Originally published July1997
In 1956 Johnson & Johnson developed the first commercial application of electron-beam (E-beam) sterilization processing for medical devices. The initial high hopes for commercializing E-beam technology were short-lived due to the poor reliability of these early systems, and the opportunity for radiation sterilization of medical products was soon seized by cobalt 60 (gamma) irradiators, which had no similar reliability issues.
With the advent of national laboratories devoted to high-energy physics research, a major effort was put into improving the reliability and performance of critical accelerator components. By the 1970s, industry's involvement in developing radiographic and oncology machines further enhanced the durability and reliability of electron accelerators. This improvement of component performance--along with the integration of computerized controls--encouraged reevaluation of the commercial possibilities of the technology and there now exists a growing interest in electron-beam-based sterilization systems.
Given the fact that both gamma and ethylene oxidegas sterilization are effective and readily available technologies, the increased focus on E-beam can be ascribed to its having the shortest process cycle of any currently recognized sterilization method. In E-beam processing, the products are scanned for seconds, with the bulk of the processing time devoted to transporting the products into and out of the radiation shielding. Overall process time, including time for transportation, averages from 5 to 7 minutes. With the use of established and recognized dosimetric release procedures, a product can be released from quarantine as sterile within 30 minutes.
A further reduction in processing time results from the ability of E-beam systems to change over from one lot to another quickly. Products are sterilized as they become available from the upstream production cycle, with no dose groupings or product staging necessary. For example, an E-beam system can make the transition from a product requiring a 25-kGy dose to a different product requiring an 18-kGy dose in the same 5- to 7-minute time frame. As the sterilization process is shortened from weeks or days to hours, the inventory working-capital requirements can be reduced proportionately.
E-beam processing for medical devices involves the use of high-energy electrons--typically with energies ranging from 3 million to 10 million electron volts (MeV)--for the sterilization of single-use disposables. The electrons are generated by accelerators that operate in both a pulse and a continuous-beam mode.2 The elevated energy levels are required to penetrate the product, which is sterilized in its final shipping packaging.
As the beam is scanned through the product, the electrons interact with the device materials and create secondary energetic species such as electrons, ion pairs, and free radicals. It is these secondary energetic species that are responsible for disrupting the DNA chains of any microorganisms, inactivating them and thus rendering the product sterile.
Current E-beam systems, as depicted in Figures 13, typically comprise four major components or subsystems.
Linear Accelerator. The power source for the electrons is the linear accelerator, generally available with energy levels from 3 to 10 MeV and power ranges from 1 to 50 kW (see Figure 1).
Figure 1. Layout of a 10-MeV, 15-kW linear accelerator and process conveyor. All Photos: Titan Scan Systems
Material-Handling System. Typical modern material-handling systems will include the following elements, designed for maximum production efficiency and process integrity:
Figure 2. Layout of a facility with overhead power and free conveyor system.
Figure 3. Layout of small-volume, self-shielded in-line or stand-alone system.
Information and Control Systems. Computerized systems are available to monitor the sterilization process, from overseeing key parameters such as the process conveyor speed to archiving historical data. Such systems control the parameters and verify the integrity of the overall process.
Safety System. For E-beam systems, safety equipment comprises the concrete or the steel/iron/lead biological shielding as well as the supporting monitoring devices that control personnel access, radiation levels, and ozone concentrations.
Early electron-beam applications did not meet expectations, and raised some serious issues regarding the overall suitability of the technology for medical device sterilization. Though public misconceptions about the process may persist, significant progress has been made in educating users about the current status of penetration, reliability, and process continuity issues1.
Penetration. Early application efforts used industrial accelerators with energy levels limited to 4 or 5 MeV. Processing capabilities were limited for case sterilization, and most successful applications were accomplished on a single-product basis. Many current E-beam systems have increased the energy to 10 MeV, and have the ability to penetrate up to 35 in. (90 cm) of 0.10-g/cm3 bulk density using double-sided irradiation.1,2 These capabilities allow a wide range of products to be sterilized in their final shipping cases.
Reliability. The accelerators featured in early applications had been developed primarily for research purposes, and were designed to provide as much energy as possible for the lowest cost. Early designs did not address the 24-hr/day, 7-day/week duty cycle and maintainability requirements now routinely achieved in support of medical product production requirements. Spare parts for critical components often took weeks or months to replace, whereas current requirements call for the system user to have critical items on-site. Today, systems can operate more than 7000 hours per year, with maintenance performed in less than 8 hours per week. Unscheduled system downtime can be held to levels of less than 5%.
Process Continuity. Directly related to the issue of reliability was the issue of process continuity and the consequences of interruptions. If the system faulted during routine production processing, what would be the impact on the dose integrity and the product? Initial systems were validated with a procedure that, when the system shut down, would identify and destroy the product in the beam. Modern state-of-the-art control systems employing programmable logic controllers have made it possible to provide a process interruption procedure that ensures a positive transition dose and maintains dose integrity, preserving the product.1
A significant volume of data exists concerning the effect of ionizing radiation on medical-grade plastics.3,4,6 The impact of E-beam sterilization on materials is similar to that of gamma radiation, with one significant difference. Gamma processing normally exposes the product to the radiation source for between 2 and 6 hours, whereas the radiation exposure time with E-beam processing is less than 1 minute. The shorter exposure time results in less oxidative damage, given the smaller time frame for free radicals to interact with oxygen molecules in and around the product.
Product carrier and loading station of a 10-MeV, 15-kW E-beam system.
Generally speaking, polymers undergo less color change and embrittlement with E-beam processing than they do with gamma, again because of the relatively shorter radiation exposure time. For certain applications, this factor can lead to substantial improvements in product shelf life and appearance.5,7
The ability to conduct in-house radiation sterilization and testing can also be a valuable tool in speeding the overall product development process, as materials can be tested quickly and often to determine optimum specifications and compounding. For high- value, short-lived products, this capability can be invaluable in getting new products to market rapidly.
REGULATORY AND LICENSING REQUIREMENTS
International standards for product, process, and installation qualification for electron-beam systems are established and set forth in ANSI/AAMI/ISO 11137 (1994) and EN 552. The site-license process is similar to that associated with other common machine-generated radiation equipment, such as medical x-ray machines and oncology therapy units. The license is typically issued through a state agency associated with radiological health issues for the given jurisdiction, and licensing can be completed relatively quickly, with no need for public notice or special/conditional-use permits. Additionally, E-beam equipment does not incorporate any radioactive materials or isotopes requiring nuclear materialshandling licenses from agencies such as the U.S. Nuclear Regulatory Commission.
There are two basic system approaches used to sterilize medical devices with electron-beam technology: in-line and stand-alone systems.
In-line Systems. An in-line system is one in which the electron-beam irradiation equipment is integrated directly into the production process. This can be accomplished with a small E-beam unit dedicated to each production line or with several lines feeding a single E-beam system. In either configuration, the system can be designed to process cartons or single products in their sterile packaging (see Figures 2 and 3). For additional information and a comparison of current in-line design alternatives please refer to page 28 of Medical Plastics and Biomaterials July/August issue.
Stand-alone Systems. A stand-alone system differs from an in-line one in that the E-beam equipment is not directly integrated into the production process. This approach is generally used to process many different types of products in their final shipping-carton configurations. Stand-alone systems come in many sizes and are generally classified according to the power of the accelerator--the larger the power, the more product volume that can be processed. Power ranges above 35 kW are available but are seldom used in medical device sterilization applications because of the difficulty of precision control at such high process rates.For additional information and a comparison of current stand-alone system design alternatives please refer to page 29 of Medical Plastics and Biomaterials July/August issue.
Because of their relatively high capital investment and low staffing requirements, sterilization systems are normally operated around the clock on a two- or three-shift basis. Most E-beam systems will maximize their effective performance at usage levels above 7000 operating hours per year. The cost of operating an E-beam system can range from as low as $50/hr for a smaller in-line system to $150/hr for a large-volume stand-alone sys-tem. Normal operating expenses include the cost of staffing, electrical power, maintenance, and supplies.
Staffing. Depending on the size of the system, operation will require from one to four material or box handlers. A trained electronics technician should be on call during system operation, and would also perform routine preventative maintenance and equipment-calibration tasks.
Electrical Power. Power consumption is directly related to the accelerator's kilowatt power, with smaller in-line systems running at approximately $4/hr and larger ones at $15$20/hr.
Maintenance. The cost of replacement parts for spent electronic components makes up the majority of maintenance expense, with most components having fairly well-known service lives ranging from 10,000 to 25,000 hours (mean time before failure).
Supplies. E-beam systems require regular purchase of dosimetry supplies, with the cost of radiochromic films averaging $3 per hour of system operation.
Device manufacturers originally moved away from in-house sterilization because they wanted to avoid the potential liabilities associated with handling radioactive isotopes or toxic chemicals. The fact that these kinds of risks do not exist with E-beam processing is one reason--improved system reliability is another--that sterilization is increasingly moving back into the production lines. When the total processing costs are considered, the use of in-line sterilization to satisfy supply management goals can provide ample justification for system capital expenditures. The higher the product value, the easier the task of moving to E-beam processing as just-in-time manufacturing objectives are set.
1. Allen JT, Calhoun LR, et al., "A Fully Integrated 10-MeV Electron Beam Sterilization System," Radiation Physics Chem, 46(46):457460, 1995.
2. Farrell JP, and Hemmerich KJ, "Selecting a Radiation Sterilization Method," Med Dev Diag Indust, 17(8):8290, 1995.
3. Saunders C, Lucht L, and McDougall T, "Radiation Effects on Microorganisms and Polymers for Medical Products," Med Dev Diag Indust, 15(5):8992, 222, 1993.
4. Sterilization of Health Care Products--Requirements for Validation and Routine Control--Radiation Sterilization, ANSI/AAMI/ISO Report 11137, Arlington, VA, Association for the Advancement of Medical Instrumentation, 1994.
5. Woo L, Palomo J, Ling TK, et al., "Shelf-Life Prediction Methods and Applications," Med Plast Biomat, 3(2):3640, 1996.
6. Woolston J, and Davis AF, A Guide to Designing for Radiation Sterilization, Swindon, England, Isotron, 1994.
7. Ishigaki I, and Yoshii I, "Radiation Effects on Polymer Materials in Radiation Sterilization of Medical Supplies," Radiation Physics Chem, 39(6):527533, 1992.
All authors are employees of Titan Scan Systems, a provider of electron-beam sterilization services and custom-built systems located in San Diego, CA. L. Ray Calhoun is director of business development, with responsibilities that include systems sales and marketing activities as well as contract service-center site selection. Company president J. Thomas Allen has an extensive background in the development and application of factory automation and control systems, including, of course, electron-beam systems. Harry L. Shaffer is vice president and general manager of the company's contract sterilization facilities in San Diego and Denver, and has experience in microbiology, quality control, sterilization methods, and regulatory requirements. George M. Sullivan is a principal systems engineer, responsible for systems design and project management activities for facility installation. C. Brian Williams, PhD, is a principal technical advisor involved in all phases of electron accelerator technology.