Medical Device Link.

Originally Published MDDI May 2001

STERILIZATION

Exploring the Feasibility of Using Dense-Phase Carbon Dioxide for Sterilization

Though still in the research stages, sterilizing with CO₂ may soon be a viable option—both economically and logistically—for medical device manufacturers.

Michael A. Matthews, Langdon S. Warner, and Heinz Kaiser

A basic schematic of the proposed CO2 sterilization chamber.

The conventional sterilization processes commonly used by medical device manufacturers—EtO, steam, gas plasma, and gamma irradiation—are proven technologies. By gauging the requirements of their products and doing cost comparisons for various methods, manufacturers settle on a sterilization process of choice. But a new sterilization process for medical devices, dense-phase carbon dioxide (CO₂), may change some manufacturers' opinions. Although still in the research phase, sterilizing medical devices using dense-phase CO₂ may prove to be a viable alternative both for OEMs and for end-users at healthcare facilities.

This article explores the technical and economic feasibility of a possible dense-phase carbon dioxide (CO₂) sterilization process, comparing it to currently available commercial processes. Dense-phase CO₂ has been shown to deactivate some microorganisms. Although research is ongoing, CO₂ may prove to have certain technological, environmental, and safety advantages compared with existing sterilization methods.

For the purposes of this article, the costs of sterilization using available equipment were determined from a survey of operations in a major research facility. The capital and operating costs of the hypothetical CO₂ sterilizer were estimated based on similar equipment that is currently being developed for other applications.

CO₂BACKGROUND

The Supercritical Fluid State. When gaseous or liquid CO₂ is heated and compressed above the critical temperature (31°C) and pressure (73 atm), it becomes a dense, highly compressible fluid that demonstrates properties of both liquid and gas. Substances in the supercritical fluid (SCF) state normally have better solvating ability than do the same substances in the liquid state. The SCF has a viscosity similar to that of a gas, but a density closer to that of a liquid. The properties of an SCF can be changed by adjustments of pressure and temperature. Because of the low viscosity of SCFs (compared with familiar liquid solvents), an SCF can penetrate small orifices. Additionally, substances disperse throughout the SCF rapidly, due to high diffusion coefficients. ¹

Dense-Phase Fluids. The liquid phase of CO₂ requires temperatures to be below ambient, but pressure can typically be decreased to between 700 and 1000 psi. The lower pressure decreases costs, but some of the unique properties of the SCF state are sacrificed as a result of the lower pressure. Nevertheless, the liquid state of CO₂ conserves some of the solvent properties of the supercritical state—namely low viscosities, high diffusion coefficients, and acceptable solvent power. Collectively, the term dense-phase fluid refers to operations in either the supercritical or liquid states.

Environmental Benefits. CO₂ is of particular interest in dense-fluid technology because it is inexpensive, nonflammable, nontoxic, odorless, and nonpolluting. Manufacturers—or healthcare workers and patients at the end-user stage—would not be exposed to toxic residues using CO₂-based sterilization. Some current sterilization and disinfection methods—EtO processes, for example—use toxic and flammable substances that have a strong odor.

CO₂ is not a hazardous substance regulated by the Environmental Protection Agency, and its use in sterilization would not contribute to the greenhouse effect because CO₂ would be captured as a by-product from other industrial activity.

COMMON STERILIZATION METHODS

Steam. Steam sterilization is widely used by medical device manufacturers and end-user facilities because it is effective, efficient, safe, and inexpensive. It cannot be used to treat heat-sensitive materials, however. The main effect of steam is to denature the proteins in the microorganisms and break down the microbial proteins, lipids, carbohydrates, and nucleic acids.

EtO. EtO is a colorless, flammable, and highly reactive compound. Due to its low boiling point of 10.4ºC (50.7ºF) at atmospheric pressure, EtO behaves as a gas at room temperature. EtO chemically reacts with amino acids, proteins, and DNA to prevent microbial reproduction. ^2,3 This alkylating agent is widely used to sterilize heat-, radiation-, and moisture-sensitive materials such as those containing plastics and microelectronics. It should not be forgotten, however, that EtO is toxic and explosive. EtO sterilization facilities require extra ventilation and safety precautions.

Gas Plasma. Like EtO, hydrogen peroxide plasma is used for the sterilization of heat-sensitive devices that cannot be treated above 60ºC. Plasmas can be created at high or low temperatures in strong electromagnetic fields. The advantage of using plasmas is the absence of toxicity after the electromagnetic field is shut down. ⁴ In this method, sterilization is achieved by the use of hydrogen peroxide gas plasma for 45 to 75 minutes total cycle time, at low temperatures and in an environment of low moisture.⁵

Table I: Loads processed in the study facility's sterile processing department during February and March.

SURVEY OF STERILIZATION OPERATIONS

To provide a quantitative basis for comparing CO₂ sterilization to existing technology, the sterilization operations at a major South Carolina hospital facility were surveyed. At this location, there are 48 machines performing sterilization that are dispersed among the different departments in the facility. The predominant sterilization method is steam, selected because of its cost advantages and effectiveness. The sterile processing department, however, has EtO and hydrogen peroxide gas plasma sterilizers in addition to the steam systems. These latter two methods of sterilization are used with heat-sensitive instruments.

Due to the diversity of the machines, chamber sizes, cycle times, rates of usage, and methods of sterilization, a cost per cubic foot was determined in order to compare costs among the different sterilization methods. The cost per cubic foot was determined by dividing the total monthly cost by the number of cubic feet processed in a month. The total monthly cost consists of the mortgage payment on the capital invested in the machines (with a fixed 7.5% interest rate for 10 years), the monthly portion of the respective maintenance cost, and the operational cost of processing each load in a given month.

The sterile processing department is the only department in the facility that sterilizes items with methods other than heat and steam. As a result, this department was more closely studied. Information about the number of loads was collected for the months of February and March 1999. Table I shows the number of loads during these two months and identifies which sterilization methods were used.

The steam loads were processed in Amsco 3053 machines, each with a capacity of 30 cubic feet. The EtO loads were sterilized with Amsco 3017 sterilizers, each with a chamber size of 5 cubic feet. The hydrogen peroxide gas plasma loads were processed in a Sterrad 100 with a 3.5-cubic-foot chamber. The cost comparison for the different sterilization methods in the sterile processing department is shown in Figure 1.

Figure 1. Cost comparison for the study's sterilization methods.

Personnel. The personnel cost for the sterile processing department was surveyed in order to obtain the personnel cost per cubic foot of sterilizing surgical instruments. At the time of the survey, there were three shifts. The function of these employees is to sort, disassemble, clean, assemble, inspect, pack, and wrap the items to be sterilized. This activity generates an additional dollar amount per cubic foot required for each of the different sterilization methods.

The personnel cost for processing heat-resistant devices is approximately $7 per cubic foot in the sterile processing department. Heat-sensitive devices have a higher personnel cost per cubic foot, however, at $37.

THE PROTOTYPE CO₂ STERILIZATION PROCESS

Based on several patents, ^6–12 as well as the experiments performed by several researchers,^13–20 a hypothetical set of process conditions was chosen for a prototype CO₂ sterilizer. The primary consideration is pressure, which may be as high as 200 atm or more in industrial SCF processes. The temperature required for supercritical CO₂ sterilization is close to room temperature, ranging from 35º to 45ºC. Agitation of the CO₂ is an important factor that may reduce the time required for sterilization. The water content may also affect the sterilization cycle time. Higher water content improves the permeability of an organism, allowing the CO₂ to penetrate the cell wall and kill it. Although the method of sterilization using supercritical CO₂ has not to date been completely defined by research, the general procedures are similar among the different researchers. This prototype CO₂ sterilization cycle uses the following steps:

• Prepare and package the materials.
• Place materials into the high-pressure chamber.
• Pump CO ₂ at the selected pressure and temperature into the chamber.
• Cycle the chamber pressure several times during the sterilization cycle.
• Stop agitation and depressurize the chamber.
• Remove the sterile material.

CAPITAL AND OPERATING COSTS

To determine the capital and operating costs of a hypothetical dense-phase CO ₂ sterilizer, several manufacturers of existing commercial equipment were contacted, along with several experts in the field. Commercial applications include dry cleaning and parts cleaning with CO₂. These processes operate at conditions similar to those expected for the CO₂ sterilization process. The annual maintenance cost, according to equipment manufacturers, ranged from 3 to 10% of the cost of the equipment.²¹

The operational cost per load is determined by considering technical aspects of a CO ₂ machine and the supplies required to comply with terminal sterilization (sterilization of sealed containers) standards. The variables affecting the cost per load are size of the chamber, degree of CO₂ recycling, cost of CO₂, cost of power, cycle time, and cost of supplies.

The Chamber. The chamber size determines the amount of CO ₂ needed to sterilize or clean the load. In this study, the chamber size is 3.5 cu ft. The amounts of CO₂ required for a 3.5-cu-ft chamber in the liquid and supercritical stages are 180 and 205 lb, respectively. Recycling minimizes CO₂ losses, but also increases the power consumption. The recycling percentage selected for this analysis is 95%.

Although the cost of CO₂ is relatively low ($0.20 to $0.25 per lb), it is an important factor in the cost per load. The CO₂ cost used in this analysis is $0.20 per pound. The hourly operating cost for this analysis is $1.50.

Supplies. There can be no accurate information given about the cost of supplies for CO₂ sterilization because these supplies are specific for each sterilization method. For example, the pouches and wraps used in the hydrogen peroxide gas plasma machine are different from those used in EtO and steam sterilization.

Wraps and pouches allow the sterilant to come in contact with the items being sterilized. Other supplies that must withstand the sterilization process include biological indicators, chemical indicators, and tape. For the purpose of this article, it is assumed that the cost of these supplies is similar to that considered in the EtO and gas plasma hydrogen peroxide methods. The cost per load of these supplies is approximately $8.25.

The cycle time influences the number of cubic feet that a sterilizer is able to process. Shorter sterilization cycles improve the turnover rate of the materials, offering more flexibility and decreasing the investment in additional equipment. A cycle time of 2 hours was selected for the hypothetical CO₂ sterilizer.

The cost per cubic foot for CO ₂ sterilization was determined following the previous model developed for steam, EtO, and hydrogen peroxide. The capital, maintenance, and operational costs were added, and this sum was divided by the maximum number of cubic feet that the CO₂ sterilizer would process per year. The principal variables influencing the cost per cubic foot of CO₂ sterilization, and the cost per cubic foot, are shown in Table II. This table depicts the conditions and values of probable equipment.

Variable	Parameter	Cost
Capital cost	Chamber size: 3.5 cu ft	$170,000
Maintenance	5% of capital cost	$8300/year
Operational cost	—	—
CO2 cost	Recycling 95% of 181 lb $0.20 per lb	$1.80 per run
Power cost	Cycle time 2 hours at $1.50 per hour	$3 per run
Supplies	Pouches, wraps, BI, CI, tape	$8.25 per run
Total cost per run	—	$13
Cost per cubic foot	—	$5.9

Table II: Variables affecting the cost of CO^₂ sterilization (prototype).

STERILIZATION METHOD COMPARISON

The steam sterilizer chosen as a basis for this study is an Amsco 3053-S prevacuum currently used in the facility's sterile processing department. This sterilizer has a maximum capacity of 30 cu ft for the sterilization of porous-, heat-, and moisture-stable goods. A microcomputer system monitors and controls all the operations and functions during the sterilization process.

The EtO sterilizer used for comparison is an Amsco 3017 that uses 100% EtO. This sterilizer, with a capacity of 5 cu ft, is equipped with an aerator to reduce the EtO levels in the breathing zone. A single-dose gas cartridge provides the 100% EtO, which is enough gas sterilant to process one load. This system also has a microcomputer that monitors and controls operational variables

The Sterrad 100 is a hydrogen peroxide gas plasma sterilizer produced by Johnson & Johnson. This sterilizer is able to process loads up to 3.5 cu ft. The installation and operating requirements consist of a simple connection to electricity; no water, steam, or air supply is needed. All of the operations are controlled and monitored by a microcomputer, which generates system performance records for each cycle. A cassette with 10 individual doses provides the hydrogen peroxide.

In the case of a prototype CO ₂ sterilizer, it is assumed that a 3.5-cu-ft vessel is used. The vessel is constructed of stainless steel in order to support the elevated pressures needed to reach the supercritical stage (200 atm). The method of agitation is important, but the precise details must be determined through further research. CO₂ machines must be designed with microcomputers that control and monitor the pressure, temperature, and time. For quality assurance and safety reasons, they must also register and print sterilization time, fluid conditions, and other parameters as is done with steam, EtO, and hydrogen peroxide sterilizers.

Hydrogen peroxide and CO₂ sterilizers operate without process steam, air, or water. Moreover, they do not require drain or gas exhaust to dispose of their process waste. The two-hour CO₂ cycle time is likely to compete with the Sterrad cycle of 75 minutes and is much shorter than the 15-hour cycle required by the EtO sterilizer.

COST BENEFITS OF CO₂

In order to introduce a new sterilization technology, of course, it must be cost competitive. The technological advantages alone may not be enough to justify replacing capital equipment if the costs do not benefit customers and manufacturers alike. The capital costs of new technology are normally higher than those of established technology due to the investment made and the lack of economies of scale. Presumably, the estimated cost of the machine would decrease over time as a result of competition among different manufacturers and additional technological improvements.

Table III summarizes the cost comparison based on the assumptions and data described above. The maintenance cost of CO ₂ sterilization is similar to that of a Sterrad 100; however, the cost of maintenance does not strongly influence the cost per cubic foot. The availability of service affects the decision of acquiring sterilizers. Service is an important factor for current customers of steam, EtO, and hydrogen peroxide gas plasma sterilizers. For example, both Steris and Johnson & Johnson offer a coast-to-coast service for repair or preventive maintenance. Other competitors offer similar service in the United States and abroad. Companies trying to commercialize CO₂ sterilization would necessarily have to offer a similar service.

The cost per cubic foot for the different sterilization methods puts all these sterilization technologies on the same basis. Capital, maintenance, and operational cost are summed in a single cost. The cost per cubic foot for steam sterilization ($1 per cu ft) is the least expensive of all the methods considered in this analysis. This is as expected due to the advantages of steam sterilization previously mentioned. The cost per cubic foot of CO ₂ sterilization is lower than that of EtO ($6 versus $19). Factors increasing the cost per cubic foot for EtO are the long cycle time, risk management activities, insurance, legal liability, and monitoring equipment, among others. Based on this cost analysis, CO₂ and H₂O₂ sterilization would most closely compete due to the cost and technical advantages.