Transcatheter aortic valve replacement (TAVR), a less invasive procedure designed to replace a diseased aortic valve, is one of the more exciting procedures to reach the market in recent years. The minimally invasive procedure is used to treat moderate- to high-risk patients with aortic stenosis, a condition in which the aortic valve narrows, and as a result, fails to open properly. The condition usually manifests in shortness of breath and fatigue, and drastically raises the patient’s risk for heart failure.

The TAVR approach relies on a small incision usually made in the femoral artery of the leg. (TAVR doctors may also decide to enter near the shoulder, in the chest between the ribs, or in the upper chest depending on a number of patient factors.) A catheter is inserted into the artery of choice while the heart is still beating. The doctor then guides the catheter to the heart and replaces the valve within the diseased aortic valve. Transcatheter mitral valve replacement (TMVR) uses a similar approach to replace a diseased mitral valve, but those technologies have lagged behind for a number of years, and are only beginning to enter the market.

Equally as important is the catheter-based delivery system to navigate the artificial valve to the heart. As the size of the valve frames decrease, so too does the catheter. Edwards Lifesciences’ SAPIEN 3 transcatheter heart valve (THV), for example, uses the company’s transfemoral Commander delivery system, consisting of an inner balloon catheter and outer deflectable flex catheter. A 14-Fr delivery system is used for the 20-, 23-, and 26-mm sizes of the Sapien 3 THV—significantly smaller than the 24-Fr catheters used for TAVR in the procedure’s infancy. Medtronic’s CoreValve Evolut R has also been designed to implant through a 14-Fr compatible catheter delivery system, the EnVeo R.

In addition to catheters, extrusion processes for the medical device field are used to fabricate IV and drainage tubing, needle and syringe caps, and any other sort of device or part requiring a profiled tube or shaft. Because minimally invasive procedures like TAVR are becoming highly preferred in the operating room, medical device manufacturers seek out tight-tolerance micro extrusion tubing to meet specifications for these devices. They also desire smaller tubing with added functionality, for example thinner wall thicknesses, smaller inner diameters that can accommodate more lumens, and tubes with higher flexibility, but still greater torque resistance.

Over the past few weeks, MPO spoke with several extrusion providers who serve the medical device industry to get a grasp of the trends and challenges affecting the industry:

Matt Bills, CEO of Apollo Medical Extrusion LLC, part of Spectrum Plastics Group, an Atlanta, Ga.-based designer, developer, and manufacturer of specialty medical plastic products.

Jürgen Bloss, head of project management USA, business unit tubing, at Raumedic AG, a Helmbrechts, Germany-based single-source provider and manufacturer of polymer components and systems for the medical device and pharmaceutical industries.

Tim Finn, a design engineer at New England Tubing Technologies, a Lisbon, N.H.-based provider of medical, specialty industrial, and custom commercial tubing.

Christian Herrild, director of growth strategies at Teel Plastics, a Baraboo, Wis.-based manufacturer of plastic tubing for the medical device industry.

Terry Hudson, business development manager, medical components at Saint-Gobain Performance Plastics, a Solon, Ohio-based producer of engineered, high-performance polymer products.

Kelly Jakinovich, extrusion project manager for Saint-Gobain Performance Plastics.

Jonathan Jurgaitis, senior extrusion engineer at Apollo Medical Extrusion LLC, a Spectrum Plastics Group company.

Ronald Lilly, vice president of business development, Americas, at Forefront Medical Technology, a Farmington, Conn.-based specialty contract manufacturer with a focus in disposable diagnostic, drug infusion, and medical device systems.

Gary Mizenko, medical tubing business development USA, at Raumedic Inc., based in Mills River, N.C.

Adam Nadeau, process technology R&D group leader at Saint-Gobain Performance Plastics.

Scott Nicora, vice president of NDH Medical, a St. Petersburg, Fla.-based custom extruder of tubing and a contract manufacturer of single-use medical devices.

Clarence Williams, vice president of extrusion services for Flexan, a Lincolnshire, Ill.-based contract manufacturer and assembler of custom, high-precision silicone, rubber, and thermoplastic components and devices.

Brusco: What recent advances are improving extrusion for medical device and component manufacturing?
Bills: Control systems on the extrusion line have the ability to control the process extremely tightly without the use of melt pumps. Melt pumps add a level of unnecessary stress in tubing, potentially weakening the tube.

Bloss: Modern inline control systems ensure all relevant quality requirements are fulfilled during the extrusion process. Laser scanners, for example, can help for the specified—mostly tight—tolerances to be met. Advances in controlling and monitoring systems can highly improve the outcome. Such devices are indispensable to assure a repeatable, reliable, and stable extrusion process.

Finn: 3D-printed tooling is a quickly evolving industry that allows us to make more intricate tooling that can’t be done using traditional manufacturing techniques. It also allows for lower development tooling costs and quicker turnaround times.

Herrild: Many of the advances we see are on the controls side. Everything from better, tighter servos and controls on equipment to PLCs that can share data and talk to other equipment. The ability to get equipment all talking together and analyzing data automatically to react before things go out of control is a big step. This “Industry 4.0,” predictive process, or lights out production (or however you term it) is a big advancement across the equipment spectrum.

Lilly: We are seeing an increase in the use of polyurethane (PU) rather than PVC material for tubing in Europe due to a move away from PVC in both Europe and California. Design complexity is also increasing to support increased functionality. For example, we are bonding PU tubing to a stainless-steel cannula for a drug infusion mixing product. We are designing braided and wire-reinforced tubing for high performance applications. We also have a project that required kink-proof tubing, which involved molding a special metal coil into the tube to provide enough flexibility and softness to protect a patient’s airway while also providing a protected chamber for retracting foreign objects.

Mizenko: One technology we are very focused on is the ability to provide reinforced shafts with virtually zero particulate in the ID. Currently, most reinforced shafts within the medical device industry are built over a processing mandrel. The process mandrel will need to be removed from the tube. In most cases, the friction between the tube and the processing mandrel will cause particles to accumulate within the ID of the tube. Any reinforced tubing built with a processing mandrel with exposure to the vascular system within our body will release those particles into the bloodstream. We have developed processes to provide various reinforced shafts without the use of the processing mandrel. We can meet even the most demanding physical properties required of reinforced catheters utilizing our coreless reinforced extrusion technology.

Nadeau: “Smart Manufacturing”—the basics/mechanics around extruder technology have only had minor/minimal advancements in the last few years. However, making extrusion lines smarter is reaping high returns. Adding additional sensor and measurement systems and combining/logging that data with all other process data has allowed a deeper dive to understand our processes. This data can be used real-time in a control system to not only adjust the process when it is going out of spec, but can be used to predict how a process will trend and adjust before it even begins to go out of spec.

Nicora: New developments in machine controls using advanced electronics and software to provide additional process stability and repeatability on top of well designed and built extrusion lines.

Williams: Some of the most significant advances made to improve extrusion for medical components has come from equipment manufacturers. They are continually listening to what we have to say to make our jobs less complicated and more efficient, and provide platforms to drive innovation. This can come from a simple measuring device that eliminates human error, to more complicated equipment such as vacuum tanks, and extrusion tooling. I would also mention the use of flow analysis to help in the design of complicated multi-lumen tooling.

Brusco: What material innovations are affecting extrusion in the medical device manufacturing arena?
Bloss: As the overall share of PVC tubing in medical technology is about to decline, alternatives to certain PVC types and traditional plasticizers such as DEHP have to be found. That is why non-PVC materials like thermoplastic polymers (TPE) are clearly on the rise. And when it comes to biocompatibility, durability, and temperature resistance, the use of silicone should be considered.

Finn: Lubricious additives are becoming increasingly common requests for medical tubing. It takes a base material, typically tacky, and adds lubricious additives which help limit tackiness and decrease the coefficient of friction. Generally, this benefits extrusion processing while increasing performance. This is gaining popularity as customers want more smaller and more flexible devices with the ability to easily slide something within the tube, or more easily slide the tube itself into a working channel.

Herrild: There continue to be more and more material choices available. The breadth of what you can source today really is staggering. We have seen growing interest in water-sensitive polymers and polymers with additives. Both are challenging and require unique skill sets. Flex PVC is always a topic of discussion as the medical market continues to evaluate more innovation around alternatives.

Jakinovich: We see a lot of requests for hybrid materials to support niche applications, which require a lot of development time. Some of the challenges we see are the costs that are the outcome of the development, the complexity of bringing in new materials to our manufacturing sites, and time needed to fully develop the new product, which we see sometimes doesn’t meet the customer’s needs.

Jurgaitis: Lubricious additives without fluoropolymers. These can eliminate liners, thereby reducing complexity and costs. The lubricious additives allow much more flexibility in catheter construction and design. High heat and ultra-strong polymers continue to replace metals in more demanding procedures and are being used in complex and micro catheters in neuro and pediatric applications.

Lilly: New material combinations are probably the biggest area of innovation. For example, one of our projects involves a microbore extrusion that includes stripes of conductive material to enable the tubing to be location-tracked by the treating physician. We are using a co-extrusion process in manufacturing.

Mizenko: Currently, we see a big push for reinforced catheters, which require thinner walls and the ability to be more durable, flexible, lubricious, pushable, and kink-resistant. Designers are developing more complex catheters, which are required to push through very tortuous and much smaller pathways within the vascular system. We have developed many technologies to accomplish this through raw resin and reinforcement materials knowledge. We can develop catheters with a wide range of different monofilaments. Our micro-extrusion process knowledge can produce exotic reinforcement monofilament materials, which can meet even the most challenging criteria.

Nicora: The use of material additives and surface treatments are providing additional properties such as reduced surface friction, permitting substitution of lower cost base materials to reduce device costs, and different methods of marking tubing and devices. Anti-counterfeiting and improved traceability can now be achieved as well.

Williams: This can be a tough question, because not everyone is involved in the innovations when it comes to material. We have been working with customers on slip additives that allow soft tacky materials to be handled and assembled with greater ease, without the hassles of sticking together or other parts sticking to them during assembly. Other innovations would be bio-degradable materials, or materials with a high moisture absorption rate after extruding, which causes other issues during the extrusion process.

Brusco: Which requests in extrusion for medical devices are the most challenging? Why?
Bills & Jurgaitis: Thin walls in relatively large diameters. We have coined the phrase sub-ultra-thin-wall to describe tubing with less than a 2 percent wall thickness to OD ratio. These configurations also tend to be requested out of softer durometer materials, which compounds the challenge of maintaining dimensional consistency with a part in the molten state—where dimensions and tolerances are set in—have minimal structural integrity and are subject to dimensional change with the slightest process fluctuation. Tolerances are also getting tighter and have become more of a driver.

Bloss: With the advance of minimally invasive surgery, the trend toward miniaturization of medical components and complex systems continues unabated. Everything has to be smaller, but even more precise in terms of tolerances. In order to extrude complex miniature components such as multi-lumen tubing with wire inlay, manufacturers are obliged to make high investments. At the same time, however, the customers aim for attractive pricing. That’s a real challenge.

Finn: A common difficulty we face is managing soft thin walls of tacky materials such as polyurethanes. Customers’ applications require the softness and flexibility of low durometer polyurethanes; however, these tend to be very tacky, which damages the tube due to handling a concern. Additionally, in reinforced products or high-precision applications that are typically manufactured over a core, it becomes exponentially more difficult to remove the sacrificial core compared to a tube with a lubricious liner.

Herrild: This is a difficult question because it is so project specific; we take on a lot of challenging projects. Each one had its set of challenges, and we haven’t seen a lot of overlap from project to project. I think some of that unknown factor at the outset of a project drives the biggest challenges. It is such a challenge because you don’t know everything you don’t know. It is easy to get caught in the thought process of trying things that have worked for new products in the past and being stuck in loops when it comes to innovation. Recognizing the uniqueness of each situation and realizing it may require a completely new solution can be a challenge, but it can be addressed with a good process and a good team.

Jakinovich: The most challenging requests we see are micro-tubing, super tight tolerances, and fast turnaround on development projects. We want to fully develop a repeatable process that produces quality product within the tight time frames that are an expectation in the industry, which is challenging.

Lilly: Co-extruding combinations of different materials is one of the most challenging aspects because different materials have different melting temperatures, specific gravity, and different properties.

Nicora: Users are continuing to push the limits with smaller diameters and thinner wall thicknesses, challenging the metrology employed to measure these products. There is increasing pressure to reduce tolerances on larger diameter tubing as well.

Williams: Customers are requesting smaller, thinner walls in their extrusion, some with less than 0.001” single wall. The challenges to this request are mainly on the extrusion processing side, with a much higher pressure drop during the run. There a couple ways to combat this, but we have developed, and gotten fairly comfortable doing these types of extrusions. Multi-lumens and geometries also present a challenge. Anyone that has experience with these knows the customer may ask for anything. Our job is to talk with the customer, listen to what they are saying, and give them what they truly need. This can be something as simple as having a mandrel that we both use as a form fit type of measurement.

Brusco: What challenges do multi-lumens specifically bring to medical tubing manufacturing?
Bloss: It is a matter of fact that the complexity of medical tubing continues to increase. Especially in the field of catheters, we have faced fairly high demands. The market is asking for more properties to be integrated into one single tube (without neglecting the tight tolerances, of course). For process engineering and toolmaking, this is a big challenge, even more so when considering micro-extrusion.

Finn: While there are several challenges to overcome while developing multi-lumen tubing, developing tooling is generally the largest obstacle. Typically new designs require several tooling iterations to get a product that meets our customer’s extensive requirements. Balancing precision and cost effectiveness of a design or development run is a challenge. Most products start with a small proof-of-concept budget, so accurate first attempts and quick turnaround are very important during the early stages of multi-lumen development.

Herrild: The cross control is a big challenge. Getting all lumens in spec at once potentially requires some give and take in the design phase to ensure targets are required and realistic. After that phase, tooling design is a big challenge. The tooling needs to be right—taking account of the material flow properties and part dimensions—to make a part in spec from the beginning.

Hudson: Multi-lumens require detailed tooling and a lot of trial and error—especially in unbalanced, asymmetrical layouts due to imbalances in pressure in the lumens during the extrusion process.

Jurgaitis: Multi-lumens are getting more complex and dimensionally challenging as minimally invasive procedures try to fit more components, tools, and functionality in a tighter space. This is really pushing tooling design and its manufacturing processes. It also requires tool designers to have excellent material flow understanding so tool iterations are minimized, saving time and money for customers. Additionally, tolerance stack ups in so many features can have very complex interactions with each other and need to be carefully considered.

Mizenko: Multi-lumens become a challenge when designers provide a request that requires unbalanced lumens or unique shapes within the catheter walls. As always, the thinner the walls between the lumens, the more challenging the tubing will be.

Nicora: There is a tendency to increase the number of lumens in the same overall diameter, which in order to produce, requires tooling that is more difficult to fabricate. Often, tubing designs do not consider processing concerns such as uniform walls and radii.

Williams: Multi-lumens can be simple or challenging. Again, usually what the customer asks for is slightly different than what is supplied, in terms of the final look of the part. Sharp edges will have a radius and lumens that are not round can be a challenge (different geometries), but this can be achieved with further development in tooling design. The most challenging extrusion is incorporating many lumens in a small shaft. The walls have to be thinner, which exacerbates the problem. This is where the extrusion engineers have to truly understand what the customer needs and wants. In these cases, clear communication is key to a successful project. The more information we receive, the better.

Brusco: In addition to extrusion, which value-added services are important to include for customers?
Bills & Jurgaitis: The three “Bs”: braiding, bonding, and butt welding. These three operations account for the bulk of additional processing related to turning a straight extrusion into an advanced catheter. Coiling, pad printing, skiving, tipping, and insert molding are among other common operations added to the extrusions.

Bloss: We support our customers during the entire development phase, which also includes an initial design concept. Depending on the project, in addition to proven experience in extrusion, know-how in injection molding can be a plus. Our customers additionally benefit from various competencies in secondary processing, assembly, sterilization processes, and packaging solutions as well as support with regard to regulatory approval processes.

Finn: Customers want more value-added work from tube suppliers as this lowers the cost of managing multiple suppliers for a single part. It also gives us more insight into how a product is being used. Centerless grinding is a popular value-added service because it provides a smooth tube without any convolutions. It can also be utilized to reduce a wall to thinner than can be achieved during extrusion. Additionally, end work such as tipping is often requested—this typically adds a radiopaque atraumatic tip at the distal end of a tube.

Herrild: We are seeing a lot of requests for testing and certifications as part of a value-add service, which is new to us. Historically, there was more interest in physical things you could do to a part (welding, punching, tipping) to get closer to a finished article. Now, there is increased focus on providing very in-depth quality data and secondary testing (percent crystallinity, percent moisture, column strength), to demonstrate product meets all specifications and will function in the customer process.

Jakinovich: We see that validation services such as biocompatibility, capability, and secondary operations such as tipping, drawing, forming, etc., are important for customers.

Lilly: I think anything that adds expertise and simplifies the commercialization process is important. In our case, customers like that we are a one-stop shop for custom designs and constructions, assembly, and packaging. We have an approved materials database that helps cut materials qualification time in the design phase, in-house mold and tooling design that enables a gated design process, and the ability to provide a scalable automation solution that evolves as volumes grow.

Nicora: Customers are trending toward requiring additional manufacturing of subassemblies, finished catheters, and increasingly sterile final product. Along with these requirements are the need to provide additional technical resources, regulatory guidance, validation studies, and packaging development and testing.

Williams: We offer many value-added services to our customers: tipping, flaring, hole drilling, printing, and overmolding. All of these are services or steps that most of our customers have to perform once they have received the extrusion. This offering eliminates the overhead and helps speed up a project.

Brusco: Where is extrusion for medtech headed? What can we expect five years from now?
Bloss: Miniaturization is the buzzword, and this trend will play a crucial role in medical technology in the years to come. Specialties such as extruding polymer coatings on super-thin metallic and non-metallic wires are also on the rise. Those wires, braids, and fibers fulfill a wide range of medical purposes. They can be used as guides in minimally invasive surgery or as signal-transmitting electrodes for neurostimulation, for example. With our single-step extrusion process, polyamides (PA) and materials like PTFE, FEP, amorphous PEEK, and PUR are directly extruded onto the substrate in a single processing step. This results in uniform, concentric coatings where the risk of material flaking is reduced to a minimum.

In our opinion, the demand for silicone solutions required for pump applications in the pharmaceutical field, for example, as well as silicone tubing for different medical purposes will increase, too. Due to its advantageous properties and versatile processing techniques, the material possesses promising application areas.

Finn: Increased customization and utilization of cross sectional areas. For example, hybrid cables and eTubing, which is a combination of wire for electrical requirements and more traditional tubing. A micro-miniature coax can be embedded in the wall of a tube, so that lumen space can be better utilized and make a smaller, less invasive product.

Herrild: I think the technology for control systems and data analysis will continue to advance. I expect in five years many extrusion lines will look more like injection molding; there will be less black art and more automatic machine-directed action plans in place. I think lights out production will be possible for those who quickly adopt the new technology.

Hudson: Extrusion is headed anywhere that pushes the limits of current technology, whether it be material or processing related. As devices get smaller and smaller, so do the extruded components attached to it. We can expect micro-extrusions to increase in popularity even further than we already are, and in five years even seeing 3D-printed extrusions get into the market.

Jurgaitis: Cost savings seems to be more of a driver in a project, and will most likely continue to be a factor in decision making. There’s more to cost savings on a project than the extruder just having a smaller margin. Cost savings can be realized by more accurate and consistent extrusion machinery, more process-friendly raw materials, and innovative raw materials and additives that can deliver more value-add directly into the polymer and reduce or eliminate the need for some typical catheter building processes or making those processes easier. Automation or more data and control integration in processes that will allow workers more capability and control will also become more prevalent. Additive manufacturing or 3D printing is just barely being realized in medical compared to other industries. While there are some novel applications of printing organs and cells, it has little adoption over making surgical models and fixturing. Incorporating 3D-printed components into actual devices for production will come about, not only for patient and healthcare provider specific tools and devices, but also for making catheter components that are expensive/difficult or impossible to make with other typical plastic processes. Additive manufacturing equipment is progressing toward more viable production, but device and catheter companies must be educated and open to looking at out of the box designs and processes.

Lilly: I think there will be increased focus on micro-bore tubing with co-extruded conductive stripes because it provides the end-use device with a wider array of features and capabilities. The trend toward minimally invasive procedures will drive greater use of micro-extrusions since these deliver the thinnest wall thickness to maximize tubing performance.

Mizenko: We believe another trend for the future will be cleaner, particle-free reinforced and non-reinforced catheters. More designers require that our tubing passes ID particle criteria. Because of this, we have been focused on providing tubing that will meet these criteria.

Nicora: Extrusion will be considered as a step in the overall manufacture of medical devices, and less as the production of a standalone component.

Williams: I would like to think that extrusion will be like the rest of the world, where we have somehow created a less manual system, and the use of automation has eliminated some of the more cumbersome parts of the job. Some say it will be more scientific, and less of what was once called “black magic.” With the advancement in equipment, we are getting closer.