For more than 50 years, Zeus Industrial Products, Inc. (Orangeburg, SC) has been a major supplier of custom polymer components for use in medical products. The company has built a strong reputation for producing high-quality membranes and electrospun products, as well as extruded components for use in intravascular access devices and other medical products.
Alerted to the need for intravascular access catheters that could be used in interventional procedures relying on magnetic resonance imaging, Zeus recently took on the challenge of identifying a polymer product suitable to replace the metallic reinforcement braiding used in such devices. The company believes it has found the solution in a thermotropic liquid crystal polymer (LCP) monofilament, a polyarylate monofilament whose properties seem likely to alter the landscape of catheter manufacturing in the not-too-distant future.
To find out more about how the use of LCP monofilament in catheter braiding is expected to support the development of advanced surgical procedures—in cardiology and beyond—MDB recently spoke with Zeus researchers Bruce Anneaux, PhD, corporate director of research and development, and Zahidul Wahab, PhD, senior research engineer.
MDB: Zeus provides medical device clients with a wide range of products and services, including custom extrusion of medical grade tubing, catheter componentry products, and bioabsorbable products. How much of the company’s business is devoted to catheter componentry products?
Bruce Anneaux, PhD: Zeus supplies components to original equipment manufacturers, a group that includes most of the medical device companies that actually design and manufacture finished catheters. A lot of the components that we manufacture and sell to those customers are intended for use in products for some sort of minimally invasive or vascular lumen-based therapy.
MDB: How much of the company’s business is medical versus other areas that the company is involved in, such as aerospace, automotive, energy, and so on?
Anneaux: Zeus has a healthy balance of business areas in its portfolio, including aerospace, automotive, fiber optics, fluid management, and energy. We do find that there can be some useful synergies among these areas—for instance, among the quality systems units for each business area. But we prefer not to discuss the particulars of our businesses in terms of the split or makeup of the overall enterprise.
MDB: In what other medical specialty areas is Zeus especially active?
Anneaux: We do a lot of work in a variety of different medical device arenas. A lot of our work is intended for use in catheter-based procedures in the cardiovascular system, but also in the gastrointestinal and neurovascular systems. Application types include devices for endoscopy, electrophysiology, and neuromodulation.
We also do a lot of work in the ancillary components area, where we supply components and perform secondary operations on products or formed tubing according to customer specifications. In turn, our customers are designing, developing, and manufacturing a wide range of medical devices, and in some cases those devices might not be used in catheter-based procedures.
Another discipline in which we do a lot of work is the bioabsorbable space, extruding bioabsorbable polymers to create bioabsorbable tubing, which can then be processed into scaffolds for drug-eluting stents, targeted drug delivery, and a whole host of other medical applications.
MDB: In the medical device industry, it is often said that product success starts with identifying an unmet clinical need. What was the need that led Zeus to its innovative use of liquid crystal polymer (LCP) as a monofilament in the medical field?
Anneaux: Some of the complex interventional procedures in which our products and components are used—including cardiac ablation for the treatment of arrhythmia—require extraordinarily precise soft tissue visualization. Magnetic resonance imaging (MRI) is the gold standard for soft tissue visualization. But that imaging modality is not compatible with products that include metallic components—including virtually every predicate catheter on the market.
In order to use preexisting catheters while performing complex interventional procedures, electrophysiologists have relied on fluoroscopy as their primary method of visualization. And in turn, to shield themselves from the ionizing radiation of the fluoroscope’s x-rays, they have had to wear extremely heavy lead garments that cause fatigue and other health concerns, such as back problems.
We heard from a number of research and development (R&D) firms, as well as from some of our customers’ own researchers, that they were looking for a way to create a catheter that could be used under the strong magnetic forces of MRI systems. Making such a catheter MRI compatible would obviously preclude the use of metallic braid, which is commonly used to reinforce a catheter’s shaft. But the finished product still needed to have the same mechanical properties of stiffness, flexibility, and torque transfer as the preexisting product. So that was essentially the unmet need we set out to tackle.
Zahidul Wahab, PhD: Other engineering plastic fibers had been tried with the same objective—to replace stainless steel braid—but they hadn’t worked out too well. When we started getting customer evaluations of LCP monofilaments, we had pretty good feedback.
MDB: What properties of LCP monofilament made it especially suited for application in cardiac catheters, and what other medical applications might the material be suited for?
Anneaux: To replace the standard stainless steel wire that’s used in reinforcement braiding, we were looking for a material with high mechanical strength and high tensile modulus—essentially a material that is both strong and very stiff. And we also wanted to identify a material that would be as close as possible to a drop-in replacement for the materials our customers were already using. We didn’t want to select a material that seemed to be best on paper, if it meant that our customers would have to completely revamp and requalify their manufacturing processes.
Liquid crystal polymers have exceptionally high strength and a very high modulus. They can be made in monofilament sizes very similar to those used for stainless steel wires, and they can survive the processes involved in manufacturing a catheter. Those processes include braiding the monofilament for use in reinforcing the catheter shaft, but also exposure to high heat during the fabrication of the catheter. So the material and resulting product needed to withstand heat and not lose their mechanical properties.
Wahab: LCP monofilament has very low shrinkage when exposed to high heat, and also very good creep properties.
Anneaux: In addition, the high strength and high tensile modulus of the LCP monofilament also result in good torque response in the finished product. Ideally, when the clinician moves one end of the catheter, the other end should move accordingly, without chattering, or skipping, or encountering a delayed response. The mechanical properties of LCP monofilament afford very high torque transfer capability in the finished catheter.
MDB: LCP is known to be difficult to process. How did Zeus overcome that challenge and make it possible for the material to be used as a drop-in replacement material for your customers’ products?
Anneaux: Zeus has a history of more than 50 years working with a wide variety of highly engineered polymers, and overcoming a lot of the processing and handling challenges that others haven’t been able to manage. Our use of LCP is one of those success stories.
We have very skilled staff members who are knowledgeable in materials science, polymer science, polymer processing, and polymer rheology. Finding the best way to approach this difficult-to-process material—making sure it would have the correct properties and dimensions, and would function as a drop-in replacement—required a collaborative effort from a lot of our team members.
Our sales and marketing teams worked with our customers and our own R&D staff to make sure we had clearly defined the properties and criteria that needed to be met. And the research team worked on developing an extruding process that could be implemented in one of our manufacturing sites, where it could be performed on a day-to-day basis.
MDB: What intellectual property rights does Zeus hold in regard to the use of LCP monofilament in medical applications?
Anneaux: There is a lot of proprietary information and trade secret information that goes into being able to process this material. For the benefit of our own business—and that of our customers—we don’t openly share that information with the world.
MDB: What is involved in processing LCP from monofilament line to its finished form in a cardiac catheter or in another medical product?
Anneaux: Most of that process happens after extrusion. Once the material is extruded and processed to have the correct dimensions and properties, it is then wound onto spools or bobbins for delivery to our customers. We can wind it onto a variety of spools so that our customers can drop it straight into a braiding or twisting machine. Some customers prefer to receive the monofilament on larger spools; from there, those customers wind the line onto payout spools that fit their converting equipment.
After we ship out the spools of monofilament, the next step would typically be for those bobbins to be loaded onto a braiding machine. Our customer would then commence to braid the monofilament around the catheter shaft for reinforcement.
MDB: How is the use of LCP monofilament for a particular application typically validated? Does Zeus validate the monofilament line, and your customers validate its onward processing and use in a particular defined product?
Anneaux: That’s typically how it works. We validate our own processes to ensure that we are extruding monofilament with precisely the sizes and properties specified by our customers. If the project involves custom sizes or other special processing requests, we fulfill the order according to whatever certification has been agreed upon. In turn, our customers validate the processed materials on their finished device, because that is the product that will be submitted to FDA for market clearance.
Wahab: If a customer has specific requirements that cannot vary, we can also make sure that new batches are consistent with what the customer has previously ordered and what we have previously produced. To accomplish this, we need to work closely with customers to understand precisely what they are requesting, and to make sure that we can produce that product satisfactorily. Once those questions are addressed, we make sure that we consistently provide the customer with products or components that exactly match the specifications and level of quality that the customer expects.
MDB: What other kinds of testing does Zeus perform to validate the use of LCP in a medical application? For instance, how have the mechanical and biocompatibility properties of the material been tested prior to application-specific testing?
Wahab: We perform mechanical and tensile strength testing, thermal stability testing, high-temperature shrinkage testing, and a few other types of testing. We have also conducted USP Class VI testing for biocompatibility. The level and type of testing we perform depends largely on whether the customer has any requirements that need to be examined with tests beyond what we would normally do. If so, we would certainly take on that testing if it is within our capabilities.
MDB: Do you also work with your customers as they perform any kinds of clinical trials with the finished products?
Anneaux: We typically work with our customers throughout the period when they are fine-tuning the final properties of their device through bench testing or animal studies. During the course of this work, customers may need to test materials or components with different sizes or properties, and we assist by providing those materials or components according to specifications.
Once the finished product is being used in human clinical trials or becomes a commercialized device, however, we typically step away from any direct involvement in our customer’s R&D activities. We support our customers as much as possible, but we aren’t involved in any type of clinical setting where a device might be used.
On the other hand, when a customer returns with a plan to resize or modify a successful product for new applications, we certainly work with them to develop their new and improved next-generation system.
MDB: Zeus is known for its custom engineering capabilities for polymer components used in medical products. What kinds of services does the company offer for clients whose specialized innovations are on the cutting edge of their fields?
Anneaux: We work very closely with our customers to help them get the right materials for their applications. Zeus excels in knowledge about materials science and the extrusion and conversion of polymers into various shapes, monofilaments, and tubes. Our research group includes a number of PhD-level scientists, engineers, and analytical lab staff members, and they all contribute to that body of scientific knowledge that Zeus brings to helping innovators look at new and better materials and products for a host of applications.
Customers do sometimes approach us with cutting-edge device projects that might be 5 years away from marketability, and they may express an interest in a particular polymer or material. But they also appreciate our experience and commitment to helping them assess which polymers or materials are really the right ones to meet their needs. Our staff work with customers to define the properties their materials should have—what they need to do, how they are supposed to behave, and what processing parameters they will undergo—and sometimes we are able to recommend a selection of materials that will perform better than those in which the customer was initially interested.
From that point forward, we work very closely with customers’ R&D staff as they develop their initial prototypes and work through their iterative design processes on the way to a finished product. This is not large-scale work; at this stage the orders are for small volumes—just enough to create prototypes and testable startup samples. But it’s often this careful upfront approach that makes all the difference in ensuring that the customer is getting the material and product with the ideal properties for their application.
MDB: How would you characterize the typical clients that work with Zeus? Are some specialty areas more strongly represented than others?
Anneaux: Our medical device customer base is very wide ranging, including companies that are developing products for cardiac rhythm management, gastrointestinal endoscopy, and structural heart repair, as well as for application in cardiovascular, neurovascular, and peripheral vascular intervention. Some of the companies we work with are just three- or four-person startups that are looking to bring their first innovative product to market, while other customers include major R&D teams from established medical device companies that have a large and varied portfolio of products.
MDB: At what stage of corporate and product development do companies typically seek out Zeus? What kinds of services are they usually looking for, and what other specialty services does Zeus make available?
Anneaux: Companies seek us out at pretty much all stages of their corporate and product life cycles. We are often asked to get involved during early R&D phases, when our role is to help with material selection and process development. But companies also come to us later on in their development process, sometimes when their research has suggested that the properties of their selected materials are less than optimal, and that they need to explore alternatives. Those kinds of customers are drawn to Zeus specifically because of our knowledge base, experience, and ability to work with a wide range of materials. And there are some companies that approach us very late in their development cycle, when they are close to being finished with everything but discover that they need help to tweak the design of a particular component. In that case, we can step in to help the company make the necessary design adjustments so that their project can move to completion.
MDB: For companies that design and manufacture medical products, achieving and maintaining quality standards is a vital part of everyday company operations. How is this reflected in companies’ work with Zeus?
Anneaux: Zeus maintains a very high quality standard for everything the company does, regardless of industry. A number of customers have come to us specifically because of that commitment to quality; they value our partnership and approach to customer service, and they know that the quality of the products we provide is second to none.
The entire Zeus corporation is certified to ISO 9001, the broad quality systems standard compiled by the International Organization for Standardization (ISO). Several Zeus facilities are also certified to AS 9100, the aerospace industry quality systems standard compiled by the Society of Automotive Engineers and the European Association of Aerospace Industries. Zeus is also registered to ISO 13485, the medical device-specific quality systems standard.
MDB: When you’re working on a specific product for a medtech client, how do the partners ensure that their perceptions of quality are in sync? How do they maintain compliance with quality standards over the duration of the project?
Anneaux: As a starting point, many customers are reassured to be given the registration numbers that our notified body has assigned to our various quality systems certifications. When we actually begin working with a customer, there may be a need to have discussions involving the quality systems groups of both entities, so that everyone knows what the customer is looking to achieve. And throughout our relationship with a customer, we routinely entertain staff who need to audit our quality system to ensure that it is as robust as the various certifications require.
MDB: In addition to design specifications and processing protocols, what kinds of regulations and standards apply to materials and processing technologies used to create catheter components?
Anneaux: In the United States, manufacturers of finished medical devices are required to register with FDA. But we don’t produce any such finished products, so we are not an FDA-registered company.
On the other hand, ISO 13485 is the acknowledged quality systems standard that applies to medical product manufacturers, and we are certified to that standard. Although it’s not required of material and component suppliers, we took the step of seeking ISO 13485 certification to ensure that our standard operating procedures—whether for receiving materials, storing materials, processing materials, controlling the environment in which materials are stored, or taking corrective and preventive actions—are all correctly documented and followed on a daily basis.
MDB: As a trickle-down result of FDA manufacturer inspections, is Zeus being audited by its customers more often than in the past?
Anneaux: Certainly, there has been a rising demand for medical device manufacturers to exercise good control over their suppliers, so I can see how that would lead to an increase in the number of audits that manufacturers carry out. But I’m not aware of any significant increase in customer audits at Zeus in recent years. With the number of groups we work with, and the complexity of their projects, we seem to entertain a fair number of audits regardless of what may be happening elsewhere in healthcare manufacturing.
When we are working closely with a customer, it’s often a natural expectation that they will want to conduct periodic audits. We consider it important to facilitate that kind of review, so that our customers can have the level of assurance they need when working with us as a supplier.
MDB: When a product is actually being processed, how important is Zeus’s experience for ensuring the quality of the completed components?
Anneaux: It’s very important, and it starts with the depth and diversity of the Zeus teams that are deployed to work with customers to help them get the best possible components for their products. Our sales and marketing teams include talented and experienced professionals who know how to help a company define its needs—and also know when it’s time to bring our technical experts into the conversation. And our technical groups are equally talented, and offer broad knowledge about what materials and components are typically used for specific applications, as well as the experience and judgment to offer alternatives when they might prove more successful for a particular product. A company that has more than 50 years of experience in processing polymers can certainly play a major role in ensuring quality at every step of product fabrication.
Wahab: Another important contribution is the way that our teams handle customer feedback—monitoring and recording comments, creating a database where comments can be tracked and categorized, and being prepared to address customer concerns immediately. Whenever a customer identifies a particular issue as either good or bad, we believe it’s important to take those comments seriously, to learn from them as much as we can, and to address major problems in a timely fashion.
Anneaux: That’s a good point. We interact with our customers very closely in order to create materials and components that are designed specifically for their needs. The vast majority of the components that we create are not commodity ’one size fits all’ items, they are highly complex and customized components intended for a very particular application. You can’t succeed with that kind of business model unless you’re pretty attuned to everything that your customers are saying—good or bad.
MDB: Do medtech customers often invite Zeus staff to sit in as members of their product development teams?
Anneaux: Yes. It’s becoming more and more critical for medical device companies to bring in others with specialized knowledge about the materials and components that are going into their finished products. And we often find that our experts are not the only ones involved; for complex devices, there may be several other suppliers that are contributing expertise about some aspect of the finished device.
But we are accustomed to working with medtech companies at the very earliest stages of product R&D—sometimes even before the manufacturer knows what kind of shape the finished device is going to take, or how it will operate. Companies know that Zeus can help even in such early stages, when all the company can say is that they need tubing with such-and-such features or performance capabilities, or a fiber or microporous material with such-and-such characteristics.
Companies rely on our knowledge about the characteristics, processing, handling, and application of polymeric materials in medical products. But when necessary to accomplish a customer’s goals, we can often push the envelope of our own expertise about particular materials or component geometries. We’ll work closely with a company to explore new applications or processing methods needed to create a proof-of-concept design, even if doing so takes us out of our current comfort zone.
MDB: What other kinds of secondary processes can Zeus perform to make components suitable for their intended use? Is it common for medtech companies to seek out such additional services?
Anneaux: Our customers typically know that we have good expertise in materials science and the processing of polymers—including secondary processes such as flaring, flanging, drilling, and other operations that can be used to create very complex shapes on the ends—or even in the middle—of extruded tubing. Customers in the early stages of a design process may be hoping to accomplish something out of the ordinary, but without a clear idea of how to do it. So they rely on us to recommend, develop, and execute secondary processes that will accomplish what they are seeking.
For some customers that want Zeus to perform secondary processing, the important thing is our expertise in handling such highly engineered polymers. They rely on our expertise to perform these operations—to drill holes that are entirely clean, or to create flared ends that are completely uniform—because it’s easier to have us do it than to build those capabilities in house. Because we know how to handle these materials, companies don’t have to take on secondary processes at their own site, and the processed components we provide are one step closer to being a direct drop-in for assembly in the finished device.