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July 1, 2004
12 Min Read
Originally Published MDDI July 2004
The success of drug-eluting-stent applications has created a wave of interest in coatings for a number of device sectors. But with greater acceptance comes higher expectations for coating processes, applications, and performance.
Until recently, some sectors of the medical device industry considered the use of coatings a luxury. Then drug-eluting stents, which used coatings to release a drug from the stent to prevent restenosis, hit the market. The resulting publicity made the industry as well as the public aware of how the right coating can radically transform a medical product.
With that optimistic outlook, then, it is not surprising that a number of next-generation coatings have come on the market recently, and many of them have sparked interest from device manufacturers. Firms with implantable products are looking to coatings to enhance a number of characteristics, including bio- and hemocompatibility, lubricity, antimicrobial action, and, of course, drug release. For other products, hardness and conductivity are among the desired features to be gained from using a coating.
Firms are looking for coatings that will enhance characteristics such as lubricity and drug release.
“Drug-coated stents are the most noteworthy development of recent years primarily because they have furthered the general acceptance of coatings on medical devices,” said Suzanne Conroy, coatings group manager at AST Products Inc. (Billerica, MA). “Even lay people are aware of drug coatings on stents. There is now the general trend to accept other coatings, such as lubricious coatings, as a matter of course.”
Andrew Jacobson, director of business development for Carmeda AB (Upplands Vasby, Sweden), said that industry has taken note not only of the enhanced capabilities that coatings can bring, but of enhanced revenues as well. Drug-eluting stents “have been a catalyst for device firms to become aware of the potential commercial benefits of coatings,” he said. “Coatings, except on stents, have been a blip on the radar in terms of market penetration. But they made stents go from a $1 billion–$2 billion market to a $3 billion–$5 billion one. Now there is more regulatory awareness of them and more guidance for them. In the past, it was a nebulous field.”
As might be expected, much research is being done on coatings that offer drug-delivery properties. This is expected to lead to products that provide more complex and precise dosing regimens than those currently available. However, these developments have forced device companies to consider new sets of factors when developing coating products and technologies, or choosing vendors for those tasks.
“It's a completely different use of coatings,” said David Garcia, president and CEO of Boyd Coatings Research Company, Inc. (Hudson, MA). “In past cases, the coating remained on the surface regardless of what it was supposed to do. Here, it comes off in some way, shape, or form. So you have to take into account why that happens and figure out how to control that.”
This characteristic has led to experimentation with materials that weren't previously considered candidates for medical device coating applications.
“There are materials that won't work with other applications that may work for this one,” Garcia said. “For example, a material that is very porous may not be considered for some device applications, but may be considered for a drug-eluting application because the drug can be embedded in the pores of the coating.”
These new uses are also leading to enhancements of other kinds of coatings. “The methodology of the application often finishes in very controlled thicknesses and very controlled conditions. This could produce methodologies that improve standard coating applications,” Garcia said. “We are always seeing new methods, new procedures, and new ways of applying coatings in a more precise manner to produce better end results.”
One breakthrough that is likely to be commercialized soon may lead to coatings that can dispense two or more substances from a device inside the body.
“More-sophisticated coatings are in the works. One that can handle two drugs? One that has a drug and a complementary technology? We are checking these out. Once we've crossed the threshold, the whole natural life cycle of products will come down,” said Charlie Olson, general manager of hydrophilic technologies for SurModics Inc. (Eden Prairie, MN). “Eluting multiple drugs will better allow them to go after many thrombus issues.”
Going beyond Stents
Jacobson predicted that in the stents of the near future, “you'll see an antirestenosis agent coupled with a heparin entity to address subacute thrombosis. Or a lubricious compound added to make for easier delivery of the stent. Likewise, in wound care, you'll see antimicrobial and growth-stimulation mechanisms combined.”
Also, Olson said, coating technologies that have caught on in the cardiovascular world could expand to other areas. “Neurological applications require some of the same techniques, just in a smaller space. These could have lubricity, hemocompatibility, and drug-eluting properties balanced and working in harmony.”
Drug-eluting coatings on tubing can prevent restenosis (click to enlarge).
In fact, he said, “we've got work going on in a lot of different areas.” Carmeda is conducting research in key sectors such as ophthalmology, orthopedics, and neurology. Neurology is like cardiology was 20 years ago in that it is just starting to do more with less, Jacobson explained. Because grafts and aneurysm repair in the brain are emerging markets with first- or second-generation coatings, he said, a lot of development work is being done in these areas.
Conroy said AST's LubriLast coating is being sought out for precisely such applications.
“The veins and arteries in the brain are tortuous. There is a need to make [coated devices] as slippery as possible to facilitate access. While lubricious coatings are completely different from drug-eluting coatings and are easier to apply, we have been able to leverage our experience with these more traditional coatings to develop stent-coating systems that have been shown to be quite effective in animal trials,” she said. “Of course, due to the nature of this new technology, we have been careful to address regulatory concerns that our customers might have.”
FDA's increased awareness of coatings is both a boon and a bane. Now that the agency has become more familiar with coatings, reviewers have a better understanding of what these products are supposed to accomplish and how they should be deployed. This awareness, in fact, could end up encouraging more firms to employ coatings. However, with increased use comes higher expectations. The agency is paying more attention to consistent application of coatings. The agency is also working to ensure that coatings are compatible with both the device and the body.
As more medical device manufacturers explore the use of coatings, the ability to respond to the regulatory environment becomes more important for coating manufacturers. “Biocompatibility is a major concern in this area. We responded to those trends with quality management systems, FDA drug and device master files, and ISO certifications,” said Lonny Wolgemouth, medical market manager for Specialty Coating Systems (SCS; Indianapolis), a Cookson Electronics company.
Adding biomolecules, proteins, and nucleic acids to device coatings to help them survive pressure and sterilization is an example of an area where more knowledge has also meant more awareness from regulators, said Lise Duran, SurModics' vice president and general manager for regenerative technologies. “There are [now] ways for coatings to be applied without affecting bioactivity. Before, almost any modified surface decreased bioactivity. But with that [advance] goes some experience in the regulatory environment,” she said. “We were not clear on how to test for [bioactivity], to ensure that [the coating] was doing what it was supposed to do.” She noted that as more firms have learned how to adequately test for decreased bioactivity, the regulatory community has embraced coatings with biocompatible properties.
Olson: There are very few devices that wouldn't benefit from some type of coating.
Parylene, a substance that has been used successfully in drug-eluting stents, is one material for which new medical applications are being researched heavily.
Medical customers typically favor parylene coating for its lubricity, transparency, chemical resistance, low permeability to moisture, high dielectric strength, and inertness. “No other polymer can offer these uniformly at thicknesses ranging from thousandths of an inch down to the angstrom level, pinhole free,” said Gustavo Arredondo, technical manager of Para Tech Coating Inc. (Aliso Viejo, CA). “Parylene has been found to have the best trade-off properties for biomedical applications and is considered a chemically stable insulator.” He said parylene has also shown a high degree of resistance to degradation by gamma rays at atmospheric pressure and under vacuum.
Radiation resistance has given parylene a major role in cell-growth applications, Arredondo added. It has an optical quality far better than other materials, such as Mylar or polypropylene, that are typically used in laboratories. “Ongoing research involves the study of different cells under exposure to low radiation levels,” he said. “In this type of application, a thin parylene film can be deposited to ideally reduce undesired radiation scattering that affects the exposure for the growing cells,” said Arredondo.
SCS recently introduced a new generation of parylene with improved temperature resistance. According to the company, the new product, Parylene HT, can withstand up to 450°C in the short term and 350°C in the long term. Other kinds of parylene have typically been unable to withstand long-term temperatures above 100°C.
“There are now opportunities for parylene that were not doable before,” Wolgemouth said. “Other qualities of parylene, such as biocompatibility and lubricity, all remain intact.” Within the medical device industry, he said that electrosurgical devices are an immediate opportunity because temperatures on electrocutting tools can go up to several hundred degrees Celsius. “Any medical product application requiring high-temperature sterilization will also probably fit well,” he said.
Thin Is In
A common theme in the new generation of coatings is the ability to be applied in extremely thin layers. Coatings that were once measured in microns are now measured in angstroms. And in some cases, dipping and spraying application techniques have given way to more-controlled methods. Techni-Met Inc. (Windsor, CT) has a new process called sputtering technology that uses a vacuum chamber to apply coatings very thinly and precisely.
“In theory, we can put coatings down into increments of angstroms, and the average diameter of an atom is 3 Å. So we can put coatings down to approximately 10–20 atoms of materials for different coatings,” said Jeff Bouchard, vice president of sales and marketing. The company is using the new process in medical applications primarily for flexible electrodes for test strips. “It's a piece for diagnostics and self-diagnostics,” he said. The benefits of the sputtering process are said to include reproducibility and precision, even at a very thin coating level. “You can get all the benefits of metal for an electrical property, yet not have to use aluminum foil, which is hard to work with. There are also benefits in flexibility and cost,” Bouchard added. In the hard format, the only way to apply coatings is to use lamination, which presents other problems, he said.
One supplier of plasma coatings does not offer coating brands but rather works with device companies on a customized, product-by-product basis. That includes selling processing equipment to be used in a device firm's manufacturing operations. It, too, is responding to device industry demands for coatings that can be applied more thinly and uniformly.
“The thinness of our coatings can be measured in angstroms—hundreds or less,” said Stephen Kaplan, general manager of 4th State Inc. (Belmont, CA). Conventional spray and dip coatings go on in microns and mils. At the angstrom level, he said, “the mechanical properties of the coating do not change the overall properties of the substrate it goes on.”
Armoloy of Connecticut Inc. (Bristol, CT) produces a next-generation coating, Bio-TDC, which is thin and uniform. It was developed as a biologically compatible coating that can provide wear resistance when applied to softer substrates such as stainless steel.
Other features of the coating include a nonreflective surface, low friction and galling, and corrosion resistance. It can be applied at a low temperature so that the process does not distort device tolerances. The firm says the coating has passed tests for cytotoxicity, systemic toxicity, intracutaneous irritation, implantation, sensitization, hemocompatibility, and pyrogenicity.
The coatings described above and other new-generation formulations have the potential to increase the capabilities of a number of devices. Often their development is based on feedback from clinicians to the device companies. Now that the mainstream is more aware of what a medical-grade coating can do, there could be even more interest from doctors and device manufacturers in the future.
“There are very few devices that wouldn't benefit from a coating. The market shift to coatings continues to be strong,” said SurModics' Olson. “We are working on hardness, conductivity, and mechanical characteristics.” The goal, he said, is to get a coating technology that does not change the mechanical properties of the device.
Coating applications are being perceived more as a central part of the manufacturing process, which is crucial to their increased use on medical devices. “Coating is no longer viewed as an add-on that only the most well-heeled companies can afford,” AST's Conroy said.
Now that device companies have a better understanding of what coatings can do, the next step is better education about processing and application issues, said Wolgemouth of SCS. He said device manufacturers must understand that coatings are both a science and an art. Manufacturers may be able to understand the science fairly clearly, “but it's an artistic effort to reliably and repeatably apply a coating to any number of substrates,” he explained. He stressed the importance of understanding the artistic nature of coatings, noting that manufacturers may struggle if they do the process themselves. To ensure outcomes appropriate to expectations, it is essential to not only know what coatings are, but also how they are applied.
Copyright ©2004 Medical Device & Diagnostic Industry
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