In this webinar, Martyn Ryder, Business and Product Development Manager at SOLO Containment, an ILC Dover Company, delves into the revolutionary impact of flexible film isolator technology on pharmaceutical and biopharmaceutical manufacturing. Martyn shares insights into how these cutting-edge systems are transforming high-containment environments, enhancing safety, and streamlining operations.
Martyn provides a detailed overview of the design and application of flexible isolators, highlighting their ability to eliminate traditional cleaning processes, reduce cross-contamination risks, and support the safe production of highly potent compounds. He explores the advantages of single-use isolators, including faster changeovers, cost savings, and enhanced flexibility in adapting to new processes.
Watch the video or explore the transcript below to learn more.
Transcript
[Martyn Ryder] 00:01 – Hello, everybody, and welcome to ILC Dover’s webinar. Today, we’re going to be taking a look at a range of specialized flexible film isolator solutions that are designed for safe handling of oxygen-sensitive materials. So, what are these materials? Well, we’re talking about microbiome therapeutics, oxygen-sensitive anaerobes, lyophilized interfaces, and cell banking.
Now, let me tell you a little bit about the ILC Dover corporation. ILC Dover is an organization of over 1,000 skilled employees. Our main area of expertise is manufacturing flexible film materials and goods. We are world leaders in this area, and if I show you our product portfolio—pharmaceutical containment, biopharmaceutical, and of course, personal safety—in this COVID year of the pandemic, we’ve been very big in PPE manufacturing. ILC Dover is also developing some very interesting flood protection systems. Over on the bottom right, aerospace—ILC Dover makes the spacesuits for NASA and Boeing. One of our great strengths is bulk packaging and powder containment technology.
Benefits of Single Use Isolator Technology
[Martyn Ryder] 01:33 – So, in today’s webinar, I want to explore the benefits of single-use technologies, especially with regard to flexible film isolator technology. You may ask, why single-use? Well, single-use eliminates batch-to-batch cleaning. We eliminate not only the cleaning but also the cleaning validation. Faster to market—a single-use isolator can be delivered pre-qualified, so we get you into the marketplace faster, and we’re selling you a consumable product and not a project.
So, comparing our flexible film isolator to a hard shell—shorter lead time, lower price, and delivered ready to run. Talking about faster—the great thing about these flexible film systems is the campaign changeover time is hours, whereas with a stainless steel isolator, you could be looking at days or even weeks to do the cleaning, the cleaning validation, and waiting for the results of the cleaning validation to come back from the lab. This flexible film technology is fast. The time savings because we’re not hanging up weeks or days with cleaning validation means you’ve got significantly lower operational costs over hard-shell designs.
A flexible film isolator is a fraction of the cost of a hard-shell stainless steel isolator, so capital savings as well. One of the things to remember about our flexible film isolator systems is that as you change or develop your process equipment, we can change the position of gloves, and we can change the isolator design slightly to accommodate any new processes or machinery. So, we think that this single-use technology has significant benefits for our customers.
Flexible Film Single Use Isolators
[Martyn Ryder] 03:40 – Here, you see a flexible film single-use isolator at the end of the campaign being collapsed down for complete disposal, and that’s how easy it is. We can change over a flexible film system from taking the contaminated isolator down, putting a new one up, and starting the run test within hours—very fast changeover.
Low-Oxygen Content Isolator Challenges
[Martyn Ryder] 04:00 – Now, when we think about our target here in low-oxygen content isolator technology, there are a number of serious challenges because we’re trying to combine containment. We’ve got low gas flows. We want to run at negative pressure to make sure there’s no API or BSL particle migration out of the isolator. We want a fully disposable system so that at the end of the operation, just like you saw in the previous picture, all the contaminated parts can be rolled up and taken away for incineration.
We can supply these systems gamma-irradiated for added purity. Now, linked to the negative pressure in the single-use system is the requirement to inert gas saturate to reduce oxygen content or relative humidity inside the flexible film enclosure, and all of these give us a significant challenge from a design point of view. But what we need to deliver to our customers is a reliable system, so it operates day after day, campaign after campaign, giving you safe containment, safe disposal, and delivering these low oxygen contents that you need for your manufacturing process today.
Systems
[Martyn Ryder] 05:34 – We’re going to be discussing three specific systems: manual gas flow control, manual gas flow control with automated fan compensation, and then a fully automated system where the gas flow control and the fan purge are all push-button controlled on an HMI.
soloLAB™
[Martyn Ryder] 06:03 – Let’s start with something simple. Here, in this image, we have what we call a soloLAB™. The soloLAB™ is a simple bench-top pop-up isolator with a carbon rod frame system. The ladies pack in nitrogen gas at the bottom right. We allow the gas and air mixture to vent until we get to the right saturation inside the isolator.
soloFLEX™
[Martyn Ryder] 07:22 – A little bit more sophisticated, we have what we call the soloFLEX™ solution. The soloFLEX™ is an off-the-shelf standard design available in three sizes: two gloves wide, three gloves wide as shown here, or four gloves wide. The soloFLEX™ operates at negative pressure, and we handle it for gas-saturated operations by applying the nitrogen inlet pipe directly to the intake HEPA filter.
Semi-Automated System
[Martyn Ryder] 09:28 – The two early ones are very manually oriented. Now, we’ve got a system here that is what we call our semi-automated system. The semi-automated system has a manually adjustable gas delivery. On the image on the right-hand side, you’ll see we’ve got the gas delivery unit. There is a gas flow meter system, and the fan with its electronic speed control system automatically modulates the fan speed to maintain 30 Pascals negative pressure within the isolator enclosure.
Gas Delivery System
[Martyn Ryder] 12:11 – So, what I want to look at now is a little bit of detail on the semi-automated gas delivery system. We’ve been building these since 2015, and essentially what we try and do here is divide the permanent installation from the single-use installation.
Flexible Film Isolator
[Martyn Ryder] 16:12 – Many of these single-use flexible film systems can be adapted to your process interface requirements. Here, we’ve taken a smaller isolator and adapted it to fit a Telstar lyophilizer. You can see that where the lyophilizer door is, we’ve made a special grooved flange part that creates a gas-tight seal around the door.
Lyophilizer Isolator
[Martyn Ryder] 17:19 – As we talk about lyophilizers, the biggest lyophilizer door we’ve accommodated today with our single-use inert atmosphere isolators is about a two-meter door size. In this drawing, you see a more common layout used in microbiome manufacturing.
Gas Delivery PLC
[Martyn Ryder] 19:48 – Now, so far we’ve been looking at what we call the semi-automated gas delivery system. That is great for many of our customers because they tend to run at the same gas saturation levels on all of their campaigns. However, some CDMOs need more flexibility, and here we can offer a PLC-driven gas delivery system.
Complete Safe Disposal
[Martyn Ryder] 22:00 – This is constructed for complete safe disposal at the end of the campaign. The HEPA filters you see at the top are clamped through the flexible film, so when we take the contaminated enclosure down, it all goes as one sealed unit with no possibility for any particle escape.
Large Scale Operation
[Martyn Ryder] 22:39 – Some of our customers have larger-scale operations. We have a system here designed around a Frewitt mill that was handling 15-kilo batch sizes. You can see we’ve got a charge bottle inlet and a product recovery below the mill with a pass-out through a DoverPac® continuous liner.
Single Use Isolation
[Martyn Ryder] 28:13 – I will bring us right up to speed on the 2021 designs. Here, we have a system that handles high-potency APIs with an exposure limit way below 10 nanograms. It is single-use and operates as low as 0.1 percent oxygen content in the work chamber while being totally disposable.
Timelapse
[Martyn Ryder] 29:32 – Bear with me, please. The video clip will be starting here. This is a time-lapse video showing how, at the end of the manufacturing cycle, we need to take the enclosure off the frame. This is just how easy it is.
Safety
[Martyn Ryder] 31:23 – One of the things we must always consider with nitrogen-inerted flexible film isolators is safety. First of all, as we’ve been pointing out, we use high volumes of compressed gas.
Conclusion
[Martyn Ryder] 33:06 – In conclusion, these nitrogen-inerted single-use technologies have been in operation since 2015. We’ve probably delivered maybe 500 replacement enclosure kits in that time, and the feedback from our customers is extremely positive.
Questions
[Martyn Ryder] 34:22 – So, ladies and gentlemen, thank you for attending this webinar today. If Stephanie’s got any questions, let’s throw the webinar up and see if I can answer your questions. Thank you very much for listening.
[Stephanie] 34:34 – Yeah, thank you, Martyn, that was a great webinar. Yeah, we actually do have a question. One of our attendees asked: What is the material of the gloves, and are they ambidextrous? With regards to glove change-out, if there’s a failure, how is that handled?
[Martyn Ryder] 34:53 – That’s a very good question, Stephanie. Thank you. We supply a range of gloves, and on a lot of our isolators, they are ambidextrous because that means you can put either your left hand or your right hand into the glove sleeve, which gives you a bit more freedom. We also have a completely safe change snap-through glove change system. If you’ve got an inert environment inside your isolator and a finger or something damages a glove, you take a new glove on a new carrier ring, pop it down the sleeve, and it snaps through, pushing the damaged glove into the inert environment. This is especially important because we’re handling super-potent products in a containment environment. We developed this technology about six years ago. If you’d be kind enough to drop your email details through to Stephanie, we’ll send you some detailed information on our push-push safe change glove system. It works really well.
[Stephanie] 35:56 – Great, thank you, Martyn. We actually have another question. How do we check the glove for a leakage test?
[Martyn Ryder] 36:03 – Another good question. On our disposable isolators, the glove sleeve tends to be welded into the main flexible film enclosure, creating a soft boundary to the glove sleeve. However, if we add a 12-inch diameter shoulder ring at the junction between the panel face and the glove sleeve, we can then use an automatic glove inflation tester. This technology is used on all of our aseptic isolators. We inflate the glove sleeve up to plus 1000 Pascals—quite a high pressure—and conduct an automated countdown over 90 seconds, giving a pass or fail result on the glove and sleeve assembly. If you provide your email through Stephanie, we’ll send you some images of how we perform this test. It’s a really smart system.
[Stephanie] 37:01 – All right, great, thank you, Martyn. That concludes our webinar for today. Thank you to the attendees. Within the next 24 hours, you’ll receive a link to the recording of this webinar. Like Martyn said, if you have any additional questions, feel free to reach out to us. You can visit us on our website at ilcdover.com, or you can reach out to the email address that will be provided when the link for the recorded webinar is sent to you. Thank you, everyone, and have a great day.
[Martyn Ryder] 37:46 – Thank you again, Stephanie. Take care. Bye, everybody.