Supercritical Carbon Dioxide Sterilisation

Supercritical Carbon Dioxide STERILISATION A gentle sterilisation process has been commercialised for the sterilisation of advanced biomaterials. This article describes the technique and relevant applications. edical 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 the properties essential to ensure optimal therapeutic outcomes, yet provide the level of safety required of implantable devices. A sterilisation process has been developed by Novasterilis, which harnesses the unique properties of supercritical carbon dioxide (CO2) in combination with a small quantity of a proprietary additive. it achieves a sterility assurance level of 106 while minimising impact on many highly specialised products.” The incorporation of new polymers, materials and porous matrices with properties that can be specifically tuned to the desired application has presented the medical technology industry with sterilisation challenges? “Because 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,” states David C. Burns, president and chief executive officer of 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." www.111ed—tecliiniiovzitlon.c0In What is supercritical carbon dioxide? The supercritical or fluid phase of CO2 is achieved at low pressure (1099 psi/73 ATM) and moderate temperature (31 .1 °C). As a supercritical fluid, CO2 maintains the 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 (Figure 1). 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 viral and vegetative bacteria. But, the inactivation of bacterial spores, the hardest to kill, to a SAL ofl O6 was not possible until NovaSteri|is combined a sub- therapeutic quantity of a liquid sterilisation additives with supercritical CO2. It is this approach of using a combination of two sub—lethal products, CO2 and sterilisation additive, that results in a lethal yet gentle sterilisation process. In its supercritical state CO2 acts like a gas and penetrates Tyvek (DuPont Medical Packaging) gas permeable packaging, making it possible to terminally sterilise devices ready for surgery. It is important to highlight the unique use of very low levels of additive (25—lOO ppm) in combination with supercritical CO2, which limits the negative effects of a chemical sterilant for the process technician, device recipient and product. Most of the chemical sterilant Med-Tech Innovation Sterilisation March 2011 I 17 Med-Tech Innovation Sterilisation is removed from the product and unit during the depressurisation cycle of the unit. This provides the user with a product ready for inventory the minute the unit has shut down. Testing on allograft products sterilised using this process has exhibited no rreasurable chemical residuals, thus reducing any potential side effect. 10,000 1,000 100 Pressure, atm 5‘ 0.1 -100 -80 Figure 1: Phase changes in carbon dioxide Nova22OO 20 litre supercritical CO2 steriliser 18 I March 2011 Mode of action There are numerous theories on the 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 the low pressure (1450 psi) 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 the microbe, which inactivates 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‘ -60 -40 -20 0 20 40 60 Temperature, °C 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 3AA for inactivating bacterial endosporesfi Application A growing number of innovative companies are developing this process for their specific materials. The gentle nature of this process makes it a valuable tool for human and xenogenic allograft sterilisation. This is an unmet medical need. Because current good tissue practices are centered on donor screening and aseptic processes, they leave the recipient of transplant tissue vulnerable to post transplant infections. Radiation and ethylene oxide have effects on the tissue or recipient, which restrict effectiveness. Other new technologies such as hydrogen peroxide (H202) plasma simply do not penetrate the tissue and achieve sterilisation in the deep layers of the tissue. In addition, H202 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 a SAL of 106 without any degradation of this valuable finished product. Additional established applications for supercritical CO2 include, but are not limited to, po|y(lactic-co-glycolic acid)—polyglycolic acid (PLGA/ PGA), polyetheretherketone (PEEK), absorbable sutures, active pharmaceutical ingredients, drug delivery devices, fabrics, polymers, 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 companies using biomedical materials that require high value and flexibility. The company 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. References 1. US patent 7108832 sterilisation Methods and Apparatus which Employ Additive Containing Supercritical Carbon Dioxide Sterilant. 2. Q.Q. Qiu et al., “lnactivation of Bacterial Spores and Viruses in Biological Material Using Supercritical Carbon Dioxide with Sterilant,” published online Wiley lnterscience, 10.1002/ jbm.b.31431, July 2009, www.interscience.wiley.com. 3. C.E. Holy et al., “Optimising the Sterilisation of PLGA scaffolds for Use in Tissue Engineering,” B/‘omateria/s,” 22, 1, 25-31 (2001 . 4, A.K. Dillow et al., ”Bacterial Inactivation by Using Near and Supercritical Carbon Dioxide,” Proc. Natl Acad. Sci. USA, 6, 18, 1034£—10348 (1999). 5. M. Shimoda et al., ”The Influence of Dissolved CO2 Concentration on the Death Kinetics of Saccharomyces Cerev'siae,” J. Appl. /Wcrobio/., 91, 2, 806—311 (2001). 6. A. White et al., “Effective Terminal Sterilisation Using Supercritical Carbon Dioxide,” J. B/otec/7., 23, 4, 504-515 (2006 . 7. PA, Clapp et al., ”The Bactericidal Action of Peroxides, An E.P.R. Spin—Trapping Study," Free Radio. Res, 21 , 3, 147-167 (1994 . Information supplied by NovaSterilis Inc, Lansing, New York, USA, tel. +1 607 330 2772, e-mail: sales@novasterilis.com, www.novasterilis.com www.med—techinn0vatior1.com