jetted A50 HipH is prepared for acidic, sensitive targets. 

To summarize, Purolite Praesto Jetted A50 HipH is characterized by elution from pH 5. Purolite Praesto 70 CH1 resin is ready for the development of Fabs, bispecifics, and non-protein affinity resins that bind to the CH1 region of the immunoglobulin.  

Thank you. I hope that clarifies [Ecolab’s Affinity Resin Toolbox].