Supercritical Carbon Dioxide: The Future of Medical Device Sterilization?

Some say scCO2 could be an ecological answer to the ethylene oxide controversy. NovaSterilis’ Tony Eisenhut says there’s no one silver bullet.

Katie Hobbins, Managing Editor

May 15, 2023

6 Min Read
Image of Tony Eisenhut
Image courtesy of Tony Eisenhut

While ethylene oxide tops headlines for its potential health hazards and EPA implications, there has been increasingly louder murmurs about the use of supercritical carbon dioxide (scCO2) as an ecological alternative for medical device sterilization. To learn more about scCO2, MD+DI sat down with Tony Eisenhut, CEO and co-founder of NovaSterilis, to understand its sterilization properties, sterility assurance levels, and potential barriers to adoption.

What is supercritical carbon dioxide? What is it currently most used for in medtech?

Eisenhut: scCO2 is a fluid in which carbon dioxide has liquid (density) and gas (diffusivity) like properties.  The supercritical state is achieved when the temperature and pressure are above its critical points (~31C and 1,070 psi or 73 atm). scCO2 has been broadly used in the medtech space for decades.

Early uses focused on extraction of natural compounds for medicinal purposes such as the extraction of paclitaxel (Taxol) from the bark of yew trees. More recently the extraction of cannabinoids from cannabis has become a large market. In addition to extraction, scCO2 is being used for material cleaning and the terminal sterilization of medical devices including both synthetic and biological based devices. 

Emerging areas in the medtech space (regenerative medicine applications) is the use in decellularization of human and animal tissues without the use of harsh chemicals such as TritonX (use has been reduced and/or eliminated in some countries). Additionally, scCO2 is used for manufacturing of products whether it be via impregnation of bioactives into scaffolds or the creation of scaffolds themselves as aerogels. The uses of scCO2 are growing rapidly in the medical device, regenerative medicine, and therapeutics industries.

How does it sterilize medical devices and products? The biggest concern manufacturers have switching from EtO to something else is that EtO is said to be the most effective sterilizer that can be used without damaging a product, so how well does scCO2 work compared to that of EtO?

Eisenhut: I would assert that all sterilization modalities impact the materials they are sterilizing. What we are all working to achieve is minimization of the impacts of sterilization such that the sterilized materials still function as intended. Although EtO is broadly compatible, it still has compatibility limitations, especially with bio-based materials. We have been working with scCO2 as a sterilant for over 20 years at this point and we have shown the ability to terminally sterilize a broad array of materials and devices. Our scCO2 sterilization platform has been used commercially in the tissue banking industry since 2008. There have been well over 300,000 devices implanted in humans over that period without any reported adverse reactions (relative to sterilization).

When comparing scCO2 to EtO there are a number of benefits. CO2 is an inert, non-reactive molecule. In and of itself, it is advantaged over EtO from a reactivity standpoint. That said, to successfully sterilize with scCO2, you need to include an entrainer (we use a peracetic acid based additive). There is a synergistic effect of between the scCO2 and the peracetic acid so you can use minimal amounts to achieve a sterility assurance level of 10^-6. Secondly, the conditions under which scCO2 is created results in deep penetration of the sterilant in the device even through torturous packaging configurations. scCO2 is the most effective sterilization modality when it comes to penetration. Similar to EtO, scCO2 is a low temperature sterilization modality (operating temperature of 35C).

Unlike EtO, scCO2 does not require an outgassing period of tens of hours (no outgassing time is required for scCO2).

In 2019 the FDA created an innovation challenge grant to identify and support alternatives to EtO. NovaSterilis was selected (along with Stryker's TSO3, Noxilizer, and Steris' vaporized hydrogen peroxide). NovaSterilis continues to work with the FDA to broaden the use of scCO2 as a terminal sterilization modality. There were multiple FDA clearances in 2022 that used scCO2 as a cleaning and/or terminal sterilization process in the manufactured devices. The cleared applications range from terminal sterilization of therapeutics to additive manufactured products to tissue derived products.

There has been talk that scCO2 could be an ecological replacement for EtO, what are your thoughts?

Eisenhut: Although I am biased, I believe this to be a true statement. NovaSterilis won the Presidential Green Chemistry Small Business award in 2007 based on the use of CO2 as an alternative to EtO.

I do not think there is a "silver bullet" for the replacement of EtO. I think there will be multiple sterilization modalities that will be viable alternatives based on the needs of the products being sterilized. I actually think that for the foreseeable future, EtO will be a part of the solution as well, albeit a smaller percentage as the regulatory pressures grow and the costs continue to rise. I do believe that the alternative sterilization solutions, including scCO2 are more economical than EtO when you look at the total cost of processing. NovaSterilis has shown the utility of scCO2 as a terminal sterilization solution.

To date, most of the applications are mid to low volume applications because of the equipment limitations for the medtech applications. Although scale is a perceived problem, it is not a true problem. scCO2 is used in some very large industrial applications including extraction applications of coffee and hops. We are aware of an industrial installation with 60,000L of scCO2 capacity. The infrastructure used for extraction is the same as that used for sterilization. The difference is related to the process not the equipment. This is a long-winded way to say that the ability to scale scCO2 sterilization to volumes processed with EtO is not a technology or engineering hurdle, it is a finance hurdle. There needs to be a forward-thinking company, with the resources that will make the investment.

If yes, what are the biggest barriers to implementing scCO2 in place of EtO? Knowledge of it as an alternative? Regulatory timeline issues? Cost of changing sterilization practices?

Eisenhut: The primary barrier is economic investment in the scaled-up infrastructure. The second issue is awareness of the alternative.  The regulatory timeline is not any longer than other sterilization modalities including EtO. We had multiple partners receive clearance in 2022 and the timelines were what one would normally expect. 

One of the barriers is professional risk. The willingness to try a "newer" — I put it in quotes because scCO2 has been used in the food industry for ~50 years — sterilization modality is tempered by decision makers fear of what it means for their career should it fail, even if the risk of failure is no greater than the other sterilization solutions. 

How is the process of sterilization changed when using CO2, or CO2 with additives like trifluoroacetic acid, peracetic acid, hydrogen peroxide, nisin, and NovaKill?

Eisenhut: CO2 alone will not allow you to achieve a sterility assurance level 10^-6.  Bacterial endospores are not able to be fully inactivated with CO2 alone. An entrainer (additive) is necessary to achieve terminal sterilization. We have explored the use of several additives. Most of the oxidative agents (trifluoroacetic acid, H2O2, and peracetic acid) can achieve success. NovaKill is our proprietary formulation, but it is a peracetic acid-based solution as well. 

As I am new to the conversation surrounding scCO2, please highlight anything that you think our readers would be interested to know or that is a common misconception of using the sterilization method.

Eisenhut: It is often believed that it is only cost effective on high value, low volume products. That is not true. The cost of operation is lower than that of EtO and often radiation when you evaluate the total cost of sterilization.

About the Author(s)

Katie Hobbins

Managing Editor, MD+DI

Katie Hobbins is managing editor for MD+DI and joined the team in July 2022. She boasts multiple previous editorial roles in print and multimedia medical journalism, including dermatology, medical aesthetics, and pediatric medicine. She graduated from Cleveland State University in 2018 with a bachelor's degree in journalism and promotional communications. She enjoys yoga, hand embroidery, and anything DIY. You can reach her at [email protected].

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