By Len Czuba, President, Czuba Enterprises, Inc.
The number of materials suppliers for long-term implants is still very small compared to the overall list of polymer resin companies. Even suppliers that already offer polymers for unique critical care applications generally require the potential user to go through a rigorous process before qualifying them to use the requested material. Sourcing some of these polymers has gotten a little easier now compared to the “Dark Ages” (I’ll explain below) of material availability, but I would still not claim that it is easy.
How did this situation get so difficult, and why do suppliers care where their materials are being used? Herein, I will review the process of developing an implantable device and qualifying it for use. I will show how well-prepared medical device engineers and designers can prepare to answer all questions to the satisfaction of a resin supplier, making it a little easier to run the gauntlet of preliminary concept creation and initial product design, through development and qualification, and on to final product manufacturing, scale-up, sale, and new product distribution.
Supplier Apprehension During The “Dark Ages”
Have you ever asked a polymer supplier if their material can be used in a long-term implant application, only to have them become very concerned and all but run away, rather than supply materials for critical care products? Although this is still the reaction of many resin manufacturers, it is not as common as it was during the ‘90s — the so-called “Dark Ages” of polymer availability for the medical device industry.
In that decade — in which silicone breast implants were alleged to cause constant joint soreness and overall achiness in women who had them — virtually all suppliers of medical-grade materials, and even those that didn’t carry medical grade-designated products, withdrew their materials from any medical applications.* It got so bad that, when design engineers even mentioned that a material was intended to be used with a medical product, or even near a patient, many suppliers refused to sell, even for non-critical device applications.
There was almost a complete exiting of material suppliers from the medical device and healthcare industries. Many, even now, have not come back. The risk/benefit equation was stacked against them.
How Did It Get This Way?
Over the years, I have observed an evolution in the way medical devices are developed. When polymers were first used for critical care devices (those designated “Class III” devices by the FDA), we usually took commonly available grades of the material of choice and tailor-made them to suit our needs, using the proper stabilizers, lubricants, anti-oxidants, etc. We modified anything else that we found was needed to make the finished polymer and polymeric component a suitable choice for long-term blood or tissue contact. I worked on developing new flexible, clear, steam-sterilizable materials for blood and solution containers. Sometimes, in working with our company, a material supplier would modify a grade of material for some specific application. Other times, the user did the compounding (mixed in the additive).
Although my work did not often involve devices that enter the body or have long-term contact with body tissue, most of the formulations I developed were for Class III devices. Examples of those other body-contact devices include a renal dialysis port for continuous ambulatory peritoneal dialysis (CAPD), a cranial shunt that drains excess fluid from the brain, and a cardiovascular stent.
I also worked on blood and IV solution containers, all of which still needed to comply with the testing required of Class III critical care products. This was because the blood was collected and stored in blood bags or IV fluids at some time in its product life, and generally would be stored for longer than 30 days before being delivered to a human patient, thereby qualifying our materials as long-term contact materials. We did far more testing, both chemical and biological, to ensure that what we developed and proposed to use was absolutely safe. In fact, we often challenged the testing by using exaggerated levels of heat, extended time of extraction, or simply multiple, repeated testing to make sure that we were not even close to being a problem after the material was selected for use.
Then, in 1990s and even a few years earlier, there began to be reports of implantable medical device failures. These failures included:
Pacemaker leads — The polyurethane wire insulation cracked, and body fluids shorted out the signal. The leads degraded (hydrolytically and oxidatively) due to the warm, moist, human body tissue exposure; it was discovered that the first urethane materials used rapidly degraded during long-term, in-body exposure. Eventually, better urethanes were created with properties that were able to survive long-term exposure to warm, moist, aggressive environments.
Replacement heart-valve frame support fractures — The heart valve problem caused several fatalities before the device manufacturer determined that the weld of the support frame could crack after the product was in place for many months. Microscopic weld defects led to a weakening of the frame, and eventual separation of one of the valve’s three frame support legs, rendering the valve unable to close properly and to pump blood as it was designed. Eventually, the manufacturer improved the weld and eliminated this problem.
Temporomandibular joint (TMJ) repair disc — This insert, made using polytetrafluoroethylene (PTFE) polymer, eroded during use, causing pain, swelling, and in some cases, permanent disfigurement. The TMJ implant was marketed under the name Proplast and sold by the inventor’s company, Vitek. Indicated to insulate a defective jaw bone from continued bone-to-bone erosion, Proplast discs were approved for use in 1983, and more than 10,000 such discs were implanted.
But by 1990, patients began reporting pain and swelling worse than had existed before Proplast disc implantation. The pain was determined to be caused by tiny, shed particles of the very soft PTFE disc, which had flaked off. The soft discs had been unable to withstand the forces exerted upon them during chewing and clenching of the jaw — clearly the wrong choice of polymers for this application. because of the extremely stable, inert properties of PTFE, there was no way that the body could rid the joint of these foreign bodies, and instead the reactions caused by the PTFE particles led to further erosion of the joint that the implants were supposed to help protect. In some cases, the body’s reaction to the PTFE debris caused permanent disfigurement.
In December 1990, the FDA issued a safety alert stopping further use of the TMJ implant, and by January 1991 had ordered a recall of all Vitek implants. In response to the reported problems with TMJ implants, a settlement fund of $22 million was set up, leading Vitek to declare bankruptcy and sending its founder fleeing to Switzerland to avoid legal prosecution. The plaintiffs resorted to suing the supplier of the PTFE, DuPont.
Although DuPont provided probably less than $10,000 worth of the PTFE polymer sold to make the implants, the company knew nothing about the design or function of the implant, they and various others involved with TMJ implants were dragged into the lawsuits. DuPont was not aware of its PTFE’s intended use when it was sold to Vitek. But because their material was used (albeit inappropriately) to make the TMJ implant, DuPont was left holding the bag and providing the bulk of the settlement funds. In addition, the legal costs to defend the company amounted to hundreds of thousands, if not millions.
In light of that anecdote, is it any wonder materials suppliers shy away from the medical device market?
Silicone breast implants — A similar situation played out with silicone breast implants. Reports surfaced that women with silicone breast implants (especially leaking implants) experienced an increase in levels of joint soreness and overall body pain. Their silicone breast implants were found to be leaking, and the material used, the silicone, was alleged to be the source of the problem. Rumors circulated that tiny drops of liquid silicone were coursing through these poor women’s veins, accumulating in the joints and leading to painful movement. Was this the smoking gun?
The FDA called for a voluntary moratorium on new silicone breast implants until a thorough assessment could determine any hazards associated with the implants. This regulatory intervention was complicated when many of the women who had reported problems with their implants began filing lawsuits, seeking relief from the companies that made and sold the products. The three major suppliers of the silicone implants — Dow Corning, 3M, and Baxter/Heyer-Shulte — all came under fire. Eventually, a class action lawsuit was launched.
As the legal action was unfolding, the scientific community continued to conduct safety testing in an effort to provide an unbiased, conclusive answer as to the safety of — or complications caused by — silicone breast implant leakage, or more specifically, by silicone itself. Some studies were even conducted by a non-biased team of scientists commissioned by the FDA. As these studies were completed, the results showed that silicone materials were safe for long-term, in-body use. The reason for the affected women’s joint or overall body pain was never able to be determined; the joint pain effect was never duplicated and no link was ever able to be found.
But, as the “deep pockets,” the companies that supplied the silicone for the breast implants, and put together the settlement funds, still ended up on the hook for paying to help the patients correct or treat the problems allegedly caused by their implants. By the time the smoke cleared, the unfounded litigation had cost the involved device manufacturers more than $11 billion in awards, settlements, and legal fees.
Dow Corning declared bankruptcy and later reorganized, offering biomedical silicones similar to the earlier materials, but with significantly more in-process testing and a much higher level of quality checks on the finished product. Unsurprisingly, considering the millions of dollars in settlement lawsuits that prompted their development, these silicones were significantly more expensive than the old silicones.
Even today, no evidence has surfaced indicating that silicones were even remotely responsible for the women’s pain. Adding insult to injury, researchers found that the percentage of randomly selected women in the general population, who reported experiencing joint pain and overall muscle soreness, matched the percentage of “victims” among silicone implant sufferers. Accordingly, silicone devices and implants are still delivering healthcare solutions to patients safely and effectively today.
Industry And Government Reaction To Supplier Blame
The class action suits, the various studies, and FDA interventions in these matters all commanded generous media attention. When large polymer suppliers, which provided materials to various other industries (automotive, telecommunications, consumer goods, building and construction, etc.), saw that the profit derived from medical products was relatively small in comparison, they decided to exit the medical business. The risks involved with product liability — particularly the penalties that could potentially be imposed upon the materials suppliers — made the exit decision an easy one.
This material supplier exodus from the medical device market left many product development teams without options for making their new products. In fact, some existing products were also affected when the suppliers began sending notices that their materials were being withdrawn, even from approved, existing products.
The material supply crisis got so bad and there was enough of an outcry in the device industry that Congress enacted the Biomaterials Access Assurance Act of 1998. This bill stated that suppliers of materials intended for use in medical devices, critical care or otherwise, would not be held responsible for any product failure, so long as the originally approved (by both the user and the supplier) polymer material specifications were adhered to throughout the life of the medical device.
The bill essentially took the burden of liability away from the materials or component suppliers for medical devices. It instead placed responsibility for the safe and effective functioning of the medical device on the device design team and manufacturer of the product. This important legislation made it safe for polymer suppliers to re-enter the medical device market, and some of the major suppliers returned to supplying their materials for critical medical devices.
Collaboration Benefits Both Suppliers and OEMs
Emerging from the material supply crisis, it became clear that no longer would polymer producers sell their high-volume commodity materials to the relatively small market of critical care devices. For one thing, a wider property range typically is normal for a commodity resin, while a medical device customer typically demands tighter specifications. A resin producer would not want to take a chance that a medical device customer may find the commodity material outside the agreed-upon specifications. So, most suppliers started offering product lines that specifically targeted the medical device market. In addition, for critical care devices, the suppliers began to require up-front indemnification agreements from the medical device producers.
The indemnification agreements stated further, and in more detail, much of what was established by the Biomaterials Act in 1998: That the medical device company would hold harmless the resin supplier. In effect, the OEM would shield the materials supplier from any lawsuit, and provide any legal defenses required by the resin supplier in the event of lawsuits related to a medical device using that particular supplier’s material.
During the almost 18 years since the Biomaterials Act’s passage, it has been tested five times. According to Frederick A. Stearns of Keller and Heckman LLP, “…in each case the Biomaterials Act was invoked and each was resolved in favor of the materials supplier. I see no reason to expect a different outcome in similar cases in the future.” This is good news for both the medical device developers and the polymer supplier community.
No longer will the large material suppliers, just because they have the deep pockets, be dragged into lawsuits where they had no voice in how the product in question was designed, manufactured, and maintained. If they simply agree with the device manufacturer on particular specifications at the onset, and then comply with those specifications, they can rest assured that they will not need to worry about unexpected medical device failures — or the typical barrage of litigation that usually follows.
As the relationships between polymer suppliers and medical device manufacturers continue to mature, the needs of the medical device industry will be better voiced, understood, and in some ways satisfied. This enables the development of more specialized polymers for even more unique and sophisticated end uses. We are seeing this play out as more suppliers are once again entering into the medical device market. Some, such as Invibio and NuSil, even focus on the medical device market for much of their business.
Finally, the medical device engineering team must aid the supplier in assessing their material’s intended application, and in becoming comfortable with allowing that material’s use for a critical care, Class III medical device. The material of choice must endure a full range of testing under all the physical / functional, chemical, and biological assessments that are typically required for devices entering that space. It would not be out of the ordinary to share the test results with the polymer producers. Once they see the full extent of evaluations done on their materials, and they learn that their materials pass all the testing, they are much more willing to supply that material, as well as next-generation improvements.
I currently am working on a medical device that is intended to be implanted in a patient’s body for months or years at a time, depending on the intended therapeutic application. At least five different materials are contained within the device and must function together for the device to work properly. I am fortunate to be working with a corporation that can dedicate proper resources to the complete evaluation of each component material. After each material passed every test, we wrote specifications for every property that the supplier felt was important, as well as what we felt was important in that resin to ensure its acceptable end use. Both the supplier and the device company accepted and signed upon those specifications.
Furthermore, as a representative of the device company, I was able to share much of the information that we knew, and more that we learned as we tested, to bring the device closer to market. This relationship allowed the polymer supplier’s management to feel comfortable, both as the supplier and as part of the team bringing a new medical product to market.
One last caution: For some new medical devices, the time it takes to do all the testing can amount to years. The supplier needs to know that the life of the agreement may be in the fives and tens of years, not in months or just a few years. But once the medical device is cleared for use by the FDA, suppliers will share the feeling of accomplishment because their material is a key component in an amazing new medical device in the marketplace.
About The Author
Len Czuba is the president of Czuba Enterprises, Inc., whose new product development initiatives include taking medical devices from concept to market. Czuba has a BA in Biosciences from Southern Illinois University, as well as more than 30 years of experience in polymer synthesis, compounding and material development in the medical device industry. He may be contacted at LCzuba@czubaenterprises.com, or by visiting www.czubaenterprises.com.
* During the “Dark Ages” of polymer availability (i.e., 1990s), only two companies in the U.S. willingly sold their materials for implantable use. NuSil Technology was able to quickly supply silicones as direct replacement for the Dow Corning silicones. Invibio Ltd., a British manufacturer of polyether ether ketone evolved from Victrex — specifically for biomedical applications — was the first and, at the time, the only company that offered PEEK polymers for long-term implant applications.