October 15, 2021

Crossing the finishing line in biotech

By Conor McKechnie and Dodi Axelson

Crossing the finishing line in biotech

We talk a lot about beginnings on Discovery Matters, but what about actually getting biologic drugs to people? Once the biologic is produced, aseptic filling and hybrid glass and plastic vials help to protect the biologic drug and the patient.

Join Dodi, Conor and their guests, Chris Weikart the Chief Scientist at SiO2 Material Science, and Ross Gold one of the founders of Cytiva's aseptic filling business, in the latest episode of Discovery Matters, talking about the end of the workflow.

DODI: Conor, we talk a lot about beginnings on our podcast, Discovery Matters. But what about the end of the workflow, actually getting biologic drugs to people?

CONOR: Yeah, and in our last episode, we talked about the innovation surrounding mRNA based COVID vaccines, but we never talked really about how do you get it to the patient after you've made it?

DODI: Exactly. So, the packaging for housing, transporting, injecting biologic drugs, including syringes, cartridges, but most importantly, today, glass and plastic vials, and that is what matters this time on Discovery Matters.

CHRIS WEIKART: I'm Chris Weikart, Chief Scientist at SiO2 Material Science. I've been with the company nine years now, before that, I was with the Dow Chemical Company in Midland, Michigan, where I worked there for about 12 years in their core R&D Centre. But what brought me here was a new opportunity to develop a new packaging product for biologic drugs.

DODI: Chris worked on developing glass-like vials to transport and house these biologic drugs. And these vials are made from a composition of a plastic container with a very, very, very thin layer of glass coating the inside. To put it into perspective, this thin layer is 1000 times thinner than a human hair.

CONOR: So, is it like when you're painting a house you put a coat of paint on the outside as a barrier against wind, and water, and other things? And is that how the glass coats the vials?

DODI: Do you coat your house with hair?

CONOR: I have a hairy house! But is that what you mean? It's like just a barrier against things that would degrade it. Does the glass coating on these vials act in the same way?

DODI: Yes. But instead of paint, an artificial plasma is applied on the inside of these containers to then apply to this glass coating.

CONOR: Okay, so this doesn't seem like too mind boggling, is this new tech? What's so cool about this?

DODI: It's been around for about 50 years. And Bobby Abrams, the founder and owner of SiO2 saw this need for improved packaging for drug products. He'd had previous experience with molding plastics for containers, which led him to see the potential of plastic and glass packaging. Some hospitals had complained about inferior glass packaging because things get broken in hospitals, of course.

CONOR: And that's not good for nurses, and they cut themselves and so on, and so forth.

DODI: And so on and so forth. And then, in about 2014 or 2015, Chris and his colleagues came up with this idea of hybrid vials made from both glass and plastic.

CONOR: So, glass and plastic together, like it has a real impact on I suppose patient and worker safety, which is of course, always really paramount in hospital and therapeutic settings. And then bringing glass breakage levels down is important, especially if somebody is self-administering these medicines, is that right?

DODI: Exactly. If you know any diabetics, then it's possible that they are self-administering medicines. And Bobby Abrams identified some serious issues with the pre-existing biologic containers, such as...

CHRIS WEIKART: ...the introduction of particles in glass packaging that can interact with a drug product, that can obviously change the efficacy of the drug. Which obviously isn't good for the patient, these can lead to things like not just injecting your body with foreign materials, but also can cause an immune response in a patient, it can lead to things like anaphylaxis, could even lead to death.

CONOR: So, this was a burden that the industry has dealt with over the years. And I suppose Bobby already knew about molding plastic containers. So, combining it with this coating technology to make a hybrid container, that just basically eliminated these problems, right? And then why just keep the glass element at all? Why not just use plastic?

DODI: Well, according to Chris, there are some characteristics of glass that are absolutely necessary to certain applications. And there are some attributes that are just impossible to eliminate. So, part of that is down to the sheer complexity of modern-day biologic drugs and diseases.

CHRIS WEIKART: Drugs once upon a time were very simple, you know, very small little molecules, right? Well, if you think monoclonal antibodies, these are huge, huge molecules. And because they're so large and complex in their architecture and their chemistry, they do tend to interact with their surroundings. They're sensitive to things like oxygen in the air, their packaging and because of that they can change and get altered.

CONOR: Okay, so these really complicated drugs, the more complicated they are, the more additional packaging you need to make sure that the drugs aren't being altered within their containers, and so on, to protect the patient. So, you know that your glass sitting on your desk may be completely fine for your soft drink or your coffee or whatever it is, or let's be honest beer or wine. It's not good enough for the current generation of drug products because they're evolving, and they continue to evolve.

ROSS GOLD: So, Chris and I met first working for a company called QLT, in Vancouver, that was among the first firms using what we call a complex dosage formulation. We were involved in the team that was developing and manufacturing this complex dosage into an injectable product. And so, I guess that innovation spirit had to continue downstream into the dosage itself.

CONOR: So, is this Ross Gold, one of the founders of Cytiva's aseptic filling business?

DODI: You bet it is!

ROSS GOLD: We are a drug product technology company within the Cytiva network, sort of the last part of the chain from idea to injection.

CONOR: So, Ross focuses on the finishing process, the very last piece of the drug manufacturing workflow, getting it into the vial, right?

DODI: That's right. And Ross and his co-founder, Chris Procyshyn, both realized that innovation on the drug product side was necessary. There was a gap. And they've been working on new tools that will allow injectable dosages to be manufactured by a broader set of companies in the industry. They looked at the process – and we've talked about innovation so many times on this podcast – they looked at things that were working just fine but could use a tweak. And Chris and Ross saw that they could take the opportunity to create a new process for filling.

ROSS GOLD: A few of the observations we had getting involved in this part of the industry were that many parts of the process, for example, were occurring in the aseptic zone that perhaps didn't have to. So really, we looked at it from that perspective, that the process itself could be innovated in order to provide something that was more of a modular work cell-based architecture. With respect to automation, there's a lot of excellent automation tools out there, but the best aseptic process is the one with the least amount of people and the least amount of automation in it.

CONOR: So that's really interesting. You want the smallest number of people and the least amount of automation to protect the patient by minimizing the contamination of the dose that you need. So, you try and make as little contact as possible with the drug, whether it's human or otherwise.

DODI: Exactly, because you just increase the chance for germs or mistakes or, you know, humans we mess up. So, Ross is envisioning that these aseptic filling machines will allow the greater democratization of producing injectable dosages. And I know you need a better explanation of that.

ROSS GOLD: So, in order to do that, the process needed to be simplified, the ability to scale the process out needed to be there and that's accomplished through standardization. This would ultimately in the future result in a state where more people are able to produce injectables more easily, more geographically distributed, and that big hairy goal would be achieved. So that was really that sort of 10 000-foot idea that we had.

CONOR: So, Ross's team focused on standardization and scaling up the process. And then SiO2 have looked at improving the packaging of biologics. So, the question is, how considerable is the difference between ordinary glass packaging and these hybrid vials?

DODI: I know it's kind of freaky that we can spend this much time thinking about glass and plastic and packaging. Well, SiO2 conducted a study with the University of Colorado, in Boulder, looking at the impact of particulates in drug formulations on immune response with human blood. And they found that there was a low particle burden, or particle load, in the plastic and glass container. So, the likelihood or the risk of an immune response to the patient is suppressed significantly.

CONOR: Okay? So, you don't want stuff that shouldn't be there in your vials going into the patient and eliciting an immune response. So, this is kind of a big deal. These vials are not just able to reduce the risk of an immune response, or like anaphylactic shock or even death, but the actual packaging is more robust. This is kind of a win-win.

DODI: So now you're understanding why it's worth spending time learning about glass and plastic in vials.

CONOR: It's incredible, isn't it? You just don't even think about these things, when they did the vaccine, they pulled it out, you just think it's a normal little glass thingy. And it's not a normal little glass thingy, there's a lot of thinking that's gone into that.

DODI: There's a lot of thinking. Now the packaging, I'm going to blow your mind even more, the packaging is an engineered polymer. It is so tough, that you can drive your car over the syringes, or vials, or hit it with high impact, and it will not break.

CONOR: Okay, I love that. It's like the Iron Man™ of the packaging world. Okay, so that's good. So, it's robust in transport. And distribution is important. And then, with the end of the workflow needing like really high demand materials, such as plastic and glass, what's happened during the pandemic when the supply chain has been under pressure?

DODI: Well, you know what the Philadelphia Inquirer actually covered this story because indeed, supplies of recycled glass were down 20% last April in Philadelphia, and the situation in New York and New Jersey was even worse, supplies down 62%. But really, let's listen to what our experts says about what happened.

CONOR: They should have come to my house and just picked up the pile of wine bottles out the back of the recycling.

CHRIS WEIKART: We don't even use any of the raw materials that goes into glass. To produce a thin layer of glass actually utilizes the raw materials that are more commonly associated with integrated circuits on silicon chips. You know, wafer chips or things that are in your computers and your other electronic devices. So, these are liquids at room temperature. As I said, they have nothing to do with glass manufacturing, they have more to do with microelectronic manufacturing. And the plastics that we use are readily available, we have a supplier Zeon from Japan, that stockpiles this in the US for us, and we have a very good relationship with them. So as far as raw materials supply and supply chain is concerned, we have no issues.

DODI: The very nature of these vials means that they are separate from supply chain problems. And they can also scale up capacity at a rapid rate. So SiO2 can produce 40 million vials within three months without your wine bottles, Conor. Whereas for glass, it could take a year or more to put that capacity in place. And so, what this means is that SiO2 was granted a big chunk of money, 316 million US dollars, to scale up capacity during COVID.

CONOR: So, the pandemic has, in so many different areas that we've explored, driven extraordinary innovation, and has helped find new ways of efficiently working with eventually drug packaging.

DODI: Exactly Conor, and I was talking about that very thing in my conversation with Ross, listen to what he says about innovation during the pandemic.

ROSS GOLD: When you have a requirement on a global scale for an injectable, like a COVID vaccine, of course, that means that all tools in the tool belt have to be exercised in order to accomplish that goal. It requires scaling up, scaling out new technology adoption. All of these things become something that are in everyday discussion. And I think that had you asked me that a year and a half or two years ago, I would have said, the industry needs to have options for scaling up, for scaling out, for adopting new technology. And I think we're on a wonderful path now because we've sort of had our hand forced.

CONOR: You know, it just shows anything can be improved if you're willing to just, you know, pick it up, look at it, ask and you've got a good reason for it. And I think what Ross and Chris have shown us is that the industry was crying out for improvement, and this pandemic has driven an opportunity to innovate out of need, right, and then apply their ideas. So, this is what I love about this industry, that at any step along the chain there's really, really good innovation going on all the time. But what's also, I suppose, frustrating about this industry is that it's taken something like the COVID pandemic to drive innovation at some really key points. They have given really, really big returns whether it's on the sustainability side, or whether it's on, you know, the robustness and efficiency of packaging, or whatever it might be so this is kind of a bit of a give and take in our industry.

DODI: I feel whiplash, absolutely I was happy and now I'm not and I don't know which way to feel Conor about the innovation here. But we do hope that you feel happy that you have listened to this episode of Discovery Matters! We sure are grateful that you did.

CONOR: Andrea Kilin is the executive producer of Discovery Matters. This was produced with the help of Bethany Grace Armitt-Brewster. Editing, mixing, and sound by Tom Henley.

DODI: Who's about to become a Papa, so we wish you the best Thomas!

CONOR: All the best for fatherhood, you're gonna be so tired. My name is Conor McKechnie.

DODI: My name is Dodi Axelson. Make sure to give us a rating on the platform you use to listen to us. Thank you so much for listening.

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