Gustavo Varca, Manager of New Applications Development, E-BEAM SERVICES, Inc.09.11.19
The need for sterilized materials remains critical as hospital-acquired infections still account for up to 1.7 million infections and 99 thousand associated deaths per year in the US1, as revealed by the Centers for Disease Control estimates. Also, the demand for sterilization continues to grow as new medical devices and single-use products enter the market.
Estimated to reach $8.43 billion within the next five years2, the sterilization market at a global level is broken down into 50% ethylene oxide (EO), 40.5% gamma radiation, 4.5% electron beam, 5% other technologies, and is dominated by the US, Europe, and Asia, according to the International Irradiation Association3.
However, recent concerns about hazardous emissions of EO have decreased public acceptance and led to the shutdown of an EO processing plant in Illinois, and another one scheduled to cease its activities later this year in Michigan4. Given the significant share of the market taken by EO, the food and Drug Administration (FDA) stated that around 600 medical devices5 and over 100 manufacturers are going to be impacted by the unavailability of the technology6. In April, some products were already unavailable, such as tracheostomy tubes7.
Medical device manufacturers are being encouraged by the FDA to report device shortages8 and to propose alternatives to replace the EO sterilization and to reduce its emissions into the atmosphere in an attempt to avoid a medical sterilization crisis and a shortage of sterilized medical devices. The two challenges are aimed towards offering some alternative technology or providing a short to medium-term solution9.
At first glance and considering the options available for the sterilization of medical devices, the solution may rely on the shifting to another technology. However, the selection of a sterilizing method for a product relies on many variables, such as material composition, compatibility with the technology, type of microorganism, and bioburden. No sterilization method would work for every product nor be effective against every pathogen.
Another point to consider is that such a change between sterilization methods may be costly, time-consuming, and often an ultimately fruitless approach due to processing incompatibilities. Now, on the verge of a crisis, it seems that the need will drive “change” or at least lead medical devices companies towards “change.” New technologies aspire to solve, but are unlikely to solve, all the requirements and meet the demands in due time. What is the alternative or perhaps the best option for the medical device industry? Currently available and short-term options refer, most likely, to existing but less used technologies.
Considering a possible shift towards gamma radiation, the second-most used technology for the sterilization of medical devices, some aspects must be considered. Although very useful and promising, its use is under concern as regulations on the shipment and transportation of radioactive material (the driving force of the technology, cobalt 60-based) are becoming stricter. Also, the shortage of cobalt 60 is increasing the costs considerably, and a medium to short-term solution is unlikely, although the industry is continuously investing in ways of overcoming the situation. Nevertheless, it is not a solution for every product; some products are incompatible with the technology and may undergo degradation, resulting in color changes and loss of mechanical properties, among other effects.
Electron beams are another source of ionizing radiation that, unlike gamma rays, relies on machine-generated electrons rather than an isotope, so the radiation may be switched on/off. It offers incredibly fast processing, high throughput and dose control that may be adapted according to product needs. However, limitations include limited penetrability and some sensitivity depending on the product. In other words, not every product can be processed by an electron beam.
What about the less pronounced technologies, which account for 0.5% of the sterilization market? At an industrial level and considering high volume processing, the alternatives become more limited, but some of them are outlined below and may represent a part of the solution to the problem.
X-ray technology is another relatively new option for the sterilization of biomedical materials, as the first facility dedicated to sterilizing medical devices using x-ray dates to less than a decade ago3. The technology features similar penetrability levels as gamma radiation does, but without the need for the radioisotope. The drawbacks are the low efficiency in terms of energy conversion, which disqualifies the process in most of the cases due to the high cost, and the low availability of x-ray facilities, although service providers are acquiring the technology at a considerable pace.
When it comes to e-beam sterilization, most people think of high voltage electron accelerators—that is, accelerators operating at 10 MeV (million electron volts), which have sufficient penetration to sterilize a large majority of medical devices in their current packaging configuration. However, an existing technology (but perhaps “innovative” to the sterilization industry) is medium voltage electron beams. With an intermediate penetration, the technology offers considerably higher throughput, quicker processing, and cost-effective technology when compared to high voltage beams.
Medium voltage electron beam processing is a proven alternative for medium to low-density products, for the short-mid-term needs of the industry with 50-60% chances of conversion success. Also, there is considerable capacity available to the medical device industry at the present time. There is no possibility to induce radioactivity in any substance, given the energy levels involved. The limitations to address are material compatibility issues and penetration on high-density products, although repackaging further improves the probability of success.
Nitrogen dioxide-based sterilization (NO2) refers to an ultra-low temperature sterilization process, which is FDA cleared, efficient, and involves a fast cycle (minutes) that consistently promotes the sterilization of biomedical devices, more often applied to tubes and open vessels. The acquisition cost is minimum compared to an irradiator, but the technology cannot be used in final packages nor products with complex geometries and is more suitable for low and perhaps medium volume processing10.
Hydrogen peroxide plasma also offers quick sterilization cycles of less than an hour with minimal to no residues. While hydrogen peroxide plasma sterilizers are safe and easy to operate, limitation involves specific packaging, small processing capacity and an inability to sterilize strong absorbers, liquids, and so on. Like NO2 technology, they cannot meet the demand for high volumes and are more likely to be applied for low volume processing11. Also, the most recent version of the sterilizer has received FDA 510[k] clearance with limited application for sterilization of medical devices12.
While no miracle technology appears, the need for proven sterilization of medical devices continues to grow. Overall, the search for new sterilization methods will continue and it is time to find an alternative—sooner rather than later—as a sterilization crisis is looming. It is unlikely that EO will disappear from the market, but rather and more logically, return upon restructuring and establishing compliance with new regulations and environmental laws, as some materials just cannot be processed by sterilization technologies other than EO. However, the resultant increased costs and risks with EO sterilization are likely to motivate significant change in the utilization rates of existing and new technologies.
References:
1 https://patientcarelink.org/improving-patient-care/healthcare-acquired-infections-hais/, accessed on 8/8/2019.
2 Global Sterilization Market 2018 - Forecast To 2024: Market is Poised to Reach $8.43 Billion. Marketwatch. Aug 28, 2018.
3 White Paper - A Comparison of Gamma, E-beam, X-ray and Ethylene Oxide Technologies for the Industrial Sterilization of Medical Devices and Healthcare Products. International Irradiation Association. Aug 31, 2017.
4 Another medtech sterilization plant will close in 2019. Medical Design & Outsourcing. Mar 26, 2019.
5 FDA: Closure of medical device sterilization facility could prompt shortages. American hospital Association. Mar 27, 2019.
6 FDA: Device Sterilizing Facility Shutdown Could Have Impact - Whether major disruption will ensue remains unclear. MedPage Today. Feb 27, 2019.
7 https://www.fda.gov/news-events/press-announcements/statement-jeff-shuren-md-director-center-devices-and-radiological-health-agency-efforts-mitigate. Press Release on April 12, 2019.
8 FDA is looking for options amid medtech’s sterilization crisis. Medical Design & Outsourcing. July 15, 2019.
9 https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/ethylene-oxide-sterilization-medical-devices. Food and Drug Administration. Press release on July 15, 2019.
10 White Paper. Nitrogen dioxide Biodecontamination: a new, effective and cost-saving option for biodecontamination Sytinge tubs prior to the filling line. NoxilizerTM. April 18, 2016.
11 Low Temperature Hydrogen Peroxide Plasma Sterilization. Tuttnauer. May 9, 2017. https://tuttnauer.com/blog/low-temperature-hydrogen-peroxide-plasma-sterilization
12 Hydrogen Peroxide Gas Plasma. Guideline for Disinfection and Sterilization in Healthcare facilities. Centers for Disease Control and prevention. 2008. https://www.cdc.gov/infectioncontrol/guidelines/disinfection/sterilization/hydrogen-peroxide-gas.html
Gustavo Varca, B. Pharm, PhD is a worldwide expert in nuclear technologies, and his expertise involves over a decade of experience in radiation processing of medical devices, pharmaceuticals, controlled substances, polymers, tissues, and biologics, focusing on radiation sterilization, material modification, recycling, micro- and nanostructuring of materials, and development of new materials, among others. Associate editor at Radiation Physics and Chemistry (Elsevier), he received 4 international awards for his contribution to the advancement of science and the sciences of ionizing radiation. Varca has authored 30 documents including published papers in scientific journals, book chapters and international patents related to radiation processing of polymers. Distinguished editorial board member, guest editor, and reviewer of several international scientific journals, scientific advisor of the International Irradiation Association (iia) and international consultant on radiation processing in the Americas and Europe. You can reach Varca by e-mail at gustavo.varca@ebeamservices.com or via the phone: (609) 655-7460.
Estimated to reach $8.43 billion within the next five years2, the sterilization market at a global level is broken down into 50% ethylene oxide (EO), 40.5% gamma radiation, 4.5% electron beam, 5% other technologies, and is dominated by the US, Europe, and Asia, according to the International Irradiation Association3.
However, recent concerns about hazardous emissions of EO have decreased public acceptance and led to the shutdown of an EO processing plant in Illinois, and another one scheduled to cease its activities later this year in Michigan4. Given the significant share of the market taken by EO, the food and Drug Administration (FDA) stated that around 600 medical devices5 and over 100 manufacturers are going to be impacted by the unavailability of the technology6. In April, some products were already unavailable, such as tracheostomy tubes7.
Medical device manufacturers are being encouraged by the FDA to report device shortages8 and to propose alternatives to replace the EO sterilization and to reduce its emissions into the atmosphere in an attempt to avoid a medical sterilization crisis and a shortage of sterilized medical devices. The two challenges are aimed towards offering some alternative technology or providing a short to medium-term solution9.
At first glance and considering the options available for the sterilization of medical devices, the solution may rely on the shifting to another technology. However, the selection of a sterilizing method for a product relies on many variables, such as material composition, compatibility with the technology, type of microorganism, and bioburden. No sterilization method would work for every product nor be effective against every pathogen.
Another point to consider is that such a change between sterilization methods may be costly, time-consuming, and often an ultimately fruitless approach due to processing incompatibilities. Now, on the verge of a crisis, it seems that the need will drive “change” or at least lead medical devices companies towards “change.” New technologies aspire to solve, but are unlikely to solve, all the requirements and meet the demands in due time. What is the alternative or perhaps the best option for the medical device industry? Currently available and short-term options refer, most likely, to existing but less used technologies.
Considering a possible shift towards gamma radiation, the second-most used technology for the sterilization of medical devices, some aspects must be considered. Although very useful and promising, its use is under concern as regulations on the shipment and transportation of radioactive material (the driving force of the technology, cobalt 60-based) are becoming stricter. Also, the shortage of cobalt 60 is increasing the costs considerably, and a medium to short-term solution is unlikely, although the industry is continuously investing in ways of overcoming the situation. Nevertheless, it is not a solution for every product; some products are incompatible with the technology and may undergo degradation, resulting in color changes and loss of mechanical properties, among other effects.
Electron beams are another source of ionizing radiation that, unlike gamma rays, relies on machine-generated electrons rather than an isotope, so the radiation may be switched on/off. It offers incredibly fast processing, high throughput and dose control that may be adapted according to product needs. However, limitations include limited penetrability and some sensitivity depending on the product. In other words, not every product can be processed by an electron beam.
What about the less pronounced technologies, which account for 0.5% of the sterilization market? At an industrial level and considering high volume processing, the alternatives become more limited, but some of them are outlined below and may represent a part of the solution to the problem.
X-ray technology is another relatively new option for the sterilization of biomedical materials, as the first facility dedicated to sterilizing medical devices using x-ray dates to less than a decade ago3. The technology features similar penetrability levels as gamma radiation does, but without the need for the radioisotope. The drawbacks are the low efficiency in terms of energy conversion, which disqualifies the process in most of the cases due to the high cost, and the low availability of x-ray facilities, although service providers are acquiring the technology at a considerable pace.
When it comes to e-beam sterilization, most people think of high voltage electron accelerators—that is, accelerators operating at 10 MeV (million electron volts), which have sufficient penetration to sterilize a large majority of medical devices in their current packaging configuration. However, an existing technology (but perhaps “innovative” to the sterilization industry) is medium voltage electron beams. With an intermediate penetration, the technology offers considerably higher throughput, quicker processing, and cost-effective technology when compared to high voltage beams.
Medium voltage electron beam processing is a proven alternative for medium to low-density products, for the short-mid-term needs of the industry with 50-60% chances of conversion success. Also, there is considerable capacity available to the medical device industry at the present time. There is no possibility to induce radioactivity in any substance, given the energy levels involved. The limitations to address are material compatibility issues and penetration on high-density products, although repackaging further improves the probability of success.
Nitrogen dioxide-based sterilization (NO2) refers to an ultra-low temperature sterilization process, which is FDA cleared, efficient, and involves a fast cycle (minutes) that consistently promotes the sterilization of biomedical devices, more often applied to tubes and open vessels. The acquisition cost is minimum compared to an irradiator, but the technology cannot be used in final packages nor products with complex geometries and is more suitable for low and perhaps medium volume processing10.
Hydrogen peroxide plasma also offers quick sterilization cycles of less than an hour with minimal to no residues. While hydrogen peroxide plasma sterilizers are safe and easy to operate, limitation involves specific packaging, small processing capacity and an inability to sterilize strong absorbers, liquids, and so on. Like NO2 technology, they cannot meet the demand for high volumes and are more likely to be applied for low volume processing11. Also, the most recent version of the sterilizer has received FDA 510[k] clearance with limited application for sterilization of medical devices12.
While no miracle technology appears, the need for proven sterilization of medical devices continues to grow. Overall, the search for new sterilization methods will continue and it is time to find an alternative—sooner rather than later—as a sterilization crisis is looming. It is unlikely that EO will disappear from the market, but rather and more logically, return upon restructuring and establishing compliance with new regulations and environmental laws, as some materials just cannot be processed by sterilization technologies other than EO. However, the resultant increased costs and risks with EO sterilization are likely to motivate significant change in the utilization rates of existing and new technologies.
References:
1 https://patientcarelink.org/improving-patient-care/healthcare-acquired-infections-hais/, accessed on 8/8/2019.
2 Global Sterilization Market 2018 - Forecast To 2024: Market is Poised to Reach $8.43 Billion. Marketwatch. Aug 28, 2018.
3 White Paper - A Comparison of Gamma, E-beam, X-ray and Ethylene Oxide Technologies for the Industrial Sterilization of Medical Devices and Healthcare Products. International Irradiation Association. Aug 31, 2017.
4 Another medtech sterilization plant will close in 2019. Medical Design & Outsourcing. Mar 26, 2019.
5 FDA: Closure of medical device sterilization facility could prompt shortages. American hospital Association. Mar 27, 2019.
6 FDA: Device Sterilizing Facility Shutdown Could Have Impact - Whether major disruption will ensue remains unclear. MedPage Today. Feb 27, 2019.
7 https://www.fda.gov/news-events/press-announcements/statement-jeff-shuren-md-director-center-devices-and-radiological-health-agency-efforts-mitigate. Press Release on April 12, 2019.
8 FDA is looking for options amid medtech’s sterilization crisis. Medical Design & Outsourcing. July 15, 2019.
9 https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/ethylene-oxide-sterilization-medical-devices. Food and Drug Administration. Press release on July 15, 2019.
10 White Paper. Nitrogen dioxide Biodecontamination: a new, effective and cost-saving option for biodecontamination Sytinge tubs prior to the filling line. NoxilizerTM. April 18, 2016.
11 Low Temperature Hydrogen Peroxide Plasma Sterilization. Tuttnauer. May 9, 2017. https://tuttnauer.com/blog/low-temperature-hydrogen-peroxide-plasma-sterilization
12 Hydrogen Peroxide Gas Plasma. Guideline for Disinfection and Sterilization in Healthcare facilities. Centers for Disease Control and prevention. 2008. https://www.cdc.gov/infectioncontrol/guidelines/disinfection/sterilization/hydrogen-peroxide-gas.html
Gustavo Varca, B. Pharm, PhD is a worldwide expert in nuclear technologies, and his expertise involves over a decade of experience in radiation processing of medical devices, pharmaceuticals, controlled substances, polymers, tissues, and biologics, focusing on radiation sterilization, material modification, recycling, micro- and nanostructuring of materials, and development of new materials, among others. Associate editor at Radiation Physics and Chemistry (Elsevier), he received 4 international awards for his contribution to the advancement of science and the sciences of ionizing radiation. Varca has authored 30 documents including published papers in scientific journals, book chapters and international patents related to radiation processing of polymers. Distinguished editorial board member, guest editor, and reviewer of several international scientific journals, scientific advisor of the International Irradiation Association (iia) and international consultant on radiation processing in the Americas and Europe. You can reach Varca by e-mail at gustavo.varca@ebeamservices.com or via the phone: (609) 655-7460.
