Episode 6: Exploring the role of agarose resins in biomolecule purification (with Dr. Andy Masters, Purolite)

Andrew: Welcome back to Imagine More, Create Solutions. I’m your host, IMCS Co Founder and Chief Scientific Officer, Andrew Lee.

Today we’re diving into the world of biomolecule purification. We’ll be discussing chromatography. It’s a key technique in this field and especially we’re going to focus on the role of agarose resins. Agarose resins play a crucial role in protein purification and bioprocessing. Here at IMCS we utilize these versatile agarose resins packed into our tips under the brand IMCStips.

Our workflows combine IMCStips with automated liquid handlers to achieve efficient biomolecule purification. In fact, one of the key ingredients within IMCStips comes from a leading resin manufacturer, Purolite, and joining us today here to share his [00:01:00] expertise is Andy Masters, Head of Business Development and Strategy at Agarose, Purolite.

Welcome, Andy.

Andy: Hi Andrew. Thanks very much for, the introduction, the opportunity to come to the podcast today. My name is Andrew Masters. I come from Purolite, which is an Ecolab company. I’m really excited to be talking about our pro purification solutions and potential collaborations that we could work on with regarding to your tips.

I have a business development and strategy role at Purolite. I joined the bioprocessor division of Purolite almost two years ago, and in that role, I have a an accountability to cultivate commercial partnerships and also guide the strategic alignment and expansion of our jetted agarose chromatography resins.

I was also tasked as well within this role to look at new business opportunities and collaborations, which fits really with what we’re going to discuss today.

Andrew: Awesome. Awesome. Thank you for making time with us. And can you elaborate a bit more about your prior experience? To joining.

Andy: [00:02:00] Yeah, sure.

Yeah, sure. I joined Purolite in 2022 and before that I worked for a company called Cytiva as a business development manager for bioprocess resins and in that role I was supporting again Life science customers and bioprocess customers who are almost always developing purification protocols. Generally going to take them to large scale for therapeutic medicines. I worked on many different projects different modalities such as monoclonal antibody recombinant protein purification, where there wasn’t an affinity solution, but also vaccine and vector related therapies.

I was also part of the commercial sales team and marketing, contributing to a number of what we call NPIs, new product introductions, which included not only resins, but chromatography systems, software columns, but as I said, we’re talking about today resins to the bioprocess market.

Andrew: I guess before Cytiva you actually worked at even uh, well, Cytiva acquired Pharmacia, right?

And you were there. [00:03:00] Yeah.

Andy: Yeah. It was a long time ago now. I started in 1994 at a company called Pharmacia, which have quite a famous logo. And over 29 periods, I’ve held chromatography positions, including tech support chromatography system and software specialist, bioprocess specialist.

But more recently, I was a bioprocess business development manager for chromatography resins.

Andrew: And of course, just going back into maybe the younger audience. Did you pursue a science degree or do you mind elaborating a little bit about your academic track?

Andy: No, sure. I went to a University of Lancaster, which is on the west coast of the UK, it rains a lot, always rains, very wet.

And I did a BSc. in biochemistry. I left, I wasn’t sure what I was going to do. I actually started working in a company called Securico, which I don’t know what, if you know what that is, but it’s a, you drive around the back of a van, delivering money to banks and football grounds. And after doing that for a brief spell, I went back and did a PhD [00:04:00] in the same labs at Lancaster University.

And then after that, I started with a postdoc back at Newcastle. So I’m back to my roots really, where I was born. And I worked in the Steve Yeaman’s lab at the university of Newcastle upon Tyne. In that role, I was purifying the lipoyl domain from pyruvate dehydrogenase complex, because it’s involved in primary biliary cirrhosis, an autoimmune disease.

Andrew: Wow. That’s that’s an interesting topic. Offline, we can talk a little bit more about your postdoc work. It’s a long history of working in this field. That’s great. It’s an honor to have a guest like this.

Andy: Yeah, I think 1 of the 1 of the stories I normally tell is that if you go into the science museum in London, they have a purification separation display on the machine that’s in the window. I was actually the product specialist for the UK. It’s called a FPLC and it really changed the way proteins were purified away from the HPLC and stainless steel and metals that could destroy proteins to more plastic that peaked that we see commonly with non chromatography systems now.

So something to show the grandkids hopefully one [00:05:00] day.

Andrew: So you joined Purolite in 2022, but as I was looking at the company, it’s over 40 years old. And my first contact with Purolite was. A couple of years before you joined Purolite. Yeah. And I was testing these resins with our tips with our dispersive solid phase extraction technology and our automated liquid handlers.

But can you tell me a little bit more about the company certifications? It’s 40 years, which is a lot longer and has been around longer than I. M. C. S.

Andy: Yeah, yeah, sure. Purolite’s been around for 40 years.

It has a heritage pretty much solely focused on resin production across three main sectors. And the first sector is what we call the core technology. So it has A wide range, I think over a thousand products for if not more for industrial processes, including things like the removal of contaminants from potable water or groundwater.

And, obviously in focus at the moment is things like PFAS [00:06:00] and they’ve got resins which can actually remove PFAS from water. They also have milling and refining resins for things like sugar. So they supply resins to the food industry and the beverage industry. They have resins which can remove radionucleotides so they can treat nuclear waste.

And they also have resins which can concentrate valuable elements, precious metals from mineral ores, such as uranium.

The next sector really is the healthcare and life sciences sector. So that focuses more on the pharmaceutical and nutraceutical industry. And that aspect supplies some active pharmaceutical ingredients.

And we have some of the manufacturing sites which worked with GMP level to support those products. And then the third sector, which is what we’re talking about today is really the bioprocessing sector, which is the newest part, if you like, for Purolite, as you mentioned, it started probably in about 2015 and focuses really on the resin production, for the development and acceleration [00:07:00] of biotherapeutic molecules, namely our agarose resins, the affinity and ion exchangers, which are used in those processes.

From a certification point of view, they’re an ISO company, 9001, but, more recently excited to share that we’ve now got EXCiPACT certification, which means it’s an annex onto the ISO, which really is required for especially the sites that are working with the excipients and the active pharmaceutical gradients, it can support our customers with, we’re working to a certain quality that they might not need to audit us as much, and give them confidence out of products of the quality that are required.

Andrew: Oh, that’s awesome. I wasn’t familiar with EXCiPACT , the add on to the ISO 9001 2015, but that’s great. That’s very stellar for Purolite to achieve those certifications. Yeah. Thank you. You mentioned early on that Purolite is Ecolab company or part of Ecolab company.

Yeah, it was acquired. That’s correct. Okay. Yeah.

Andy: I joined after they were bought by Purolite. In 2021, November, 2021, I think it [00:08:00] was, Purolite was acquired by Ecolab. If you don’t know who Ecolab are, they’re a global leader in water hygiene, and they provide a lot of infection prevention solutions and services.

They also bought by Equel, which is a isolate and handle device, which is used a lot for gene therapy type applications. And they’re a fortune 100 company. So it’s really been fantastic for us. I think it means that the people who have been already using our resins have got even more confidence now that we’re here to stay.

We’re here for the long run. We’re a credible supplier and the investment that we’ve been given is really fantastic. It’s allowed us to increase our capacity and we’re already planning to have dual manufacturing sites on different continents, which will obviously give confidence from a security of supply perspective to our customers, but it also allows us to reduce our lead times as well within the different regions.

The mission really of Ecolab and Purolite is commitment to improved access to complex therapeutics and ultimately support better patient outcomes. So we’re really [00:09:00] proud to be in this industry. We’re here to be a long time and it’s been fantastic, the acquisition through Ecolab.

Andrew: That’s a huge backing for Purolite. This collaboration between Purolite and IMCS, it’s a very small company, IMCS with a very large company. This is fantastic. And it’s pretty recent, so I don’t think IMCS was on Purolites radar until more recently, I think, Penny reached out and it was a conversation between you and, Penny and I think one of our staff members, Douglas Waites.

So what made you interested in our technology?

Andy: Yeah, it was Penny that brought IMCS into the business development discussion, because we do have many customers across a wide range of institutes, including academia, emerging biotechs, multinational CDMOs and pharmaceutical companies, and they’re all a Developing by purification processes, but for the obviously the larger ones, they’re developing them to scale these up to potential therapeutics.

They [00:10:00] all have different, slightly different ways of working and priorities for developing the purification processes. So it’s important that Purolite understands that and that we can supply formats which facilitate them to actually carry out these process developments quickly and expedite their processes really so that they can facilitate their workflows to be able to get this development work done quickly. We do already supply some small formats. We work with Repligen and we, like many of the resin companies do to supply OPUS columns, which are very small columns, which can be used for dynamic development, validation and scale up, but we were looking to expand the range of formats that we can offer customers, especially those who are using liquid handling systems, where we can supply them with something which is more of a 96 well format, which might have some flexibility benefits over existing type 96 well plates full of chromatography resins. And that really led us to look at the IMCS tip technology since they have some interesting benefits over chromatography tip suppliers. [00:11:00] And from my research before we spoke, I could see that they had a bit more flexibility than the standard 96 well plate.

You could use multiples of 8, 16, 32 rather than have to use the full plate. So it’s, it seemed like an interesting opportunity to evaluate it. We wanted to have a look to see whether we could get our new jetted affinity resins into the tips as well as the ion exchange portfolio.

And it was it was interesting when I spoke to you when I first met Andrew that you’d already had some positive experience of using our jetted agarose Protein A in your tips. So that’s was really exciting to hear. So we were keen to expand on this and investigate what we could do further, with our latest jetted affinity resins and ion exchange resins.

Andrew: Yeah, we actually presented some results with that Praesto A50. Sadly, at that point, our collaboration was under the radar and we renamed the resin instead of Praesto A50. We named it like resin B or something else. But I think this kind of collaboration, we can definitely, hit all of the brand names and [00:12:00] refresh some of the technical work that our team at IMCS has accomplished and we’ll put a button on the 8, 16, 32, that flexibility of wider screening approaches. We’ll definitely revisit that later down the road. But really one of the interesting parts is that you mentioned Purolite’s commitment to improving access, that mission statement, and that would in turn impact the health outcomes of patients who rely on these biotherapeutics.

There’s this interesting offering of Purolite’s resins, the different diameters from 40, 45 microns all the way up to 90 microns. How is that part of the commitment or this mission statement for Purolite?

Andy: The actual bead sizes it’s part of that when you’re designing a chromatography bead, you’re usually designing it with the intended application in mind. So for the affinity capture, which is part of many of the manufacturing processes for important therapeutics, such as monoclonal antibodies or fragments, you’re always setting off with the goal to be able to supply a resin with [00:13:00] a really high capacity. With as high a floor as possible, that’s going to be suitable for large scale manufacturing.

You’re thinking of the end in mind. The user is going to have specific productivity goals that we want to achieve. They want to have a robust process. They want to have good overall process economy and how we design that bead, the bead size and the capacity that the bead can deliver is gonna help support that productivity goal. We do have Affinity Resins are coupled to two different beads currently, 50 micron and 80 micron beads are the classic ones that we use for affinity resins. However, most of our Protein As are probably on the 50 micron. We are bringing another one we particularly talk about later.

The APc+, it’s gonna be on 80 micro bead. And the reason we did that was that it’s almost the perfect size for a capture step. It’s gotta. smaller bead, but you can still get good pressure flow characteristics to it. And when you optimize the ligand coupling, you get really good fast mass transfer of binding and elution of the antibody.

And fast mass [00:14:00] transfer just means how easy it is for the antibody from, to get into the bead, to bind to the site under certain conditions. And then when you change the conditions for elution, how quickly it can come back out. So it lends itself to having quite fast kinetics and ends up with a concentrated product at the end of your purification.

It might be something that you, I think you saw potentially in the IMCS tip work, which you talked about before.

Andrew: Yeah, that fast mass transfer with the 50 micron bead I kind of envision it as the surface- to- volume ratios and as the smaller the particle, you’re going to have a larger ratio of the surface to the volume, but you’re trading it off like you said to the back pressures.

Andy: Yeah, I think you might have even, I think you saw that the capacity consistent across all of the different conditions, but also you saw that when you do two elutions from the tips that their overall recovery was really good as well. So again, I think it’s contributing to that, the mass transfer that you’ve seen from this more uniform bead.

Yeah, in terms of some of [00:15:00] the other, going back to the the bead size having the difference of bead sizes and having this fast mass transfer it’s allowed our customers to, to go away a little bit from the norm to some extent, because most of the times you do a 20 centimetre bed heights, with the fast mass transfer, you can actually run very quickly. So the residence times are short in a shorter bed and achieve some good process intensification goals. A lot of our customers are using that mass transfer to run in this way, and it’s driving down the amount of resin that they have to use, the amount of buffers that they use, especially for early clinical manufacture, where this sort of savings are really in focus. And I think the fast mass transfer of the 50 micron bead is probably the reason why it performs so well for both the standard chromatography, but also in your tips.

Andrew: IMCStips definitely falls into that similar context where 45 work really well. The 90 micron also works, but of course, slightly decreased capacities due to the smaller surface to [00:16:00] volume ratios, but faster.

Now, depending on the applications, you can use different particle sizes, but the unique thing about Purolites offering is that they have very narrow size distribution particles using its jetted technology. Can you elaborate more on that jetted technology?

Andy: Yeah, sure. The jetted technology is used for all of our chromatography beads now we have used emulsified in the past, but purified Purolite resins are manufactured using this patented jetted technology. It’s used to manufacture most of our affinity chromatography resins and all of our ion exchange resins. The jetting of the agarose allows Purolite to target specific be diameters for the intended application.

As we mentioned before, you’ve got 90, 80, 70, 65 or 40. And depending upon where you want to put that resin within the purification process, you might go for a bigger bead up upfront, but you want the best, better pressure flow capabilities. And when you go down to a smaller bead. you can get better resolution.

Generally speaking, when you use [00:17:00] jetted product, you have a much narrower distribution around the actual required bead diameter, rather than what you would get from an emulsified technique, which we’ll talk about later on. It means that you’ve got much smaller quantities of beads, which are larger or smaller, either side of that targeted bead.

And when you’re making a resin in normal ways of working, you have to remove those smaller and larger beads. You have to do something called sieving. You have to do quite a lot of it. And this is one of the most time consuming steps in traditional manufacturing. You use a lot of water. So jetting allows Purolite to shorten the manufacturing times.

Which overall will impact on shortening the lead times. It’s a continuous process and I know you haven’t seen the skid, but it’s very small and modular. And one of the things, that we can see that it will facilitate tech transfer to other lines. And obviously the planned other manufacturing sites, in the different regions.

We can set this up pretty quickly. It only needs a small footprint and it really lends itself, to [00:18:00] facilitate our. ongoing security of supply program. One of the key features, which has found a lot of interest in, with our customers is it uses a lot less organic solvent. Obviously everybody has a focus on sustainability these days, so in terms of not using harmful reagents, we’re trying to. And then we’re going to use the jetted to minimize the impact of that on the on the environment as a whole. And in addition to this, Ecolab own Nalco Water. So we have one of the world leaders in water management we are looking at our water usage they’re using their equipment and technology.

It’s installed now to optimize, our water quality and the water flow. It has like intelligent solutions which actually monitor and help you really Minimize your waste and get the maximum sustainable benefit from your process. And I said, Purolite is fully focused on this now, Ecolab are a world leader in sustainability, Purolite is going to benefit from this massively, and we are all about supporting our [00:19:00] customers to sustainability directive, whether that’s indirectly or directly, but all customers are evaluating their critical raw material suppliers now, so having a technology like Jetted, which delivers not only high quality products with precise precision around the bead, but also has sustainability benefits.

It’s. Is, has really generated a lot of interest in our customer base.

Andrew: You mentioned this difference between emulsion feed manufacturing versus the Jetted you touched upon it, just. Just now, yeah, and then the security of the supply using this manufacturing skin could we dive, could you dive a little bit further into this uniform bead size, the manufacturing process?

It seems to be at the crux of what differentiates Purolite resins, the jetted technology, can you just walk us through that manufacturing process explaining some differences between the traditional methods. And Purolite’s this new patented technology.

Andy: Yeah, sure. At Purolite, we have made both to be fair, we’ve made, we started making emulsified beads in 2015 [00:20:00] but we had the jetted technology was part of the core industry, which is that implemented for the agarose resins and it’s brought with it many different benefits. The method is patented for the jetted technology, but both cases, you start with seaweed, so all agarose resins are derived from seaweed, and red seaweed in particular, and that seaweed is harvested, processed, and then it’s supplied to Purolite as a critical raw material.

So the bead then can be processed in two ways. You can either use this emulsification technique as you mentioned, or we can use the jetting technology. In both cases, the agarose is melted at high temperatures but in the case of emulsification, it’s dropped into a stirred vessel containing all of these organic solvents, and the actual bead size is determined by the speed of an impellor which sits at the bottom of the vessel. So that’s the speed that impellor spins and the rate at which you drop the agarose into the vessel then determines the bead size. So you haven’t really got a fine [00:21:00] control over the bead size. It’s more difficult to get this uniformity around your target bead, you can get a wide what you would call Gaussian distribution around the actual bead size that you’re aiming for.

So for example, a 90 micron bead from an emulsified manufacturer, you’re going to have beads ranging from 40 to 140 microns. And then obviously that’s after you’ve done the sieving, you have to remove the smaller and larger ones and you still end up with this range. When you use jetting technology, the agarose is melted in the same way, but it’s dissolved in water.

And instead of it being dropped into a vessel of organic solvent, it’s pumped actually into what would called a vessel or a tin, which has been precision engineered. So you have holes all the way through and the diameter of those holes align with the bead. So if you want a 50 or a 60 or 70, you’d have a different tin.

So you have large holes on the inside and the outside bead will give you the diameter of the agarose as it comes out. So the agarose is then pumped and squeezed through the walls of the, this engineered [00:22:00] vessel, but at the same time, the vessel is moved up and down. It’s oscillated, which creates a cutting motion on the agarose streams as they come through the vessel.

When that happens and the agarose is cut, it immediately forms a bead. For the situated mineral oil, it drops to the bottom of the vessel where it’s collected. So it’s like a continuous process which is why the actual rig is quite small in relation to an emulsified process. I think, the control then is much finer for the bead formation because you can control the viscosity of the agarose, the flow of the agarose through that vessel, and the oscillation frequency.

If the previous explanation was a bit too technical, I’ll try and help you visualize what Jetting’s like by giving you a, an example using Play Doh or plasticine. When you’re a child, you would often roll Play Doh or plasticine into a ball. And there was a device which looks like a garlic press with holes on the outside and a handle on the top and you put the the Play Doh, the plasticine into this device, you would [00:23:00] squeeze down, apply pressure on the Play Doh, and it would come out or extrude through the the side of the device.

And then you would have a pair of scissors to cut it into little pieces. That’s very much what jetting does. If you imagine the garlic press with the Playdough inside is like the melted agarose inside the vessel. You apply pressure with the flow rate. The agarose then extrudes out through the vessel, and the vessel is moved up and down, which is acting like the scissors to cut it.

That then cuts the agarose into the small pieces, which is I mentioned before. It’s situ with mine mineral oil. Those agarose sections will then immediately fall beads of the desired diameter and then fall to the bottom of the vessel for collection.

Andrew: Yeah, Andy, that image with Play Doh is quite interesting. It gives us a nice visual image of how jetting technology works. In 2019, we actually did some work on your resin, the Praesto A50, and that was also jetted. And we compared it against some other [00:24:00] manufactured resins. The theoretical capacities extrapolated using IMCStips were in line with the product specifications. We were able to show the ratio of that initial capture rate, the fast capture rates. So the goal of this collaboration between Purolite and iMCS, would be to showcase similar studies on high throughput formats.

Are there any other resins beyond Praesto 850 that you have in mind that would be useful to highlight for the audience, like the high pH or the CH1?

Andy: Yeah, we do have other Protein A and Affinity resins. And as you mentioned, we have one called Praesto Jetted A50 high pH. It was only introduced into the market in 2022. And to be honest, we’ve had some fantastic results from our customers and partners since it’s launched.

The name a bit of a giveaway. It talks about a resin, which allows the elution of antibodies at a higher pH than you would typically expect from a standard protein A which is a bit more [00:25:00] restrictive. Normal protein A, you can only elute between something like 3. 5 to 4. Whereas for Praesto high pH, it facilitates elutions from 3. 5 up to five and it’s been, an excellent choice then for resins for general mAb purification, but particularly when the target molecule might be unstable or tend to aggregate.

Andrew: Yeah, that high pH is definitely interesting. It’s not a common feature for many of the protein A affinity resins where you can elute off at a slightly acidic pH rather than a very acidic pH, right? Typical elution profiles are pH 2. 5, 3, 3. 5, which are not probably the best for your therapeutic targets.

So here now you’ve got a higher pH that you can elute, a gentler elution profile. That’s got to be an advantage.

Andy: What we do see is the current trend to improve therapeutic efficacy is that there are a lot more antibodies are being [00:26:00] engineered.

They’re more complex. Some of them are prone to aggregation or instability issues. And you really can’t get or use traditional Protein A protocols without suffering some loss in recovery. We’ve sampled a lot of high pH to customers and the feedback has been fantastic, really, this ability to operate with a wider elution pH window has meant that they’ve had significant increases in recovery.

If you have mentioned 20, 30 percent increases over what they could have got with, standard protein A.

Andrew: Wow, 20 to 30 percent improvements in yields. That’s fantastic.

Andy: And we recently had one customer presented the conference for us from Mabplex where they described, the real benefit of using this for bi specifics.

Andrew: So this reference that you’re talking about, we can find this reference elsewhere.

Andy: I’m sure we can send you the link for that paper if you’re interested. Again, we’ve seen from customers, which is the not only this, the high pH elution. But we’ve seen that the purity of the elution is much [00:27:00] higher. There’s a big reduction in host cell proteins and recombinant DNA in the elution pool, which then really has a knock on effect.

It makes the overall purification process much more robust because there’s a reduced challenge for the subsequent polishing steps in the the overall purification process. Interestingly, as part of the feedback that we’ve had customers who’ve used this high pH resin in tip formats as part of their discovery programs.

They came out very small purifications for a range of early molecules, and they found that the high pH resin can allow them to massively increase their monomer yields to, to high percentages, 98, 99%, which means that they don’t have to do a small scale size exclusion step in order to be able to have enough sample to do some early analysis or discovery work.

Andrew: And we’ve covered all the Protein A stuff, but this new resin that, CH1, Affinity Resin, can you cover a little bit about that detail? It’s a new product that you’re about to launch, right?[00:28:00]

Andy: Yeah. We’re also really excited to announce a new affinity resin called CH1 or Praesto CH1.

Andrew: And when should a customer use CH1 over a classic protein A resin?

Andy: It’s designed really to bind the constant region of the heavy chain of antibody fragments, the CH1 region. And this design allows for the purification of complex molecules, asymmetrical molecules, where you have a hetero and dimers with different constructs, where a protein would bind both of these molecules.

Something like Praesto CH1 would be able to identify between the two molecules and give you a purification of the desired target molecule. There are not many competitors out there for this CH1 resin and we’re really pleased to see that the feedback from customers is that we’re getting up to two times the capacity of their existing resins that they’re using. And it also has. increased ability to hydroxide, which means that you get good productivity.

You get a good capacity plus the ability to run for many cycles, which drives good process economy. So really [00:29:00] excited about that. And we hope to see that now appearing in more molecules going forward.

Andrew: Yeah, Andy, you’ve covered quite a range of key features of resins. These features that the end user should pay pretty close attention to.

Not only the purity, but what contaminants are carried through, the elution parameters. You’ve got this high pH profile on this resin, the high pH resin. That’s fantastic, especially to provide additional stability. And then your CH1, you have your affinity selections. Each resin is going to behave differently.

They’re going to want to screen some of these resins pretty quickly. And the ability to screen these, again, this collaboration with IMCStips, that’s one of the focuses here. That’d be fantastic. Just kind of changing gears, but, um Spending a little bit more time on the key features of the resin, what should an end user really start to pay attention to?

I know I just kind of listed some of those details, and you’ve covered some of those in a [00:30:00] lighter touch, but maybe you could actually start looking at the ligand details, the capacities, the reusability the cost. Of the washing and the resin or the per production runs, just some of the details that you’ve come across.

If you mind sharing those.

Andy: For customers to optimize a purification process, it’s really not uncommon for a company to screen many different resins from many different vendors and for the purification of antibodies. Although, many resins have the protein a tag, how the actual protein a ligand is engineered, and then how it’s coupled to a base bead influences the selectivities, so what parts of the antibody do they bind to?

And as you mentioned, the elution page, the capacity as well is influence, how much mAb can they bind to per mL of resin? And the productivity of the final column is influenced by, the, this, these two parameters. So how much gram, of mAb can be produced per mil per [00:31:00] hour gives us a productivity calculation for the resin.

As we discussed before, we are seeing an increase in therapies benefiting from these more engineered antibody molecules such as bispecifics or FC fusion proteins. And therefore evaluation of different Protein As is becoming more common, in order to identify the most suitable.

Protein A resin, which delivers the expected or required purity and selectivity and recovery goals. This is in focus with our customers and in order to facilitate this approach, they tend to use high throughput screening formats using automated liquid handling systems, such as things like Hamilton, the Tecan robots are the ones that we typically come across and technologies such as the IM CS tips containing the different protein A resins.

The same screening approach can obviously be used for other resins, such as ion exchange, which we also have in the portfolio. But for now, we’re covering the protein aspect of it.

There are other considerations outside the resin performance, as you touched on at the [00:32:00] beginning, different customers will have different priorities or requirements. For example, some of the smaller biotechs value a high level of technical support and how the vendor can support them to optimize their process.

And in this respect, we offer a wide range of services from. In house technical support to what we call FESs or field application scientists, and they can either work on site with the customer or we’ve just opened a lab in King of Prussia recently where we’re open to doing process development work for customers who perhaps haven’t got the resources using our affinity line and exchange resins.

In that respect, then, we can produce a robust process with them, which if they want to, they can then tech transfer to a CDMO of their choice.

In comparison, you might have a large pharmaceutical company or CDMO. And they’re probably going to be more focused on, the quality of the product, timely delivery and making sure, that they’ve always got access to resin from their vendors. So they want to secure their supply chain.

Similar to [00:33:00] small biotechs, these organizations. do benefit and do enjoy having a strong technical partnership with their resin provider. And that’s something, that we’re committed to. We like to have scientist to scientist discussions to make sure, we are giving good value to the customers who are using our resins.

Andrew: Right, Andy, the technical discussions among the scientists are so important. There’s certain details that not every sales pitch would cover. I mean, It has to be a technical discussion. One aspect you previously touched upon is the supply security, and the supply chain logistics is so important, especially for these resins and the production of biologics.

What’s Purolite’s experience with these agarose resin supplies?

Andy: I mentioned security of supply there. I’m basically, during COVID there was very long lead times for chromatography resins. So it is in the forefront of customer’s mind now is that they’re having a more strategic [00:34:00] plan to address critical raw materials, which resins are as part of their process and making sure that they have.

Not only dependence on one supplier, but that they can use other suppliers, and then they can perhaps even file processes with the two different resins compared to the old way of filing with one resin, which gives them more flexibility should something like this happen again in the future. And we’re happy to support customers to do that.

It’s something, we we want to get involved with. We want to look and help them get better performance if it’s possible from second generation processes or more modern resins.

And Purolite is always striving to build on, our existing portfolio. So all I can say here now is uh, watch this space.

Andrew: We discussed so much on affinity purification, but The ion exchange resins also go hand in hand. Purolite offers a range of ion exchange resins. Do you mind covering some of these details, both the cation anion exchanges? And for the listeners who are less familiar, could [00:35:00] you explain the difference between the two resins?

Andy: You’ve probably heard of this saying for relationships that opposites attract. That’s the basis of how ion exchange works. You have a, an anion exchange resin where the bead has an overall plus charge and a cation exchange resin where the bead has a negative charge. So dependent upon the protein or the specific contaminant, such as a whole cell protein or DNA in the case of Mabs, under specific buffer conditions, mainly the pH and conductivity, the protein or the contaminant will have an overall positive or negative charge.

So based upon this opposite subtract, ion exchange resins such as our Praesto Cube product line will carry a positive charge. and they’ll bind to molecules which have an overall negative charge. Whereas cation exchange resins, such as our Presta SP products, carry a negative charge ligand and they will bind to molecules who have an overall positive charge under those specific [00:36:00] conditions.

In many cases, our customers understand the properties of their products in relation to the contaminants that are there, especially for monoclonal antibody purifications. So they know what they’re trying to remove.

But again, for ion exchange, they will often use. High throughput formats such as the IMCS tips to really quickly screen and identify potential optimal conditions, particularly the pH and conductivity, and they do this usually before they take the resin through different optimization skills to, to full scale manufacture, and it allows them to take a quality by design approach to process development.

Andrew: Right, It’s just kind of confusing. with It has negative charge and it binds the positively charged proteins. Hence the cation exchange resins, right? And the anion is vice versa. Um, Just to kind of wind things down, purolite has two upcoming conferences, right? One in Barcelona, Spain for Bioprocessing Summit.

That’s held in [00:37:00] March, this month. And another one in early April, Bioprocess International Europe. They sound so similar. Now, where is BPI Europe held?

Andy: Yeah, we’re going to go to Bioprocess International Europe in Vienna, in Austria, on April the 9th to the 12th. And at those conferences, we intend to be presenting our work with the resins that we’ve discussed during this podcast.

Andrew: Oh man, those events in Europe sound like a blast. I wish I could go to Europe and meet the PuroLite team in person. Uh, we could talk a lot more about chromatography resins there.

Andy: Yeah, that’d be great. And you know, just to sort of back that up, if any of your listeners have any questions about our chromatography resins, um, you know, please get in touch through our website or join us at the events that we’ve just mentioned.

We have field support, technical support, and account managers are going to be more than happy to assist you or your listeners with any questions they have.

Andrew: Fantastic. Again, thank you so much, Andy, and good luck with all your endeavors.

Andy: Thanks very much, Andrew. I really enjoyed the podcast and it was great talking to you.

Andrew: [00:38:00] Well, let’s wrap it up folks. I hope you enjoyed this episode. If you want to stay connected, follow us on LinkedIn. And for more episodes, find us on Spotify or visit our website, www. imcstips. com. Catch you on the next one. Take care. [00:39:00]