Potential Hidden Dangers of Coatings on Limited-Duration Devices

Imagine you’re a medical device manufacturer looking to place a new limited-duration device on the market. You know ISO 10993-1:2018 inside and out, and you’re well-versed in the regulatory guidance around preclinical biocompatibility testing and how to apply ISO 10993-1. You’ve developed and documented the device’s concept, built a final finished device, and determined the correct submission pathway based on your device. Now you’re compiling your technical data, manufacturing details, and risk analysis documentation, and when you’re done, you’re ready to submit your device for regulatory clearance.

Then you receive a deficiency letter from your regulatory body that you never expected. The regulators have questions.

Your limited-duration device contains a hydrophilic and/or hydrophobic coating that could peel, flake, shed, delaminate, or slough off inside the body. Basically, the coating you used turned your “limited duration” device into a long-term device based on the potential for chemicals and/or particulates from that coating to remain in the body beyond 24 hours. This new classification is not only incongruous with your device’s intended use but also comes with a host of complex and costly preclinical and clinical testing, post-market surveillance, and labeling considerations that don’t usually apply to your device.

Regulators, however, cannot be too careful; too much information is available about what happens when coatings fail or get left behind. In fact, regulators have known for years about serious adverse events that can occur when hydrophilic and/or hydrophobic coatings separate from intravascular medical devices. Agencies warn of coatings from guidewires, sheaths, catheters, retrieval devices and embolization device delivery wires. Some of the adverse events cited include pulmonary embolism, pulmonary infarction, myocardial embolism, myocardial infarction, embolic stroke, tissue necrosis, and death.

This reality underscores a critical yet often overlooked aspect in medical device manufacturing: Carefully considering and evaluating the coatings used on devices—particularly those intended for limited-duration use—to prevent unforeseen complications and regulatory hurdles.

Why Coatings Are Not Always Considered

Limited-duration medical devices have less than 24 hours of contact with the human body; transient contact devices have less than a minute. While manufacturers of long-term devices (i.e., more than 30 days) likely know the risks of coatings and plan for extensive chemical characterization, limited and transient duration products are different. Applying coatings on these devices may not be considered for many reasons, including an assumption that the coating does not contribute to the device’s efficacy. Other reasons may include:

• Perceived low risk: The brief duration of exposure for these devices significantly reduces the risk of infections or adverse reactions, making specialized coatings less necessary.
• Awareness and/or expertise gaps: Smaller or new manufacturers may not be fully aware of a coating’s potential benefits or may lack the expertise to develop and apply them effectively.
• Cost: Coatings can add significant expense to the manufacturing process, which might not be justifiable for disposable or low-margin products.
• Complexity: Incorporating a coating requires additional manufacturing steps, specialized equipment, and stringent quality control measures.
• Regulatory challenges: Adding a coating to a medical device might necessitate a different regulatory classification or additional testing to ensure safety and effectiveness, complicating the regulatory submission.
• Alternative focus: An assumption may be made that the device performs adequately without a coating based on its ease of use, patient comfort, or functional
• efficacy.
• Short shelf life: The long-term benefits of coatings, like enhanced durability or functionality, might not align with the device’s intended use, rendering them
• unnecessary.

While coatings can offer significant benefits, their omission in limited-duration medical devices can be attributed to various factors. Medtech manufacturers must weigh these factors carefully to ensure their decisions align with patient safety and the device’s intended use and efficacy.

Advantages of Using Coatings

Perhaps the most important reason to apply a coating to devices is to reduce friction. This is particularly beneficial for products like catheters and guidewires, as a smoother surface eases insertion and manipulation, making the process less traumatic for patients. Likewise, improving biocompatibility is an important consideration. A suitable coating can reduce the body’s immune response, minimizing the potential for irritation or inflammation. This is especially crucial for devices that contact internal tissue and/or blood.

Another reason to use a coating on medical devices is to reduce infection. Antimicrobial coatings can inhibit bacterial growth on the product’s surface, a vital feature for devices that breach the skin, mucous membranes, or those used in sterile surgical environments. In addition, some medical devices incorporate coatings to facilitate drug delivery. For example, a coated stent may slowly release a drug to prevent the re-narrowing of an artery, combining treatment with the device’s primary function.

For products that contact blood—vascular catheters or stents—thromboresistant coatings are crucial. These coatings help reduce blood clot formation, a significant concern in many vascular interventions. In some cases, coatings are designed to provide a controlled release of therapeutic agents, beneficial for maintaining therapeutic drug levels or prolonged treatment regimens.

Finally, coatings can prevent tissue from adhering to devices during surgeries, reducing postoperative complications and discomfort. This aspect, along with lubrication enhancements, contribute significantly to procedural efficiency and patient comfort, especially in minimally invasive procedures.

Each coating application demonstrates the intricate balance of engineering and medical science, aiming to enhance patient outcomes, reduce complications, and improve the overall effectiveness of medical treatments.

Coating Conundrum Recommendations

Regulatory rejection is a costly outcome but ineffective devices that compromise patient safety are simply unacceptable. Device manufacturers have three primary avenues to avoid a coating conundrum.

First, go with what you know. Additional time and consideration are needed whenever medical devices are built using novel or innovative materials. Sometimes, these materials create regulatory quagmires that ultimately do not lead to successful submissions. Using a coating that has been on the market for several years and for which there is ample supporting data can be a foolproof way to sidestep delays.

Second, be proactive. If a manufacturer has chosen a novel or innovative coating material, the biocompatibility and chemistry programs should take this into consideration. The coating material may have unique biocompatibility or toxicological properties that regulators have not seen, and as such, additional testing may be necessary. The bottom line is that using a novel or innovative coating material will undoubtedly require more resources and lengthen submission timelines.

Finally, schedule a pre-submission (“pre-sub”) meeting. The pre-sub process is vital for manufacturers to gain early regulatory insights on aspects of their devices before formally submitting them for clearance. Device modifications and classification are two of the most compelling areas of discussion during these meetings. Engaging with regulators early in the development process can improve the device’s development strategy, streamline testing methodologies, and provide a clearer understanding of regulatory expectations.

A Final Word on Coatings

Introducing a new, limited-duration medical device to the market—especially one with a coating—requires meticulous attention to detail and a strategic approach. Coatings can provide enhanced biocompatibility, reduced infection risk, and improved device functionality, but they also come with challenges.

Manufacturers are strongly encouraged to engage in early regulatory dialogue proactively. Scheduling pre-sub meetings with regulatory bodies is a critical step. These meetings offer opportunities to gain early insights and feedback on aspects of the device that could shape its development and inform further strategy.

Device manufacturers who do not possess the expertise to compare novel versus well-established coatings or test those materials may consider working with a trusted laboratory testing partner. Those unsure about navigating the regulatory landscape in this area may also consider leaning on expert guidance. This essential collaboration can provide the specialized knowledge and support needed to overcome technical challenges and ensure the device adheres to the highest safety standards. 

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Kim Ehman, Ph.D., DABT, has over 20 years of toxicology and medical device experience, with expertise in toxicological risk assessments for medical devices, food and beverage products, and electronic nicotine delivery systems. Before joining WuXi AppTec Medical Device Testing, she was a toxicologist for RTI International, Toxicology Regulatory Services, and Altria Client Services. She received her Ph.D. in parasitology from McGill University and conducted postdoctoral research at the U.S. EPA in developmental neurotoxicology. In her current position, Dr. Ehman provides medical device manufacturers and suppliers with technical and regulatory support for biocompatibility test programs and conducts quantitative toxicological risk assessments to support product safety and risk management decisions.

Sandi Schaible is the senior director of analytical chemistry and regulatory toxicology at WuXi AppTec, specializing in extractables and leachables studies. She is a U.S. delegate and international delegate for ISO 10993 part 18 in chemical characterization, and a U.S. delegate for ISO 10993 part 13 and the particulates committee (TIR42). Schaible has experience working in the pharmaceutical, medical device, environmental, and R&D industries, including over 25 years of analytical experience in GLP, GMP, FDA and ISO regulated laboratories.