In this webinar, Martyn Ryder, Business and Product Development Manager at SOLO Containment, an ILC Dover Company, delves into the transformative impact of ILC Dover’s full life cycle safety innovation on high-containment pharmaceutical and biopharmaceutical manufacturing. He highlights how advanced flexible film isolator technology is redefining containment practices, ensuring unmatched safety for operators, and optimizing workflow efficiency in handling highly potent APIs and ADCs.
Martyn offers a comprehensive overview of the innovative features of flexible isolators, including automated pressure decay testing, single-use designs, and enhanced containment performance validated by rigorous testing. He discusses how these systems eliminate traditional cleaning processes, mitigate cross-contamination risks, and facilitate safe disposal, all while significantly reducing downtime and operational costs. The presentation underscores the adaptability of these isolators for diverse manufacturing needs, demonstrating their vital role in supporting both safety and productivity in high-stakes environments.
Transcript
Introduction
[Martyn Ryder] 0:00 – Hello everybody and thank you for joining another ILC Dover webinar. Today we’re going to talk about ADCs and other highly potent substances and the containment of these. We’re also going to look at Dover’s full life cycle safety innovation. I’d like to thank thank Scott Patterson of ILC Dover for by providing some of the supporting material here. I am Martyn Ryder of the Solo Containment Division, based in Manchester, UK. Today we’re going to look at the full life cycle safety work through. We’re going to look at transfer devices, and we’re going to look at the elimination of cleaning. All these things we believe are absolutely essential in us winning that battle for safe containment in the workplace.
ILC Dover – Company Overview
[Martyn Ryder] 0:51 – So, ILC Dover is 70 years old. We are a company of 700 plus skilled employees with locations in Delaware, Houston, Texas, Juarez, Mexico, a large manufacturing facility in Blaney Island, and Basel, Switzerland, where we have our Powder Technology Division, Jet Solutions.
I’m talking from Stockport, UK, which is the Solo Containment office and factory. And then we have a very active team in Singapore covering the Asia-Pacific market.
What Is Full Life Cycle Safety?
[Martyn Ryder] 1:40 – ILC Dover has been working on this for a number of years. We’ve got several steps now. Let me talk you through these.
The first thing is what we call the process score application evaluation. The process score is a risk and hazard assessment method that allows us to develop the isolated design or the containment solution design to more carefully fit your application’s risk and hazard profile. Very, very important because we want to make sure we’ve got the right technology on the isolation system. So even in a bad day when maybe SOPs aren’t being followed all that carefully, we’ve still got super safe levels of containment.
Now, we put that into the next step, which is quality by design. We want to ensure that our design for the solution we’re going to offer you is absolutely correct in terms of film selection, transfer systems, manufacturing automation, and even things like how you get the product into the facility, then into the isolator, and how you get the product out of the isolator.
By defining all of these with our quality by design system, we’re giving you a very clear specification and understanding of what we will be delivering, and that can be checked out later in the stages of the factory acceptance test.
The third step in our full life cycle safety innovation is manufacturing integrity. So, ILC Dover are a powerhouse of flexible film manufacturing. Today, the fact that they put the spacesuits on the guys from NASA proves the integrity of ILC Dover manufacturing.
Every single flexible film isolator that they manufacture—either in Frederica or in Blaney or here in Solo in the UK—these isolator enclosures are pressure-tested with positive pressures to about 10 times normal operating pressure.
This very rigorous pressure testing regime brings out any weaknesses we may find in welds or damage that nobody’s seen during the manufacture. So our manufacturing integrity, we believe, is as high as we could possibly get in the field of flexible film manufacturing.
The fourth part of our full life cycle safety innovation is our factory acceptance test. Why is this important? Well, we’ve gone through the process score, we’ve gone through quality by design, and of course, we’ve just talked about manufacturing integrity.
We want to make sure that before we deliver our containment solution to you, you can take a look at it. You can make sure it exactly matches the performance criteria that we’ve laid down, that we’ve agreed between us, and that dimensionally contained performance, light levels, noise levels, etc., all meet your factory and facility requirements.
Another great thing about factory acceptance testing is it allows us to develop safe SOPs with your manufacturing team. So, rather than have the isolator turn up in your facility and people scratching their heads saying, “Well, what do we do with this?” you bring your manufacturing team to one of ILC Dover’s global facilities, and there we work together.
We show your people how to load product into the isolator, how to operate the isolator, how to collapse the isolator at the end of the campaign. And we believe at Dover that this factory acceptance test and development of safe SOPs is a real bonus in making sure that you get safe, long-term containment performance from the device that we provide you.
Now, after the FAT, the isolator has gone to your facility. We want to do a Smith Pack test. We want to prove the containment performance.
We do this using SafeBridge as our specialist testing authority. We’ll be using Naproxen Sodium as our surrogate API, and we’ll be running the evaluation of the test samples to EN 689. EN 689 2018 requires that our containment performance is below 10% of the containment performance target—not 50%, not 25%. Our pass/fail line is 10% of the safety yardstick that you set during the Smith test of the containment testing.
Again, we can develop operator training because we believe that the hardware and the people who run the hardware—if you like, the software, the operators—there are definite links in attaining performance by having everybody working together in the correct procedures.
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Now, as part of our assurance to you that we’re going to deliver long-term safety performance with our isolated technology, Dover has an automatic pressure decay cycle.
Every time you go into the facility to use the isolator, you press the pressure decay test. It runs a 90-second cycle, and it looks out for any leaks or damage in the flexible film isolator. If there are leaks or damage, it will say “Failed test – do not use.”
We believe this simple application of a negative pressure leak test on every run cycle is a very good way to confirm the isolator is safe for use.
The final two steps in our full life cycle safety innovation are to eliminate cleaning. We believe if we eliminate cleaning, it minimizes the exposure risk. And anything we do in your facility to minimize operator exposure to high potency APIs is a win in our book.
So how do we eliminate cleaning? Well, we’re going to look at some examples further on in this presentation, but we need to be able to securely transfer contaminated parts out of the isolator and then take the enclosure down—the contaminated enclosure down—leaving nothing behind that has any drug contamination on it.
The last part in our full life cycle safety innovation is using the fan—the exhaust fan—to collapse down the contaminated enclosure. Again, it’s another one of these simple systems that eliminates exposure risk.
No leak paths exist; there are HEPA filters on the inlet and the exhaust side of the flexible enclosure. Therefore, no molecules of the high potency API can escape. So if we collapse it down so you can incinerate it, that’s a big win from where we stand in minimizing exposure.
The Full Life Cycle Safety Continuum
[Martyn Ryder] 9:06 – Looking at it more simplistically, there are three phases in our full life cycle safety continuum:
- Solution Development and Manufacturing
- Quality Assurance and Process Startup
- Operation and Single-Use Disposal Benefits
Let’s look at it a bit more pictorially.
Working Through the Full Life Cycle Safety Cycle
[Martyn Ryder] 9:34 – The process score. ILC Dover has developed a computer algorithm that allows us to look at the containment performance target anywhere between 100 micrograms down to 10 nanograms.
We look at the dust potential—the dust generating potential—of the product you’re handling. Is it not dusty? Is it very dusty? Is it somewhere in between?
We look at the quantities of material you’re going to handle, from grams to hundreds of kilograms. And then we look at the process. Is it milling—high-velocity parts spinning around? Or is it something very gentle like sampling?
These four factors create, on our algorithm, a process score. The lower the process score, the more simplistic the isolator can be. The higher the process score, the more safety factors we’ve got to build into that flexible film isolator to bring up alarm conditions, to make sure we’ve got multi-stage HEPA filtration, and of course, this automatic pressure decay test.
The process score and our very detailed site survey questionnaires give us a basic understanding of your application, so we can then proceed to Quality by Design.
The design teams, both at Frederica in the United States and here at Solo Containment in Manchester, UK, have got years and years of expertise behind them developing flexible film isolators.
There are very few applications we have not conquered in our history working together.
In image three, you can see the high-pressure integrity test at the ILC Dover facility in Delaware. Ten times normal operating pressure is an extreme test of any flexible film enclosure.
We do it day in and day out, and this guarantees to our customers that every isolator is the same performance, dimensionally perfect, and we de-snag everything before it gets to you.
In the factory acceptance test, here is the opportunity to make sure all the performance criteria meet the schedule that we’ve agreed together. And we bring in the operator training.
In image five, you can see a typical Smith Pack test being conducted. People with the personal monitors on them, looking for any trace exposure during a realistic batch operation.
We will look at your manufacturing activities, replicate these with similar quantities of product—a product that is equally as dusty—and we’ll work the isolator in just the way that you would.
The automatic pressure decay test. We have two systems here. We have what we call a Quantum smartphone that does a negative pressure decay test, and now a much more sophisticated system on the ACM, manufactured by ILC Dover.
When it comes to elimination of cleaning, we are now adopting many single-use, incinerable parts. This means no dismantling, no taking the isolator to pieces to take out HEPA filters, which would be contaminated.
This is a great safety step forward. If we can eliminate the cleaning by making the entire isolator a disposable kit, in our book, that’s a massive win to add safety to your operations, to save you time, and to save any hang-ups you might have during an enclosure change.
You get a complete kit from ILC Dover. You use it, and you dispose of it. Another complete kit from ILC Dover.
In image eight, you can see a collapsed enclosure on the table. The table is completely free from any drug compounds. That collapsed enclosure can go into an incineration tote, and it’s gone.
Solo Inert Gas Solids Transfer to Reactor
[Martyn Ryder] 13:57 – Let me talk about typical flexible film isolated designs. So, we need to create for you a secure and reliable containment bubble for your activities.
Here, in this image from, I think, 2014, we have a single-use isolator that was used for product charging into a process vessel. You’ll notice the flexible film base is sitting over the stainless steel table.
The stainless steel parts at either side are attached by very long sleeves so that at the changeover point of the flexible film enclosure, none of these parts will have seen any drug contamination. That means it’s very easy and clean to change over—no cleaning validation.
And it adds to safety.
On this particular design, we had a PTFE transfer spigot that was considered single-use, which carried the slide valve below the work table. You can just see there’s a contained slide valve underneath there, and this was carried on a single-use PTFE spool piece.
This particular enclosure was inerted by a pile clean pack filter with nitrogen, so it operated at a very low positive pressure. Obviously, this is not suitable for high-potency drugs and is limited to low-hazard materials.
Taking this a little bit further, here you see a more advanced isolator design.
Here, we’re using a loading airlock to make it easy to get the product into the isolation chamber. Double zip. One zip on the front to put the drum of material in, close that zip, and then, using the glove sleeves, we open the inner zip, and we can start to dispense the product as seen in the central image.
So here, the containment bubble is containing any API aerosol generated during powder dispensing.
And of course, that flexible film isolator will become contaminated.
So, we make this single-use. We make it so the HEPA filters that do the filtration, the continuous liner parts—every single contaminated component of that isolator bubble—can be collapsed by fan vacuum and rolled up.
A totally safe disposal. No aerosol escape is possible because we’ve got H14 filters on all sides of it.
Here’s another example—similar process—but this time we’re targeting cytotoxic drug materials.
This isolator is designed for adding cytotoxic powders into a compounding glassware vessel. The compounding glassware vessel sits on a raised lower platform at the near side end of the isolator.
And here we’ve got an extra-long sleeve that goes around the glassware vessel so that at the end of the operation, that glassware vessel can be overbagged and taken away from the flexible film isolator to a cleaning station.
Again, the entire isolator sits above the stainless steel table, so the table, the frame, and any active components involved in the manufacturing do not see any high-potency API contamination.
Any parts that do can be bagged out—like the glassware—through the extra-length sleeve in the base.
This particular isolator operates with three H14 HEPA filters—one on the inlet, the central HEPA filter goes between the airlock and the powder transfer chamber, and on the right-hand side of the isolator, you’ll see the exhaust HEPA.
This exhaust HEPA is piped to the exhaust fan, where we have three electronically operated ball valves that control the automatic pressure decay test.
So, in this very simple design that is designed for single-use, we’ve got extremely good levels of containment performance.
That’s the typical layout of the isolator.
We can see the compact design—less than 10 feet long. The work chamber is about five feet long, and we’ve got gloves so operators can work from both sides.
Results
[Martyn Ryder] 18:51 – What this isolator was tested for in June of 1919 using the SafeBridge team from the UK.
And as you will see, the actual performance characteristics we got from the single-use isolator were extremely good. Every single test run we took on the powder handling and static samples were below the limit of detection.
This client opted for a previous version of EN 689, where the pass/fail was 25% of the containment performance target, which in this case was 500 nanograms. So, in all cases, the containment performance was sub-nanogram.
Very exciting. We’re very pleased about that.
Yet a further development of this design is what we call the soloADC™. In some ways, it’s a little bit more sophisticated in that we’re trying to keep as many manufacturing components outside the isolator as we can.
You’ll notice in the center of the isolator there’s a square plate below the work deck, and that is designed to carry a magnetic stirrer that will actually drive the stirring pod in a glass beaker or flask that is sat inside the isolator.
We’re trying to, if you will, depopulate the working chamber so we have fewer parts to remove at the end of the contaminated campaign.
The soloADC™ is designed for handling products with a typical containment performance target of below 10 nanograms. Extremely toxic materials. Very, very dangerous. And with this sort of product, we cannot afford to take any chances.
The control package for the soloADC™ has a gassing tower with various functional alarms on it. For example, the airlock has a proximity switch on it. Even though it’s a flexible film zipper, the proximity switch on the airlock will go into alarm if anybody opens the airlock during the manufacturing campaign.
The soloADC™ gassing tower runs the system at negative pressure, and it will allow the system to be gassed down to 0.5% oxygen content during a campaign if that is required.
Now, let’s go to the next slide. I just want to talk about how we get this contamination-free isolator disposal.
This is a little time-lapse image, and what we’re doing here is we’re showing that at the end of a manufacturing campaign, when that flexible film isolator enclosure is potentially contaminated with an ADC toxin, we want to be able to get it off the frame without causing any positive pressurization of that flexible isolator.
Using the fan exhaust, you can see how it collapses the isolator down very easily.
Now we’re just going to lift out the two-stage exhaust HEPA housing from the back—there it is—and slide the contaminated enclosure onto the trolley and take it for disposal.
Very, very simple. Very effective.
In fact, this design was developed with our customer ADC Biotechnology, based in Wales in the UK. We manufactured two isolators for them in 2018.
You can see our design has come on a little bit since then. We’ve got the gassing tower and different control valve technology.
Containment Testing – 2018 Customer
[Martyn Ryder] 22:51 – But even back in 2018. the containment test data we got from the soloADC™ was absolutely outstanding. So, we have a containment performance target of 10 nanograms per meter cube task-specific.
Our pass/fail was 10% of that, so we had to be better than 1 nanogram per meter cube task-specific.
Our customer wanted a very wide range of tests done because they wanted to account for every potential adverse condition.
The first thing we did is we spent an entire day removing contaminated items through the continuous liner. We deliberately put Naproxen Sodium-contaminated parts into the continuous liner pouch. We shook it about, made sure it was as dusty as possible, and then heat-sealed it off.
We’ll show you the heat sealer in a moment. But all three of the results, both personal and static—three runs, sorry—were below the limit of detection. So, we were very, very happy.
Then we did the typical toxin linker dispensing, and again, three personal results out of three runs, 15 static results, all below the limit of detection.
Now, to really challenge the design, we wanted to do a power failure. So, partway through the toxin linker dispensing, we pulled the plug on the fan. So, all power to the isolator stopped.
And yet again, all three of the personal results were below the limit of detection, and 15 of the static results, again, below the limit of detection.
We then repeated this test using an induced contaminant. So, this isolator had a peristaltic pump hose line transfer part in the end of the isolator, and into this, we drilled a 12-millimeter diameter hole—replicating if a glove would fall off.
Sorry, if a finger would fall off a glove, which is, I know, highly unlikely. But we put a one-finger-sized hole in the end of the isolator during the three test runs.
Of course, the fan went into alarm conditions. We got flashing lights and sirens. But we continued to dispense the product over each of the three runs.
And yet again, all the three personal results were below the limit of detection, and 15 of the 15 statics, again, below the limit of detection.
The final test we did over this five-day test period was to do the contaminated isolator collapse.
Now, after four days of testing with Naproxen, it’s fair to say that the interior was quite contaminated.
So, we used the fan vacuum collapse method that you saw in the time-lapse to collapse it down so we could take it off the table and put it into an incineration bag.
Again, two of the personal results and three of the statics were below the limit of detection.
For sure, it would have been nice to repeat this over three test runs, but the cost of the components made it a little bit prohibitive.
SOP Development at FAT – Key to Safe Operation
[Martyn Ryder] 26:12 – Now, as part of our full life cycle safety evaluation, we’re going to use the factory acceptance test to develop good SOPs.
Our client ADC Bio really did an excellent job with the FAT. So, they had five people come down to the factory for the FAT. Instead of a typical one-day FAT, I think it went over four days.
Every single procedure was rehearsed by different people. It was recorded on video. It was written up. So, they had a policy of, if you will, really benchmarking how to do every specific activity within the isolator, as if they’d learned it by rote.
It was extremely good, up to the full disposal. The totally disposable features in the soloADC™—you can see the HEPA filter housing on the left is made out of plastic. No changing the HEPA filters; the entire thing is disposed of.
It’s sealed to the flexible film enclosure and the spill bond or spill tray in the main work chain. It has 100 liters capacity, but it’s made out of soft EPDM film. So, it rolls up when the flexible film containment enclosure is rolled up.
It doesn’t hinder any compacting down of the volume because we’re targeting the lowest possible volume for easy disposal.
Here, we have the heat sealer. There’s a nice little video available from ILC Dover that shows this heat sealer in use.
Contamination Removal
[Martyn Ryder] 27:48 – Now, why do I like heat sealing? Well, of course, crimping technology is common with many continuous lines. Crimping, on a good day, is extremely effective.
Now, when you’re dealing with ADC toxins and you’re targeting a one-nanogram exposure limit, that’s pretty much like the sort of pollen haze you’d get on a bad hay fever day. You can’t see it.
With pollen, it would give you the sneezes. With an ADC toxin, probably the effect it would have on you would be far more harmful.
So, we need to look at a method of chopping down the continuous liner that is, if you will, bulletproof. And we’ve sourced a toxic dust heat sealer.
The toxic dust heat sealer makes two weld lines, and there is a cut line right in between the two weld lines. If there’s any residual toxin powders in that liner pouch when it’s cut off, they’ll be submerged in melted polymer.
On the video that we’ve just released, you’ll see that when we swab test the cutoff pouch that’s heavily contaminated, there is nothing coming out.
We’re using a UV material—UV fluorescing material—and UV light to prove there’s no migration after the heat sealing process.
Now, we’ve talked about several areas of what we call our full life cycle safety innovation.
An isolator isn’t going to be very productive unless we can get product in and product out. So, what I want to talk about now is the various options to transfer products and materials through the containment bubble to make your containment bubble work for your process.
In essence, this is part of our Quality by Design. So, early on in our discussions with you, we’ll have done the process score. We’ll know exactly what size containers, batch sizes, and operational characteristics you have in your facility.
That allows us to look at many of the various containment transfer types that are available.
Transfer Options
[Martyn Ryder] 30:20 – One of the best-established systems is the DPTE system. Some people call it an RTP—Rapid Transfer Port. These have been around for about 50 years. They were pioneered for aseptic processing because they allow you to bring aseptic materials in a transit container into an effective isolator without the need for any interstitial decontamination.
The lid of the transit container and the lid of the isolator door seal together so that any microbial contamination in there cannot get into the aseptic isolator.
Well, of course, we’re going to use this kind of DPTE system for getting products into a containment isolator running at negative pressure.
What are the problems? One of the things you can see in the image on the right-hand side is that the interface flange on a DPTE is fairly complex. It’s got to seal. It’s got to latch together with the door.
If we get product powder into there, it will no doubt damage the seal points. If you get excessive product on these seal points, eventually, it compacts the powder, and you get flakes of material coming out when you disconnect.
So, one of the golden rules with a DPTE system is there is never any loose powder inside that DPTE. If you’ve got materials in containers, pots, small drums, or bags, they must be scrupulously clean before they go in there.
Once they’re presented to the isolators, you can see on the central image, you dock that transit canister on, open the door in the isolator, bring your product through, and then you can process it.
Now, one of the very practical ways of powder handling is to use a split butterfly valve. Split butterfly valve technology has been around probably since the early 1990s, and there are several very good suppliers out there that make excellent technology.
Split butterfly valves are available in sizes from possibly two inches in diameter to 12 inches in diameter. Lots of companies make them. Some of these are fully automated, so they dock, they open, and they close again at the end of the transfer.
However, one of the things that you do find with split butterfly valves is that when the valve closes, it can take some residual powder with it, and you get what we call a compaction ring, as you can see on the right-hand image.
Now, various manufacturers claim this is not an airborne product, so therefore, it’s nothing to worry about. But there is physically some material occasionally compacted on the seal, and this may be a cause for concern.
I believe most split butterfly valve manufacturers now offer some very effective either airflow washing or even liquid washing technology to reduce the impact of this compaction ring.
These are very good systems, particularly in the field if you’re doing direct transfer of a product into an IBC bin or you want to get product into a process vessel.
Split butterfly valve technology is available with a wide range of solvent- and chemical-resistant sealing technologies, sealing gaskets, and it is very versatile for that chemical plant environment and in many other environments. Solid technology, very reliable.
At ILC Dover, we have a partnership with the AVAC system, which is a very cost-effective, single-use split butterfly system. I think this is limited to a four-inch diameter port at the moment, which is about 100 millimeters in metric.
One of the other popular transfer options is the contained slide valve. Now here, you’ve got one of the popular designs visible in the images.
The slide valve has the benefit that it can be single-use, and it does give you a full bore transfer. It’s available from four inches, I think, to eight inches in diameter.
It is good for transferring things like tablets or capsules, where the split butterfly valve may damage or fragment the product at the end of the transfer.
The container operates within, and it’s got a full bore transfer. Many customers put a feeder funnel right down through the open valve before powder is applied to keep the internal surfaces completely powder-free.
The benefits are low cost, relatively single-use in the injection-molded versions, and fairly good containment performance.
For many years in flexible film isolator technology, bag-in bag-out canisters have been the norm. These are still extremely effective.
One of the great benefits of the BIBO canister is that if you’re operating in an inert gas environment, you do not dilute the gas environment by introducing air, as you would with an airlock transfer system.
This is often seen in chemical plants where we’re using an inert atmosphere to suppress any ignition tendencies at a reactor charge or a vessel charge point.
The downsides, however, of the BIBO canister are that they’re not 100% gas-tight unless a zipper cover is added to the flexible film isolator.
Crimping technology from ILC Dover is an extremely well-developed process.
If, however, you do need to be in and out of the isolator more frequently with an easy transfer route, you can use the double zipper airlock.
But I just want to point out that if you’re operating within an inert environment, the double zipper airlock will need a second purge system.
As you can see in this image, we’ve got one purge system on the top left side of the isolator to purge down and gas-saturate the airlock, and one on the right-hand side to gas-saturate the main work chamber.
In this particular design, we can take the airlock back to 100% fresh air for safe loading of additional supplies at any point during the manufacturing campaign.
This particular design was powered by an Allen Bradley PLC, and you can see the HMI screen there.
One of the final parts of our full life cycle safety innovation is this elimination of cleaning. Let’s look at some very good examples of how we can work towards this.
Decontamination Risk
[Martyn Ryder] 38:05 – For example, when we started our pathway with isolators for ADC manufacturing, some of our early customers were removing their electronic balances through a transfer sleeve to decontaminate them between batches.
Now, with a product that has a 10-nanogram exposure limit, we didn’t think that was particularly safe.
So, after doing some research, we found a very cost-effective two-place disposable balance.
On the left-hand picture, you can see the yellow fascia of this—it’s called an A&D balance, manufactured in the United States. I think they’re about $300 apiece.
In this particular ADC isolator, we’re using a battery-operated balance, which we consider disposable, and we’re using a battery-operated magnetic stirrer.
So, all the manufacturing componentry—the balance, the stirrer, even the glassware—we’re considering them consumables. This means we don’t have to take them out and do a cleaning task.
Similarly, with the peristaltic pump lines, where once we may have used tri-clamps in a stainless steel base pan, we’ve now advanced our technology at ILC Dover.
We’re using fully welded-in plastic peristaltic hose lines. We’re using an EPDM soft film base tray instead of a stainless steel base tray.
All these steps are eliminating the need for cleaning, reducing decontamination risk, and reducing the risk of an operator becoming contaminated during the cleaning process.
The base plates above the EPDM liner are what we call a crack-fold system. These are nine-millimeter-thick plastic base trays that are machined seventy percent of the way through on the underside.
When you want to dispose of that contaminated enclosure, these snap down into extremely small parts to reduce the disposal volume.
The heat-sealable continuous liner is mounted on an incinerable plastic spool piece, which is clamped through the film.
At the end of the campaign, that lifts off. We class it as a consumable part.
Not only does it reduce any risk of dismantling during strip-down, but it also saves time. Because when you’re putting your new flexible enclosure on, the liner is already mounted on the spool piece, ready to go, and you’re in business more quickly.
Complete Isolator Enclosure Assembly Ready for Incineration
[Martyn Ryder] 40:47 – Here, we have a complete isolator assembly—a contaminated assembly ready for disposal. This was at the end of the five-day containment test.
That flexible isolator fits into a 700-liter incineration tote.
We have developed designs that will even fit into a 200-liter Mauser drum. If we can get to work on the componentry, we can make the incineration very cost-effective.
This is a partnership that we cover down at the quality-by-design stage.
Customer Value Comparison: Hard-Shell vs. Single-Use Flexible Film
[Martyn Ryder] 41:32 – One of the things we’ve touched on here is that by eliminating cleaning, by making our system single-use, we believe we save our customers significant revenues during the course of the manufacturing year.
Let me explain.
Supposing we’ve got a 100-nanogram containment product. One way of doing this would be to buy a rigid stainless-steel isolator.
Now, a rigid stainless-steel isolator for this kind of application—let’s say the price is $775,000.
The ILC Dover soloADC™ isolator to do that exact duty would be about $70,000. So, we’ve got a fairly huge price saving there.
Now, let’s focus a little bit on the consumables.
The consumable costs on a rigid stainless-steel isolator—we’re thinking about HEPA filters, gloves, gauntlets, gaskets, seals—let’s say they come to $2,000 every campaign change.
On a flexible film isolator, it’s a little bit higher, a little bit more intense, because every single component is disposed of. So, with a flexible film isolator, the typical cost for the complete kit is $10,000.
Now, let’s just look at the cleaning validation.
With a stainless-steel isolator, we’ve got six sides to clean. We’ve got beautifully covered surfaces, but stainless steel, under an electron microscope, is an extremely complex surface structure.
To clean this surface structure will take about 16 hours. It may take another 12 hours of lab analysis time to look at the swabs to make sure that the isolator is truly decontaminated between one batch and the next.
All of that cleaning validation work might take as many as five production days.
So, on a campaign change with a rigid isolator, we’re probably going to lose five manufacturing days, which could be $100,000 a day. Very conservative. That’s $500,000.
Now, with ILC Dover’s single-use system, there’s no cleaning validation, because every single part goes into the incineration tote.
The change downtime between getting that vacuum-collapsed enclosure off the frame and putting a new one on is easily done within one working day, including the pressure decay test.
Multiply that up by six manufacturing campaigns in the course of a 12-month period, and the savings with the single-use technology are enormous.
With the rigid isolator, you may lose 30 manufacturing days, which racks up a cost of about $3 million. With a single-use system, we’re saving you 24 days of manufacturing time. Even with the perceived-to-be-expensive replacement kit, the total cost for operating over six campaigns is, say, $663,000.
Conclusion
[Martyn Ryder] 45:23 – We believe that a well-designed flexible film containment system delivers equivalent, if not better, containment performance than a hard-shell isolator.
Because we back up our technology with this full life cycle safety innovation, we manage the complete risk profile—from assessing the risk and hazard at the outset with our Process Score, to leveraging our years of expertise during Quality by Design.
Hard-shell isolators need maintenance. Single-use flexible film systems are new every time. You take it from the three-layer pack, put it on the frame, do the pressure decay test, run it, collapse it, and incinerate it.
We believe there is a massive benefit in single-use technology.
So, my friends, in conclusion, at ILC Dover, we believe our full life cycle safety approach sets a new bar in the field of containment technology.
From the very beginning, when we talk to you about your application, to going through the factory acceptance test, to partnering with you on SOP development, and then providing all our very neat disposal systems, we think we’re adding layer upon layer of operator safety in your facility.
I hope you’ve enjoyed this webinar, and may I just thank you for your attention.
