Announced in the wake of harsh criticism over its 510(k) clearance pathway and product safety concerns, FDA officials pledged to include patients, device manufacturers, researchers, and physicians in the ongoing effort to better evaluate medtech materials and their potential risks. There are several substances and products on the agency’s radar, including silicone breast implants, metal-on-metal hip replacements, nitinol-based devices, innovative materials like graphene and nanoparticles, and animal-derived materials (i.e., additives for device coatings or heart valves made from pig tissue).
Coincidentally (or not), the FDA issued final guidance on animal-derived disease transmission on the same day it unveiled its materials science initiative. The guidance covers bioburden/sterility assessment test methods; facility decontamination measures; virus validation studies; risk management; sourcing, collection, and handling controls; and TSE (transmissible spongiform encephalopathy) agents elimination/inactivation efforts.
A 2016 guidance document from the agency addressed material biocompatibility evaluations to ensure medtech manufacturers adequately assess their products for possible adverse biological responses. Although the FDA considers current testing methods to be “a reliable predictor of a material’s safety,” it recognizes the importance of evaluations both before and after a product is commercialized to help reduce patient risk and maximize benefits.
In taking a closer look at medical device materials, the FDA is attempting to provide safer alternatives to substances that may cause an adverse biological reaction in patients. “Enhancing our collective understanding of materials science could lead to identifying materials that may cause an exaggerated response in sensitive individuals and advance the development of safer materials,” former FDA Commissioner Scott Gottlieb, M.D., and Jeff Shuren, M.D., director of the Center for Devices and Radiological Health, said in the FDA statement.
In detailing its medical materials initiative, the FDA emphasized the importance of incorporating patient safety and “sound science” in any new regulations. “Our understanding of medical technologies evolves over time,” the statement read. “As we learn more about long-term effects of materials and as materials science advances and new innovations become a reality, it’s imperative our regulation of devices evolves along with these advances to ensure patients are protected.”
Indeed, patient protection is an important consideration in medical device materials science. But so is product design and performance. Advancements in materials is expanding device capabilities, improving their mechanical, chemical, and electrical properties. In some cases, these enhancements have led to the development of entirely new materials.
Researchers at the University of British Columbia (UBC)-Okanagan, for example, have created a synthetic heart valve made of plastic-like materials for patients who are too high-risk for open heart surgery (those aged 75 and older). The valves would be inserted via catheter in a 30-minute procedure rather than invasively in a three- to four-hour surgery. The valve itself is comprised of small components, including “gels, vinyl, and cellulose,” and potentially could solve many of the issues associated with implanting animal tissue in humans.
“It feels like [human] tissue,” said Hadi Mahammadi, assistant professor at the Heart Valve Performance Laboratory at UBC’s school of engineering. “It’s 90 percent water. It actually is like tissue.”
Though the valve is nowhere near ready for human implantation, its market potential is huge, as the valve replacement industry is currently valued at roughly $8 billion in the United States and Canada, according to industry estimates.
To gain further insight on the market potential for new medical device materials, as well as the trends and challenges affecting the industry, Medical Product Outsourcing spoke with a number of experts over the last several weeks. They included:
Olivia Blouin, development engineer; Bobby Schroeder, development engineer; and Dylan Spink, senior director of Quality & Engineering at Boyd Technologies, a Lee, Mass.-based advanced materials and technology company operating in the medical device and life sciences market.
Neal Carty, Ph.D., senior director, global R&D; and Deepak Prakash, senior director, Marketing; at global materials science firm Avery Dennison Medical.
Ronn Cort, president and chief operating officer; Mark Denning, medical market business manager; Dennis Kelso, appLab manager; and Sean Stabler, R&D manager at SEKISUI SPI, a global inventor and manufacturer of specialized high-performance plastics.
Lars Gerding, vice president of Technology at Freudenberg Medical, a global partner for the design, development and manufacture of medical devices, components, and product solutions.
Darpan Parikh, global product management leader—LNP Specialty Compounds; and Ashir Thakore, global segment leader —Healthcare at SABIC, a petrochemicals manufacturer headquartered in Riyadh, Saudi Arabia.
Neel Patel, vice president at Florida Anodize System & Technologies Inc., a Sanford, Fla.-based aluminum anodic surface coatings provider serving medical, aerospace, defense and specialty manufacturing OEMs.
John Tranquilli, materials manager at Apple Rubber Products Inc., a designer and manufacturer of seals and sealing devices located in Lancaster, N.Y.
Michael Barbella: What industry trends are you noticing with regards to medical device materials?
Olivia Blouin, Bobby Schroeder, Dylan Spink: OEMs are requesting customized materials that provide a specific solution from suppliers. This is leading to a greater specialization of materials—ones that adapt to a particular use case.
Mark Denning: Medical device materials are currently going through an evolution in response to increased attention to biological solutions, design flexibility, technological advancement, and human factor controls. Cleanability and chemical resistance without degrading material performance are keys to material selection. In a medical environment, machines are sanitized often, and certain chemicals can degrade some materials. As hospitals shift from hypochlorite-based cleaners to more aggressive cleaners, traditional materials are beginning to fail. Many OEMs are increasing their initiatives to validate current materials along with new materials being introduced to more aggressive disinfectants like quaternary ammonium, also known as “Quats.” SEKISUI SPI, manufacturer of KYDEX Thermoplastics, regularly tests materials for biochemical solutions to ensure patient safety and product integrity. KYDEX Thermoplastics resist bacteriological and fungal development, which makes them ideal for use in medical environments. They do not readily provide a source of nutrients for bacteria and fungi to grow. One source of these nutrients is an additive known as plasticizer, which is not used in KYDEX Thermoplastics.
Design flexibility is on the rise, with a desire for integral colors, custom color creation for brand identity, and product solution customization. Medtech designers are acutely aware of the human factor controls and are introducing patient desires into the design process. Designing equipment to feel less sterile and plain can have a positive influence on patient mindset. Additional customization comes from converting from injection molding materials to thermoformed materials. Injection molding has high volume identical products with limited design and increased tooling costs. Thermoforming utilizes more cost-effective prototyping tools, which allow for rapid innovation and regular design updates. Because this leads to shorter campaign and design cycles, the cost of tooling isn’t amortized over as many units, making it an attractive and less costly option for medical material selection.
Technology also plays a part in the future of medtech devices. There is a need for Electromagnetic Interference (EMI) shielding with the influx of compact devices. As technology and 5G increase, medtech devices are getting smaller, enabling their use in home care, remote outreach, and wearable health technology. Lightweight material solutions, such as thermoplastics, make it easier to bring medical technology into a patient’s home, lowering overall healthcare costs.
Lars Gerding: Often we see that material selection is overlooked and customers prefer to use a material they have worked with in the past and are familiar with. This can be a mistake and can require additional steps or processes. It may not be the best material for their new device and customers may be missing the opportunity to use materials with special properties. This will be a big issue later with the accelerated aging of devices, instances where customers are not aware of the effects of aging on certain materials. Customers want to save time by increasing temperatures and this may affect the polymer. It’s important to consider not only the suitability for the final application of the device but also the conditions, like sterilization and acceleration aging, and contact with other media like coatings or lubricants that may be applied.
Additionally, today, many medical manufacturers are relatively “cemented into” using one provider and they are not aware of the full scope of material options out there that might fill an application. When in the prototype or early launch stages of a product, focus is not so much on the cost of every material used in a product. But as volumes increase price becomes an issue and suddenly, the customer will realize they are being held captive by a single-source supplier. It’s often time to switch from specialty to standard material.
Darpan Parikh, Ashir Thakore: There are several industry trends driving changes in medical device materials. With patient safety at the forefront, the healthcare industry is mobilizing to address the concerns of increasing patient infections associated with medical care, known as HAIs (hospital acquired infections). To help meet this challenge, medical equipment and high-touch surfaces in patient care settings are repeatedly wiped down with increasingly aggressive chemical disinfectants. Manufacturers of medical equipment for patient monitoring, imaging, diagnostics, and fluid and medication delivery need materials that offer improved chemical resistance to the more aggressive disinfectants used today in healthcare settings. SABIC’s LNP ELCRES CRX resins leverage unique copolymer technology to provide improved chemical resistance for healthcare devices and equipment.
Further, the increase in home-based care is encouraging the development of devices that are more aesthetically pleasing and are more durable to withstand common impacts associated with portable equipment.
Also, the increasing use of wearable devices to monitor one’s health calls for materials that enable miniaturization and weight reductions. Metal replacement continues to be another major trend in the healthcare industry and contributes to the ever important need to reduce costs.
Another important movement in the healthcare industry is the adoption of increasingly strict regulations, such as Unique Device Identification (UDI), where laser marking and other similar technologies are used.
Neel Patel: A move towards two ends—on one hand, we have cost and other pressures moving us toward single-use devices and plastics, but on the other hand medical professionals are using more complex systems that require robust and durable materials. I think we have more options than ever now, which is great, but finding the right material for the right job is more important than ever.
This also goes hand-in-hand with a more disciplined and knowledgeable approach to human factors engineering. Medical device companies are now far more conscious of the ROI of human factors engineering and the feedback they’re getting from formative testing, and it’s directly feeding into materials selection as well. The realization that materials and markings are important not just for the patient and the operator, but also for the decontamination team, sterilization technicians, and reprocessing personnel, etc. We’ve seen a drive towards materials that are versatile—they meet the technical engineering requirements, but also the human factors requirements, and even take into account the needs of transportation, storage, and marketing.
Deepak Prakash: The healthcare industry is focused on simplifying the supply chain, with an eye on expediting speed to market, controlling costs and reducing risks. Medical devices must support evidence-based positive outcomes and delivery of affordable, convenient healthcare. Against this backdrop, medical device materials often must provide more performance characteristics at a greater economic value than ever before, and they need to be manufactured with environmental sustainability in mind.
John Tranquilli: More companies are looking for rubber materials that will not leach out contamination from the rubber seal. With new regulations like EU MDR, companies need to assure restricted chemicals are not part of the rubber formulation. Companies want full material declarations, but rubber formulations are proprietary to many rubber companies.
Barbella: How have medtech materials evolved over the last several decades?
Blouin, Schroeder, and Spink: One thing that stands out is the ability of raw material manufacturers to tailor materials to specific performance characteristics. Adhesives used in advanced wound care is one area in particular where, depending on the type of wound, necessary duration of the bandage, and ideal water vapor transmission rate (among other attributes), you can have tremendously varying traits to suit very specific applications.
Denning: In the early stages of the industry, medtech equipment was made of painted metal that was clunky with limited aesthetics. Design was based on functionality and the ability to meet UL requirements. As the industry matured and aesthetics became more of a focus, injection molding and structural foam were introduced to add visual appeal to the machines. Following aesthetics, designers focused on the patient experience, ensuring machines were less invasive and more inviting. To achieve a better patient appeal, material selection required color, branding, patterns, sustainability, and a softer look. KYDEX Thermoplastics give the design community the freedom to meet these requirements with custom colour and pattern creation.
Through direct collaboration with OEMs and designers, SEKISUI SPI supports innovation with education on product and process capabilities. The appLab and designLab innovation centers were specifically created to foster collaboration. They offer a space where designers and engineers can explore their design and engineering concepts in real time. The next generation of materials will need to address higher heat requirements, increased biocompatibility, and light-weighting while adding strength, new developments in cleanability for disease prevention, and sustainability.
Gerding: The change is, for the most part, toward cleaner materials that contain less byproducts. Regulations have become tighter in drug-device combination products containing pharmaceuticals. There are strong regulations for leachables and extractables, and we often find companies are using materials no longer suitable by today’s standards. In those cases, we look for substitute materials. Price is also a concern. For example, a startup that becomes successful and increases its volumes might need to find a more cost-effective material.
Parikh and Thakore: Materials and process technologies continue to evolve and medtech materials, in particular, are evolving at a rapid pace. For example:
Certain medications can be self-administered (e.g., insulin) and this requires drug manufacturers to move to self-injectables that can be handled by a wide range of people (ranging from children to senior citizens). This led to the development of lubricated materials that make it easy to administer consistent and accurate doses at lower forces.
Device housings that were once primarily metal have been converted to plastics and with increased exposure to harsh chemicals, they now require solutions that can withstand these chemicals.
With increased prevalence of connected devices, EMI/RFI shielding is critical and requires unique material solutions.
Additive manufacturing is enabling the faster development of parts and more personalized solutions.
Patel: Obviously, there are more stringent controls over all medtech materials, and that includes along every step of the manufacturing process. Where you used to be able to use off-the-shelf components and materials, now you have to consider every aspect of the material and component that goes into your completed device. Specifically, you can look at colorants in medical devices—there’s more emphasis on making sure materials are compatible with sterilization processes and there are no leachates, and each component material can withstand, without any degradation or loss of colorant, the reprocessing and sterilization operations.
Moving on from that, there’s an importance placed on traceability in medtech materials. So how materials move within the manufacturing process and ensuring there is accountability at every stage of the build process—goes directly into QMS requirements and having medtech materials suppliers who have ISO 13485 or equivalent systems that ensure downstream suppliers are managing their risks appropriately.
Prakash: As medical devices have gotten more complex over the decades and been required to do more, so too have medtech materials. Every decade the industry develops materials with unique properties and characteristics, powered by advances in technology and automation. This includes innovations to the physical structure such as surface modifications, as well as the ability to blend different materials. For example, there have been significant advances in polymer synthesis and composite materials.
Tranquilli: Rubber compounds being introduced into the medtech industry require more biocompatibility testing. Testing that follows the ISO 10993 test matrix is typically required. Companies want to be sure materials will pass before even being molded into prototype parts. New regulations might even require extraction testing to identify any leachable. Material suppliers need to spend more money on testing to make sure materials will be accepted to the market.
Barbella: There is often a complex relationship between medtech materials and the media they come in contact with. How does this relationship affect material selection and development?
Blouin, Schroeder, and Spink: Selecting materials that are biocompatible is an obvious concern. Another important consideration when building the bill of materials is their compatibility with each other and with the chosen sterilization technology. Knowing materials may not perform in the real world like their specification sheets suggest is crucial for engineers to understand during the product development process. Understanding what effect materials used as a process aid will have on the finished product is also critical.
Neal Carty: It is critical to have a holistic understanding of the entire device and its purpose. Many wearable devices, for example, have plastic casings, batteries, sensors, and other components made of multiple media. There is a need for construction layer materials to hold all those components together and then there must be a skin-layer material to attach the device to the patient’s body. If that casing is not breathable, or if any of the construction layer materials are not breathable, then the device developer will need some means of absorbing moisture from the skin while the device is worn. An absorbent material that can soak up moisture and remove it from the skin is needed. On the other hand, if the device can be constructed with porous, breathable materials that allow moisture to wick and evaporate, that is another approach. Sometimes surprising combinations can work. These variables affect device design and construction, and so early collaboration between supply chain partners is best.
Dennis Kelso: Chemical and biological media contact has a significant impact to material selection and development. One material rarely meets all physical and chemical property needs while also achieving desired aesthetics. Many OEMs will experience significant failures when materials interact with more aggressive disinfecting agents like Quats. KYDEX Thermoplastics have been developed to work well in these applications. SEKISUI SPI is partnering with manufacturers of infection prevention products to develop solutions for our current product portfolio and new materials. As infectious disease resistance to sanitization becomes more aggressive, so must the sanitization processes and the integrity of medical housings. During the development phase, SEKISUI SPI evaluates its materials to media they may come in contact with. Through relationships with major manufacturers, SEKISUI SPI evaluates the new cleaners and disinfectants for compatibility with KYDEX Thermoplastics.
Parikh and Thakore: When selecting materials for any medtech application, we need to consider the full usage cycle. This includes the manufacturing and assembly process, the function of the part (including interactions with external factors like bodily fluids, chemicals, or pharmaceuticals, etc.), the environment in which it will be used (including sterilization), and disposal. All these factors must be taken into consideration when designing and developing a device. One main reason we are introducing this new family of LNP ELCRES CRX copolymer materials is to address the challenge of harsh disinfectants that may attack the plastic and cause cracking and/or discoloration.
Patel: Medtech materials and the media and other materials they come in contact with truly impact material selection. One point that is fairly straightforward to understand is that from a regulatory standpoint, the FDA and other oversight bodies are far more comfortable using materials that have a long and well understood medical device history.
When a new material is being used, there is often not enough history of the interactions of that material not just with the human body but also with sterilization and reprocessing media to make regulatory bodies comfortable with its use, and so this often requires additional validation which means additional time and costs.
Another factor that needs to be considered is not just the materials’ relationship with standard reprocessing media, but with materials that are less common or which are not standard presently but which may be used in the future. Sterilization processes, procedures, and materials are evolving, and material selection today has to be made with an eye on what may be used in the future. So rather than using the newest material, it may make sense in certain situations to use standard materials that are well understood and those we know are inert to the widest variety of environments and media.
Tranquilli: Depending on the chemical characteristics of the pharmaceutical, it can attack the polymer chain of the different rubber types. Acidic and basic materials will attack any unsaturation in polymer chains. That is why nitrile rubber compounds are not good for these applications. When permeation is important to prevent air from oxidizing chemicals or to block other medical gases, silicone is not a good choice. Using halogenated butyl or FKM work well or permeation resistance.
Barbella: What factors are taken into consideration when selecting a material for product development?
Blouin, Schroeder, and Spink: This is very project dependent, but generally speaking, the concern is focused on material performance in order to get proof of principle off the ground. However, looking at the big picture in designing for manufacturability in the early stages of product development can save a lot of headaches down the road.
Ronn Cort: At high level, companies need to compete on imagination. Imagination lies upstream of innovation: to realize new possibilities, we first need inspiration (a reason to see things differently) and then imagination (the ability to identify possibilities that are not currently the case but could be). This is why our company is not a traditional model focused solely on production and process equipment. Imagination is a uniquely human capability—artificial intelligence today can only make sense of patterns in existing data. As machines automate an increasing share of routine tasks, companies will need to focus on imagination to stay relevant and make an impact.
Gerding: What mechanical and physical properties the part needs to fulfill as well as pricing and any special regulatory requirements. Changes have to be monitored closely. In terms of cost, you don’t want to necessarily choose the highest, best-performing polymer. You need to provide balance because if the product is not affordable in the end, nobody wins. As the device becomes a success, this becomes a bigger concern. Freudenberg now has a materials database. It combines all the experience we’ve had with materials over the years, from different global locations and different applications for TP and silicones.
Parikh and Thakore: The full use cycle needs to be considered when selecting materials. This starts with the requirements of the device, the manufacturing process, the expected life of the device, the use environment (including sterilization, etc.). All these factors will influence the material selection. Suppliers like SABIC can be a valuable asset if engaged early on in this process, as we can bring a strong knowledge of materials, testing, and processing, along with experience with other industries that can help customers pick the right materials and help reduce development time and cost.
Patel: Material selection in medical product development is an expansive subject area, and there are inputs from several medical device disciplines that have to be taken into consideration when selecting a material for product development. One of the most closely linked disciplines besides regulatory approval is human factors engineering. With HF engineering, product designers get the greatest understanding of how their devices are going to be used, not just for the intended use, but more importantly in the unintended uses.
As the discipline is becoming more valued, we’re seeing that medical device companies have to design not just for the medical operator but also for everyone else who will be “using” the device, and so the design, and material selection, has to fit the most robust use cases.
So really, you need materials that can be manufactured precisely, be well understood by device designers, engineers, and regulators, and also adhere to good human factors principles, be versatile for many different uses, and also robust enough to face the harsh chemical environments and media of current and future sterilization systems. Not a short requirements list.
Prakash: Important factors to consider include the device’s purpose, use and manufacturability. Regarding purpose, the material must enable the device to reliably deliver proven outcomes. As for use, this refers to factors such as comfort and convenience. How does the material help ensure the patient will wear it as intended? Sometimes the purpose can be clear, but the reality of the patient experience can be quite different. Supply chain partners with experience across different product applications and patient groups can share insights to make a product that performs well and is patient friendly. And manufacturability relates to the economic model for the device. What different materials are required to produce the device, and how efficiently can it be manufactured to meet the economic target? When device developers and materials suppliers work together, they can identify paths to success. Sometimes they can find ways to deliver the required feature-function mix with a single material instead of multiple materials, streamlining the production process and conserving costs.
Sean Stabler: The first step for consideration is asking the right questions during the market analysis phase.
- Is there a gap in the market for a solution?
- Is the market looking for a way to improve a particular characteristic?
- Once we determine the product meets the market’s needs, we examine the whole ecosystem through questions such as:
- What fundamental properties does the material need to achieve?
- What process will be used to convert the material to a finished or semi-finished part?
- What regulatory standards influence the material or part?
- What other gaps are present that we can address with design or material selection?
Tranquilli: For rubber medtech applications, physical properties are the first priority. A seal application requires a good compression set. Banding applications require low tensile set properties. Once physical properties are satisfied then chemical compatibility is checked. After than, biocompatibility requirements are established.
Barbella: Can you give an example of an innovative material solution your company came up with to meet a challenging customer request?
Blouin, Schroeder, and Spink: As our customer, Seres Therapeutics, began clinical trials for its lead development candidate, it identified critical supply chain challenges that it would need to solve to gain FDA approval. Initially, the development work began by using off-the-shelf products for storage, processing, and filtration of its microbes. While this is common for early, proof-of-concept work, this presented clear challenges for the company in the long term because they would need to establish the necessary controls for a commercial pharmaceutical supply chain. In particular, the company needed to identify the material composition of all materials that came in contact with the product and establish appropriate change controls down to tertiary suppliers.
Our first task was to perform Fourier Transform Infrared spectroscopy (FTIR) and chemical composition tests on all of the materials. Separately, we also needed to classify the filtration functionality of one of the raw materials, which acts as a filter mesh in the final product solution. To do this, we conducted an analysis of the particle size and distribution from the mesh. Following the testing and analysis, we were able to accurately identify the component materials and construct a bill of materials for the component device.
Having identified the raw materials required, the next step was to engage our commercial supply chain partners. In this circumstance, we needed suppliers who had appropriate change controls in place, could support smaller volumes before commercial scale-up, and were equipped to handle the quality and regulatory requirements for pharmaceuticals. Working within our network of flexible materials manufacturers, we partnered with suppliers who could create custom materials while still meeting the rigorous standards required of a pharmaceutical supply chain for the bioprocessing device.
Carty: Avery Dennison Medical recently developed a new hydrocolloid formulation to address cost pressures from the market. We focused on cost engineering by reviewing the bill of materials for an existing hydrocolloid and researching alternatives. We found more cost-effective materials that we could use without sacrificing performance. There are always new suppliers on the market and new options, and it’s important to review what you are using in your products to determine if there are any new materials that are less expensive or more sustainable.
Gerding: A customer came to Freudenberg with a valve seal created from an isoprene rubber, which is a proprietary rubber formulation that only one supplier formulated and offered at a set price. In the beginning this was not an issue but now the manufacturer required more volume and their supplier could not provide more. The seal had to fulfill specific requirements, mechanical properties, and characteristics. In order to find a suitable material substitute we 3D imaged their part, then simulated forced displacement characteristics based on data we had from their measurement placements and required characteristics from existing parts. In the same model, we applied our material characteristics and model for liquid silicone rubber. With the resulting information about displacement characteristics we were able to identify a specific silicone suitable for the application. It was done without any actual prototyping or using the material in an actual mold. The process saved the company both time and money.
Parikh and Thakore: With patient safety at the forefront, the healthcare industry is mobilizing to address the concerns of increasing HAIs. One solution is to repeatedly clean medical equipment and high-touch surfaces in patient care settings with increasingly aggressive chemical disinfectants. SABIC’s LNP ELCRES CRX resins leverage unique copolymer technology to provide the improved chemical resistance necessary to clean healthcare devices and equipment with harsh disinfectants. Compared to traditional PC, ABS, PBT, and co-polyester resins and blends—which are potentially incompatible with highly aggressive disinfectants such as quaternary ammonium compounds—the new LNP ELCRES CRX resins can help prevent stress cracking and mitigate crack propagation.
Patel: One of the innovative material solutions we’ve developed specifically for the medical device market is a unique anodic process we call FAST Colourlock. To prevent corrosion, all aluminum components undergo a surface finish called an anodize. We were hearing from our medical device customers that the colors from their traditional anodic coatings were fading after repeat sterilization processing. They were concerned about the potential of colorant leaching from the surface and wanted something they could use not just as a protective finish, but something that made their products more eye-catching. We took that customer need and developed a process that allows for fade-resistant anodic coatings. Since then, we’ve been able to refine the system to produce a greater variety of vibrant colors and shades, and also to impart graphics and markings resistant to fade from harsh chemical sterilization processes. Our customers are now able to use color in ways they hadn’t considered earlier, not just for their branding, but also as part of their human factors designs.