Yulex and TechDevice partner to provide allergy-resistant catheter technology.
“Where a new invention promises to be useful, it ought to be tried.” —Thomas Jefferson
In addition to his well-documented roles as founding father, author of the Declaration of Independence, statesman and U.S. president, Thomas Jefferson also was a masterful inventor. Monticello, his home in northern Virginia, is filled with examples of Jefferson’s creative insight.
Dr. Katrina Cornish, senior vice president of research and development at Yulex, examines medical products made from guayule, a desert plant grown in Arizona.
Photo courtesy of Yulex Corporation.
Now, TechDevice—a medical device manufacturer that produces balloon catheters and guidewires for a variety of endoscopy, urology and vascular applications—is preparing to submit its 510(k) application to the U.S. Food and Drug Administration for a balloon catheter made with the material.
Officials at TechDevice estimate they’ll be prepared to file their submission with the agency during the second quarter of 2009, and expect approval soon thereafter.
Given the groundwork that’s been laid thus far, it seems that both sides have good cause for optimism.
Yulex Corp., based in Maricopa, Ariz., manufactures its brand of latex using the guayule plant, which grows in the desert and is native to the U.S. Southwest. The company is the exclusive licensee of two patents developed by the U.S. Department of Agriculture (USDA)—one for the process of producing guayule latex and the other for the latex itself. Despite its modern applications, guayule is not a 21st century discovery.
During World War II, the plant was used to help supply domestic rubber needs as traditional sources of rubber in Southeast Asia were cut off. Once the war ended, use of rubber (which is less expensive than guayule natural rubber latex) resumed, and guayule went the way of Rosie the Riveter until recent events made its unique properties particularly useful.
Purified Yulex natural rubber derived from guayule is poured. According to the company, Yulex natural rubber is the only plant-based latex for manufacturers of medical devices and consumer products that is safer than other alternatives for people with Type I latex allergies. Photo courtesy of Yulex Corporation.
According to one well-cited study of blood donors, more than 8.2 percent had evidence of latex antibodies. That translates to millions of Americans that may have developed sensitivity to Hevea latex rubber. Symptoms of severe allergic reactions can include difficulty breathing, itching, rash, hives, and, in some rare cases, shock and death.
“If something is low in protein, it is very unlikely to cause the development of latex allergy,” said Katrina Cornish, Ph.D., senior vice president of research and development for Yulex Corp. “It is impossible to get a meaningful dose of protein from a guayule latex product; the protein level is just too low, plain and simple. Animal studies have very clearly demonstrated that there are no super-allergens in there that would be particularly sensitizing. And 90 percent of what little protein it does have belongs to a class of protein known not to be involved in human allergies.”
Guayule latex is proven to contain less than 200 micrograms of total protein in the raw material, which is about 1 percent of the protein in Hevea latex, Cornish explained.
She also noted that the explosion in Hevea latex allergies is “a reflection of severe over exposure.” While a scientist at the USDA-ARS in the 1990s, she developed and patented the first process for producing guayule natural rubber for medical devices. Cornish told Medical Product Outsourcing that demand for latex examination gloves went from 2 billion gloves a year in 1998-1999 to more than 100 billion today.
“New manufacturers sprang up to meet the demand, and, in order to reduce cost, they stopped washing gloves at the end of the [manufacturing] process,” she explained. “A washed glove and an unwashed glove look exactly the same, so they cut out that process. As a result, existing manufacturers saw that other companies were doing it cheaper, so they stopped washing, too. The problem is that if you don’t wash it, 50 percent of the protein in Hevea latex that normally would be washed away easily because it is readily soluble in water, stays in the matrix of the glove.”
The problem was compounded by powder used to coat the gloves, Cornish said. By the time the glove is removed from the box, the powder also is covered with the soluble proteins from the latex.
“Healthcare providers replace their gloves for every new procedure and powder pops into the air,” Cornish said. “This filled the atmosphere in hospitals with airborne allergens. And people working there breathed it in and out all day long, which is why so many people became sensitized. By the early 1990s, many healthcare workers were sensitized and multiple-surgery patients also were affected. If you have a full-blown Type I latex allergy, you may not be able to even walk past a doctor’s office.”
As a result, Yulex Corp. filed its own 510(k), which the FDA labeled as “latex-free” for examination gloves made with guayule natural rubber. The company received clearance in April 2008, paving the way for other products—and companies—to use the material in medical products.
“This approval has the potential to make a significant difference to both the general public and the medical community at large,” Daniel Schultz, M.D., director of the FDA’s Center for Devices and Radiological Health, said in a statement following the agency’s OK of the Yulex natural rubber gloves. “Gloves made from guayule may prove to be a safer alternative for some people with sensitivity to traditional latex. And yet they will not sacrifice the desirable properties of traditional latex such as flexibility and strength.”
The sensitivity, of course, applies to more than just surgical and examination gloves; it includes other medical and consumer healthcare products using natural rubber, such as balloon catheters and medical adhesives—even condoms. Synthetic latex has been used as an alternative, but, according to Cornish, it has drawbacks. She says petroleum-based manmade materials may be allergy-free, but fail to offer the elasticity, tensile strength and durability of bio-based materials.
There may also be hazards posed by residual chemicals from polymer manufacturing. In 2006, ASTM, one of the largest international standards bodies, created a new latex category specifying, for the first time, performance standards to ensure safety based on protein content, without lowering the performance standards to accommodate stynthetic materials. According to Yulex officials, its natural rubber was the only material that met the category’s safety and performance requirements.
A “Natural” Fit
The agreement to develop balloon catheters using Yulex natural rubber may have been signed as recently as 2007, but the relationship between TechDevice and Yulex began much earlier.
“We read about Yulex and thought it would be a good fit with the work we do, so we reached out to Jeff Martin [CEO of Yulex] in 2003,” said Leigh Hayward, director of project development for Watertown, Mass.-based TechDevice. “After working with the raw material for a while, we developed compounds that worked very well for catheter applications, and we were able to turn them into a Yulex balloon.”
According to Hayward, TechDevice discovered that Yulex natural rubber offered improved physical, chemical and biological properties to high-end synthetic materials often used in balloon catheters. It also is more effective with better tensile strength than enzyme-treated tropical natural rubber latex, he said.
“Our product is a natural material, but it has unmatched elongation properties. So, for comparable strength, it is a very stretchy, strong and soft material, which makes a very good catheter balloon—just about better than any other material you could use to make a catheter balloon,” Cornish added. “Our development scientists have been working closely with Leigh to help make product samples along the lines of what TechDevice customers are looking for. We need to make sure that the technology is transferable—so that if we can make it in our lab, the team at TechDevice can make it.”
Balloon catheters manufactured by TechDevice using Yulex natural rubber.
Photo courtesy of TechDevice Corp.
Hayward said TechDevice is working with the latex—and Yulex scientists—to meet customer requests for different balloon properties. The original balloon TechDevice developed was for cardiovascular applications.
At present, the company has four different sizes of balloons that will inflate from 11 to 27 millimeters, with the length of catheter varying from 40 to 110 centimeters.
“Yulex has a wealth of experience with different types of formulations, what to vary, how to vary, and how it affects the final product,” he explained.
“Right now, we’re getting a lot of requests for different properties. One customer, for example, wants a lower yield and a higher strength, so we’re testing different combinations.”
Extensive testing data from the Yulex 510(k) application for exam gloves also will help as TechDevice moves forward with its submission to the FDA.
Cornish said more than 400 Type I latex allergy-sensitive people were tested with a variety of methods, and not a single reaction was recorded. Even a Yulex consultant who has a severe latex allergy demonstrated her ability to safely handle the material as part of a presentation to the FDA’s Office of Device Evaluation. The FDA officials appeared impressed, according to Cornish.
“We didn’t pursue the 510(k) at the time because we did not intend immediately to market our own exam gloves,” Cornish said. “We did it so that all the material properties and the research behind Type I latex allergies could be put into the appendix of the 510(k). We had a massive amount of appendices attached to it. This allows other companies, like TechDevice for example, to reference that basic data in their own 510(k) so that they don’t have to reinvent that wheel every time they go around. There are fundamental properties that every Yulex natural rubber product would have. That’s what makes it a great material for medical devices.”
Bob Lamson, director of marketing and sales for TechDevice, said both biocompatibility and performance testing for the new catheters are on track prior to the upcoming 510(k) submission.
“Once it gets to the market, there will be a competitive advantage,” Lamson predicted. “A lot of things we’re working on with companies are still in development. It’s still early on, but I think people are pleased with the characteristics when they test it in their compliant applications. They find that it gives them a good material, excellent strength and imitates the characteristics of traditional latex with enhanced performance in some areas.”
Though TechDevice initially will use Yulex natural rubber for the development and manufacturing of balloon catheters used for vessel occlusion, stone retrieval and thermodilution indications, company officials believe that catheter balloons are only the first part of numerous possibilities for devices incorporating Yulex.
Michael Brown, vice president of operations for TechDevice, said the company is exploring multiple device segments and product options. In addition to new product development, Brown said immediate new business opportunities could include replacing existing products that currently use traditional rubber with Yulex natural rubber, as well as offering an alternative for a new generation of products currently on the market that use materials such as silicone because manufacturers have been “concerned” by the allergy-causing properties of Hevea latex.
“I think having 510(k) clearance for a Yulex balloon catheter should provide medical device companies the confidence they need to go ahead and submit their products for approval using this material, and we’re here to partner with those companies and help them get their products to market.” Brown said.