Designing and Manufacturing Medical Devices with Antimicrobial Technology
Today's technologies pose a strong alternative to current sterlization processes -- and manufacturers need to be ready to implent them.
By Arif Sirinterlikci
School of Engineering,
Mathematics, and Science
Robert Morris University
Moon Township, PA
A new breed of medical devices is being equipped with antimicrobial technology to prevent microbial contamination and infections. In the US alone, about 1.7 million cases of infections occur annually, causing approximately 99,000 deaths and $45 billion in added healthcare costs reported by Centers for Disease Control and Prevention (CDC) and various other resources.
Recently, legislatures have amplified their demands on healthcare providers to prevent hospital-acquired infections. According to the National Conference of State Legislatures (NCSL), currently 27 states require hospitals, and sometimes other healthcare facilities, to report data on infections. Some states look to monitor process measures, such as how frequently an antibiotic is given to a patient prior to surgery, while others require the reporting of measures such as occurrences of certain types of infections.
Since state laws vary in their requirements, making comparisons across the states is difficult. The CDC National Healthcare Safety Network (NHSN) is the only US national system designed for the collection of infection incidence rates and associated prevention data. In late 2008, Medicare started reducing reimbursements for costs associated with some of the most common infections, including surgical, and vascular and urinary tract catheter infections. Collection of data to date points out that the biofilm buildup within or on medical devices is responsible for at least 50% of the reported infections.
Advancements in medical-device sterilization methodologies are rapidly increasing. The most simple and long-lasting sterilization process has been heating the medical instrument in boiling water. In situations where one did not have enough time to heat the instrument, this process was replaced by the use of antiseptic scrubs and cleansers. According to the CDC, there are a variety of modern sterilization processes in use: thermal, chemical, and radiation.
The oldest, used since the 1950s, and the most commonly used low-temperature sterilizer is ETO, or ethylene oxide. ETO is a highly flammable and explosive colorless gas, which can be used for either temperature or moisture sensitive medical devices. Until 1995, there were two different types of ETOs available for use: one was pure ETO and the other was a mixture of ETO and chlorofluorocarbons (CFCs). Since CFCs were being phased out due to their harm to the earth’s ozone layer, many states began reducing the use of ETO technology. Currently, technologies allowed by the FDA are based on 100% ETO, and use a different inert carrier gas to replace the CFCs. ETO-based sterilization is essentially a combination of four parameters: gas concentration, temperature, relative humidity, and exposure time. The basic cycle for sterilization consists of five stages: preconditioning and humidification, gas introduction, exposure, evacuation, and aeration. The process may take a few hours, but due to the nature of ETO the devices need to be exposed to air for eight to 12 hours afterwards, allowing them ample time to rid themselves of harmful residue.
Hydrogen peroxide gas plasma, was introduced to the US in 1993. These gas plasmas are generated in a vacuum or microwave situation that excites the free radicals which are essentially used to disrupt the growth of microorganisms. After the process takes place, the materials can be freely handled—unlike with the use of ETOs—and there is no need for a waiting period after the process has taken place. The cycle times for the process were reduced more than half with the help of software modifications in the hydrogen peroxide diffusion stage and the unit being able to remove most of the water from the hydrogen peroxide.
Peracetic acid was introduced in 1988 and became a common sterilization technique that removes surface contaminants with chemicals. Water-diluted peracetic acid and an anticorrosive agent are placed together in a container at the time of sterilization. The container is punctured and the lid is closed, the sterilant is then pumped through the container for a few minutes to clean the medical devices. Then, the peracetic acid is discarded and the instruments are rinsed four times with filtered water, then purified air is run through and across the devices to remove excess water.
Ionizing radiation is a type of low-temperature sterilization that uses cobalt 60 gamma rays. It can be used to clean pharmaceuticals, medical devices, and tissue transplants, as well as disposable devices, but is rarely used because of its cost, especially compared to the previously stated sterilization methods. The need for storage of a radioisotope that has the necessary gamma ray properties also gives pause. Although it is a promising route to take for large-scale sterilization, there are not yet any FDA-approved methods for healthcare use. X-rays, electron beam processing, and ultraviolet (UV) radiation can also be used in a similar fashion or scale.
Dry heat sterilization is a method recommended only for use on products that cannot be treated by moist heat methods, including but not limited to petroleum products, powders or sharp objects. This method does have its advantages, including the fact that it does not harm the environment, is nontoxic and noncorrosive, has low costs, and is done in a unit that is easy to install. The process of dry heat sterilization is time-consuming, however, running anywhere from 60 to 150 minutes, depending on the temperature of the specific process.
Although there are other various types of liquid chemicals that are FDA-approved for sterilization, which can range anywhere from a three to 12-hour process, they are not as well understood as most of the methods mentioned above. There is no specific guideline or test to verify that a device is sterile after using a liquid chemical process. Overall, use of such processes may not assure the same quality of sterilization as other methods.
Antimicrobial technologies pose a strong alternative or complement to sterilization processes, and are not new. Ancient civilizations employed them in keeping their water clean and food safe by prohibiting growth of microorganisms. Today’s antimicrobials may be either natural or synthetic and are introduced into the material of the product or medical device. They kill or suppress the growth of organisms including algae, bacteria, and fungi. Medical devices in particular are prone to biofilm buildup—a bacteria or virus-based slime layer resistant to antibiotic interference—and can benefit from antimicrobials. Technologies associated with antimicrobials help control odors, staining, and discoloration and changes in mechanical properties as well as cross contamination. Various antimicrobials and methods are available:
Silver-based antimicrobials slowly release silver ions using an ion exchange mechanism based on ceramic zeolite or silicate carriers entrapping the ions. In the presence of microorganisms the silver ions will move to the surface of a treated medical device to prevent biofilm buildup. After reaching the cell of the microbe within the biofilm, ions attach themselves to the DNA of the microbe and stop cell replication. This method is used on plastic parts to keep bacteria from spreading. It is a slow and regulated process but provides a lasting effect. Silver nanoparticles are also employed in other silver-based applications.
Zinc-pyrithione antimicrobials stop the growth of yeast, fungi, and mold. They are used in cosmetics and beauty products. They are also used in paints and sealants as a component to help with the strong odor. They depolarize cell membranes’ electro-potential in microorganisms to hinder fungal and bacterial substrate transport mechanisms.
Isothiazolinone-based antimicrobials are employed mainly in cosmetic, household, and industrial products. This technology acts on microorganisms by oxidizing or interacting with cellular thiols.
"This new technology needs to coexist with the sterilization processes in the medical-device field,
but with the hope of eliminating sterilization in the future."
Oxybisphenox-arsine (OBPA) is used in the flexible PVC and polyurethane industries. It is an organometallic compound with excellent heat stability.
Thiabndenzole-based antimicrobials cause distortion of germinating spores and disrupt cell division of many different types of fungi.
Triclosan inhibits growth of fungi and bacteria by disrupting cell walls using electro-chemicals. The penetration into the cell wall causes cell functions to be disabled, thus stopping the microorganisms from functioning or reproducing, similar to that of silver ion attacked cells.
Commercial successes of antimicrobials have been well documented. Silver Clene 24, a silver ion product of Agion Technologies (Wakefield, MA), is used as a liquid disinfectant and is proven to kill bacteria and viruses within 30 seconds after the spray. It keeps surfaces almost 100% clean for up to 24 hours while posing no harm to people or animals. The amazing thing about silver ions is that they can be built into the body any type of product or deposited with a coating. The technology can be applied from fabrics to paper to paints to medical devices, and even to food-storage packaging. The products based on this technology are also being considered for use in sporting-good equipment, uniforms, and footwear. Agion Technologies and Thermoplastic Biologics LLC (Newton, NJ) have recently joined forces to apply silver ion technology to tubing systems, from use in water transportation to medical devices.
Antimicrobial-reinforced medical devices on the market today include those devices associated with health-acquired infections, such as urinary catheters, central venous catheters, and wound-care products. Some of the medical devices with antimicrobial technology have been through clinical trials and gained FDA clearance.
Selecting the right antimicrobial technology
Manufacturers of medical devices can look to those antimicrobial technologies that are compatible with their manufacturing processes and meet the requirements of the target medical devices. Jeff Trogolo, CTO of Agion Technologies, has detailed the key factors in selecting the right antimicrobial technology as manufacturing processes, sterilization, safety, and efficacy. We’ve added a separate design factor, conflict of functions, to his list:
Manufacturing processes: Antimicrobials can be applied to medical devices as a coating to the device surface or integrated into the material of the device. Manufacturers must choose technologies that are compatible with their manufacturing process capabilities.
"Manufacturers of medical devices can look to those antimicrobial technologies
that are compatible with their manufacturing processes."
Conflict of functions: Designers need to make sure that multiple functions of their designs are not in conflicting nature. If a manufacturer is using a coating for lubricity requirements and embeds an antimicrobial into the medical-device material, the additional coating may block the release of the antimicrobial ions making them dysfunctional.
Sterilization: Even with the idea of replacing sterilization, the antimicrobial technologies still need to coexist with the sterilization processes. Manufacturers need to identify a compatible sterilization method for each antimicrobial technology to prevent stabilization problems when subjected to the chemicals, radiation, and heat of the sterilization processes.
Safety and efficacy. Manufacturers must consider the safety and efficacy factors for their target devices. A catheter used on an adult patient for a few days may not be suitable for draining critical fluid of a pediatric patient for longer time periods, for example.
Antimicrobials have been successfully used in a wide range of products, including medical devices. This new technology needs to coexist with the sterilization processes, but with the hope of eliminating sterilization in the future. ME
This article was first published in the January 2012 edition of Manufacturing Engineering magazine. Click here for PDF.