In this webinar, Scott Patterson, Vice President of Pharma and Biopharma Technical Support at ILC Dover, provides an in-depth exploration of the DoverPac® flexible containment system and its applications in pharmaceutical manufacturing. Scott highlights how the single-use DoverPac® enhances safety, reduces cross-contamination risks, and simplifies processes like chemical synthesis and oral solid dosage production. He also contrasts the benefits of flexible containment with traditional stainless-steel systems, emphasizing cost savings, ease of implementation, and environmental advantages.
Scott discusses the technical attributes of the ArmorFlex® film, including its solvent resistance, electrostatic dissipation, and durability during automated operations. He shares data from SMEPAC studies to demonstrate the system’s reliable containment performance and addresses key audience questions about sustainability, disposal, and automation. This webinar showcases ILC Dover’s commitment to advancing containment solutions and preparing facilities for future challenges.
Transcript
Introduction
[Paulo] 0:04 – Good morning or good afternoon, depending on where you are joining us. I would like to thank and welcome you for participating in this webinar organized by ILC Dover. ILC Dover is a worldwide leader in the design and manufacture of engineered flexible protective solutions for critical applications, from aerospace to pharmaceutical industries. My name is Paulo, and I have the honor to host this session about high-containment single-use FIBCs for pharmaceutical operations.
The speaker today will be Scott Patterson, Vice President of Pharma and Biopharma Technical Support. Scott has been with ILC Dover for over 14 years, leading innovative and advanced solutions for the pharma and biopharma industries in single-use containment technology.
Today, we will talk about the DoverPac®, a reliable high-containment single-use FIBC, which was invented more than 20 years ago. At that time, ILC Dover’s focus was developing and manufacturing spacesuits for NASA, which has been their core business since 1947. Basically, a spacesuit is a containment system for protecting astronauts in a very aggressive environment. Based on this experience, going back to 1997, the pharmaceutical industry really challenged ILC Dover to go beyond boundaries, and they developed the single-use containment system to provide exposure levels of less than one microgram per cubic meter.
The product contact materials meet all international standards, and they are designed to be robust and suitable for contact with a wide range of solvents used in the industry.
But before starting, I would like to welcome you all and inform you that if you have any questions, please type them into the question box and click submit. At the end of the presentation, Scott and I will try to address all the questions.
So now, welcome Scott, and let’s start with the DoverPac®.
[Scott Patterson] 2:03 – Thank you, Paulo, and welcome, everyone. Welcome to our virtual tradeshow experience as a webinar. We appreciate your attendance this morning.
Our overview of the program today will focus on the DoverPac® high-containment system, which is our FIBC product, a flexible intermediate bulk container. We’ll give you a little bit of background about the quality by design that has been built into the DoverPac® over the years. We’ll then specifically look at the applications where the DoverPac® is used in API processing as well as HPAPI processing through chemical synthesis and oral solid dosage.
With that, we’re always obligated to show the performance of the DoverPac® following the industry-standard ISPE SMEPAC protocol. We have some case studies and data to share, along with a comparison of the DoverPac® to stainless steel equipment. Specifically, we’ll look at the cost and performance of using a single-use product over a rigid stainless-steel product.
As Paulo mentioned, at the end, we’d like to have your questions and any discussion points. So, as we go, if you have a question, type it in the box, and we’ll prepare to answer those at the end of the webinar.
DoverPac® High Containment
[Scott Patterson] 3:25 – So, again, the DoverPac® is a high-containment FIBC. Paulo mentioned that the original goal in 1997 was to create a high-containment system with containment levels of less than one microgram per cubic meter. Currently, the data shows us that the typical DoverPac® in a pharmaceutical process will achieve less than half a microgram per cubic meter, and the data that we’ll review shows even better performance than that.
As you can see, in this process, we’re showing the DoverPac® on the left being filled from a dryer discharge and, on the right, going back to a reactor for additional chemistry. The beauty of the DoverPac® is that on the left, it’s filled and then simply lifted and transferred to the next area—no inverting, no costly lifts, no split butterfly valves, or other valves to aid in the containment. It is connected and discharged. It’s quite an easy system to use.
Other Benefits
[Scott Patterson] 4:31 – Besides the containment aspect, which is really the critical part, other benefits of FIBC technology include standard sizes, whether it’s for a bulk-handling process or low-volume HPAPI. The DoverPac® system follows the critical design standards of containing at the source with no open nozzle charging.
Instead of relying on isolation technology or local exhaust ventilation technology, we follow the idea of containing at the source, so that all the powder stays within the process. This minimizes exposure to the operator and the environment.
One of the key advantages of using flexible IBC technology is the flexible wall, which is essential for handling poor-flowing powders. This is often an overlooked but critical aspect of using a DoverPac®. Even very poor-flowing powders—whether they are sticky powders or have very light densities and don’t flow well—can be effectively discharged. The operator, or some automation, can manipulate the sidewall to ensure all the powder is discharged. There’s confirmation of this either manually or, again, through automation to ensure 100% discharge.
This process is quite difficult with standard stainless steel IBCs. Often, containment has to be broken to check if the bin has been fully discharged.
Other aspects of the DoverPac® include its static-dissipative ArmorFlex® film, which is very critical. There’s also sampling capability, which we’ll take a closer look at. Additionally, the DoverPac® can dock to a system without needing to be in a completely vertical position.
In many cases, such as reactor charging, there may be a drive for the reactor agitator in the way. Using FIBC technology, you can dock at a slight offset, something stainless steel IBCs cannot do. Finally, there are certain certifications that the DoverPac® carries, which are critical for many regions and processes.
Quality by Design
[Scott Patterson] 6:42 – From a quality by design standpoint, the DoverPac® was developed specifically for pharmaceutical powders. This isn’t a derivative of some other product that was brought into this space, but it was developed specifically for high containment of handling pharmaceutical powders, with the key part of it starting with the ArmorFlex® film and the quality of that ArmorFlex® film, which we’ll show through some details in another slide.
Standard sizes, again, were developed for small batch sizes to bulk processes up to 2,000-liter bulk processes. The static-dissipative film and solvent resistance of the film, the ArmorFlex®, again, were built for powder handling. So it’s not a derivative product that’s brought into the space with shortcomings; it’s really built specifically for this application.
The shape of the FIBC was well thought out at the beginning. The repose geometry—or, if you’re familiar with the development of hopper designs to allow for good flow—we know that the bottom of hoppers needs to be angled at a particular angle, the repose angle, if you will, to get the best flow. The DoverPac® system also was developed that way to facilitate the flow, again ensuring that we can get 100% discharge and a nice mass flow transfer from the DoverPac® into the next process.
Finally, a lot of effort was put into the design for safety factors for lifting and loading. You’ll see through the manufacturing process that the integrity of the system is taken care of, but when it’s being used in a pharmaceutical plant, high levels of safety factors have been applied to ensure that there’s no failure in use.
Operator Use
[Scott Patterson] 8:28 – And then also, part of the quality by design was to understand the operator use. The DoverPac® does require manual operation from operators, but the idea was to create a system where, when filling the DoverPac® and discharging the DoverPac®, the operations were exactly the same. So, the operations would be repeated, and this allows for great operator efficiency and enhanced use.
Again, the DoverPac® system, as we can see, is a closed charging system. Very key: contain at the source. Again, a design philosophy. So, when we say that, the picture on the left shows a DoverPac® that has already been discharged into a vessel, and the shower cap, if you will, remains in place until the picture on the right, where the operator will dock a new DoverPac® to discharge the next batch and then remove that shower cap through the bag-out sleeve.
In this process, the nozzle or the charge point is never left open and is always protected. This is key for containment, but also key for cross-contamination protection. This is really of great value as we look at more and more multi-use facilities, and cross-contamination becomes an extreme key.
Sampling
[Scott Patterson] 9:49 – Also, it was understood that many of the processes that DoverPac® would be used in, and are used in today, require sampling. An example of that would be a micronized operation where typical micro nozzles, perhaps at the beginning of the run, end of the run, and possibly even on a regular interval, every 15 minutes or every 30 minutes.
So, the DoverPac® was designed with an integral sampling sleeve, that a sample could be taken at any time, and this would be a contained sample in the sleeve, as shown on the right. We’ll see later in crimping that there’s a seal and separation to allow that sample to be taken away and analyzed at a lab without any exposure at all.
So, this is part of the whole design process, where it was built for a pharmaceutical application, knowing that sampling is always a key to ensure the process is in line.
Welding
And then we have the manufacturing side of it at ILC Dover and our factories in the United States and in Ireland. It was understood that, in general, FIBC big bag technology that existed before 1997 had welding processes prone to a high level of failures, and that could not be allowed when dealing with pharmaceutical APIs. So, we invented the lapsing welding technique, which changed the weld areas from the weakest point of the assembly to the strongest point of the assembly. The lapsing welding is overlapping one inch of the material and welding it together. So, in essence, at the weld seam, we have double the thickness and most of the strength.
We also have automated the whole process, from pattern cutting to piece-part matching. The welding equipment is PLC-controlled for time and temperature. So the entire process is put together to assure that the product and the integrity of the product are the same time after time after time. The final test, as shown in the picture on the left, is an inflation dwell test to ensure the final assembly integrity, that the welds are strong, and there are no defects in the film.
Documentation
[Scott Patterson] 12:07 – Documentation in the pharmaceutical industry is always key, and ILC Dover, with a history in the space industry, was very strong in documentation. We followed through with that for documentation in pharmaceutical applications.
So, here you can see an example on the right: our certification of conformance. This comes with each product to assure the product was built to the specifications, and the regulatory requirements that it followed are also outlined in the certification of conformance.
Through the documentation at ILC Dover, we have a completely traceable quality system to allow for any review that needs to be done or any questions that are brought forward. In fact, this quality system has been audited by dozens of major pharmaceutical companies, and we’ve never had any major findings or failed audits.
So, all of this is part of the documentation—from the certification of conformance to the packaging of the products in sealed bags with labels containing traceable data, to drawings for all the products, manuals, and document packages showing how the assembly is done. The ArmorFlex® material includes a complete data book on all specifications, including physical specifications and regulatory specifications.
So, very heavy on documentation to support the needs of the pharmaceutical industry.
Physical Properties
[Scott Patterson] 13:36 – And lastly, back to the ArmorFlex®—a full range of regulatory standards that are met from a global standpoint and also the needed physical properties.
When we look at the physical properties, we’re really looking at something built for purpose: powder handling in high containment for pharmaceutical processing. This includes some critical aspects, such as being able to inert the DoverPac® with nitrogen or to create a low relative humidity level, which is very, very important in some applications.
So again, the ArmorFlex® was designed with only the pharmaceutical market in mind.
Chemical Synthesis
[Scott Patterson] 14:14 – So, now we go to the actual applications of the use of the DoverPac®, and we start with the chemical synthesis process with the DoverPac®.
Again, typical chemical synthesis of an API has the reaction stage, an isolation stage, a drying stage, and then it’s often repeated. As we can see here in the demonstration with pictures, early in the stage with the reactors, a DoverPac® can be used to charge the reactor while keeping the nozzle closed, which is key.
We know many companies have policies that they do not want open manway charging at the reactor. We also know from experience with FDA inspectors that they have a preference for a closed nozzle and no open manway charging. So even starting at the reactor with non-potent materials as the chemical synthesis process starts, the DoverPac® is extremely valuable.
From there, it moves into isolation, where a centrifuge would be used—a peeler centrifuge-type of system—discharged into the DoverPac®, which can then be taken to the dryer, discharged into the dryer, and the dryer discharged out into a DoverPac®. Again, the idea is that, in any of these steps, we might go back to the reactor for more chemistry.
In fact, it’s very typical in chemical synthesis to have multiple steps of going back from the centrifuge or the dryer to the reactor for additional chemistry. The DoverPac® was designed with that in mind, to be able to hold materials, even wet cake from the centrifuge, while waiting for the next process.
So, chemical synthesis is very straightforward. What we were trying to accomplish is to have a direct transfer between the centrifuge, dryer, and reactor, being able to perform the chemistry steps while always maintaining a closed manway. It also allows for holding materials, whether they are dry powders, potent powders, non-potent powders, or wet cake that might come from a centrifuge.
Basket Centrifuge
[Scott Patterson] 16:26 – Not everyone has the same type of equipment. In the chemical synthesis process, we often see basket centrifuges. On the left, if you have one of these basket centrifuges, it’s really not possible to use FIBC technology.
However, it’s not over in terms of containment and isolation. As you can see on the right, two centrifuges of the basket centrifuge type are completely contained using flexible isolators. Flexible isolator systems will be covered in a future virtual trade show that we have.
But again, just having a basket centrifuge does not eliminate the idea of achieving high containment—it’s just a different technology that we would apply, separate from the DoverPac® technology.
Tray Dryer
[Scott Patterson] 17:14 – The tray dryer challenge, for the most part, is that many processors see the containment of a tray dryer as a very complicated and difficult process. There are some organic challenges, particularly as we get to larger tray dryer systems.
The reality is that many chemical synthesis processes go into the tray dryer in a final stage or an intermediate stage, so there needs to be a way for containment. Again, we apply the flexible isolator technology to that, which we’ll cover in detail in a future trade show.
But tray dryers, and all types of dryers, are very much possible for high containment. It’s just about deciding when to apply DoverPac® technology or when to apply flexible isolator technology.
Oral Solid Dosage
[Scott Patterson] 18:08 – Moving on to after chemical synthesis, we move into the oral solid dosage processing. Here, we’re really looking to contain the transfers between each process and the full range of processes, including wet granulation, dry granulation, direct compression, hot melt extrusion, and some processes that aren’t shown in this diagram, such as encapsulation.
All of these can be contained in the transfers from step to step to step with the DoverPac® technology. We’ll show some examples of that for some of these steps.
CoMill
[Scott Patterson] 18:42 – So here we have the example of a CoMill process. In this case, this was a demonstration to prove a customer application of taking a material in a DoverPac® and feeding it into a CoMill. In this case, a U20 CoMill from Quadro. Then, after milling, it’s discharged back into another DoverPac®.
The DoverPac®s were very unique in being able to perform this process without any modification to the CoMill. CoMills typically have a tri-clamp connection on the inlet and a tri-clamp connection on the discharge, which facilitates the hardware connection for the DoverPac® docking extremely well.
So, here, without modification to the core CoMill, we were able to apply the high-containment DoverPac® system for this milling step in oral solid dosage. Later in the program, we’ll show this picture again and include the SMEPAC study that was done, along with data for the end result of what the containment was during this milling step.
Dispensing
[Scott Patterson] 19:54 – Another oral solid dosage process that we’ve looked at and completed is shown on the left. It is a weigh-in, dispense-type system where material was received in drums and needed to be subdivided or dispensed to a specific weight into a DoverPac® so that it could be taken to the next process to be discharged.
Here, combining flexible isolator technology with the DoverPac® allowed for the subdividing of drums into a DoverPac® for a contained transfer in the oral solid dosage process. This is very key in handling this type of process.
In many cases, this process involves handling a drug substance. So now, we really have a high-containment challenge in dealing with 100% of the active drug versus downstream processes where excipients have already been added. The containment challenge when dealing with the drug substance or the API is a little bit different, but here it is always a critical application, ensuring that the transfer to the DoverPac® is high containment.
The picture on the right shows a slightly different application where this customer had a policy of no open reactor charging, which we touched on before. Here, we are transferring multiple drums of material into a very large DoverPac®—a 700-liter DoverPac®.
The idea was, instead of taking six drums to a vessel to discharge all six drums, which is very time-consuming and involves having an open vessel, why not transfer those into one DoverPac® and make a single discharge into that vessel? This approach is very efficient when it comes to using a DoverPac® for dispensing.
Containment Assessment
[Scott Patterson] 21:48 – So our containment assessment, number one, is again the project here where ILC Dover worked with a third-party industrial hygiene company.
The DoverPac® system was used. Again, when we talk about a system, it uses our docking hardware, the Dover inlet canister, and special clamps that are used. There’s a technique called the clean zone, which further assists in ensuring the best possible containment.
Then there’s the seal-and-separate method, crimp-lock, which we’ll touch on as we go through this. It’s very key to use the proper seal-and-separate method for containment at the point of separation, but also for further risk assessment.
This is a 700-liter DoverPac®, and the surrogate was lactose.
Data Table
[Scott Patterson] 22:41 – So here’s the data—one of the data tables. Now, this was from discharging the DoverPac®, so charging into a vessel.
As you can see, in the typical SMEPAC protocol, there are three iterations: run one, run two, and run three. In this case, the data table summarized the geometric mean in micrograms per cubic meter.
The thing to note closely here is that, on run number two, in the second personal breathing zone, we had a reading of 0.23 micrograms. This is the highest reading we’ll see in this SMEPAC test.
Then we’ll take that data and take a look at what that means for the actual containment performance of the DoverPac® system.
Discharge
[Scott Patterson] 23:28 – Also, in this test, we looked at discharging the vessel. So, after the first test where we filled a vessel, we then discharged that vessel into a 700-liter DoverPac®.
Again, the data table follows the same concept of three iterations of the run. The data is quite good here. Anytime we see the “less than” number, that’s referring to the level of detection—we were below the level of detection when the air sampling was done.
So, our readings were extremely good, and seeing the arithmetic mean or the geometric mean, the numbers are extremely low for the level of containment.
Seal & Separate
[Scott Patterson] 24:13 – And lastly, we looked at the seal-and-separate process. Here, we conducted air sampling around the seal-and-separate process.
Traditionally, before ILC Dover brought the DoverPac® system forward, the standard was a twist-tie, tape, and cut method for separating an FIBC or a big bag product. That process is very operator-sensitive, as the twist and tie can loosen over time and so forth.
It’s very key, as you can see here, that we went through three iterations of the seal-and-separate process. The geometric mean, again, is very nice—very good, very low numbers.
This is very key to examine because the seal-and-separate process can be a worst-case scenario in many cases for operator exposure when a seal-and-separate system is not as secure as the crimp-lock process. The key to this is that if there is any residual gas left in an FIBC, it can cause aerosolization of powder through a poor seal—let’s say, a seal that wasn’t as tight as the crimp-lock system allows for.
That aerosolization can cause operator exposure. So, it’s very key to look at the entire process through the system.
In this study, we looked at filling a vessel, discharging a vessel, and then we examined the seal-and-separate process to ensure we captured any risk of operator exposure along the way.
Reverse Analysis
[Scott Patterson] 25:57 – To reverse analyze this from a mathematical standpoint, we looked at the data, and as I had noted, our one reading was 0.23 micrograms per cubic meter. That was our highest reading, so we would take that and say, “Okay, we need to do some analysis around that.” Taking all of the data from the test, we would do a geometric mean statistical analysis, which would give us a 95% confidence factor. That statistical analysis would show us 0.13 micrograms per cubic meter.
Different companies—pharmaceutical companies—have different rules. There are some industry rules that are followed in some cases. One of the industry standards is that pharma companies will use a 50% rule. Using the 50% rule, we would look at the 0.13 micrograms of the geometric mean and double that.
So, we’re reversing the application. Typically, the OEL is set, and then you go down from that, but we’re doing this in reverse based on the data. This would indicate that our containment performance target for the DoverPac® would be 0.26 micrograms.
In a stricter application of that, applying the statistical analysis of EN 689 and the 2018 version—the new version—which speaks to the containment performance target being 10% of the OEL, this would take the containment performance target to 1.3 micrograms. Our 0.13 is 10% of that. Applying that strict rule, we get a slightly different view of what the containment performance target is.
Essentially, different companies have different rules for determining what the OEL is and what the target containment should be. Having an understanding of how the rule will be applied and mathematically how to analyze the containment is very critical.
Again, actual containment performance is based on the characteristics of the powder, the process, the volume being transferred, and the mass transfer of the powder. There can be some variance. Also, as we noted, milling is always very difficult from a containment standpoint.
Here’s that CoMill again. We took this system and conducted the same type of SMEPAC study on it, using a third-party industrial hygiene company. Instead of using a 700-liter DoverPac®, we used the 110-liter DoverPac®. Each time, it was filled with 25 kilograms of the surrogate, which was lactose again.
The data here is very similar to what we had on the 700-liter system. We can see that in one of the breathing zones, we had one reading at 0.35 micrograms per cubic meter. When we look at the geometric mean analysis, we’re getting really good numbers again, well under the 0.5 micrograms per cubic meter that we started the presentation with.
What this test data shows is consistent results. ILC Dover has performed dozens and dozens of SMEPAC studies, and one of the things we’re confident in is that the data is always very, very consistent. There are outliers in some of the tests that have been done, and we look to mitigate those through operator experience, training, and continued evaluation of the system to identify any gaps where improvements can be made.
As noted, milling systems are a containment challenge because milling tends to add a lot of energy and fluidization of the powder, which can make containment more challenging. CoMills present a smaller challenge; hammer mills can present a much higher challenge.
Again, understanding the process, understanding the volume of powder, and understanding the characteristics of the powder are very key when establishing what the containment performance of these systems can be.
Lifecycle Analysis
[Scott Patterson] 30:24 – So, moving on a bit, we wanted to compare the DoverPac®, or in general single-use products, to rigid stainless-steel products. We’re going to look at a brief analysis as we go forward on the DoverPac® versus a stainless-steel IBC product.
Before we do that, we thought we’d borrow some information from the biopharma industry, where there is a massive reliance on single-use products. This reliance is as much for the process as it is for containment. The biopharmaceutical industry has a tremendous amount of information that’s important when we look at single-use products and compare them to stainless steel products.
There has been a lot of lifecycle analysis done to show the significant savings. Here, we’re referencing a table from a Thermo Fisher paper that highlights significant utility savings. We’re looking at both water consumption and energy consumption, which are really tied to the cleaning processes and so forth.
When we look at a full lifecycle analysis, it’s very interesting to see the level of savings that can be achieved by using single-use products. Cleaning, cleaning validation, and hold times all slow the production cadence in a manufacturing operation. All of that is required when you’re using a stainless-steel product. Single-use products eliminate much of that and minimize the risk of cross-contamination from retention.
The biopharma industry looks at it from a different aspect, but in pharmaceutical manufacturing, we focus on retention as described in the ISPE Risk-MaPP document. Retention is the number one reason for cross-contamination—residual material left on a surface after cleaning gets into the next batch, potentially causing cross-contamination.
When we compare the DoverPac® to a stainless-steel IBC, we remove 100% of the risk of retention because the DoverPac® is a completely disposable, single-use product.
[Scott Patterson] 32:42 –
Drums. We also don’t want to forget about drums—they are everywhere. Drums require significant manual labor, and in most applications where they are used, there’s an overall lack of containment. Containment often relies on isolation or ventilation systems, such as localized exhaust ventilation systems.
As referenced earlier, any time we can transition from using drums to containing the material in a DoverPac®, process efficiency is improved.
We see different processes involving drums, as shown here. On the left is a sampling operation in a drum, where the DoverPac® offers a sampling sleeve. The middle picture shows an inverter being used to invert into a bin with drums—a very messy process where a lot of powder often escapes into the environment.
Lastly, in the right picture, there’s gang filling of drums. There’s not much containment here, and the operators are relying on PPE as their primary protection.
As we always note, in regulatory writing such as OSHA in the United States, PPE should not be used as a primary containment method. The hierarchy of controls states that engineering controls are preferred whenever possible. DoverPac® complies with the concept of an engineering control, which is the preferred method.
Cleaning
[Scott Patterson] 34:28 – So again, back to that comparison of IBCs versus FIBCs, and really we just wanted to run through what that means in terms of operation costs and so forth, comparing cleaning versus disposal.
The typical process for a stainless-steel IBC starts with an unknown amount of powder inside the IBC because we can’t see it, or we have to break containment to see it. Since we don’t want to break containment, there’s always some unknown amount of retained powder, which is active.
The first rinse is always captured for disposal, and when we say “captured for disposal,” that typically means it’s sent to incineration. Again, it’s not very efficient to burn water, if you will. Then we move on to a wash with detergent and another rinse. This rinse is either treated or sent for disposal, and again, disposal typically means incineration.
Next, there’s a drying period, which adds additional energy costs for the desiccated drying of the inside of the IBC. Typically, if we’re working with high-containment systems, there has to be a containment valve of some sort, like a split butterfly valve. These valves always have to be removed for complete cleaning of the seals and maintenance of the seals.
There are also a lot of hidden costs with IBCs in this cleaning process, including the space needed for a bin washer or CIP (clean-in-place) stations. This is dedicated floor space, and in a pharmaceutical facility, floor space is at a premium. Eliminating the need for cleaning a large bin washer or CIP system frees up significant floor space.
Additionally, there’s the floor space needed for storage of the IBCs when they’re not in use. So, a lot goes into the idea of cleaning IBCs. It requires significant attention in terms of labor, materials, and floor space for storage.
On the FIBC side, the process is much more simplistic. After the IBC is discharged, there’s typically a process to evacuate gas from the inside. There might be some retained gas, and we don’t want to create a balloon, if you will, so the gas is evacuated through a simple HEPA filter.
Then, the seal-and-separate process is done using the crimp-lock system, and the FIBC usually goes into a drum for disposal. DoverPac®s, typically used in pharmaceutical processes, are incinerated. The polyethylene-based film, along with the polypropylene-based outer restraint for support, has a minimal carbon footprint.
In an actual analysis—mostly again coming from single-use technology in the biopharma market—the overall carbon footprint is significantly less when using single-use products versus the carbon footprint associated with developing, manufacturing, transporting, and cleaning stainless steel products.
A lot of evaluation has gone on in this area, and this needs to carry over to the pharmaceutical industry to demonstrate that the operational costs of using single-use technology are very desirable. When analyzed, it clearly proves the value of single-use technology.
Capital Cost
[Scott Patterson] 37:52 – So here, we’ll look at the capital cost in a typical IBC versus an FIBC. We just put together a scenario—you can see the notes at the bottom.
Again, we assume product contact is 316 stainless-steel for the IBC technology. We’re looking at a container performance target of less than 1 microgram per cubic meter. We’re saying that because there needs to be a containment valve when dealing with less than 1 microgram. Perhaps if we’re dealing with something above 10 micrograms, a standard butterfly valve could be used, which could save money, but it doesn’t really provide containment.
In this calculation for six batches, we required five IBCs or five FIBCs per batch. Those are the numbers we used to come up with this brief analysis.
You see the stainless-steel IBC on the top. First, we need to purchase the IBCs, the high-containment split butterfly valves, and determine how many are needed. That’s a really good question because, in this analysis, we said six batches require five IBCs or FIBCs. You’re always going to have IBCs in hold time for washing or other purposes.
So, if the batch size needs five, oftentimes the purchase needs to be closer to ten or more so there are enough bins to handle the process, cleaning, hold time, and so forth.
Then, we have to purchase a precision post lift. Using an IBC with a split butterfly valve requires extremely precise docking. Here, we estimated $125,000 for such a post lift. Oftentimes, they’re even more sophisticated, which drives the cost up.
Next, there’s the cost of a washing machine, which could be a bin washer or CIP system. All of these costs come out to, in this analysis, about $650,000 to be ready to run this process of six batches requiring five units.
On the DoverPac® side, shown in the bottom analysis, we only need to purchase the high-containment docking system—typically one for filling and one for discharging. This results in a capex of $40,000 for two high-containment docking systems, which are ring systems.
Then, we only need a simple hoist to lift the DoverPac®. That’s one of the key benefits of the DoverPac®—it can be lifted with a simple hoist system. There’s no need for a sophisticated post lift system. Here, we estimated closer to $50,000 to buy a stainless steel-grade simple hoist system.
Lastly, there’s the cost of the high-containment DoverPac®s, which are roughly $600 per unit. These can be purchased as needed, and the beautiful thing is they can sit in storage. With a five-year shelf life, they don’t take up much space and are available for purchase as required.
We looked at this analysis and arrived at a capex cost of $108,000—a dramatic savings on capital costs. As we refer to when considering the complete use of an IBC versus an FIBC, the operational expense cost of the IBC never catches up to the capex cost savings of the FIBC. In the operational expense, there continues to be a benefit in using single-use technology.
Project Time Complexity
[Scott Patterson] 41:33 – And then we look at project time and complexity.
On the right, we’ve got the IBC project. In an IBC project, the complexity includes selecting how many IBCs are needed, determining the size, selecting the containment valve, and deciding on the precision lift. We also have to figure out how the cleaning process will work.
There’s a need to manage the floor space because there’s going to be a lot of dedicated floor space required for post lifts, bin storage, and similar equipment. Additionally, we need to manage controls, including electrical classifications. When using this type of equipment with a post lift and other components, the electrical classification of the room becomes very critical.
In contrast, with an FIBC project, we don’t need to consider electrical classification.
For an IBC project, we also need to manage the FAT and SAT, operator training, validation documents, and more. Roughly, a typical project using stainless steel IBCs can take up to 30 weeks.
For an FIBC project, the process is much simpler. We select the FIBC size, and units can be purchased as needed. They’re available for purchase as required, and since they’re a single-use product, they’re not a hard asset that needs to be acquired upfront.
There’s no containment valve required because the DoverPac® system contains itself. A simple hoist is used, so there’s no floor space required for complex lifting equipment. The FAT and SAT typically take one day because the system is so simplistic, operator training takes one day, and the validation documentation is minimal. This brings the total project time to about 10 weeks for an FIBC project from start to finish.
There are also other considerations. Recognizing the changes in the pharmaceutical world from 10 or even 20 years ago, master site planning has largely disappeared.
Previously, pharmaceutical sites had extended master plans that detailed which products the site would manufacture and the sizes of batch production. Today, planning is more focused on the next three to five years, based on projections. Sales projections can vary widely—some drugs may have very high sales, while others may have lower sales.
These projections impact equipment use and lead to tech transfers. If a drug product has strong market value, additional manufacturing through CMOs or international transfers may be needed.
With an FIBC system like the DoverPac®, tech transfers are very easy to manage. In contrast, with an IBC system, we’re dealing with fixed assets that require additional projects, management, and capex expenses.
So, when looking at project time and complexity over the long term, FIBC projects are very quick to implement and can be easily transferred globally as needed.
Next Webinar
[Scott Patterson] 44:40 – So, that was the content of our webinar today. I thank you very much for attending.
Again, as we said, we’ll have time for your questions. But before we go, watch for our next webinar planned for May 6th, where we will discuss flexible isolator technology throughout the pharmaceutical value chain.
There will be some applications in chemical synthesis and a lot of applications in oral solid dosage.
So, with that, I’ll throw it back to our host, Paulo, and Paulo will address some of the questions that have come in.
[Paulo] 45:23 – Yes, thanks, Scott, for speaking about this technology and how flexible containment and DoverPac® can help with the manufacturing process.
Basically—and I’m just trying to catch a few points—the DoverPac® can accelerate the transfer of powders into the process. If we look at the drum charge into a reactor, it’s quite different. With an IBC fully charged, it will accelerate our production.
It will also protect, somehow, our patients because we are reducing the risk of cross-contamination, and we’re protecting ourselves, which basically means bringing ourselves and our colleagues home safely at the end of the day.
And last but not least, it prepares facilities—especially shared facilities—for future challenges. It makes it easier to accept new products, provides effective flexibility, and reduces downtime for non-productive operations like cleaning or validation.
Q&A
[Paulo] 46:30 – So, the first question, I will try to combine two questions into one, as they are really complementary. The first part asks about documentation: during the introduction and presentation, you talked about the material being compatible with a range of solvents and meeting all international standards—where can we get this information?
The second part asks how you resolve the electrostatic problem with an API that can create risk and cause issues with uniformity of contact. Have you faced such a situation?
[Scott Patterson] 47:20 – Yes, I think both parts of the question reflect experiences we’ve had with several processors.
In terms of solvent resistance, the ArmorFlex® film was developed with that in mind. We selected polyethylene materials that are highly resistant to the typical solvents used in pharmaceutical processing. This information is contained within the data book, which is available to our customers.
In the data book, we’ve conducted testing for more than two dozen typical solvents used in pharmaceutical processing. The testing was done using a standard ASTM test, and we quantified the results by submerging the ArmorFlex® material in a 100% solution for 48 hours.
The data is very compelling. Most solvents had less than a 10% impact on the physical characteristics of the ArmorFlex® material. All of this is summarized in two detailed data tables in the ArmorFlex® data book, which we encourage our customers to reference to understand the methodology and ensure the solvent issue is addressed.
For the second part, about electrostatic charge and surface adhesion: if I understand the question correctly, it’s about the surface adhesion of the powder inside the DoverPac®. During discharge, this surface adhesion could retain residual material inside the DoverPac®.
This is where the flexible wall technology is advantageous. At the end of a discharge, we always suggest that the operator physically takes the wall of the DoverPac® and shakes it—just like shaking a blanket. We’ve found that this generally releases almost all surface adhesion caused by an electrostatic charge.
Additionally, the DoverPac® has a static dissipative effect by design. It naturally resists building up a static charge and holding particles. However, there may still be some surface adhesion, which shaking can release effectively.
[Paulo] 50:04 – Thank you, Scott. Let’s move to the next question about robustness and automation.
Someone is asking what kind of automation we need to ensure that the DoverPac® is fully discharged when working with poor-flowing powders. What happens if it isn’t fully discharged? How can we ensure that the DoverPac® isn’t damaged when using automation for discharging?
[Scott Patterson] 50:54 – The automation for charging is typically straightforward. Even with poor-flowing powder, the DoverPac® can be placed on a scale. Using a known weight, the DoverPac® can be filled, and the operator can monitor this as filling progresses.
For example, if the target weight is 200 kilograms, as the weight approaches 150 or 175 kilograms, we suggest that the flow rate of the powder into the DoverPac® is slightly restricted. This ensures we don’t overfill it. Overfilling is key to avoid, and most customers control this by placing the DoverPac® on a scale or using a dosing system. The dosing system controls the flow and automatically shuts off when the target weight is reached.
For discharging, ensuring 100% discharge and maintaining the integrity of the DoverPac® assembly can involve using automation, such as a bag massager. Bag massagers are commonly used in other industries, like food and plastics. However, their systems are often less robust than the DoverPac®.
The DoverPac® has been designed to be highly durable. From the outer restraint to the strength of the ArmorFlex® film, it’s built to withstand automation for assisting powder flow without compromising system integrity. This reflects the quality-by-design approach, which includes the ArmorFlex® film, lap-seam welding, and other features ensuring safety and reliability during automated discharging.
[Paulo] 53:12 – Now, let’s move to a question about sustainability. Taking into consideration the global challenge to reduce or eliminate the use of plastics, how does single-use technology compare to stainless steel IBCs or rigid isolators? And what is the disposal policy for the DoverPac®?
[Scott Patterson] 53:47 – It’s easier to answer the second question first and then return to the first.
The typical disposal method for a DoverPac® in the pharmaceutical industry is incineration. Most of our customers take the used DoverPac®, place it into an empty drum, and send it to their chosen incineration facility.
Some customers may opt for landfill disposal, treating it as hazardous material because of the potent products involved. However, incineration remains the primary method. The materials used in the DoverPac® are polyethylene-based, resulting in a generally low carbon footprint. Unlike materials such as polyvinyl chloride (PVC), the DoverPac® does not release chloride gas during incineration, making it an optimal disposal method.
For the first part of the question, analyzing sustainability requires a comprehensive study. Borrowing from the biopharma industry, stainless steel systems often require significant CIP (clean-in-place) processes. These involve large amounts of water and energy—first for converting water to WFI (water for injection) and then for the cleaning process itself.
When considering the full lifecycle, from manufacturing and cleaning to incineration, studies show that single-use products often have a smaller carbon footprint. While single-use plastics might initially seem less environmentally friendly, the energy and resource demands of cleaning stainless steel systems make single-use technology more desirable from both cost and environmental standpoints.
Conclusion
[Paulo] 57:05 – Thank you. Due to time constraints, we won’t be able to answer all of your questions today, but we will provide answers via email soon.
As you understand, containment is a very complex matter, and success relies on accurate data and complete risk assessments. For example, when working with highly potent APIs, containment must be scientific, reliable, and thorough.
Using reliable technology alongside strong training programs makes all the difference, creating confidence and trust from operators to senior managers, shareholders, and customers.
Thank you for joining this webinar. It was a pleasure for Scott and me to share this presentation with you. As Scott mentioned, we hope to see you again on May 6th, where we’ll discuss flexible isolator technology.
If you have further questions, comments, or experiences to share about our technology, please don’t hesitate to contact us through your Regional Sales Manager or our website at www.ilcdover.com.
Please stay safe, and thank you again. Have a great day. Goodbye!
