By Jan H. Schut
Plastic surfaces on medical devices and equipment in hospitals and clinics make great breeding grounds for bacteria, including some of the nastiest germs around. The typical solution to infections in hospitals is antibiotics for patients and biocidal cleaners for the hospital room. The unintended consequence, however, is that bacteria may develop resistance, particularly to antibiotics, making them far more dangerous, like MRSA (methicillin resistant Staphylococcus aureus), the so called “flesh eating” germ, or multi-drug-resistant “gram-negative” bacteria.
Prevention is the new cure. The New Technology Forum on “Advances for Antimicrobial Technologies in Plastics” at the Society of Plastics Engineers’ ANTEC 2011 Conference will present the state of the art on May 4 at 1:30 p.m. in the Hynes Convention Center in Boston (www.4spe.org/antec2011 -registration). Five experts will set out the latest developments, analyze regulatory and testing hurdles for antimicrobial chemistries, and introduce two new chemistries to the plastics industry for the first time. The full ANTEC program May 1-5 also includes three Medical Plastics sessions (T13 Tues. a.m. on May 3; W3 and W25 Wed. a.m. and p.m. on May 4).
“The big issue will be silver,” says Roger Avakian, vice president, scientific development at compounder PolyOne, Avon Lake, Ohio (www.polyone.com), who is co-chairman of the New Technology Forum on antimicrobials and also a presenter. “How can we get something as good as or better than silver?”
Silver has traditionally been the active ingredient in most antimicrobial plastics for decades. It’s typically either a silver ion bound to zeolites (aluminosilicate) or some other inert carrier, or nano-scale metallic silver in liquid, known as colloidal silver. Ionic silver antimicrobials are made by four companies in Japan: Ishizuka Glass Company in Nagoya (www.ishizuka.co.jp) offers IonPure encapsulated in glass; Sianen Co. Ltd. in Nagoya offers Zeomic (www.zeomic.co.jp); Fuji Chemical in Osaka offers Bactekiller; and Milliken sources silver sodium hydrogen zirconium phosphate for its AlphaSan antimicrobial from Toagosei Co. Ltd. in Tokyo (www.toagosei.co.jp).
But after decades of being considered environmentally harmless, silver is being questioned for possible environmental side effects like harming beneficial microbes in the soil, harming fish and stunting sperm cell development (Aug. 2010 issue of Toxicological Sciences”).
PolyOne’s Avakian will give an overview of antimicrobials, analyzing the different types of microbes, which can actually form a living film of germs on surfaces, known as biofilm, and what technologies are being used and developed to fight them. “Hospital acquired infections (HAIs) kill more Americans each year than AIDS, breast cancer and auto accidents combined,” PolyOne’s Avakian says. HAIs like ventilator-acquired pneumonia, bloodstream infections, urinary tract infections and surgical site infections aren’t systematically studied or counted, but the Centers for Disease Control and Prevention in Atlanta estimated in 2002 that there were about 1.7 million cases/year including 99,000 deaths in the U.S. The CDC estimated the cost of treating HAIs at $28 billion to $35 billion in 2007. After 2008 Medicare stopped reimbursing hospitals for HAI costs, putting the burden onto hospitals.
Yet despite increasingly dangerous microbial adversaries and high costs for hospitals, big chemical companies in the U.S. and Europe aren’t investing much to develop new and better antimicrobial chemistries, says presenter K. Mark Wiencek, senior microbiologist at chemical additive producer Milliken & Co., Spartanburg, S.C. (www.milliken.com). The reason, he asserts, is primarily regulatory.
Antimicrobials in the U.S. are regulated by the Environmental Protection Agency. “To register and get approval for a new antimicrobial chemistry takes many years and millions of dollars, so few companies can justify doing it,” he explains. “There have been very few new active ingredients for incorporation into plastics commercialized over the last three to five years.” Antimicrobial R&D is also drying up in Europe, where the European Union is creating an EPA-like body to regulate antimicrobials under the Biocidal Products Directive, he adds.
Does this mean the antimicrobial pipeline is running dry just when better chemistries are needed most? Not quite. Milliken’s Wiencek will present “Battling the Bugs: Antimicrobials for Plastics in Healthcare Applications,” putting the regulatory scene in perspective and showing where to look for new antimicrobials. They are still being developed in Asia, where regulation is laxer. The Chinese are also trying out some less stringent natural antimicrobials like chitosan, a derative from crab shells, and bamboo fiber, which ran afoul of EPA regulators in this country.
New chemistries and ideas are also coming out of academia, Milliken’s Wiencek says. Surface textures designed to reduce attachment of microbes is another avenue for defense against germs. University of Florida, Gainsville, professor Anthony Brennan, discovered that micro-embossed patterns similar to those on sharkskin form a surface pattern to which bacteria can’t attach. It’s being commercialized by Sharklet Technologies Inc., Aurora, Colo. (www.sharklet.com). If the surfaces repel microbes, rather than killing them, they may not be subject to EPA regulation.
New chemistries are hard to commercialize in building materials, handrails and furniture, but they can be commercialized in medical devices. “Antimicrobial technologies are becoming more prevalent in the medical device industry,” notes Steven Elliott, director of microbial assays at WuXi AppTec Inc., an independent contract testing firm headquartered in Shanghai, China (www.wuxiapptec.com. “Hospitals and physicians are preferentially using medical devices proven to reduce the risk of HAIs because the cost of treating many HAIs isn’t reimbursed. So antimicrobials are being incorporated into a lot more.”
WuXi’s Elliott will present “Antimicrobial Evaluation—Test Methods, Medical Device Industry Trends and More” elaborating on the latest trends in antimicrobial testing for product approval and labeling. Medical devices are regulated by the Food and Drug Administration, which tests and evaluates the efficacy and hazards of a device as a whole, rather than regulating each ingredient in it like the EPA. “We typically deal with the FDA perspective, not the EPA,” he explains. Clinically relevant testing has to demonstrate significant reduction of the challenge organism—bacteria for an antibacterial device claim and fungi as well as bacteria for the broader antimicrobial device claim. WuXi has three U.S. R&D and production sites in Philadelphia, St. Paul, Minn.; and Marietta, Ga.
New Biocidal Chemistries
Two new chemistries will be introduced to the plastics industry for the first time in the forum.
Steffen Helmling, vice president of business development at emerging biotechnology company PolyMedix Inc. in Radnor, Pa. (www.polymedix.com) will present “PolyCides – Broad Spectrum Antimicrobial Materials for Industrial Applications.” PolyMedix’s multi-patented antimicrobial chemistry uses the same principle as antimicrobial host defense proteins, a component of the body’s own defense system. PolyMedix developed small synthetic protein mimics that have one lipid-loving face and one water-loving face (amphiphilic molecules). This allows them to kill bacteria by selectively inserting themselves into the bacterial cell membrane. “Our mechanism is different from other commercially available antimicrobials. It’s a biophysical approach that targets and destabilizes the bacterial cell membranes, whereas silver has to be metabolized,” Helmling explains. “This mechanism also makes the development of bacterial resistance unlikely.” The PolyCide compounds are between 5800-2500 molecular weight and are incorporated into plastics like PVC or polyurethane at levels of 0.5-1%. “Our molecules have certain properties, which lead them to aggregate at surfaces, where they are active,” Helmling notes. They can also be used in a surface layer. PolyMedix is testing its PolyCides with a number of partners primarily for medical device applications, but would like to expand testing to include working with compounders to create biocidal plastic additives.
James L. Delattre, vice president of global marketing at new technology company NanoHorizons Inc. in Belafonte, Pa. (www.nanohorizons.com) will present “Developments in Antimicrobial Polymers,” in particular NanoHorizon’s development of a nano-scale silver additive. It is nano scale like colloidal silver, but can be integrated into polymers without agglomeration. NanoHorizons, a spin off from Pennsylvania State University in State College, Pa., combines its patent-pending nano silver with dispersible thermoplastic polymers including PE, PP, PEBA (polyether block amide), nylons and polyesters. It’s most effective with nylons and polyesters because the moisture they attract oxidizes the nano silver more rapidly. It’s still slower acting than ionic silver zeolite, but is reportedly more durable. It has been commercial in fibers for four years and in thermoplastics for two years.
The panel discussion following the presentations will tackle fundamental processing issues for the different chemistries. “Thermal stability and dispersion are critical issues in addition to efficacy. All antimicrobials aren’t alike,” notes co-chairman of the forum and panelist Vaman G. Kulkarni, R&D fellow at Americhem Inc. (www.americhem.com) For example, triclosan and other organic antimicrobials, which are commonly used in liquid preparations, but not in plastics, can be used in lower temperature polymers like PVC and PE, but aren’t suitable for engineering polymers and fiber-forming resins. Dispersion is also a lot more critical in fibers or thin film, he notes, than in molded parts because poor dispersion can cause processing problems and breaks in film or textile fibers.