MedTech Expert Explains Low Temperature Hydrogen Peroxide Sterilisation | Pressure Tested

Hey, I’m Pierre Benoit. I’m expert in medical device. I’ve been working in this industry for 10 years, and today I’m going to be pressure tested on VH2O2 sterilisation of medical device.

What is a sterilisation process?

So in general, sterilisation refers to achieving a sterility assurance level, which is commonly referred as a 10 to the 6, 10 minus to the 6 inactivation of microorganism. There are different methods to achieve sterility. There are physical processes, chemical processes. My expertise is more in a VH2O2 sterilisation, which is a chemical sterilisation method.

What is low temp sterilisation?

So low temp sterilisation or low temperature sterilisation refers to methods that are not using very high heat. So it means, in the late ’90s or ’80s, there has been an emergence of medical device appearing on the market using new materials or new technologies, typically electronics or heat and moist sensitive device. And these devices typically require to be sterilised at a lower temperature than the steam sterilisation, which is one of the most common sterilisation method. So steam sterilisation is a physical sterilisation method where we apply a saturated steam combined with pressure and high temperature. And, in, let’s say, the past years, many technologies, many materials have emerged that cannot sustain such high temperature sterilisation. So this is why we usually go for low temperature sterilisation such as ethylene oxide. VH2O2 formaldehyde were also used in the past, but now one of the most common is VH2O2 sterilisation.

Is sterilisation in healthcare different than in industry?

So typically in healthcare facilities that are hospitals, clinics, even veterinary or dental facilities, we reprocess items. So it means that we use, in operating theater or during surgeries, different equipment and tools that are meant to be reprocessed. It means cleaned, disinfected, and sterilised and reused. Usually, when we are addressing the industrial segment, we are discussing single-use device sterilisation, which means sterilisation is a terminal sterilisation of a product that will be sold sterile, and that is usually not meant to be re-sterilised. So typically, we are talking about implants. It could be, or the single-use medical device, or some pharmaceutical packaging could be as well in the scope. This would be the main difference, so the type of product and the way to use them. So in healthcare, everything is about reprocessing, so gaining a lot of high turnover to return these sterile surgical equipment to the operating theatre as fast as possible and to deliver the best patient care by giving the surgeon tools that are functional, safe, and without residuals. And in industry, we have, let’s say, less importance about the turnover. I mean, workflow is something because usually the volume of production is bigger. But, we don’t have the pressure to return this to an operating theatre. So this is, let’s say, two different mindsets because on one hand, reprocessing items, on the other hand, single-use items.

What are the principles of VH2O2 sterilisation process?

So typically, VH2O2 sterilisation is a low-temperature sterilisation. It’s a chemical deactivation method, so it means that by opposition to steam or gamma radiation, which are physical method, this is the chemical reaction with a sterilant, in this case, a vapor of hydrogen peroxide that will deactivate the pathogen. So it means that it’s also meant for surgical equipment or implant that cannot sustain high temperature or implants with electronics that cannot sustain gamma radiation. So VH2O2 emerged in the late ’80s, and it has gained adoption in the ’90s and 2000 in the hospital segment. In industry, EO is still widely used, and VH2O2 is gaining traction because of a better safety profile and also an easiness to implement VH2O2 sterilisation system as it’s non-carcinogenic, non-mutagenic, and non-reprotoxic by opposition to ethylene oxide, which is today the most common low-temperature sterilisation method in industry.

What kind of cycle parameters are critical to measure in VH2O2 sterilisation processes?

So typically, as it’s a chemical deactivation, the influence of temperature and pressure is less important than in physical methods like saturated steam. Although these parameters are important to be monitored because they are optimising the efficiency of the H2O2 vapor. So typically, our most important parameter is the H2O2 concentration. Also, with the time of exposure, it’s a cumulative effect of time and dose of H2O2 that will lead to the deactivation of pathogens. Pressure, temperature, and also in some systems, the power of the plasma phase are critical parameters to measure as well. But let’s say that they are not directly involved in the deactivation of pathogens.

EO versus VH2O2, what are the differences?

Though there are many things to take into consideration when discussing that. The first thing would be from the chemical comparison. So both are low temperature and chemical inactivation methods. They are not using the same sterilant. One is ethylene oxide, the other one is hydrogen peroxide. So they have a different safety profile. Ethylene oxide is typically carcinogenic, mutagenic, reprotoxic, and explosive as well, so it’s difficult to handle it, especially for a medical device manufacturer who would like to implement it in-house. And H2O2 is widely used because it’s very safe. So we can have it at the hairdresser at 3% for hair discoloration. You have it as an antiseptic at 5%, and you have it in decontamination and sterilisation facilities to various percentage. So it’s not explosive, not carcinogenic, and not mutagenic and not reprotoxic. The main difference would be the way of action on the biomolecules. So ethylene oxide will be an alkylating agent leading to the deactivation of pathogens, and H2O2 would be oxidising agent. So this is for the chemistry part. Now, if you look at it from an organisational point of view, ethylene oxide sterilisation today is one of the most used low-temperature sterilisation methods for industrial products, typically implants. And today, the business is structured in a way that it works with external contractors. So many medical device manufacturer will ship their production to an external EO contractor, which has a very large facility that will handle the sterilisation, often directly in the secondary packaging, often in the pallets, and then return to each medical device manufacturer his load. Usually, loads are mixed as well. So it makes it somehow challenging for a medical device manufacturer to deal with logistics, with the cost, with the quality system of this external contractor. So for all these reasons, at some point, medical device manufacturer are seeking to internalise the sterilisation. This is where you have an issue with EO being so challenging in a way that it’s also explosive. So in terms of risk management and implementation in medical device manufacturing facility, it will be clearly a no-go. This is where VH2O2 come in the picture because it has a much better safety profile, so safety first for the patients and the workers, because residuals are non-carcinogenic, non-mutagenic, and non-reprotoxic. It’s restricted to irritation, only. And also, it makes it a perfect Tool to put in line your production at the point of manufacturing. So this is, let’s say, a switch from a world where we used to ship production to a centralised external factory using EO, where you can actually use VH2O2 in-house to do in-line and continuous manufacturing and sterilisation. We use EO sterilisation.

Can I switch from EO to VH2O2 sterilisation process, and how can I do that?

So EO sterilisation is typically the market that we are addressing because we are really an alternative for that. So VH2O2 sterilisation will be, and actually is becoming more and more popular, especially since its enforcement by the FDA. FDA has pushed in January 2024, the VH2O2 sterilisation in the established category A of sterilisation, together with dry heat, saturated steam, gamma radiation, and ethylene oxide. This means that if you are switching within a category A sterilisation modality, and the switch does not affect the biocompatibility or the functionality of your device, you will have only to document the change for FDA and not to do a new submission.

Now, in practice, what does it mean? So we need first to check that all the materials that you use for the medical device itself or for the packaging is compatible, and we need to define the load configuration that will fit also with your workload. So this may differ from your current EO method because volumes of sterilisation chamber are different in VH2O2. Also, we need to remove any incompatible material that we can usually find in EO-sterilised devices, such as cellulosic materials. So this is for packaging, but also for stickers, labels. Adhesives can also be an issue, so we want to check that it’s a compatible one together with the packaging and all your materials used in your product. Once this is done, it goes through the sterilisation process validation as, let’s say, any other modalities. So it means we would identify the most challenging product, make inoculation, direct inoculation, or use spore strips, and we will go for a sterility efficacy testing on a typical load that you will have approved. And after that, you will be go to, to go for production.

Why can’t I just stay with EO process?

So there are different approach to this question. The first one would be, let’s say, the general context. So as I explained before, the ethylene oxide is carcinogenic, mutagenic, and reprotoxic. So this means a potential risk for operators, but not only. It could be also for patients that are undergoing a surgery with the medical device that has been treated with EO. And it goes also ultimately, it is a challenge also for the environment. So if you check newspaper in the US and you type EO litigation, there are dozens of litigations undergoing in cities that have EO sterilisation factories because the cancer rate in the neighborhoods of these factories is way higher than the normal cancer rate. And now many companies have come to a settlement where they have to pay damages. So this is also another impact that you have on the general environment. So it’s not only operators and patients, it’s also potential neighborhoods of your facility. So this is the first thing to consider. So due to that, the FDA has pushed a lot for the past three to four years to look for alternative, to fund projects to find alternative to EO sterilisation. And to date, for industrial sterilisation of medical device, VH2O2 is one of the most recognised, known, and advanced sterilisation technology. So this is why also they pushed it in the category A. So the funny thing is that it was, until January 2024, considered as a novel technology for industrial sterilisation, but actually it is used in hospital, and it has replaced ethylene oxide in hospitals for the exact same reason 30 years ago. So the switch is now happening in the industry, and people are sometimes skeptical, or they think it’s a novel technology, but we operate millions of patients every day with medical device that have been sterilised with VH2O2 in hospitals. So you can think you will stay with EO, but you have to take into account some environmental aspects, some safety aspects, and also regulations that will move, most probably first in the US, and then in EU it will become a topic as well. So there is no choice. You must find an alternative at some point. Also, in terms of logistics and planification. So if you are relying on an external sterilisation company using EO, in the US, there are many litigations, so it means some of them had to be shut down. It means also the possibility of getting a slot for your product is getting scarce. And if you have something in-house, you may have the case also that your current supplier, or actually the steriliser supplier, is getting rid of this product line. So this is really a technology that is not prone to a good future.

What products I can’t sterilise with VH2O2?

So VH2O2, as any other sterilisation modality, has limitation. There are clear physical limitation with material that cannot sustain deep vacuum, with liquids, and with powders, though these are really physical limitation that we cannot overcome. There is also a chemical incompatibility with cellulosic material, which means that sterilisation of textile, of gauze, of paper, or everything that contains cellulose is not recommended because it’s anyway interacting with H2O2, diminishing the efficacy, and ultimately resulting in a failure. So these are the most common and documented negative effect or incompatibilities. For the rest, you need also to consider that this is a surface sterilant, so it means it penetrates lumens and cavities that are made accessible to the gas, just like EO. But it does not sterilise through matter. So it means it will not deactivate a pathogen that is trapped inside a polymer. This is not like gamma radiation. So gamma radiation will go through matter and sterilise inside. But this is not the case for chemical sterilisation.

Is plasma VH2O2 the same as non-plasma VH2O2 sterilisation method?

So in the sterilisation, they are similar. So they work with, it’s a low temperature, it’s a gaseous process. It uses H2O2 as a sterilant. If we look at it on the sterilisation point of view, this is the same process. Now, as any other sterilisation modality, there is a particular attention to be paid on biocompatibility after the process and on toxicological results, or let’s say, the profile of the sterilant residual left after the sterilisation. So for that, and especially since VH2O2 sterilisation replaced EO in hospitals where surgical equipment are meant to be reused right away after sterilisation, some companies have decided to include a so-called plasma phase, which is meant not for the sterilisation efficacy, but for the decomposition of residuals. So in most of the cases, this plasma phase will be used to accelerate the natural decomposition of H2O2 gases in water and oxygen. So this is an extra safety for the worker, first, that will open the chamber at the end of the cycle, but also for the patient that will be operated right away after sterilisation of this equipment. So this has no or close to no impact on the sterilisation efficacy, but it’s really about the decomposition of the H2O2. Some other companies just use a catalytic filter and some venting steps. Some others use that in combination to the plasma phase. So in a nutshell, plasma phases and the residuals, let’s say it makes sense for healthcare, for the patient protection and patient safety, and in the industrial segment where the patient is supposed to receive the implant many months after, so probably the residuals will be below limit of quantification. It makes more sense for workers’ protection and worker safety.

What is the typical concentration of the sterilant?

So typically, for sterilisation, it ranges from 58% to 95%. The volume injected inside the chamber depends on the application as well as the concentration we choose, but our baseline is 58%. Now, for decontamination cycles, we can also aim that with H2O2. We would typically use lower concentration that are more in the range of the 35%, or for instance, other application like hairdressers use at 3% for discoloration. So you see the range is very proportional to the effect you want to have, but typically in sterilisation from, let’s say, 50% to 100%.

How do you deal with lumens?

So this is a question I get a lot, and I completely understand why, because usually VH2O2 sterilisation is referred as a so-called surface sterilisation. So this is completely misleading because it can be understood like it can sterilise only surfaces, but actually it will definitely sterilise lumen surfaces and cavities that are made accessible to the gas. So it’s not like gamma radiation. It does not go through matter, but it goes inside lumens and cavities. There are limitations to that, but also you must consider that the VH2O2 sterilisation process is happening with some kind of back and forth of pressure, vacuum, and injection. So this means, together with the diffusion of the vapor, this gives some capacity to the gas to go inside these lumens and cavities, which are typically and usually the most challenging place where we put our biological indicator for the efficacy testing.

What is ISO 22441?

So it’s an international standard published in 2022 to specifically put a normative framework on the VH2O2 sterilisation process validation. So it does not refer to the steriliser. It does not refer to the biological indicator. It refers only to how you need to validate your sterilisation processes, and this is applicable for industry, but also for hospitals. So we share the same standard. So everything you need to know about validating your process and even implementing it in your factory, you can find it on ISO 22441. This is now gaining adoption or adopted in almost everywhere. So some countries are still under the generic standard for sterilisation validation, but now it is really a widely adopted and recognised standard.

Is there a standard cycle for VH2O2 that I can use for my products?

It really depends what is your application and what is your product. So if your goal is to sterilise a very difficult product, which has microfluidic channels and needs a lot of diffusion time, et cetera, you will need definitely to get a longer diffusion time. So to put it short, no, there is no standard cycle because the critical parameters of our concentration, time of exposure, number of injection of H2O2, and also plasma power in some cases, or the temperature and the pressure, are to be defined according to your needs, your product specificities, and the challenges of your load. So this is something in VH2O2 we can adapt and we can change depending on the project.

What is the challenge with the packaging?

So in most of the cases, the project we have come from medical device manufacturer, which have already a process in place. This process is mostly EO or gamma radiation, which means that the packaging has been designed and materials of the packaging have been chosen for these modalities. So we cannot just copy-paste and put this packaging right away in a VH2O2 sterilisation cycle. Two main reasons. The first one could be, especially for gamma radiation, there is a need to have more access to the gas. So we have had some cases where some of the packaging was really wrapped around the device and didn’t leave enough space for the gas to access all the surfaces. And also the second thing could be not about the design of the packaging, but the choice of materials, adhesives, Tyvek, or even plastics used for the blister pack that are not specifically designed for VH2O2. And this is something we also learn after some few tests and some few projects. So it was also a learning curve, when you start to transfer EO to VH2O2 processes. Adhesive is in most of the case an issue because it’s meant for EO and gamma and you cannot just say, “Yeah, this is also a low-temperature sterilisation, so this will work.” No. Typically, EVA-based adhesives or water-based adhesives are clearly a no-go for VH2O2 sterilisation. It affects the efficacy, but it also leads to delamination, so potentially the integrity of the sterilise biosystem is compromised. So you cannot just copy-paste the packaging and hope that works. And the last thing would be more for the organisational point of view. As explained before, people who choose to implement a VH2O2 process, one of the main driver is the fact of having the possibility to have it at the place of the manufacturing. So this is key. So it needs to be thought as a continuous way to sterilise the production instead of preparing a shipment in carton box, in pallets, and ship it to an EO contractor, receiving back. So this is different. We will sterilise in the primary packaging. So this means we do not put something inside the carton box. So let’s say 10 devices in primary packaging in one carton box or in one pallet inside the sterilisation chamber. This is not how we do. We do it directly in the primary packaging, and we do the palletisation of secondary packaging after. So let’s say packaging is really a critical point to review for compatibility and efficacy on one hand, but also for organisational and logistic issue on the other hand.

What’s the interaction between VH2O2 and polymers?

So this is a critical point to address in the material compatibility phase where we are assessing that. It really depends on the polymer and especially if the polymer has a tendency to be attacked by strong oxidiser like H2O2. So we realise, actually, what is most relevant to consider is if you will need to re-sterilise, so to get the polymer multiple exposure to H2O2, and this will have an effect, of course, over time, or if we are talking about a single-use medical device, so in that case, sterilisation will happen only once. We realise now that the VH2O2 sterilisation is gaining traction in the industry and more adoption in the industry. So for single-use medical device, that actually we have polymers that have been classified in the past as subject to degradation with VH2O2 or with a non-degradation pathway with VH2O2. That are actually okay to get sterilised for single-use medical device with VH2O2. So it means that there is some degradation happening, we see it, but to an extent that if you sterilise it only once, it does not compromise the functionality or the biocompatibility of the product. And we learn a lot about materials like this because, in the past, VH2O2 was typically implemented in hospitals, so for reusable medical device. So of course, if you expose 50 times polyamides to a very high concentration of H2O2, it may not look good at the end. But actually, one single pass or even up to four or five to a lower concentration will be completely fine. And we realise it with also polymers, some polysaccharides as well. So this is really some discovery that we make that actually we never thought it would be sterilizable. But actually, if you lower the concentration, you increase the diffusion time, and you do it only once. On one hand, you keep the sterility efficacy optimal, and you maintain the integrity of the device. So this is what you have to consider with polymers.

Which standards apply to VH2O2 sterilisation in industry?

So VH2O2 sterilisation is covered by ISO 22401 from 2022. So this standard covers both validation of sterilisation process using VH2O2 in industry and in healthcare facility. The way to validate the processes differs. So in industry, we can use either bioburden, combined BI bioburden, or overkill approach. So these are three different ways to validate the process. For hospitals, it is restricted to overkill due to its conservative nature and the fact that in hospitals you get surgical equipment that comes back from an operation theater, which have different contaminants, different level of contamination, so much more viability. And this makes the overkill approach is the method of choice because it’s conservative, so it’s for a better patient safety.

Does FDA recognise VH2O2 sterilisation as a valid sterilisation process?

So this is clearly recognised since many years, but more recently, on January 2024, they published guidance for industry goods sold sterile, so typically guidance for industry for implant manufacturing or single-use medical device manufacturing, where they even elevated the status of evidence and of reliability of the VH2O2 to an established Category A. So this means that without any doubts now, no matter what you can find or say or hear, FDA recognise VH2O2 as as efficient as saturated steam, dry heat, gamma radiation, and ethylene oxide.

How are biological indicator used in VH2O2 sterilisation process?

So in VH2O2 sterilisation process, you need to use biological indicator for both the process validation, so at the lab or the beginning of the project, and also for the routine monitoring of every load. So this means that you would like to choose a challenge microorganism that is most difficult to kill than your usual pathogens that you have on your devices, even after cleaning. In 99% of the cases, we use Geobacillus stearothermophilus, a gram-positive sporulating thermophilic bacteria, also not pathogen. Even though there is no standard specific to the use or the requirements of biological indicator for VH2O2 processes, we rely on the general requirement for sterilisation processes, and Geobacillus stearothermophilus is one of the most used bacteria for the reason I listed before. But also it has extensive peer-reviewed literature published for the past 20 to 30 years. So this is clearly the most common challenge microorganism you can use for VH2 processes.

VH2O2 process and residuals, what’s the risk?

So like any other sterilisation modalities, you need to verify the biocompatibility or as part of that, the residual left by the sterilising agent. So in our case, this is the vapor of H2O2. Naturally, it will decompose into water and oxygen, so it’s pretty much safe. But depending on the concentration you are working with, right away after sterilisation, you may still have some H2O2 residuals. Though this needs to be measured, it’s required by the standard ISO 22401, and this needs to be interpreted considering the use on patient, how long is going to be the medical device in contact with the patient, and this is a bit of a toxicological, let’s say, study to be done and to interpret. So with VH2O2, the good thing is that you get its natural decomposition in water and oxygen. So when we say water, don’t imagine to have a chamber full of water at the end of the sterilisation cycle. We are talking about 5% relative humidity, which is way drier than any apartment or normal situation. So this is a dry sterilisation process, and this is why it works very well with electronics. Some manufacturers of steriliser have this plasma phase to accelerate this decomposition. Some others just do venting and use a catalytic filter. In any case, you need to measure these residuals after the sterilisation cycle and to interpret the value. But the worst thing you can risk is potentially having irritation. So this is how H2O2 is usually documented. So it’s only about irritation effect, and it’s absolutely not carcinogenic, mutagenic, or reprotoxic as other sterilisation method like EO.

Where does EO, VH2O2, and gamma radiation fit in the next 10 years?

So first, I think there is places for every technology. It’s just that we believe that there will be a restructuration, let’s say, of the business model. As I said, today EO and gamma radiation, these are typically outsourced. This means you have a model where you produce, you package, you package in secondary in pallets, you ship. Sometimes it’s abroad because some countries have abandoned gamma radiation, have abandoned nuclear energy. So it also leads to a lack of gamma radiation facilities. You receive back your merchandise. With VH2O2, we offer the possibility to have it in-house, so it’s a complete change of mindset, which does not fit all medical device manufacturers. But we believe that there will be actually a traction and interest in VH2O2 sterilisation, especially for medical device manufacturers that want to get rid of dependencies of an external partner, that want to have a better view or simplification of logistic flows, not only for the time to market, but also for the qualification of suppliers. So it means you ship your production away to someone that sterilise it. You will be liable for what happens, but you don’t know everything that happens, or you need to audit, you need to maintain that in your quality management system, even though it’s outside of your company. There is also another aspect of the logistics to deal with, with an external partner is CO2. So we have talked about sustainability in terms of EO and gamma radiation impact on environment, but we can talk also about the CO2 of this shipment. So having your sterilisation in-house It’s definitely a gain in logistics simplification, time to market, CO2, quality management systems. It’s under your scrutiny. So it’s a different mindset. Perhaps it does not suit everybody, but I believe there will be places for all three technologies. Gamma radiation and EO still are capable of addressing huge volumes of sterilisation. On the other hand, VH2O2 offers more flexibility, capacity to implement in-house, capacity to customise cycles, to adapt cycles to new product development. So it also makes sense for startups or companies that are not at the commercial stage but are still at the clinical stage because it’s very versatile. So it means you are changing your design, we can adapt the sterilisation cycle parameters, and then you can sterilise, ship your products to clinical trials. So this offers flexibility in a way. So there are pros and cons in all sterilisation modalities in low temp, but we believe VH2O2 will gain traction in the future and definitely will take some market share, especially to EO and gamma radiation.

What is the typical pathway in terms of timeline and cost for transfer to VH2O2 sterilisation?

So first, we would look at your products. What are the materials? What is the packaging? Does it keep its function after a basic sterilisation cycle, even without adaptation, without efficacy problem? And we will identify among all your products you want to sterilise with VH2O2 what would be the most challenging candidates. Among the product family, we usually pick the most challenging one, and then we don’t have to validate all of them. After that, we go for the sterility efficacy testing, so it means fractional exposure to VH2O2 concentration, also customisation of the cycle if your product is susceptible to some conditions. And after that, again, we would correlate the inactivation behavior of an inoculated product with the inactivation behavior of a commercial biological indicator that you will use for routine production. Residuals need also to be measured in a typical load configuration. So after that, you have achieved what we call the process validation. It still needs to be implemented in your factory. But let’s say that overall, you need to take into account at least minimum two to three months if you have really prepared well and if your products are really well-known, and you can also provide samples for testing. This is the minimum. Then more realistically, we can say six to eight months to get this implemented and running. This does not include some work you must do for the FDA or the EU MDR certification. So for the FDA, it’s a documentation where biocompatibility and product functionality is not affected by the change of sterilisation modality. For EU MDR-certified products, it’s a new submission, so obviously more years, more time to take into account.

What is the most complex medical device that you have been able to sterilise with VH2O2?

Actually, there is not one single medical device. There are, let’s say, two or three different cases. So two of them are made of a polymer which was, in theory, incompatible. So the first attempts led to complete depolymerisation of the device because the concentration was too high. So actually, by reducing the concentration but keeping it in a window where we could achieve sterility, maintain the device in a good state, and actually we could overcome the initial results and the initial limitation of the depolymerisation. Similarly to that, we have had cases where some kind of polymers or, let’s say, organic polymers were sterilised using VH2O2, and it was also not expected to deliver a good outcome, but it still did. And now in terms of complexity, we have usually to deal with heat and moisture-sensitive devices, but also devices that have electronics that are really small, so it means cavities or lumens to access. So these are the typical candidates that we have for VH2O2 sterilisation. So your heat and moisture-sensitive medical device, typically small with electronics, and this is a good candidate for VH2O2 transition from EO or from gamma. Gamma, probably there is no electronics inside. But this is a typical candidate that we have, and of course, these are challenging because of these designs with microfluidic channels or very thin loads.

What’s the typical VH2O2 sterilisation cycle time?

Well, it depends on how we build the cycle. Typical patterns would take 60 minutes, typically, with no aeration after or no post-treatment. So it means after 60 minutes of treatment, you can take your load and potentially put it to the warehouse for commercial release. Of course, you need to wait for the biological indicator to be read out, but this is our typical cycle duration. So to date, we have been designing cycles, let’s say the fastest one is around 20 minutes, 24 minutes, and the longest we have had for a very challenging medical device is six hours.

So thank you. That’s it for my side. I’ve been pressure tested. I hope this helps to get some clarity and some understanding of the VH2O2 sterilisation process. So maybe a takeaway message. So even though this is still considered in industry as a novel technology or as something that is emerging as an alternative to existing methods, keep in mind that this technology is used in hospitals for 30 years. Most of these manufacturers of VH2O2 steriliser have more than 20,000 devices installed and running worldwide. So this is really something where, in addition to peer-reviewed literature evidence, we have real-world data and real-world evidence for the past 30 years. Thank you.