CONTRACT SERVICES - When Choosing Stent, Catheter & Tubing Partners, Less is More

INTRODUCTION

Increasingly, MedTech companies are seeking contract de­sign and manufacturing partners that can accompany them on comprehensive product journeys – from initial concept to valida­tion to large-scale manufacturing, and everything in between. The ability to combine ideation and early stage development with materials science and process technologies has, in recent years, become a differentiator across a variety of device categories.

This relatively recent dynamic runs decidedly against the his­torical grain. In a globalized supply chain that frequently relies upon numerous design and production partners providing sepa­rate components for sophisticated, mission-critical medical de­vices, a single-partner approach seems almost quaint. But the advantages offered by truly turnkey partners – ones that can steer a complicated, often multi-component medical device from ma­terials selection and prototype engineering straight through ramp-up production and broader commercialization, with par­ticipation in critical steps along the way – have never been more evident.

This value is magnified when the medical device in question is a “niche within a niche.” As the healthcare solutions landscape becomes more intricate, more MedTech companies are eschew­ing “stay in your lane” specialists for multilane partners capable of running from starting gun to finish line. This “under one roof” mindset favors contract development and manufacturing organ­izations (CDMOs) with holistic strategic skillsets rather than piece­meal tactics that must be stacked upon elsewhere.

If too many chefs can ruin an entrée, too many design, en­gineering, and production partners can limit and delay the real­ization of a complex medical device. Nowhere is this consolida­tion-centric concept truer than with advanced stents, catheters, and tubing products.

STENTS & CATHETERS: PRODUCTS INFORMED BY PROCESS

A comprehensive dissertation encompassing the myriad va­rieties of stents and catheter combinations would require a book rather than a few pages, so instead let’s explore one sliver of this market – a “niche within a niche within a niche,” so to speak. For starters, let’s take a deep dive into a category known for its heightened levels of design, engineering, and manufacturing challenges: neurovascular stent systems.

All stents are miniscule; neurovascular stents are exceedingly so, frequently measuring just two or three millimeters. The tiny tu­bular devices are implanted within blood vessels in the intracra­nial cavity to treat a vascular abnormality, such as those resulting from aneurysms or strokes.

Here, the bird’s eye view becomes the proper perspective. Neurovascular stents are an exceptionally intricate device that, after being coupled with another device (a catheter), will be the focal point of a delicate, difficult medical procedure. The entire process – not only design through manufacturing but design through implantation – must be as optimized as possible. This optimization requires not just individually perfected steps but the synchronization of those steps.

Here, categorization comes into play. Whereas many stents come preloaded into their complementary catheter delivery systems, neurovascular stents occupy too lim­ited a landscape for such conveniences. Given the narrow, twisting tortuous path that must be navigated for successful placement, preloading a neurovascular stent in a catheter would make the latter too stiff for the task at hand.

Rather, neurovascular stents are placed by first inserting a small-diameter microcatheter, typically about 150 centimeters in length. Once the microcatheter reaches its destination, the guidewire is re­moved; the stent is then fed through the distal end and, ever so gently, pushed to the precise implant spot.

This process places a premium on the interaction between a neurovascular stent and its microcatheter. The tracking must be smooth and free of bunching, and the final step – the removal of the stent from the mi­crocatheter’s tip – must be seamless.

With neurovascular stent systems, then, we’re confronted with intricate sys­tems that must be designed with their pay­loads in mind. The right catheter will meet its stent’s needs for column strength with­out an overabundance of compliance, be­cause if it stretches too much or too unpredictably, the procedure becomes more complicated and less informed. De­ployment accuracy also is critical; for ex­ample, a particularly springy stent will need a custom-designed catheter mecha­nism to prevent premature deployment.

With catheters and stents, there are typically several design tradeoffs when holistically considering the tortuous path, stent radial force, and catheter compli­ance. Striking the right balance among these attributes will yield an optimized stent-catheter combo whose procedural application is repeatable, and whose ulti­mate effects are positive and enduring.

Already, we can see the pitfalls of a multi-partner building block approach. The various parties involved would need constant, ultra-detailed inter-organiza­tional communication to ensure best pos­sible compatibility between the stent and its delivery device. In this example, opti­mized stent concepting and prototyping must consider more than the attributes of the stent itself. While stent-specific ele­ments like size, radial force and crimping characteristics are invaluable, equally in­valuable is understanding how that stent will conform to its delivery vessel: the catheter.

Notably, such intricacies apply not only to stent-catheter combos but also a wide array of adjacent and next-genera­tion solutions. For example, it’s becoming increasingly common for complex catheter systems to include stent-like devices like stentrievers and other devices for thrombectomy. Such sophisticated con­structions also benefit greatly from exten­sive experience in traditional stents, catheters, tubing solutions and other inter­ventional medical devices.

DRUG DELIVERY: THE DESTINATION DICTATES THE JOURNEY

Unsurprisingly, this dynamic of inter­connectivity stretches beyond device deliv­ery into the realm of targeted drug delivery. Let’s briefly touch upon a few of these categories.

For a variety of reasons, a growing number of drugs are locally deployed through catheters, on catheters, and on medical devices. Many of the catheters uti­lized for such purposes require special or even one-of-a-kind properties to reliably and compatibly handle a specific drug – a process whose complexity increases in parallel with the corresponding medicine’s intricacy.

Here’s an example: A few years ago, a novel perfusion catheter capable of de­livering liquid paclitaxel was the focus of a first-in-human study. Dubbed the Occlu­sion Perfusion Catheter (OPC), the tubing solution was designed as a universal drug-delivery catheter for delivering liquid paclitaxel to the medial layer, treat multiple lesions with a single device and, critically, minimize drug loss. A report published by the National Institutes of Health showcases the catheter’s hyper-customization.¹

The OPC delivers paclitaxel by creat­ing a treatment chamber between two oc­clusion balloons through which the agent is delivered. The delivery of liquid pacli­taxel is mechanically driven using pres­sure, measured in real-time. Local liquid delivery provides a novel approach to de­liver paclitaxel uniformly into the vessel wall and potentially overcomes the short­comings of current procedures to treat [below-the-knee] arterial stenosis.

Notably, paclitaxel also can be deliv­ered via drug-eluting stents, another area where overarching design, prototyping and production control can be beneficial. As the stent must be paired with its corre­sponding drug, so must the catheter be paired with its corresponding stent.

Drug-eluting stents also may be em­ployed to deliver drugs like sirolimus, everolimus, zotarolimus and biolimus, which help prevent the arterial narrowing that can occur following stent implanta­tion. In any application, developing the comprehensive system becomes a chain – and the fewer links along that chain, the lower the chances for costly, time-consum­ing inefficiencies or even oversights that send engineers back to the drawing board.

Several other oncology drugs are sim­ilarly applied hyper-locally. As a result, those catheter developers and suppliers with established expertise designing tubing solutions for the high-potency drugs typical to this field have a leg up. A deep bench of experts and an ample knowledge bank can narrow down what can otherwise be a protracted trial-and-error process. With oncology APIs always highly potent and often in short supply, the advantages to finding the right tubing solution expedi­ently become obvious, as does the value in keeping the process under one corpo­rate roof.

Tangentially, it’s also worth noting that catheter design also must consider com­patibility with other devices besides stents and drugs, including interactions with an­cillary, non-proprietary components such as guidewires, introducers and guide catheters. A singular entity with the knowl­edge set to consider the myriad variables is in a decidedly advantageous position.

GREATER THAN THE SUM OF ITS PARTS

All this leads to one destination: the operating room. While the stents and drugs may be the stars, the stage is just as important. Considering the complex catheter-dependent applications – delicate neurovascular stent implantation, painstaking high-potency oncology drug delivery, medicines that mitigate trans­planted organ rejection – healthcare per­sonnel conducting such procedures take on crucial supporting roles. Everything from stent design to catheter compatibility to skillful implantation and drug delivery must coalesce in support of one goal: suc­cessful acute deployment and, in the case of stents, long-term device viability.

Can this process be successfully con­ducted through a multi-partner approach? Certainly. But there are indisputable in­sights and best practices that can be more thoroughly developed and honed with an overarching view of how both stents, catheters and other tubing solutions are designed, produced and utilized. The whole of the process is greater than the sum of its parts.

One substantial benefit to containing the entirety of the development and proto­typing process in one facility is expedient trial and error. Savvy designers often have in-house simulation labs that precisely mimic how doctors would utilize (for exam­ple) a stent-catheter combo. This can in­form potential modifications to stents, catheters or both.

Compatibility simulations and the foresight they afford are but one area in which medical device CDMOs can show­case value to potential MedTech cus­tomers. Further upstream from such prototype trials, CDMOs with in-house materials testing and analysis programs help MedTech companies understand pa­rameters and potential pitfalls before com­ponent construction even commences. Here, experience matters; an outsourcing partner with firm roots in stent-catheter and drug delivery systems development can draw upon a deep well of knowledge and seasoned team of engineers who’ve successfully designed, produced and launched unique yet similar combinations.

Indeed, even in scenarios involving novel, patented designs, ingrained niche knowledge helps a stent-catheter or drug delivery system development process hit the ground running for enhanced speed to market. For example, new stent and catheters concepts typically require ap­proval from regulatory authorities. This in­cludes design stress tests, such as how a stent will handle the strain of crimping. Here, expertise becomes an expediting agent, because even new designs share similarities with existing ones. This means that certain device modeling parameters can be largely informed from an estab­lished knowledge base of stent develop­ment.

The human body is an exceptionally complicated, interconnected design. Com­panies producing targeted direct-delivery drugs, or providing invasive or implanted medical devices, naturally must develop their products in relation to this – and, cru­cially, according to the operatory proce­dures used to introduce or employ them. With so many considerations to juggle, more MedTech companies are finding re­assurances with turnkey partners, whose comprehensive product and process ex­pertise make them less likely to drop the ball.

REFERENCE

1. Bunch, P, Nair, G. Aggarwala, E. Dip­pel, E. Kassab, M. Khan, C. LeCroy, J. M McClure, T. Tolleson, C. Walker; Na­tional Institutes of Health, “A universal drug delivery catheter for the treatment of infrapopliteal arterial disease using liquid therapy,” February 4, 2020, https://pmc.ncbi.nlm.nih.gov/arti­cles/PMC7496530/.

Andrew Filachek is Global Head of Design & Development – Interventional Devices for TekniPlex Healthcare, which utilizes advanced materials science expertise and technologies to develop and deliver critical solutions for medical and diagnostic devices, drug delivery systems and sterile barriers healthcare packaging applications. In the medical device niche, TekniPlex Healthcare embodies a comprehensive CDMO partner capable of servicing every stage of the product life cycle, from design and development through component manufacturing and final assembly. www.tekni-plex.com/ healthcare.