Carbon dioxide commercialised as a steriliser
Medical devices are increasingly more complex and the materials that make up devices and regenerative products more specialised. These products require delicate sterilisation technologies to maintain properties essential to ensuring optimal therapeutic outcomes, yet must provide the level of sterility required of implantable devices by regulatory agencies. NovaSterilis has developed a green sterilisation technology harnessing the unique properties of supercritical CO2 in combination with a small quantity of a proprietary additive, to achieve a device industry Sterility Assurance Level of 10-6 (SAL6) while minimising impact to many highly specialised products.
As the medical device industry develops and incorporates more specialised materials, the challenge of sterilising devices incorporating new materials grows. Sterilisation by nature is destructive; many current devices are simply constructed of metal or durable plastics that withstand current harsh sterilisation technologies. In addition, these products are not porous reducing the risk of retaining residual toxins used in chemical sterilisation processes. The incorporation of new polymers, materials and porous matrices with properties that can be specifically tuned to the desired application has presented the industry with sterilisation challenges due to tight material property tolerances. NovaSterilis is meeting the sterilisation needs of a growing number of these specialised products.
“Since today’s highly technical products require very specialised handling, the sterilisation of smaller batches and a desire to maintain custody of product is more important to many of our customers,” stated David Burns president and ceo, NovaSterilis. “We are able to offer customers an in-house ‘green’ sterilisation solution that can be completed in minutes to hours, the customers can maintain custody of their products and prevent inventory delays.”
What is supercritical CO2?
The supercritical or fluid phase of carbon dioxide is achieved at low pressure (1099 PSI/73 ATM) and moderate temperature (31.1°C). As a supercritical fluid, CO2 maintains ideal properties of the liquid and gas phases; as a liquid, CO2 is an excellent organic nonpolar solvent, and the gas phase has no surface tension providing unsurpassed penetration.
Historically there has been a desire to utilise CO2 for sterilisation and a number of respected researchers attempted to achieve this with some promising results on viruses and vegetative bacteria. But, the inactivation of bacterial spores, the hardest to kill, to a SAL6 was not possible until NovaSterilis combines a sub-therapeutic quantity of a liquid sterilisation additives with supercritical CO2. It is this approach of using a combination of two sub therapeutic products, CO2 and sterilisation additive, that results in a very lethal yet gentle sterilisation process. In its supercritical state CO2 acts like a gas and penetrates Tyvek gas permeable medical packaging making it possible to terminally sterilise devices, ready for surgery.
It is important to highlight NovaSterilis’ use of very low levels of additive (25–100ppm) in combination with supercritical CO2 limiting the negative effects of a chemical sterilant for the process technician, device recipient, and product. Most of the chemical sterilant is removed from the product and unit during the depressurization cycle of the unit; this provides the user with a product ready for inventory. Testing on allograft products sterilised using the NovaSterilis process has exhibited no measurable chemical residuals reducing any potential side effect.
Mode of action
There are numerous theories on mode of action of this technology, but it has been shown that a physical destruction of the microbe is not responsible. In the context of low pressure (1450psi) and temperature (35°C) supercritical CO2 process, two components are suggestive of a mode of action. These components include the presence of water and a method for enhancing mass transfer of CO2 and additives that affect cell viability.
Together, these factors point to the formation of carbonic acid inside of the microbe inactivating the microbe. Carbonic acid is generated from the reaction of CO2 with water, this may be responsible for a portion of the inactivation of cells through the transient acidification of the interior of the microbial cell and/or inactivation of essential enzymes. NovaSterilis Peracetic acid (PAA) based additive is both an acid and peroxide. As an acid, PAA may have transport properties in supercritical CO2 that contribute to overall intracellular acidification. The same mass transfer enhancement may also facilitate the delivery and/or action of PAA as a sporicidal agent. This hypothesis is consistent with the synergy observed between supercritical CO2 and PAA for inactivating bacterial endospores.
NovaSterilis has a growing number of customers developing this process for their specific materials. The gentle nature of this process makes it a valuable tool for human and xenogenic allograft sterilisation, an unmet medical need since current good tissue practices are centred on donor screening and aseptic processes they leave the recipient of transplant tissue vulnerable for post transplant infections. Radiation and ethelyne oxide have effects on the tissue or recipient that restrict the effectiveness. Other new technologies, for example H2O2 plasma simply do not penetrate the tissue and achieve sterilisation in the deep layers of the tissue.
In addition H2O2 plasma technology produces large quantities of free radicals to achieve sterilisation. These free radicals can react with materials being sterilised. The Tissue Banking Industry made great strides in reducing risk, but the addition of a sterilisation technology with minimal impact on tissue can further improve the safety of the tissue supply. A small company is developing this sterilisation technology for a new twist on an old material, one that needs a very sensitive approach that will not degrade the material. Supercritical CO2 was able to achieve SAL6 without any degradation to this valuable finished product. Additional established applications for SCCO2 include but are not limited to PLGA/PGA, PEEK, absorbable sutures, active pharmaceutical ingredients and drug delivery devices.
The NovaSterilis supercritical CO2 process is safe for many polymers, allograft tissues, plastics, and surgical metals. NovaSterilis manufactures 20 litre and 80 litre fully automated, computerised, and network capable sterilisation units. Designed with a small footprint, these units are ideal for biomedical material companies that require high value and flexibility. NovaSterilis provides supportive technical services; assisting customers to determine if this process is appropriate for specific products, establishing cycle times, and developing validation and regulatory plans.