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“WE NEVER STAND STILL” ABBOTT’S DR. NICK WEST ON THE INNOVATION-FUELED EVOLUTION OF DRUG-ELUTING STENTS

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HERE’S WHAT WE SEE

Getting the inside scoop behind top medtech innovations

utumn is upon us, and it is once again time to sip a pumpkin spice latte — or a pumpkin beer — and crack open our latest Medical Device Handbook. Once again, we’ve reached out to experts across the industry to curate dozens of “what is” and “how to” types of articles that cover a breadth of categories: components, drug delivery, manufacturing and machining, materials, product design and development, regulatory, software, sterilization services and tubing. As the years go by, I’m proud that we’re including more insights from the major medical device companies in each succeeding issue. This time around, we spoke to experts involved in some of the major industry innovations of the past decade: •

Now VP of R&D for Medtronic’s cardiac diagnostics and services business, Leonardo Rapallini was the Micra effort’s senior program director for nearly ﬁve years. He goes over insights gained from the creation of the tiny implantable pacemaker.

•

Stryker executive Naomi Murray described how additive manufacturing is advancing orthopedics during one of our DeviceTalks Tuesdays webinars.

•

Dr. Brian Dunkin, chief medical ofﬁcer of Boston Scientiﬁc’s endoscopy division, discusses the challenges the company overcame to make single-use scopes a reality.

•

Mark Day, iRhythm’s EVP of R&D, tells the story of a heart rhythm monitoring company seeking to change the game in a space that has been dominated for years by the Holter Monitor.

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CardioFocus VP of Engineering Jerry Melsky describes the components and design considerations that go into making successful ablation catheters to treat AFib.

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Chris Newmarker Executive Editor Medical Design & Outsourcing c n e wm a rk e r@ wtwh m e di a .c o m

Sean Chow, a senior director of R&D at Edwards Lifesciences, goes over three pitfalls that creators of catheter-based delivery systems should avoid.

We also have articles in which top U.S. researchers describe work on everything from pacemakers that dissolve inside the body to building better protective masks. And as usual, we tapped the industry’s large network of contract manufacturers, suppliers and consultants for contributed articles that are high on usefulness and low on self-promotion. On top of the Handbook, I’m excited to announce that Medical Design & Outsourcing has a new managing editor: Jim Hammerand. Jim’s past experience includes nearly a decade at American City Business Journals, most recently as managing editor of the Puget Sound Business Journal serving the Seattle region, where he is based. I worked with Jim when he ﬁrst covered medtech as a digital editor at the Minneapolis/St. Paul Business Journal. He’s a quick study, a skillful writer and editor — and one of the most decent people I know. I’m excited to see where Jim takes MDO in the future. 6

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CONTENTS

medicaldesignandoutsourcing.com ∞ September 2021 ∞ Vol7 No5

• • • • • THE MEDICAL DEVICE HANDBOOK

COLUMNS 6

HERE’S WHAT WE SEE:

12 COMPONENTS:

Advanced glass diffusers, Proportional isolation valves, Fitting a battery into Medtronic’s tiny pacemaker, Six degrees of freedom wire-winding, Check valves

24 DRUG DELIVERY:

Using RVI to prevent contamination and maintain purity, Two-part versus three-part syringes, Overcoming vaccine delivery device design's top challenges

32 MANUFACTURING & MACHINING:

Additive manufacturing and MIM prototyping, Connected workers, Salt baths and Nitinol devices, Laser processing, Stryker is using 3D printing to advance orthopedics

46 MATERIALS:

Wearable devices and fragile skin, Choosing the right rubber material, Pacemakers that dissolve into the body

FEATURES

56 PRODUCT DESIGN & DEVELOPMENT:

How iRhythm sought to outdo the old-school Holter monitor, Achieving proactive product development, Embracing connectivity and data, Human factors in the design process, IoMT-based wearables, How bioengineers tackled the leaky mask problem, Ensuring your medical device product design isn't biased, Challenges Boston Scientiﬁc overcame to make single-use scopes work, Value analysis/value engineering, Pain points to avoid, Categories of medtech vendor partners

78 REGULATORY, REIMBURSEMENT, STANDARDS & IP:

COVID-19 changed medical device clinical trials forever, Protecting your medtech AI, ISO 10993-17 updates

86 SOFTWARE:

Software as a medical device and the regulatory landscape

90 STERILIZATION SERVICES:

How to better clean ﬁber optics in medical devices

94 TUBING:

The advantages of laser-cut tube (LCT) catheters, Making ablation catheters to treat AFib, Pitfalls to consider when creating catheter delivery systems

112 AD INDEX 10

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104 THE INNOVATION-FUELED EVOLUTION OF DRUG-ELUTING STENTS

Abbott executive Dr. Nick West believes the company offers the “best-in-class” drug-eluting stent with its Xience platform.

108 DEXCOM CEO KEVIN SAYER SAYS G7 WILL BE ‘WONDERFUL’

As we enter what may be the “new normal,” Dexcom’s CEO bets the company can pave the way in continuous glucose monitoring.

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• • • •

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Advanced glass diffusers bring precision light delivery to the brain Laser interstitial thermal therapy (LITT) has proven to be a successful and eﬃcient treatment method for various brain diseases.

It’s possible to use LITT during minimally invasive brain surgery to kill tumor cells or disrupt lesions responsible for epileptic seizures. Image courtesy of Schott

Anthony Cappabianca Schott North America

hanks to advances in imaging, lasers and light delivery technology, it is now possible to use laser light to ablate lesions in the brain without the need for a craniotomy. This emerging neurosurgical procedure, known as laser interstitial thermal therapy (LITT) or laserthermo ablation, can kill tumor cells or disrupt lesions responsible for epileptic seizures. Because the treatment is performed through a tiny opening in the skull about 4 mm in diameter (1/8 in.), recovery time for patients is greatly reduced. Although just two LITT systems are approved for clinical use in the U.S. and one in Europe, additional systems are under development. There is a growing interest in this light-based therapy as more surgeons become aware of its benefits and better understand the best ways to apply it. Light delivery is an essential component of LITT. The therapy uses high-power laser light delivered into the brain through a flexible fiberoptic catheter with a self-cooling probe. Light diffusers at the end of the probe homogeneously spread out the focused laser beam so that each cell receives the same amount of light. These diffusers might

Medical Design & Outsourcing

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seem like a simple component, but they are critical for the precision surgeons need to avoid damaging healthy tissue during the procedure. Treating the brain with light Compared to traditional neurosurgery, LITT is quicker to perform and comes with a shorter hospital stay for patients. So far, it has been used to treat primary and secondary brain tumors, epilepsy, damage from radiation treatment and even chronic pain. LITT can be especially useful for brain lesions that are difﬁcult to surgically access or for patients who can’t undergo surgical procedures or haven’t responded to standard treatments. LITT’s therapeutic power comes from heating and ablating cells. This process requires high-power laser light delivered in a very targeted, predictable and homogeneous way. Monitoring thermal changes in the lesion during the procedure is essential to ensuring that the ablation is complete, so LITT systems include an MRI machine that provides real-time temperature maps that neurosurgeons use to monitor tissue ablation during the procedure.

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COMPONENTS

Diffusers are usually cylindrical in shape with a distal end that has been coated to eliminate forward light emission. They emit 360° light along a length of about 10 mm or less with a core ﬁber diameter that is usually 400 microns. Selecting the best diffusers When selecting diffusers to incorporate into LITT systems, there are several important considerations. For one, the diffusers must emit light power evenly distributed across the component’s entire length so that laser light is delivered homogeneously to the target area. This improves control of the delivered laser power and avoids hotspots, making it much easier to keep temperatures within a range that will produce predictable results. Generating enough heat to ablate cells requires laser powers high enough to create photonic absorption and thermal conduction. Therefore, it’s critical to use diffusers that won’t melt or overheat when combined with higher wattage lasers.

New applications expand light delivery needs As the number of available LITT procedures increases, surgeons have begun to express a desire for even more control over the area to which light is delivered. This can help them perform more delicate procedures while further reducing the risk of unwanted tissue damage. It’s possible to produce glass-based diffusers in a variety of geometries. They serve as a very important component in state-of-the-art LITT systems, ready to meet surgeons’ growing needs for ﬂexibility and versatility during their procedures. As innovation continues for the procedures themselves, it also must continue for the components necessary to make these advanced operations possible. Not only does this improve the efﬁciency of the procedure, it also further improves patient outcomes.

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Anthony Cappabianca is principal business development manager medical at Schott North America. He has been with Schott for over 25 years. He is an expert in medical fiber optic illumination solutions in fields such as laser treatment, endoscopic and robotic surgery, dental applications and clinical diagnostics. Schott has been a significant designer and manufacturer of fiber optics and LED products for 60 years.

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9 • 2021

This factor makes using glass-based diffusers an ideal solution for LITT. These diffusers incorporate unique scattering elements to achieve the required homogeneous light radiation. They can deliver laser light powers of 20 W or more with efficiencies typically between 80% and 90% for visible and near-IR laser radiation, including the 980 and 1064 nm wavelengths used in today’s commercial LITT systems. Such high efficiencies are possible because the diffusing material absorbs very little light, allowing delivery of more power to the target cells. The circumferential distribution of energy for these diffusers is highly reproducible, very efficient and extremely homogeneous along the entire length of the device, allowing surgeons to heat tissue in a controlled fashion. Precise temperature control virtually reduces unwanted hot spots and prevents the tissue from overheating, which helps avoid damaging tissue near critical structures. With a highly reproducible product quality, surgeons can expect the same performance and reliable treatment results every time a LITT procedure is performed.

www.medicaldesignandoutsourcing.com

What is a proportional isolation valve? A “proportional” isolation valve can bring the next level of control and design for engineers, especially in life science industries. Doug Paynter Clippard

hen we talk about proportional valves, whether they are pneumatic or hydraulic, we typically refer to valves that vary their flow path when you apply an increasing or decreasing amount of power/current to the proportional valve’s coil. This input to the coil will generate an ever-increasing (or decreasing) magnetic field capable of moving the proportional valve’s internal poppet or spool-designed mechanism. For example, using a low wattage pneumatic proportional valve, 0-185 mA (nominal 0-10 VDC) can be used to generate 0-65 LPM @ 100 psi working pressure. Another means of proportional control would be using a stepper motor to position a needle or plate.

The Eclipse proportional isolation valve Image courtesy of Clippard

So, typical proportional valve performance provides smooth, repeatable control of all types of inert gases and media — or at least that’s true if we do not use the word “isolation” in the valve’s description. There are all types of isolation valves in the field today — pinch, rocker and diaphragm valves, to name a few types — where their job is to ensure that whatever media is processed through the wetted area does not encounter any other materials that can contaminate that media. Here are four contributing factors that all need to be first and foremost when designing an isolation valve: www.medicaldesignandoutsourcing.com

• Dead volume: The volume inside the valve cannot be flushed during normal operation. Minimizing or eliminating dead volume is essential in applications where cross-contamination is an issue, such as drawing diagnostic samples from multiple patients. • Internal volume: The volume trapped inside the valve assembly when the valve is closed. • Swept volume: The volume of the flow path within the valve assembly. A streamlined flow path where swept volume is equal to internal volume means zero dead volume. • Wetted materials: Any material that comes in contact with the media flowing through the valve. Taking in all the factors as mentioned earlier, we have with isolation valves and now putting them toward a “proportional” isolation valve brings a next level of control and design for engineers to consider, especially during the medical/life science industry evolution we’re going through now. Providing the ability to vary the isolated wetted areas flow path is paramount to sensitive application success. Whatever the means of isolation, eliminating the pulse, shock, on/off characteristics of a standard isolation valve is achieved with a proportional isolation valve. It’s now possible to achieve soft start/smooth delivery of sensitive media to the test area. Proportional isolation valves can also provide enhanced close-loop results — compensating for various viscosities, repeatable flowrates, positive and/ or negative pressure variation, bi-directional control, latching capabilities at specific flow rates and more. Doug Paynter is proportional valve and controls product manager for Clippard in Cincinnati. He has over 30 years of application experience within the industrial fluid power, medical and life science industries.

9 • 2021

Medical Design & Outsourcing 15

COMPONENTS

How Medtronic fit a battery into a tiny pacemaker Medtronic’s Micra pacemakers are one-tenth the size of what was previously out there. How the medtech giant did it provides lessons for anyone looking to shrink an implantable device. Chris Newmarker Executive Editor

t was an all-hands-on-deck effort that consumed Medtronic in the early 2010s: the in-house creation of a pacemaker small enough to go inside the heart via a catheter. The tiny pacemaker could be a game-changer because it would do away with connecting wires to the heart — a major source of complications. To get there, though, the Medtronic development team had to solve signiﬁcant challenges involving battery life and energy use. How could they create a pacemaker that was roughly one-tenth the size of a traditional pacemaker but still last at least seven years inside someone? “It would be like taking your car and reducing the size of the tank by a factor of 10 — and now asking this same car to go the same amount of distance,” Leonardo Rapallini told Medical Design & Outsourcing in a recent interview. Now VP of R&D for Medtronic’s cardiac diagnostics and services business, Rapallini was the Micra effort’s senior program director for nearly ﬁve years. Rapallini and his colleagues solved the challenge — and more — as they boosted device longevity to 12 years for many patients. The FDA initially approved the Micra in 2016. Last year, it approved the next-gen Micra AV that uses additional internal atrial sensing algorithms to provide therapies associated with dual-chamber pacing systems. During a May earnings call, CEO Geoff Martha announced that Micra has quickly grown into a $400-million-a-year business. Here are three insights that Rapallini gained from the Micra’s creation:

Medical Design & Outsourcing

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1. Keep the whole system in mind “We obviously couldn’t only think about the battery in isolation. We also had to think, ‘How do we make sure that we use the energy that we have in that battery as smartly as possible?’” Rapallini said. “It was pretty clear from the beginning that we couldn’t have a team just building the battery in isolation from the team that was building the electronics and then put them together.” The core team that Rapallini led had representatives from all the different areas of expertise needed to put the Micra system together versus the previous approach of different groups working on various components. Rapallini credits the setup with enabling his team to think of the whole system at once as it considered potential efficiencies. They asked about making the Micra’s electronics more efficient. They examined how they might better position the device in the heart to use the least amount of energy, and they considered battery design improvements. Said Rapallini: “Take a system view first because the whole thing needs to work together.”

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2. Be picky about what you change The Micra’s creators needed to push the envelope to enable the device’s battery and electronics to last for years. However, they intentionally kept some things the same.

The next-gen Micra AV is the size of a large vitamin pill — the same as its predecessor. Image courtesy of Medtronic

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The Micra battery’s chemistry, for example, was a proven variation of a lithium-ion. “What we had is something we had a lot of knowledge of, and we knew that it was a really stable battery. We could guarantee that it would last long.” The electrode — the part of the device that stays in contact with the heart — was a proven component from another catheter-based device. What Rapallini and his team chose to radically change was the battery’s form factor. Instead of the battery being a wafer-shaped component that went inside the pacemaker’s “can,” the can itself became the battery’s container. The lesson is that it’s best to quickly decide where to push the envelope — and where not to innovate, according to Rapallini. “You probably cannot change everything at the same time.” Changing everything adds too much risk, Rapallini said. “The Micra is a combination of incredible innovations — and also portions of the system that are really proven.” 3. Understand the use condition As the Micra moved into clinical studies, its creators gained another vital insight: that the majority of the patients only needed pacing part of the time. “That obviously saves a lot of energy,” Rapallini said. Patients who only needed occasional pacing could see the Micra last more than 12 years, well past the original seven-year goal. Medtronic could have added even more battery life to the Micra by making it longer. However, the Micra team still opted to make the device shorter compared with the Nanostim pacemaker that St. Jude Medical acquired, according to Rapallini. (St. Jude Medical, now part of Abbott, halted Nanostim implants in 2016 over potential battery problems.) The decision to go shorter — even if it made the battery life challenge tougher — was based on an analysis of the range of heart sizes out there. The Micra simply had to be shorter to accommodate a broader range of heart anatomies, Rapallini and his colleagues decided. “Try to really understand the use condition in which this device will be used.” 18

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Six degrees of freedom can boost minimally invasive surgical techniques Tiny and precise, smarter 6DOF wire-winding technologies can increase surgical access and improve outcomes. Garrett Plank TT Electronics

inimally invasive surgical procedures require advanced motion tracking technology that can locate surgical instruments and tools inside the human body when there is no clear line of sight. Electromagnetic tracking (EMT) technology enables this performance: Electromagnetic coils drive the “six degrees of freedom,” known as 6DOF, that empower surgeons and clinicians to clearly visualize and navigate the human body. Today, advancements in electromagnetics are increasing 6DOF accuracy without increasing the size of the device.

Ultra-ﬁne wire-winding techniques enable sensor data acquisition via new angular 6DOF, a measurement reference to a device’s capability for accuracy based on multiple axes across which the device can move. In electromagnetic solutions, coils wound with ultra-ﬁne wire are used to navigate through a 3D view of a patient’s anatomy; by moving across separate x, y, and z axes, they operate as sensors for acquiring spatial location and orientation data within the human body. Hidden within a given surgical device or tool, these electromagnetic coils power surgical navigation by transmitting data in real-time to enable on-screen images that guide surgeons. Image courtesy of TT Electronics

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Where 6DOF traditionally required two different coils wound separately, a new angular method of ultra-fine wire-winding allows device manufacturers to employ angled coil configurations to deliver highly precise 6DOF sensor data. These angled coil configurations are designed to deliver the same or better procedural accuracy than what is delivered by the traditional solution. Expect expanded use of them in very small surgical and therapeutic devices. Reflecting the diversity of medical design, it’s possible to use 6DOF advances as a sensor ready to integrate into a manufacturer’s device — or as a complete navigation system that includes the tracking platform, sensors, and surgical navigation instruments. This is creating a path to an even greater slate of minimally invasive treatment options, helping surgeons reach further and deeper into the human body while patients benefit from reduced risk and shorter recoveries. Advancing the art of ultra-fine wire-winding 6DOF is a measurement reference to a device’s capability for accuracy, based on multiple axes across which the device can move. (A greater number of degrees of freedom equates to a greater capacity for precision movement.) In electromagnetic solutions, coils wound with ultrafine wire enable navigation through a 3D view of a patient’s anatomy; by moving across separate x, y, and z axes, they operate as sensors for acquiring spatial location and orientation data within the human body. Hidden within a given surgical device or tool, these electromagnetic coils power surgical navigation by transmitting data in real-time, to enable on-screen images that guide surgeons. 9 • 2021

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MEDICAL

COMPONENTS

Manufacturers wind the electromagnetic coils with wire about onetenth the diameter of a human hair. Ultrafine wire-winding techniques incorporate film-insulated copper magnet wire, for example, from AWG 45 (0.0018 inches) to AWG 60 (0.0003 inches), enabling miniaturization for a slate of advanced devices and applications. Angular 6DOF takes this potential even further, placing the wire at a defined angle to the coil axis. The design improves the signal intensity and aids in the reduction of the number and size of coils — driving smaller devices that can reach more critical areas such as the heart, brain and lungs with less surgical trauma. As medical practitioners can access more of the human anatomy with highly precise 6DOF tracking and visualization, patient care and recovery improve in step. Next-gen electromagnetics reduce complexity in sensor integration Manufacturers and health providers favor electromagnetic tracking because of its accuracy, low cost and reliability. At the same time, it’s an area ripe for innovation, as many of today’s EMT systems were designed decades ago, long before some modern advanced procedures even existed and seamless integration was not as critical. “Electromagnetics design demands a specialized engineering skillset, one not necessarily found at the heart of the typical medical device development team,” said Andrew Brown, co-founder and CEO of Radwave Technologies, a provider of customizable, next-generation electromagnetic tracking platforms. “A robust electromagnetic tracking system must navigate the entire procedure space to accurately locate medical instruments that are out of line-of-sight and perform seamlessly with existing medical equipment. It’s no easy feat, yet it is a crucial part of the device design process, particularly as the industry continually works to remove risk, reduce costs, and accelerate development.”

Technologies used to accurately place surgical instruments are numerous and complex, including impedance and optical tracking, robotic information, or intraprocedural imaging options such as ﬂuoroscopy, computed tomography (CT or CAT scans), cone-beam computed tomography systems (CBCT), ultrasound and more. It’s critically important for positive patient outcomes that these complex technologies work well with each other to provide accurate instrument placement. For example, systems must provide tracking information while ensuring distortion-free intraprocedural imaging. Improving patient care with sensor science Considering the complexity of procedures and technologies at play, strategies for sensor deployment may be as critical as the sensor choice itself. “Along with advances in sensor precision and accuracy, the medtech market has begun to recognize the need to improve and streamline developer access to electromagnetics technology at both the sensor and system level,” added Brown. “Ideally, conﬁgurable EMT systems can access the value of 6DOF advances, tracking medical instruments over the entire patient’s volume while also providing robust detection of electromagnetic interference with high positional accuracy.” 6DOF sensors — offering increased precision and accuracy based on advanced wire-winding techniques — are compatible with a range of intraoperative imaging technologies with minimal image artifacts. Placed within medical devices, on tools, or used as position references, they provide accurate knowledge of locations and orientations when surgical and therapeutic instruments are out of line-of-sight. As the use of minimally invasive surgery continues to grow, 6DOF advancements play a crucial role in extending minimally invasive techniques to new applications enabled by smaller, more precise devices.

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9 • 2021

Medical Design & Outsourcing

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COMPONENTS

Duckbill valves

Image courtesy of Vernay

Designing the best check valve for your medical device An elastomeric check valve ensures that regardless of any back pressures in the system, there isn’t a reverse ﬂow causing cross-contamination. Ta r a B r y c e Ve r n a y

he complexity of the elastomeric check valve in your medical device requires considering this important function in the early stages of design and development. Postponing an in-depth consultation with your check valve supplier can cause delays and expensive redesigns. As today’s medical device market becomes increasingly complex and technology takes huge leaps forward, the check valve remains an integral part of the performance and reliability of each device. An elastomeric check valve ensures that regardless of any back pressures in the system, the drug, blood, saline or other fluid/material doesn’t encounter a reverse flow causing cross-contamination. There are multiple types of elastomeric check valves designs and multiple material choices available in the market. However, finding a standard off-the-shelf part isn’t always an option when looking for a check valve for a new device. For custom medical devices, you need to partner with a supplier that has geometric design experience, material formulation expertise, and functional performance based on prototyping capabilities. Some of the most common elastomeric check valves used in medical devices are duckbills, umbrellas, disks, v-balls, combination and bi-directional valves. These valves come in different shapes, sizes, thicknesses and materials. All of these variables play together to allow the valve to perform at its optimal level. The precise size, thickness, composition, and the valve’s seat within the device determine the valve’s performance. For example, a duckbill is a “normally open” valve and generally allows for low cracking pressure to open and provide a nontortuous path for fluid to follow. On its own, it will need a certain back pressure to close firmly and completely, and even then, there is always a risk of backflow leakage. However, with slight changes to the geometry of the duckbill and the seat that it rests in, a duckbill can be made to become “normally closed.” Achieving a normally-closed duckbill requires design knowledge and flow control knowhow. Umbrella valves are “normally closed” but only work well when matched to a sealing surface.

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9 • 2021

For materials, the obvious concerns are the biocompatibility of the elastomer, the chemical reaction of your fluid to that elastomer, and leachables and extractables. However, there are other factors besides compatibility. Concepts like compression set, tackiness, durometer, elongation and more all come into play in the design of the compound used for your check valve. Primary materials used in medical devices range from silicones to polyisoprenes to fluorinated polymers to EPDM’s. Each of these materials matches well to certain processes for molding and finishing. It’s important to consider the combination of all these factors as well as custom formulations designed for your drug or custom performance needs. In every project, simulation techniques such as mold flow, FEA (finite element analysis) and CFD (computational fluid dynamics) are essential to predicting the proper design and construction of your check valve. Functional prototyping is just as important, though often disregarded. Prototype samples of the check valve with the precise geometry and molded with the required (custom) formulation, not with a generic material, are pivotal. Testing at the beginning of a project with functional check valves saves time, money and effort. Going into clinical trials with a “first time seen” functional check valve can be disastrous to a project. You need to have functional prototype check valves at the beginning of the project, where you can easily and affordably make adjustments in geometry and/or material.

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CMY

You can make all the plastic parts in the world ﬁt together nicely, but if the check valve doesn’t work, then the device fails, to no one’s beneﬁt. Therefore, you should consider the check valve design process as critical to the function of your device. It is the “make it or break it” part of the device most of the time. Tara Bryce is global medical business unit manager at Vernay. She has been in the medical device/pharmaceutical primary packing industry for over 10 years, working with startups, large pharma and global medical device manufacturers as a supplier and CMO in business development, sales and marketing. Combination valves

Image courtesy of Vernay

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DRUG DELIVERY

Using RVI to prevent contamination of pharmaceuticals

Here’s how remote visual inspection (RVI) can help pharma companies prevent contamination and maintain product-line purity requirements.

Hafees Fraisada Olympus

Videoscopes allow inspectors to check inside process pipes, tubes, tanks and vessels for residue, corrosion and the growth of microorganisms.

Image courtesy of Olympus

acterial or foreign-particle contamination in production-line equipment can cause serious health issues for consumers and shake public conﬁdence in the industry. Strict purity and contamination control of pharmaceutical manufacturing facilities is required under various international standards, such as ASME (American Society of Mechanical Engineers), AWS (American Welding Society) and local regulatory authorities such as the U.S. Food and Drug Administration. Preventing contamination in medication production lines also is one of the main goals of good manufacturing practices (GMP). Following GMP is a prerequisite for the pharmaceutical industry to prevent poor quality or incorrect mixtures of elements from reaching the consumer. GMP requirements include implementing strict equipment maintenance and cleaning protocols supported by quality control (QC) and quality assurance (QA) inspections and audits, all backed by detailed documentation. Drug manufacturers use a combination of indirect and direct QC techniques to prevent contamination throughout the production line. Remote visual inspection (RVI) is a practical tool that can help drug manufacturers prevent contamination and maintain product-line purity to meet GMP requirements.

Medical Design & Outsourcing

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This article discusses how facilities can leverage remote visual inspection using videoscopes and borescopes to reduce contamination threats. Further, it offers three ways to maintain pristine pipe welds in pharmaceutical plants using visual inspection. Four ways videoscopes can improve drug plant preventative maintenance Videoscopes and borescopes allow direct access and evaluation of hard-to-reach areas inside facilities. Videoscope insertion tubes can have an internal diameter as small as 4 mm (0.16 in.) and a length up to 30 m (98 ft), making them ideal tools to reach often inaccessible locations inside process pipes, tubes, tanks and vessels. With their outstanding image quality, videoscopes can be used to check welds for signs of corrosion or monitor locations where microorganism colonies tend to grow. Here are four ways manufacturing facilities can incorporate a videoscope or borescope into their proactive maintenance: 1. Validating the compliance of new processing equipment: Before the initial operation of new or replacement equipment, drug production facilities can perform a baseline videoscope inspection to ensure compliance to standards and regulations for welds on pipe bends, elbows, joints and tanks.

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Residue in tube

Image courtesy of Olympus

Specifically, the colors of heat-affected zones (HAZ) and surface porosity indicate the quality of the welds. Therefore, a videoscope with a high-quality image processor can balance the illumination and color representation to ensure that the images demonstrate the actual weld condition based on established discoloration acceptance criteria for welds and heat-affected zones. 2. Monitoring problem areas for residue buildup: Between production batch changes, pharmaceutical plants need to thoroughly clean and inspect the processing equipment. Videoscopes enable quality assurance inspectors to check key contact locations for residue buildup or corrosion and monitor potential microorganism growth areas. 3. Checking metal walls of pipes and vessels for corrosion: During periodic plant maintenance, RVI can be used to check and monitor any deterioration of processing equipment, such as corrosion or erosion. 4. Documenting inspection images to comply with good manufacturing practices: After each visual inspection, an inspection report is required for auditing and validation. All videoscope inspection images or video footage can be documented as evidence. The software capabilities of borescope or videoscope systems directly impact the efficiency of the report generation process. Well-designed inspection software enables a streamlined workflow.

Newer videoscopes offer high image quality, adjustable color saturation, “inspection assist” software and other features to ease processing equipment veriﬁcation and record keeping.

Medical Design & Outsourcing

• High image quality provided by advanced optics resulting from a century of expertise • Innovative image processors that reduce noise and sharpen images for a high probability of detection (POD) in low-light and reﬂective environments; • Adjustable color saturation to enhance the visibility of the weld’s heat-affected zone (HAZ) • Interchangeable light sources in white and ultra-violet options • Modern “inspection assist” software for efﬁcient image data management; • Portable and ergonomic design for inspection in restrained spaces • Easy-to-use user interface for simple operation • Stereo measurement upgrades for quantitative defect assessment

Process pipes can have thousands of welds and joints in inaccessible locations. Corrosion, leaks or contamination can occur if even one of those welds is deﬁcient.

Image courtesy of Olympus

The latest videoscopes provide QA/QC inspectors in pharmaceutical manufacturing facilities with numerous features to ease processing equipment veriﬁcations and record keeping. These include the following:

Image courtesy of Olympus

9 • 2021

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How to maintain pristine pipe welds in pharmaceutical plants using visual inspection Weld quality control and assurance is critical in drug manufacturing facilities. Yet it’s one of the biggest challenges, given that process pipes can have thousands of welds and joints in inaccessible locations. Corrosion, leaks, or contamination can occur if even one of those welds is deficient. Both automated and manual welds on stainless steel processing pipes can be a challenge to inspect. Methods such as ultrasonic and X-ray testing are commonly used to identify internal flaws and defects within the volume of a weld and on the parent material. However, after the welding and heat-treatment processes, inspectors need to visually examine the weld’s inner diameter (ID) and the weld root. Because of restricted access, remote visual inspection is a viable, nondestructive solution. Videoscopes and borescopes help ensure all pipework and welds are fit-forpurpose and comply with welding codes and industry standards. Here are three ways to incorporate videoscopes into pharmaceutical process pipeline inspection: Validate the welds in new equipment installation or repair work. Before initial operation of equipment or during plant expansion or repair work, QA inspectors can use RVI equipment to check all welded parts that require validation: • Internal diameter surface finish • Defects in the root section of the weld (i.e., root undercut, incomplete root penetration, burn through, etc.) • Heat-affected zone (HAZ) near the weld (i.e., color differences as per ASME BPE 2016) • Geometrical mismatch between welded pipe such as excess weld metal, weld overlap, etc.

• Markings (numbers) on the pipes to identify the location of each weld. Such numbers can be used for the corresponding recorded inspection video and images. • An optional UV light source that can be used in combination with penetrant testing to identify surfaces defects that are invisible and undetected with white light.

Videoscope inspection of a weld in stainless steel pipe showing a lack of root penetration Image courtesy of Olympus

Wide-angle view optical adaptors, such as a 220° direct view lens tip, allow a complete profile view of the weld ID, increasing the inspection efficiency and speed without compromising the probability of detection (POD). The 220° adaptor shows a complete view of the condition of both the front and backside of the weld.

Check for residue after batch-to-batch cleaning and product-to-product changeover: Welds and the surfaces inside process pipelines must not disrupt the flow of products passing through them. If the product becomes lodged, it can either spoil or contaminate products flowing through later. Welds, elbows and joints in pipes are key problem zones for residue buildup. After maintenance personnel have cleaned the equipment between batch or product changes, RVI is recommended to check for residue to avoid crosscontamination in these inaccessible problem zones. In addition, inspectors can use the videoscope or borescope to verify the cleanliness of all welds that are in areas in contact with the flow of the product. Regional regulators, such as the FDA, typically recommend these inspections. Ways to ease residue and buildup checks When checking for residue around welds, elbows and joints, there are a few videoscope/borescope features that help make the job easier: • For a quick yet thorough inspection, using a wide-angle optical adaptor provides a complete panoramic view inside the pipe for viewing any medication remnants directly on the videoscope screen.

Residue inside pipe seen on the screen of the videoscope Image courtesy of Olympus

It’s essential to have RVI equipment with features that ensure a thorough inspection of welds in the complicated process piping network. Ideal features include: • Insertion tubes of various diameters (starting at 4 mm) and lengths (up to 30 meters), offering direct viewing access to inspect weld roots and IDs of complex geometry and extensive networks of stainless steel pipes. www.medicaldesignandoutsourcing.com

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Medical Design & Outsourcing 27

DRUG DELIVERY

• Halation caused by highly reﬂective surfaces, such as stainless steel pipes, can impede videoscope or borescope inspection. Operators usually need to manually adjust the illumination brightness to see properly. Some videoscopes are equipped with features to resolve this problem: o Processors that interact with the illumination system, actively adjusting the brightness level for the operator to deliver an optimized image that is clear and sharp. o Image processing technology supports a wide dynamic range, maintaining visibility in dark areas even when the brightness is decreased to avoid halation. • Some videoscopes offer scope tip articulation to allow fast navigation and precise control (joystick or touchscreen) to the target through complex pipe networks, tight corners and restricted spaces. • Other newer videoscopes offer software that include features supporting user-friendly inspection data management. Periodic inspection for corrosion and structural integrity: Pharmaceutical production facilities are not immune to corrosion and other structural integrity problems. As a result, process water that passes through the pipes is periodically monitored to check the content of impurities. The cause of this contamination can include microorganisms that nestle around pitting corrosion and proliferate in biological residue inside processing equipment. To ensure the hygienic soundness of process pipelines, it is a good practice to implement videoscopes or borescopes to inspect all welds and inaccessible locations as part of regular preventative maintenance. Ultraviolet light reveals microorganisms: Colonies of microorganisms are challenging to locate with white light. Therefore, borescopes or videoscopes that offer a UV light source option help detect microorganisms in processing pipes, vessels or tanks because the UV light source exposes this organic material through its ﬂuorescence. 28

Medical Design & Outsourcing

9 • 2021

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Checklist for videoscope or borescope inspections in pharmaceutical manufacturing plants Here is a summary of my tips for inspecting stainless steel pipes or other process equipment: • Choose the correct length and diameter insertion tube for your application. Videoscopes and borescopes with various lengths and diameter insertion tubes are available. • Select the suitable optical tip adaptor for your application needs. I recommend a 220° “ﬁsh-eye” lens for a fast, efﬁcient inspection with a high POD. • Maintain proper hygiene during and after inspection — wipe down the videoscope insertion tube with isopropyl alcohol (IPA) before and after use to remove contaminants. • When inspecting weld integrity, ensure the white balance is correctly set before use. Observing with accurate color representation is crucial to detect discoloration in the HAZ to validate that it meets the acceptance criteria. • Adjust the light source’s brightness to reduce halation inside shiny stainless steel pipes, tanks and vessels. Consider videoscopes that have dynamically adjusting light sources that do that for you. • Thoroughly inspect the welded section of pipes by rotating the insertion tube with a side view adaptor. For largediameter pipes, use a centering device to support placing the insertion tube at the center of the pipe. • Thoroughly record and document your inspection. Record still images and videos of entire weld inspections as evidence for quality control validation and audits. Remote visual inspection is a practical tool that can help pharmaceutical manufacturers prevent contamination and maintain product line purity to meet GMP requirements. Newer videoscopes and borescopes offer features that help perform thorough, reliable inspections, especially in hard-to-access areas such as welds, where problems often originate but can go unseen until it’s too late. Hafees Fraisada is product marketing manager for Olympus in the EMEA region. He has more than 15 years’ experience in the medical and industrial industries. Based in Hamburg, Germany, Fraisada is a member of Olympus’ remote visual inspection team.

What is the difference between two-part and three-part syringes? Syringes remain an integral part of the medical industry, yet they are often an afterthought in the R&D or production phase. William Foley A i r- T i t e P ro d u c t s

ith the wide variety of options available on the market containing fundamental differences in design and composition, can the syringe selection affect the end-product? It’s possible to manufacture a syringe from many different materials: metal, borosilicate glass, COP, COC and Zylar, to name a few. However, the more common syringes are plastic disposables for single use. Disposable syringes allow the user to worry less about cross-contamination, particularly important when dealing with toxic or infectious materials. Most of the single-use, disposable syringes are made of polypropylene. While not appropriate for every application, disposable syringes are typically an inexpensive option for many laboratory uses. Occasionally, a researcher or engineer may have difficulty identifying the source of various contaminates in their process. Sometimes the source is either the rubber or silicone oil found in common three-part syringes. If that becomes apparent in your process, there may yet remain another low-cost option by way of a two-part syringe. Two-part syringes are slightly different because they do not use a rubber tip on the plunger to create a vacuum seal. Instead, these syringes have been specifically designed to not introduce additional materials such as rubber or even silicone oil. When you see black rubber present on the tip of the plunger in a syringe, that syringe typically requires a lubricant (most often silicone oil) to prevent the rubber from “grabbing” the sides as it slides up and down the barrel. These are the most common type of disposable

syringes, known as three-part. Typically, when someone asks for a disposable syringe, they are requesting this type of syringe. Alternatively, these syringes may be referred to as regular, conventional, standard or rubber tip plunger (RTB) syringes. These syringes are popular for their smooth gliding motion, low cost and wide variety of functions. The rubber gasket on the tip plunger acts as a sealant against the barrel and creates a vacuum for drawing material into the syringe. To prevent the sticking of the rubber against the solid material of the barrel, a manufacturer sprays the lubricant into the barrel during the assembly of threepart syringes. While standard three-part syringes are used for a much wider range of applications, two-part syringes offer distinct advantages for some applications. To circumvent the need for an added lubricant, two-part syringes (known as Norm-Ject or HenkeJect) utilize a precisely engineered, slightly oversized plunger head that expands the barrel to create the vacuum. These two-part syringes are made of a polypropylene barrel and a polyethylene plunger. The design allows for a smooth gliding plunger that maintains vacuum pressure without the rubber gasket. These syringes are useful for many sensitive applications. Common applications include chromatography, ophthalmics, industrial solvents, glues, paints and various laboratory applications. In addition to the two-part versus three-part considerations, it’s possible to purchase both options in several different formats including luer lock, luer slip, oral tip, catheter tip, centric, eccentric, sterile, unsterile, bulk, mini-bulk, as well as by box or by case. Luer lock and luer slip syringes accept a standard hypodermic needle if intended for injection or fluid transfer. For higher volume applications, manufacturers can also provide custom solutions such as ungraduated, unassembled, unique colors, light-restricting, special volumetric markings or company logos. When in doubt, call a company of syringe and needle experts, let them know what you are looking for and see if they have an off-the-shelf option or a custom solution for you. A good supplier will guide you in the right direction, even if they don’t offer the solution you seek. William (Will) Foley has been active in the medical device industry since 2001, with experience in a variety of roles. He has worked for Air-Tite Products for four years, where he is currently vice president of sales and marketing.

Image courtesy of Air-Tite Products

www.medicaldesignandoutsourcing.com

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Medical Design & Outsourcing 29

DRUG DELIVERY

Overcoming vaccine delivery device design's top challenges Vaccine delivery has long been a hot topic and only got hotter in the ongoing push to vaccinate against COVID-19 around the world.

Inovio Pharmaceuticals announced in July that it received $71 million from the Department of Defense to support its Cellectra 3PSP smart device, shown here. Image courtesy of Inovio

Sean Whooley Associate Editor

ost would probably associate vaccines with the standard jab injection with a syringe. Over the past year and more, companies have touted ideas for other avenues. Inovio has a “smart” delivery device for a COVID-19 vaccine, while Intravacc is developing a nasal COVID-19 vaccine, plus there are many more in between. Whether it’s standard delivery devices or the innovative ones various companies are trying to bring to the market, there are difficulties in creating the vessels for the potentially life-saving therapeutics they deliver. MDO sister site Drug Delivery Business News spoke with Scott Thielman — chief technology officer at Product Creation Studio, a company that offers insights to deliver designs for a range of entities, including medical device companies — to learn about some of the biggest design challenges in the hot field of vaccine delivery. “The vaccine delivery space was active before COVID-19, it’s no fluke that researchers were able to pivot quickly to produce candidate vaccines,” Thielman said. “We had ongoing work in the space and that interest continues. “Much of the work lies with the microbiologists, chemists and drug formulators. The lipid nanoparticle (LNP) delivery mechanism utilized in the Moderna and Pfizer vaccines is an amazing story. But there are also exciting opportunities to move past the syringe administration and introduce novel devices for the delivery of next-generation vaccines. Oral administration would be the holy grail, bypassing patient fears of discomfort. But transdermal patches, intranasal and biolistic solutions are just a few options where device innovators will continue to have influence.” Here are four major design challenges in creating vaccine delivery devices, according to Thielman:

Medical Design & Outsourcing

9 • 2021

1. Matching distribution and administration model to the technology (and vice versa) ST: As with any drug delivery challenge, it’s important to match a workflow to the realities of the technology and also meet the needs of the users. For instance, the PfizerBioNTech vaccine requires specific cold-chain storage and two doses administered by intramuscular injection, requirements introduced by the LNP formulation. The chain of delivery from factory, storage, logistics, preparation to injection is driven by the need for mass vaccination at large clinics, a workflow that mitigates the challenges of storage and dose management. Additionally, the syringe-based delivery process is recognizable and well understood by healthcare clinicians. A remote distribution model with intermittent dosing schedules and limited cold storage may drive the need for alternate distribution models and delivery technologies. There is room for medical device innovators to take up the challenges along the way. Designers need to zoom in to get the final step of administration and delivery — from package to patients’ cells — right. But they also need to zoom out to look at all the other aspects of production, distribution and disposal. 2. The hypodermic needle shouldn’t be the end of the discussion. We need more delivery technologies. ST: The success of LNP formulations delivering mRNA vaccines is fantastic, but doesn’t mean we should close the book on other delivery mechanisms and administration techniques. Poor patient compliance due to fear of needles can be a major drag on mass vaccination efforts. Additionally, cross-contamination from reused syringes and unwanted disease transmission from inadvertent needle sticks are also significant downsides.

www.medicaldesignandoutsourcing.com

If DARPA is to be believed, there is a need for systems that can rapidly produce and deliver customized vaccines to fight local outbreaks and variants. In such a future, potential epidemics could be stopped in their tracks by rapid local responses, saving lives and economies. Platforms that provide flexible and adjustable genetic payloads with fewer storage and logistics constraints should be developed. Even if unit costs are significantly higher than the ubiquitous hypodermic needle, the benefits of rapid vaccine response worldwide would be a boon for the larger population. 3. The tissues targeted can make a difference. ST: The entryway for most pathogens is through the skin and mucosa. Many infections start in the tissues of our nasal passages, lungs or sexual organs. While the intramuscular injections for COVID-19 have been shown to mount strong immune responses, a direct challenge to the mucosal tissues may be beneficial in vaccinations for other diseases such as HIV or for those with weakened immune systems. This is where innovators need to look beyond the ubiquitous vial-and-syringe combo for methods that deliver to alternate tissues. Opportunities for administration via transdermal patch, intranasal spray and biolistics are all being pursued. Each has its own set of technical challenges and strategies to get past the barrier effects of the tissues. For instance, in our work with Orlance on their biolistic administration via gene gun, we’ve seen that there is a sweet spot for particle distribution and velocity to attain proper immunogenicity in dermal cells. Alternate techniques to bypass the barrier characteristics of the skin and cell membranes include iontophoresis and electroporation. These involve the application of electrical potentials to the skin to assist in the introduction of vaccine molecules. You can begin to imagine the need for electrical engineers to join the bioengineers and mechanical engineers on these development efforts. 4. Get the user experience right. ST: These alternative delivery opportunities are where it gets interesting for the medical device designers and engineers. Establishing a new administration method can have ripple effects throughout the workflow. It is up to device teams to capture the user needs and translate novel delivery technologies into understandable processes for the administrators. 9 • 2021

Medical Design & Outsourcing 31

SMOOTH. LINEAR. FLOW. Introducing KNF FP 70, delivering 120 – 850 ml/min while producing up to 29.4 psig (2 barg) pressure under continuous operation. Integrated dampers provide a smooth, gentle flow and innovative 4-point valves ensure reliable self-priming even at very low motor speed. FP 70 is well-suited for a range of applications including medical technology, inkjet and 3D printing, and analytical instruments. With its introduction, the KNF smooth flow pump series now boasts a flow rate range of 120 ml/min to 12.4 l/min. Learn more at knf.com/en/us/solutions/pumps/innovations/ fp70-smooth-flow

MANUFACTURING, MACHINING & MOLDING

How additive manufacturing can complement MIM prototyping

Metal-injection-molded parts

Image courtesy of Advanced Powder Products

Nick Eidem Advanced Powder Products

n today’s drive toward optimization, where projects survive or collapse in terms of days rather than weeks, it is imperative to consider all available prototyping venues. Time to market is especially critical in the medical field, where product maturation curves are shorter and regulatory efforts are extensive. In addition, moving a component from concept to production is often an arduous process; it needs to be accurate, repeatable and well documented. Metal injection molding (MIM) technology can efficiently and economically deliver thousands or millions of parts. Still, it relies upon customdesigned and built hard tooling — the simple reality of all MIM processors. As a result, medical device engineers frequently ask, “How do we capture the efficiency of MIM through the design and production validation stages? Is additive manufacturing the answer?” While not to diminish the significant contributions and developments in additive manufacturing, some constraints still need addressing. Additive manufacturing may be the fastest way to get functional metal components, but

Medical Design & Outsourcing

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When designing medical device components, you don’t need to choose between additive manufacturing and metal injection molding. Think of them as complementary.

the components are not production representative. Compared to production MIM components, the “grainy” or “granular” surface ﬁnishes and tolerance capability demonstrated by additive are inferior; it’s simply where the technology is today. The choice between additive manufacturing and MIM is complementary. Medical design engineers and MIM manufacturers are applying their material expertise to binder-jet 3D printing technology. Binder-jet 3D printing is an additive manufacturing process using MIM powders and sintering furnaces to create 3D-printed functional MIM parts. A part generated via binder-jet 3D printing is not identical to a true metal injection molded part. However, many MIM processors utilize the technology to conduct processing experiments to shorten the development lead time while proving quick design iterations. The question remains: How do we bridge the gap between 3D metal printed prototypes and production tooling? The logical solution for the engineering and supply chain communities is to build prototype “hard” tooling that replicates actual MIM production components. Ultimately

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this allows for a shortened time to market without complicating the validation and regulatory process steps. The productionproof properties of MIM components produced via prototype tooling are a valuable solution to this conundrum. The key to this is the concept of creating prototype tooling that can be designed, built and modiﬁed, producing MIM components in a more expedited fashion. While this seems like a no brainer, it isn’t as easy as one might initially imagine. Intuitively, the design community assumes that MIM tooling and plastic injection molding tooling — at least in the prototyping phase — are analogous. Designers sometimes think they can make the tooling out of a lower hardness speciﬁcation material, maybe even aluminum. That assumption is inaccurate because of the abrasive nature of MIM powders, the turbulence characteristics of MIM powders under pressure, and the unique viscosities associated with MIM

powders. Understanding the constraints of traditional tooling design provided MIM processors the impetus to research alternatives. Production tooling is designed to maximize efficiency and capability and often includes advanced technologies to monitor cycle times, feedstock flow and cavity pressure, which increases the time to build and speed to market. Speed to market can be a significant constraint in the medical device market, resulting in pressure to consider alternative paths. MIM industry initiatives are evolving to create advances in prototype tooling alternatives, some cutting the time by as much as 50%. The natural segue for any metal injection molder is to drive changes in the tooling development process. Developments in MIM prototyping inhabit today’s world of MIM and should be of serious consideration for the medical device industry. MIM prototyping can also generate immediate parts up

into the thousands, a nice segue in launching any program or even modifying an existing MIM component situation. In addition, the costs basis is a fraction of production tooling, which gives the enduser an additional level of conﬁdence in the development-to-production phase. MIM is an exciting and developing new technology process that requires considerable collaboration between the medical device team and the processor. Collaborating with Advanced Powder Products (APP) offers a unique technology platform that includes prototype tooling, ProtoMIM, and other complementary additive manufacturing capabilities, even binder-jet. To learn more about APP’s Rapid MIM Prototyping, visit advancedpowderproducts.com. Nick Eidem is the director of business development for Advanced Powder Products. Nick has over 10 years of experience in manufacturing sales.

At OKAY Industries, we’ve built a culture of quality and continuous improvement that reigns over everything we do. Just ask Jim DeVecchis, Director of Manufacturing Engineering. Jim and his team make sure every component that leaves our facilities meets your exact design and performance specifications. Across our organization, quality means paying attention to the details – even details that are as thin as 0.006mm – like in this heart valve stent. Internally, we call our commitment to quality The OKAY Way. As our customer, you’ll call it peace of mind. What we manufacture is Part of Something Greater. Learn more about this project at okayind.com/king.

“QUALITY IS KING”

Jim DeVecchis Director of Manufacturing Engineering

M E TA L S TA M P I N G • C N C M A C H I N I N G • L A S E R P R O C E S S I N G • A U T O M AT E D A S S E M B LY 200 Ellis Street New Britain, CT 06051 Tel (860) 225-8707

245 New Park Drive Berlin, CT 06037 Tel (860) 225-8707

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32B Building | Z Industrial Park Alajuela, Costa Rica Tel + (506) 2442-1011

860-225-8707 okayind.com

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Connected workers are key to meeting medical device manufacturing demands Image courtesy of Free-Photos from Pixabay

Here’s how medical device manufacturers can navigate the “year of the connected worker.”

Louis Columbus Delmiaworks

“Getting real-time data to workers, ensuring they know their roles, their goals for the day, and keeping them aware of quality objectives is working much better than tweaking a given machine for slightly more output,” the CEO of a tier-2 manufacturer in the medical device industry told me. “Our people adapt and ﬂex faster than any machine or series of machines ever could.” In empowering workers through automation, several proven strategies have emerged. Following are seven of the approaches gaining the most traction:

erhaps the only thing that medical device companies and contract manufacturers can predict for 2021 will be continued unpredictability across supply chains, market demand, sales forecasts and skilled workers’ availability. In the United States, elective surgeries are on the rise after being postponed due to the pandemic, leading to higher demand for medical equipment, artiﬁcial joints and other devices used in routine procedures. However, the application of the Defense Production Act (DPA) continues to prioritize the availability of materials and manufacturing resources in the ﬁght against COVID-19, resulting in shortages elsewhere. The workforce also continues to be impacted by the pandemic. Many parents have quit working to care for children schooled remotely, reducing available job candidates. Meanwhile, many employees continue to work remotely, whether out of convenience, fears over going on-site, or the manufacturer’s need to allocate more of the facility to production to meet spikes in demand. Fluctuations in demand are also leading some manufacturers to rely on temporary workers for some functions. Medical device companies and contract manufacturers alike recognize that automation throughout the organization is critical to maintaining agility in a year of rapid change while expanding and optimizing operations to meet production demands in high-growth sectors. It is why 2021 has emerged as the year of the connected worker. www.medicaldesignandoutsourcing.com

1. Smarter, better sensors blur the line between workers and systems, improving everything from efficiency to health and safety. For the many manufacturers with production and process monitoring systems in place, the rapid improvements in Internet of Things (IoT) sensors and interfaces are helping to bring greater contextual information and insight to workers. For example, one medical device manufacturer upgraded the sensors used for in-line quality testing and discovered new data on how workers could reduce work instruction steps and improve quality. IoT-based data on cycle times and in-quality testing also helped ensure worker safety by revealing that several machines needed maintenance and more lubricant to alleviate the possibility of a lock-up or accident. 2. Real-time analytics provide employees the information they need to spend more time on creative problem-solving to improve production throughput and quality. The essence of what makes a connected worker strategy successful is information and knowledge sharing throughout the manufacturing process. Medical device companies are using real-time analytics at every phase of their manufacturing execution process to fine-tune work instructions, improve machinery selections and optimize each worker for a given task. They find that sharing real-time analytics across the shop floor creates greater ownership of every order’s outcome and higher productivity. Workers look for new ways to make the metrics applying to them improve. 3. Intuitive, touchscreen-based shop floor interfaces to enterprise resource planning (ERP) and manufacturing execution system (MES) software improves production efficiency. These interfaces enable on-the-job training 9 • 2021

Medical Design & Outsourcing

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that streamlines the onboarding process for new production workers and flattens the learning curve for all employees working with new technologies. The touchscreenbased interfaces also ensure that workers have the latest real-time data on every order being built on the shop floor and greater control over and adaptability in dealing with changing forecasts and their impact on build schedules. 4. Digital workflows that capitalize on the strengths of touchscreen-based shop floor interfaces guide workers through complex tasks, preventing the most common types of human errors. Medical device producers are taking advantage of the configuration functionality in their manufacturing software to customize digital workflows to meet their unique costing, quality management and time-tomarket requirements. Once in production, these manufacturers make course corrections to their digital workflows based on a combination of data from real-

time production and process monitoring and insights related to workers on the shop ﬂoor. The strategy leads to greater productivity gains than relying on a single metric alone. 5. Remote access continues to be key to keeping supply chains, production scheduling, shipping and customer service moving. Giving employees remote access to ERP, MES, quality management, customer relationship management (CRM) and logistics systems has enabled medical device manufacturers to maintain business continuity. These companies also have recognized that allowing employees responsible for back-office functions to work from home frees up more of the facility to expand production capacity. With more critical business functions being handled offsite, manufacturers are strengthening their security with measures like multi-factor authentication (MFA).

Louis Columbus is presently serving as principal of Delmiaworks (formerly IQMS). Previous positions include product management at Ingram Cloud, product marketing at iBASEt, Plex Systems, senior analyst at AMR Research (now Gartner), marketing and business development at Cincom Systems, Ingram Micro, a SaaS startup and at hardware companies.

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7. Digital training tools can reduce training time by as much as 75%, further increasing the expertise and knowledge of production team members across locations, according to the World Economic Forum. By maintaining a commitment to upskilling and continually providing additional training and certiﬁcations for workers, medical device manufacturers can attract and retain employees by enriching their jobs and help create a more connected workforce. As the manufacturing vice president of one medical device company said, “It’s most important to connect workers with expertise ﬁrst. Build the learning ecosystem with people, and the results will follow. Tech is secondary to their trusting each other and becoming more knowledgeable as a team.” Those are wise words on how to create, nurture and scale a connected workforce.

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6. Enhanced quoting and pricing through the use of three-dimensional (3D) images is addressing the need for faster time-to-market, greater channel visibility and more visually compelling quotes of custom-configured medical devices or components. Quotes incorporating 3D models enable medical device companies and contract manufacturers to confirm the specifications of products, parts, and/or any required molds — and ensure pricing accuracy. The results are greater customer confidence, a more efficient production line with no unnecessary waste, and higher profitability.

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A D V E R T O R I A L

Design for manufacturing considerations for injection-molded parts There’s wisdom in leveraging manufacturing and engineering experience early in the design phase of an application. Proper expertise could lead to better material choices, product-specific process and manufacturing options, reduced costs, and longerterm product reliability. This is particularly true for parts that use plastic injection molding. Just ask Jonathan Cottrell, lead program manager with PTI, a custom injection molder and manufacturer of plastic components and assemblies. “A proper understanding of how a part can be made allows a designer to apply principles that are specific to that manufacturing process,” he shares. Cottrell has nearly 25 years of experience in the industry. “Too often we get designs that look great on paper; however, the part is not conducive to injection molding but are ideal for machining. By not understanding the requirements needed for the molding sector, a lot of time and costs are lost when developing a product.” Cottrell has followed the lifecycles of countless products throughout his career, which has led to invaluable experience using design for manufacturing practices. When designing plastic parts, there are several key factors to consider. Here are just a few. Materials One early design consideration is the material, or the resin for an injection-molded part. Before making a choice, Cottrell suggests a few questions to consider first. “It’s basically developing a story,” he says. “First determine what environment that the material is going to reside in. For example, is it going to encounter any chemicals or extreme temperatures? Will a higher, engineered-grade material be required for performance? What’s it being used for exactly?” Cottrell adds: “It’s similar to what we learned in grade school — the who, what, where, when, why, and how. Once we answer those questions, we can hone in on the ideal material.” Gating Gating is where the material is injected into the cavity for the part’s geometry or shape. It’s important because it dictates how far the part flows, if there are any holes to go around, where the knit lines would be, etc. Gating also affects the visual and tangible aspects of the part. “For instance, a gate on the A-side or front surface of a part may leave a bit of a gate vestige,” explains Cottrell. “if we are manufacturing a medical device that a surgeon needs to touch and they’re wearing a rubber glove, that gate vestige could tear the glove — potentially exposing the surgeon’s hand. Clearly, this must be avoided and shows why gating considerations are critical.” Cottrell also points out that the material selection and gating styles should work together, as one choice affects the other.

PTI created a DFM reference tool — a hands-on device to aid in the designing for manufacturing process. Learn more at https://teampti.com/design-tool.

Draft The draft is the angle that’s applied to each side of an injection-molded part, so the part can release from the tool. “I’m asked a lot about how much draft is needed,” says Cottrell. “The typical rule of thumb, and what we recommend as a starting point, is one-and-a-half degrees. We’ll see designs that don’t have any draft, but you’re chancing that part will stick to the tool or result in deformation, so it could later crack or stress.” Aesthetics It’s also important to consider the backside of the part. “The features on the backside are structural components or connection points, such as the ribs, bosses, and clips,” he says. “How well they’re designed affects the A-side of the part. So, a rib should only be about 50% as thick as the walls it’s connected to. If it’s thicker, you’ll see what’s called read-through or extra mass on the A-side — which can affect the aesthetics.” Cottrell says doing a bit of homework goes a long way when manufacturing a part. “For us here at PTI, we enjoy getting in on the ground floor and at the design phase of a part. We’re here to help.” To learn more, listen to a Design World’s Technology Tuesday podcast with Jonathan Cottrell at https://bit.ly/3eeEvZ4

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MANUFACTURING, MACHINING & MOLDING

Salt baths increase stability in the medical device tempering process Calibration baths, like salt baths, were originally for calibrating temperature assets. But there’s another use for them: manufacturing Nitinol medical devices. Tr a v i s P o r t e r Fluke Calibration

itinol is a nickel-titanium alloy that exhibits both thermal shape memory behavior and superelasticity. It’s a great metal to use in medical devices because it’s possible to set the wire or mesh design into a form using the tempering process. Then, fold it up into a fraction of end size to use in minimally invasive surgeries or procedures, and it returns to the designed size and shape of the form post-compression. The precise heating and quenching of these forms are what allows for the shape memory to be locked into the Nitinol for use. Offering a manufacturing facility more control over their proprietary process can help shape the devices without fear of breakage or disforming from their initial cast design. Picture blood clot ﬁlters or stents folded up and inserted into a catheter. A health provider guides the catheter during the insertion procedure, following twists and natural paths through the body. Because the device is compacted, it can travel without damage to the individual or the implant. Once in place, the patient’s natural body temperature causes the device to return to its original cast shape and size.

The Fluke Calibration 6050H Extremely High Temperature Calibration Salt Bath can handle high temperatures (550° C) with stability (±0.002° C) and uniformity (±0.005° C). Image courtesy of Fluke Calibration

Medical Design & Outsourcing

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Nitinol tempering process The general medical device quenching and tempering process involves heating a Nitinol wire to incredibly high temperatures, then quenching to create the shape memory. The formula, temperatures and timing can differ from company to company, but the overall process remains the same. That also means each company is taking the steps, refining their processes, and striving for a process that remains consistent and repeatable. The result is to have as little deviation as possible from one device to the next during the manufacturing process. Having a developed process that is repeatable with consistent results and creates uniform, high-quality pieces is paramount in the medical device manufacturing industry. It can help cut down on quality control issues down the line. Using a salt bath for tempering and forming When it comes to the tempering process for Nitinol, a salt bath system can maintain temperatures at a more stable and uniform rate. Ensuring an exact environment each step of the way — and a consistent and repeatable process — makes salt baths a great advancement for the medical device manufacturing field. A salt bath provides stability and uniformity specifications that are up to 10 times more precise than a typical heat-treating bath. The precision allows manufacturing companies to create a consistent and repeatable method for heat treating, tempering and quenching the metal alloy. As a result, some have seen increased quality control and optimized workflows using a salt bath during the wire forming process. Temperature precision A temperature calibration salt bath can be set to exact temperatures, creating a highly controllable process. Because salt baths are designed for calibration, the temperature inside is also precise for both the heating and cooling steps necessary for the tempering process. For example, some baths offer +/-1.0° C over the range of 180-550° C. Setting the temperature while heating — and inducing 1,000 W of boost heating during the initial quench of the wire forming process — helps create precision while also being easily repeatable, netting a better quality product and possibly lowering risk due to a manufacturing deviation.

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The Fluke Calibration 6331 Deep-Well Compact Bath can handle both high (300° C) and low (-80° C) temperature with excellent stability (±0.005° C) and uniformity (±0.007° C). Image courtesy of Fluke Calibration

Stability and uniformity A high-quality salt bath can offer a maximum temperature of 550° C, allowing the temperature to be held consistently within a ±0.008° C and hold uniform (top to bottom/side to side) temperature within ±0.002° C deviation. The consistency creates a level of certainty for the manufacturer that allows manipulating a best-case environment for the heattreating of Nitinol devices. In turn, that can lead to a better-quality product with fewer quality control issues between devices. Versatility Salt baths come in a variety of specifications. Whether you’re looking for a specific temperature range, fluid type, size or shape, there are a wide variety of specifications to choose. Many calibration bath manufacturers are even able to customize to specific needs. Depending on your specification choices, selecting a salt bath can offer a temperature range from 180° C to 550° C for your tempering and quenching process. Travis Porter has spent nearly 22 years as a temperature calibration expert with Fluke Calibration and the former Hart Scientific. He has held a variety of roles, including in technical support and manufacturing, and is now an inside sales account manager for Fluke Calibration.

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Medical Design & Outsourcing 39

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What laser processing can do for medical device manufacturing

A laser-engraved hearing aid

Image courtesy of ASCYS Lasertechnik US

Laser processing provides automation and eﬃciencies that help meet FDA regulations and produce superior medical device components. David Locke ACSYS Lasertechnik US

aser systems have become essential to the production of better-designed medical devices. The precision, repeatability and scale needed to manufacture next-generation medical products rely heavily on lasers’ advantages to contract manufacturers and medtech manufacturing. MarketsandMarkets Research expects the laser technology market size to grow from $11.7 billion in 2020 to $17.6 billion by 2025 due to the growing demand from healthcare coupled with the performance lasers achieve compared with legacy material-processing procedures. So let’s review how laser cutting, engraving, welding and marking enhance medical device designs. We’ll look at the various applications and the qualifications all medical device manufacturers should be familiar with before planning and building a complex laser system as part of the product manufacturing process. Application types There are numerous applications for lasers in medical device and surgical instrument manufacturing. For example, endoscopes, surgical knives and probing devices, wire stents, vascular clamps and stent markers all require welding, engraving and cutting operations for manufacturing. Compact implantable devices, such as pacemakers, can benefit from improved manufacturing using laser processes such as precision engraving, welding and cutting. In the case of laser welding, there is a significant reduction in heat output from this process compared to conventional welding. Laser welding delivers a very small heat-affected zone, which typically leads to less need for follow-up processes such as trimming and grinding than devices welded through traditional methods. It also means tighter welds to produce smaller micro-pieces and allowing welds to occur in smaller physical footprints. A smaller heat-affected zone also enables rapid cooling. Curtailing the amount of heat annealing that occurs over

Medical Design & Outsourcing

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the surface contour of a piece delivers fewer chances of deformation and less scrap. With some medical devices, it’s important to limit physical contact with the parts due to sterility concerns. Think smaller implantable devices and devices that contain microelectronic systems with electrodes (such as pacemakers, auditory implants and pumps), which often require hermetical sealing. The devices benefit from through-transmission lasering, where parts are clamped together and treated with a pinpoint laser beam in precision laser welding. Pulsed laser welding is another process used for implantable devices, as it works well for sealing the titanium cans utilized in these devices. Laser-welded joints in a medical device can withstand high-temperature sterilization, possess pore-free surfaces and typically eliminate the need for secondary finishing operations processes, which is a crucial requirement for biocompatible components. Medical instruments — including endoscopic instruments, bone screws, surgical devices and blades, bellows and diaphragms — almost always require some kind of permanent marking such as a serial number or unique device identification (UDI) to provide patient protection. There are also notable laser drilling applications on microfluidic sensors and sensor disposables. Laser marking and engraving performs these requirements elegantly in the form of a marker band, bar code or 2D data matrix code. Process validation and qualification of laser system solutions Process validation serves as a form of documented verification to show that it’s possible to manufacture a product in a defined process sequence, with all manufacturing qualification requirements addressed. The qualification of laser processing systems for the manufacture of medical products is a clearly defined requirement from the rules of Good Manufacturing

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Practice (GMP). The laser systems provider and medical device manufacturer often collaborate during process validation to ensure that functional requirements of the component are met reliably and consistently. Several regulations govern process validation, especially covered under the standards for ISO 9001, ISO 13485, and 21 CFR Part 820. While validation can be a complicated and laborious process, it can also produce some meaningful benefits. The data derived from validation can help troubleshoot issues and reduce validation efforts during inspection, saving time in the manufacturing process. Validation also assures complicated processes remain consistent and reliable and mitigates risk to the device maker and the patient. Technical expertise and deep experience in laser systems must encompass quality engineering know-how and a comprehensive understanding of the laser process itself. Lasers’ impact on the future Laser technology is transforming medical device manufacturing these days. As a result, contract manufacturers and medical device OEMs benefit from more efficiency, accuracy, reliability and scalablility at much lower costs than before — all while achieving higher-quality medical devices and instruments for healthcare providers to use. Precision laser systems excel in the creation of corrosion-resistant black marks and surface texturing with new ultra-short pulsed (USP) lasers, while permanent UDI and other marking with short-pulsed lasers of various wavelengths continue to expand. There are advancements in cutting and welding thin materials with pulsed, continuous-wave fiber and USP lasers, resulting in high-quality edges and minimal thermal distortion. Many medical device parts are now made via 3D printing from metal powders, creating the ability for mass-customization with the possibility of using other laser systems to selectively polish surfaces to very high smoothness. Automation advancements through robotic loading and vision systems to locate, orient and confirm parts and processes mean longer-term lights-out production is possible. The ability of systems builders to apply and integrate laser technologies enables advancements in technology that translate into increased capabilities and throughput for medical device manufacturers. David Locke is technical sales manager for ASCYS Lasertechnik US, where he advises customers on customizable laser systems for cutting, marking, welding, and engraving. He has a degree in physics from St. Michael’s College and has worked in the industrial laser industry since 1984. 9 • 2021

There is no room for error when working with human lives Emerson’s fluid control & pneumatics portfolio addresses the unique needs of analytical instrument & medical device manufacturers. Our team of experts work with you to provide a complete customized solution, based on your time to market requirements. Learn more at: Emerson.com/medical

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MANUFACTURING, MACHINING & MOLDING

Ramping up manufacturing for single-use surgical instruments: What you need to know Manufacturers can optimize functionality, use and volume to deliver highperforming, high-quality single-use surgical instruments to customers. Steve Santoro Micro

Image courtesy of Micro

urgeons and hospitals increasingly need singleuse surgical instruments, as they offer several distinct advantages over reusable products. Disposable instruments designed for single-use don’t need to undergo expensive and timeconsuming cleaning, sterilization and reprocessing. Reusable instruments such as articulating laparoscopic devices with sophisticated, intricate parts also can be difficult to clean and thoroughly disinfect, thus increasing the risk of infection to patients. Single-use medical instruments are pre-sterilized and individually packaged. Health providers can dispose or recycle them after use. Unlike their reusable counterparts, single-use instruments aren’t subject to wear and tear, dulling, chipping, denting and rusting that can damage reusable products and impact functionality over time — an important consideration for products used frequently in the operating room. As a result, single-use scissors and other cutting instruments, for example, are optimally sharp every time, making surgery more efficient, safer and with better outcomes for patients. Medical device manufacturers want to know that they can get disposables manufactured without sacrificing cost or quality. With advances in technology and materials like highgrade stainless steel, it’s possible to cost-effectively produce robust single-use instruments that meet all functional requirements. One can achieve welldesigned, high-quality, highperforming products using a design for manufacturability (DFM) process tailored to the intended use of the product. It’s important to identify from the outset whether an instrument will cut, dissect, seal, stitch, staple or insufflate — and understand whether it will need to articulate or stay rigid or be required for hot and cold cutting during surgery.

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Once you identify functionality and the project’s overall goal, examine its commercial, technical and compliance risk parameters. The next step allows you to select the optimal materials and processes that meet the needs of a project, ensuring the life and function of the product. Design prototyping and feasibility testing are essential steps to complete early on in the process. Prototyping and testing a functional product design allow manufacturers to evaluate production material and refine design and production elements. As early as possible, use production style processes to make prototypes. As part of the DFM process, the prototyping and testing can determine the most efficient and effective production process needed to meet customer goals, resources and turn-around time. Often customers focus on the back end, output and cost. With DFM, manufacturers can optimize designs upfront so they’re capable of being manufactured at high volumes. DFM also provides a blueprint for ramping up with a validated, evidencebased development process that saves time and money downstream. For high-volume projects, automated processes like stamping dies, automated machining centers, laser cutters and welders with inline inspection vision systems are quite effective. It’s possible to amortize upfront equipment costs over time if technology investments are needed. Articulation joints are a great candidate for laser cutting in particular, but any number of processes can have advantages depending on specific design needs. Lower volume projects are better suited for less automated technologies that can be quicker to market. If volume needs to increase as the product gains market acceptance, a manual process can be replaced by a more automated process without significant interruption. Considering alternative engineering processes during DFM will allow manufacturers to accommodate volume or other changes later on. Stainless steel tubing is a primary support feature of single-use hand-held surgical devices. It’s possible to produce tubing efficiently and cost-effectively using a number of engineering processes, from manual production to fully automated systems. Depending upon the device, volume and feature

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needs, one can use drawn or stamped and rolled tubing to manufacture metal tubes. An assessment of component size, tolerance, the thickness of the tubes, and whether the device will require the tube to move or remain static will help determine process selection. Another important factor is wall thickness. Most single-use medical tubing is thin-walled (typically 0.010 in.), and any number of processes can be effective. If a thicker wall (0.030 or 0.040 in.) is needed, a machining process

may be required to accommodate features such as grooves and slots. A progressive stamping process can effectively produce high-volume rolled tubing with complex features such as holes, slots and windows. We can stamp a tube out of flat stock using this innovative method, resulting in a finished tube with complex features. The process helps reduce production time, as it’s possible to stamp and roll a finished tube in seconds using a power press versus drawing raw tube,

cleaning and cutting to desired length and secondary processing. The method is well suited for single-use surgical devices, including scissors, graspers, dissectors and tissue-holding forceps. Steve Santoro is EVP of Micro (Somerset, New Jersey), a full-service contract manufacturer of precision medical devices, injection/insert/metal injection molding, fabricated tube assemblies, subassemblies and complete devices.

How Stryker is using 3D printing to advance orthopedics

TUESDAYS

Orthopedic device giant Stryker uses additive manufacturing to make porous geometries that wouldn’t otherwise be possible. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

How Stryker is using 3D printing to advance orthopedics Orthopedic device giant Stryker uses additive manufacturing to make porous geometries that wouldn’t otherwise be possible.

printing, also called additive manufacturing, provides the ability to create new products and designs that are incredibly complex and hard to machine. For 20 years, Stryker has been on a journey to use additive manufacturing speciﬁcally to produce complex orthopedic implants. As a result, the company has made great strides when it comes to the way that orthopedic implants are designed and produced. On a recent episode of our DeviceTalks Tuesdays webinar — sponsored by GE Additive, Foster and Siemens — Stryker executive Naomi Murray detailed the company’s two-decade additive manufacturing journey. Murray, the company’s director of advanced operations for additive technology, described how innovations utilizing 3D printing make healthcare better. Here are four takeaways on how additive manufacturing is advancing orthopedics: www.medicaldesignandoutsourcing.com

1. 3D printing enables game-changing innovation. For Stryker, there were two main drivers behind pursuing additive manufacturing: design freedom and rapid concept development. Design freedom makes it possible to create new products and designs that have complex, hard-tomachine geometries — including hybrid structures and implants with functionally located porosity. Employing 3D printing “was really freeing in that we could make new geometries that we couldn’t otherwise make,” Murray said. Additive manufacturing also enables rapid concept development where it’s possible to quickly develop and iterate prototypes and implants. Murray observed that one of the beneﬁts of additive manufacturing as both manufacturing technology and prototyping technology is using the same material properties and tolerances when testing as in ﬁnal 9 • 2021

Medical Design & Outsourcing

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manufacturing. The result is that data gathered during testing is the same as the data and performance expected during actual manufacturing. 2. Much of Stryker’s focus in using additive manufacturing for orthopedics has been on porous design. Porous implants are important in orthopedics because they help promote biologic ﬁxation, which gives as much space as possible for the bone to interdigitate. However, historically it has been challenging to manufacture porous implant designs using traditional methods. In working on porous structures for more than 15 years and then using the power of additive manufacturing, Stryker has become a world leader in metal 3D printing of porous implants. Murray was delighted to share a photo that showed bone growth through a porous structure produced using additive manufacturing. One crucial decision by Stryker, explained Murray, was maintaining complete control of the 3D printing technology, including strict and extreme control of the porosity structure. “Additive manufacturing allows that control for us to be able to use the technology to give us the features that we need,” Murray said.

and place implants more accurately. According to Murray, “When you put [these tools] together — revolutionizing design … and then a procedural innovation … it makes an exciting future for additive manufacturing in the orthopedic space.” 5. Additive manufacturing has sustainability advantages — but more progress is needed. Murray is of the view that sustainability is part of the additive manufacturing story. Already, 3D printing is more sustainable than some other technologies. Still, Murray sees it as a corporate and industry responsibility to ensure that additive manufacturing becomes even more sustainable. Therefore, she challenged the industry to look at ways to minimize post-processing from 3D printing. Provided to Medical Design & Outsourcing by BullsEye Resources.

Stryker has been a pioneer in 3D printed orthopedic implants. Image courtesy of Stryker

3. SOMA is pushing the boundaries of ortho implant design. SOMA — Stryker Orthopaedics Modeling & Analytics — provides an evidencebased design approach. The foundation for SOMA is a comprehensive database of CT scans of bones, referred to by Murray as “the bone database.” The database and software tools customized specifically for Stryker provide data for modeling and designing custom implants. The software suite, as part of SOMA, facilitates measuring, fitting and optimizing implants. Murray commented that these tools transform the design process. In conjunction with the designs created through SOMA, Stryker uses additive manufacturing to “deliver industry-leading implants fit to our customers,” according to Murray. 4. Multiple tools used in combination will create what’s next. In the future, Murray envisions the use of multiple tools in concert. Specifically, she sees the SOMA database used in conjunction with 3D printing and robotic surgery tools that enable surgeons to plan www.medicaldesignandoutsourcing.com

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Medical Design & Outsourcing

MATERIALS

Wearable devices and fragile skin: How to select the right adhesive Design considerations are crucial when choosing an adhesive to stick wearable medical devices to fragile skin. Del R. Lawson 3 M ’s M e d i c a l Solutions Division

one are the days where we had to be in the hospital to track and collect data from our bodies. We’re now able to create smaller, smarter, more accessible devices that integrate into our everyday lives. The advantage of adhering a device directly to the skin is it creates an intimate interface between the device and the wearer that enables a sensor to measure a key attribute and transfer data to the device. However, these conveniences mean new considerations for device design engineers, speciﬁcally when selecting adhesives intended to stick to fragile skin. Skin is a major factor in the design and performance of a wearable device, but it often gets overlooked. When it comes to adhering a device to fragile skin, it’s not the same as adhering to static substrates or even non-fragile skin. Although fragile skin makes many people think of the elderly and infants, it can affect everyone. Physiological factors, such as the skin’s location on the body (face and eyelids), play a large role in fragility, in addition to pathological (acne, rosacea, etc.), circumstantial (environmental, mechanical) and latrogenic conditions (medicinal treatment, aesthetic procedure).

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A designer should consider the challenges of fragile skin when selecting an adhesive because it will affect the user and how the device performs. Before choosing an adhesive for fragile skin that will work best, it is critical to consider the intended design of the device. Design considerations Because devices are a system made up of smaller parts that need to all work in unison, it’s crucial ﬁrst to understand the device’s construction, components, application and end-user requirements. Consider the following ﬁve key questions when designing a stick-to-skin device.

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Skin of all ages can be fragile, inﬂuencing your adhesive choices.

Image courtesy of 3M

MATERIALS

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What is the application? Skin adhesives can serve multiple purposes, including protecting a device while holding it onto the skin as a cover tape and bonding a device directly to the skin. Understanding each component’s requirements and how all of them interact with one another is key to ﬁguring out what types of adhesives are ideal for the application. How long will the device be worn? Wear time is critical in selecting the best adhesive because its properties, chemistries and strength should match the product’s required wear time. Also consider reapplication of the same device or a replacement device adhering to the skin on the same site repeatedly. When not planned for, either instance can result in skin damage, especially for fragile skin. Who will wear it? A device speciﬁcally intended for the elderly

sleep or snoring device, are inherently low-activity and may not require the same adhesion level as an active user. Environmental inﬂuences — including increased movement, sweating and climate conditions — should also be considered.

or infants requires fragile skin considerations. Since fragile skin conditions can affect anyone, consider the health and condition of the wearer’s skin. And if the device is for a speciﬁc medical condition, think about how the condition may affect the skin. •

•

Where will it be worn? Consider the intended location on the body on which the device will be worn. Gentle to skin silicone adhesives are advised when adhering to sensitive areas of the body, such as the face, around the eyes and neck areas. Another consideration is the contour of the body where the device will be worn. Adhesives, backings and device components made with materials that move and give with the body during use will improve performance. What is the end user’s activity level? The adhesion requirements for a sedentary application, such as a

Medical adhesive options There are three main categories for stickto-skin pressure-sensitive adhesives (PSA) for wearables, and each has its beneﬁts: 1. Acrylic/acrylate: Proven compatibility with skin, variable adhesion proﬁles, low sensitization, good processability 2. Silicone: Repositionable, gentle removal, very low sensitization 3. Synthetic rubber: Good initial tack, adhesion to low surface energy, good moisture resistance When it comes to fragile skin, silicone adhesives are known for their gentle adhesion, inert chemistry and pain-free removal. Due to inherently different physical properties that enhance their behavior in application and removal, silicone adhesives are often ideal for fragile skin applications. Designing a wearable device for fragile skin brings its own set of challenges. By identifying adhesive requirements and understanding design considerations early on, you will be able to select the suitable adhesive to ensure the device operates properly while keeping the end-user as comfortable as possible. Del R. Lawson is R&D Manager in 3M’s Medical Solutions Division. He has over 25 years of experience at 3M in laboratory management, strategic product platform creation, and Lean Six Sigma operations. His experience has involved new technology creation in advanced analytics and sensors, biotechnology solutions, and medical adhesives.

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How to choose the right rubber material and process for your medical parts Creating a medical component with a rubber material requires careful attention to various factors that will affect performance and manufacturability. Material choices and manufacturing options present many trade-offs. Don Bonitati Minnesota Rubber & Plastics

Elastomer components

he long list of material properties impacting an elastomer component’s performance includes your prospective polymer’s end-use environment, chemical compatibility, hardness, compression set, tensile properties and manufacturability, to name a few. Although the selection process may appear daunting, understanding your application, your material options’ physical and mechanical properties, and the interaction with mating components will go a long way. These key attributes, in conjunction with understanding volume ramp schedules, will drive the proper manufacturing processes to ensure a successful product launch. This article will walk you through some of the factors and trade-offs you’ll need to address when selecting a polymer for your medical component. It will also describe some of the capabilities that rubber and plastic specialists can provide you to enhance your product development. Cleanliness and safety drive material needs for medical parts Begin your material selection process by reviewing the product’s design intent, including clinical operation requirements. With any medical part, patient safety and cleanliness play a critical role in the material you choose. Assess where and how your part will be used, as well as any sterilization

Image courtesy of Minnesota Rubber & Plastics

processes it may encounter. For instance, molded rubber seals have wide use in medical equipment, including implantable devices. Accordingly, you’ll need to know the following about your material: • Biocompatibility: Will the material make contact with the skin? Will the product be blood or sterile fluid contacting? Is it intended for either temporary or permanent implantation, the latter of which is considered 10 years or more? Rubber specialists can offer materials that meet USP Class VI standards and materials that comply with ISO 10993 biocompatibility standards. • Sterilization needs: It isn’t enough to ask yourself whether your part will be sterilized. Some materials can’t survive high-temperature steam sterilization and instead undergo ethylene oxide (EtO) sterilization, while others are more suited for the deep penetration of gamma radiation. In addition, chemicals and solvents used for cleaning can cause a part to shrink. • Physical and mechanical properties: As with any rubber part application, you must consider temperature extremes, as well as the stresses your material will undergo that may cause it to stretch, deform or compress. Liquid silicone rubber (LSR) is often selected for medical device products. Still, in many applications, high consistency rubber (HCR) has been proven to be a better choice that can drive down overall part cost and reduce time to market. Understand your material’s physical properties Hardness Hardness is defined as the rubber’s resistance to indentation by a harder object and is an important consideration for critical medical components and seals. It’s possible to measure rubber hardness using a Shore durometer — according to ASTM D2240 — and the values are expressed in Shore hardness scale units. For example, the hardness of thermoset rubbers ranges from 20 Shore A to 90 Shore A, and harder thermoplastic elastomers are categorized as Shore D. However, the most common hardness range is 50 Shore A to 80 Shore A.

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Medical Design & Outsourcing 49

MATERIALS

Your application needs will dictate your required material hardness. For example, sealing products typically use materials with a hardness of approximately 70 Shore A. If your parts have complex geometries or require deep undercuts, look for a material hardness between 30 Shore A and 80 Shore A. Material permeability When it comes to medical components, a gas or other medium’s ability to penetrate rubber is important in material selection. Components that endure sterilization are vulnerable to moisture incursion, so the material’s permeability must be as low as possible. In addition, a material’s molecular size and polarity, the ﬁller material in your compound, your application’s temperature and other factors will determine permeability. Mechanical properties: Testing and evaluation Tensile strength Material specialists like Minnesota Rubber & Plastics will analyze a rubber to see how it will behave under extension following ASTM D624 or ASTM D412 speciﬁcations. In a typical tensile strength test, gradually heavier loads are applied to a material sample, stretching the material to various lengths. This data is plotted graphically to create a stressstrain curve on an X-Y axis, with: Y-axis = stress (MPa, force per unit area) X-axis = deformation of the material (elongation length) The material’s performance can be seen in different regions of the stress-strain curve: •

• •

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Elastic modulus: Part of the elastic region, the elastic modulus is the initial slope in a stress-strain curve where it’s possible to reverse deformation when removing stress. Yield stress: The peak stress, just before fracturing occurs. Necking: Following the yield stress point, a small region of the polymer sample experiences a large amount of nominal strain. Cold drawing: The process whereby the neck extends with the direction of the applied stress as polymer chains break down. This linear region of the graph is ideal for product design. Strain hardening: The slope in which the material is permanently strained to increase its peak stress.

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Fracture: The polymer chains fail.

If you require a stiff, rugged rubber, a steep curve will indicate a tough material that offers good resistance to deformation caused by elongation. A more gradual curve means the material deforms more easily. Ultimate elongation / elongation at break (Eb) Ultimate elongation is the percentage of the increased length to which the elastomer can be stretched (strained) to the break point. It is measured against the original length of the specimen. Tensile stress is usually measured and reported at predetermined strains — 50%, 100% and 300%— before the break occurs. The tensile values at different strains are reported as moduli. Compression set resistance Rubber deforms under compressive load and rarely returns completely to its original dimensions when the load is removed. The difference between the original and final dimensions, expressed as a percentage, is known as the compression set. Compression set measurements are usually performed following ASTM D 395 Method B (compression under constant deflection). This property is one of the most important aged properties, as it describes the ability of a molded article to maintain a seal under a compressive force. As many molded rubber articles are used in compression, it’s possible to define sealability by measuring compression set resistance. Manufacturing process considerations In addition to matching your application’s criteria with a material’s physical and mechanical properties, manufacturing processes and their volumes will impact your choice of material and the unit price of your part. Manufacturing processes present cost trade-offs, and certain processes may not be ideal for some materials. The most common rubber manufacturing process options include: Injection molding In this process, uncured rubber is fed into vessels for heating. When the rubber reaches the desired temperature, the material is extruded into a mold cavity where it hardens and cures. Taking the geometric factors involved with tooling into consideration, injection molding is the most efficient manufacturing process. Its www.medicaldesignandoutsourcing.com

high precision also makes it suitable for custom projects or parts that have complex shapes. In addition, injection molding can effectively handle volumes as high as tens of millions of units, and it has the added benefit of generating little material waste. Transfer molding Another popular method used with complex designs, transfer molding is well-suited for parts requiring multiple cavities. Here, the material is preheated and preformed for placement into a pot located between a closed mold system’s top plate and plunger. Then, the material is pushed out of the pot through sprues and into the mold cavity, where it is heated and pressurized. This process is typical for colored rubber parts. Compression molding Known for its simplicity, compression molding involves placing a preformed, uncured rubber compound directly into a heated mold cavity. Once in the cavity, the compound is compressed into its final shape by the mold closure. Compression molding is inexpensive and fast, and it can be used for most materials. Each process involves trade-offs when it comes to achieving certain characteristics. Flash is one example. This condition can be defined as excess material that protrudes from a molded part’s surface at its parting lines. A combination of factors plays into whether the flash has a permissible thickness. Eliminating the extraneous rubber from a part will change the tooling geometry to achieve the desired precision. Because the tooling is more delicate, tooling life diminishes, and the cost of the reduced tooling life can influence your choice of manufacturing method. In addition, certain materials are harder to process, which can lead to damaged parts. Due to this combination of material and process factors, consult with your rubber parts specialist to understand all the options involved with selecting the right rubber compound and manufacturing process to best achieve your goals. Narrowing your selection Once you have determined all of your desired properties and characteristics, you can identify your potential material and manufacturing options with the help of your rubber expert and their information library. Our team will create a chart that allows you to crossreference your criteria with the materials.

For example, suppose you require a silicone. In that case, your MRP material science partner will list the compound numbers that match your needs for biocompatibility, sterilization, insulin capability, temperatures or any other criteria you require. Customize a compound Although there are many standard materials to choose from, no two applications are alike. Therefore, for applications with specific needs that a standard material may not be able to satisfy, it pays to choose a rubber specialist that has the capability and expertise to create a custom formulation that can best match your requirements. To help determine whether a custom formulation is more suitable for the application than a standard material, Minnesota Rubber & Plastics applies many different test methods and devices to measure the material’s physical and mechanical properties.

Using a process called compounding, we can enhance materials with additives to boost a property or make it more suitable for a specific manufacturing method. Still, compounding often creates more trade-offs. By enhancing one property, another may diminish. Your rubber specialist can walk you through the trade-offs to ensure you get the best performing material for the application. Minnesota Rubber & Plastics has a proven history of helping medical OEMs design high-performance molded parts, and we also have the capability and expertise to develop the best-performing elastomeric for the application. From silicone molding, rubber to thermoplastic elastomer (TPE) conversion, cleanroom assembly or compounds that comply with ISO 10993, USP Class VI and FDA standards, we can solve your rubber parts design, development or manufacturing challenges no matter the volume.

Application examples include insulin and glucose monitoring instruments for diabetes, POC diagnostics testing, delivery systems for transcatheter aortic valve replacement and other cardiovascular tools and surgical instruments. Explore our design tools and resources at www.mnrubber.com. Don Bonitati, medical market director for Minnesota Rubber & Plastics (based outside Minneapolis), leads the company’s global medical market strategy, including ongoing expansion efforts into emerging markets.

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MATERIALS

Could people one day get pacemakers that dissolve into the body? Wireless, battery-free, fully implantable pacemakers made of bioresorbable components could represent the future of temporary pacing technology. Liz Hughes Contributing Writer

lexible, dissolvable electronics could soon pave the way for temporary pacemaker wearers to avert the risks associated with surgical procedures from initial implantation to the removal of the device once its job is done. Northwestern and George Washington universities have developed what they say is the first-ever transient pacemaker that’s not only wireless, battery-free and fully implantable — but also disappears when it’s no longer needed. Its biocompatible components can naturally absorb into the body over five to seven weeks, eliminating the need for surgical removal. In a study published on June 28 in Nature Biotechnology, researchers demonstrated the device’s efficacy across a series of large and small animal models. They cited several critical needs for an alternative, temporary pacemaker technology that can deliver the needed electrotherapy while addressing the associated physiological complications. Northwestern Engineering’s John A. Rogers led the device’s development. “Hardware placed in or near the heart creates risks for infection and other complications,” Rogers said in a press release. “Our wireless, transient pacemakers overcome key disadvantages of traditional temporary devices by eliminating the need for percutaneous leads for surgical extraction procedures — thereby offering the potential for reduced costs and improved outcomes in patient care. This unusual type of device could represent the future of temporary pacing technology.” Health providers presently use temporary pacemaker devices as a bridge to permanent pacing therapy or implement them temporarily following cardiac surgery. For temporary pacing after openheart surgery, surgeons sew the temporary pacemaker electrodes onto the heart muscle. Those electrodes have leads that exit the front of the patient’s chest and connect to an external generator that delivers a current to control the heart’s rhythm. This hardware carries a considerable risk of complications including infection from bacteria that can form biofilms on pacing leads. Since the device is not fully implanted, the externalized power supply and control system can inadvertently be dislodged when caring for or mobilizing a patient. Additional complications can happen upon removal

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The device is shown at various stages of dissolving. Images courtesy of Rogers Lab/Northwestern University

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MATERIALS

The device, seen here mounted on the heart, could have many beneﬁts for post-cardiac surgery patients. Image courtesy of Rogers Lab/ Northwestern University

"This unusual type of device could represent the future of temporary pacing technology."

including laceration and perforation of the myocardium, which can occur if the pacing leads become enveloped in ﬁbrotic tissue at the electrodesmyocardium interface. The transient pacemaker sidesteps the risks of infection, dislodgement, torn or damaged tissues, bleeding and blood clots. It’s light and thin, weighs less than half a gram, and is 250 microns thick. The soft and ﬂexible device encapsulates electrodes that softly laminate onto the heart’s surface to deliver an electrical pulse instead of using wires. Researchers say this approach could serve as the basis for the next generation of postoperative temporary pacing technology. Rogers, who has a background in electronics materials science, says 54

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the idea was born from a two-way convergence of needs and capabilities — electronics that can dissolve in water for reducing solid waste and temporary implants that provide some sensing and therapeutic function that naturally disappears after. “We’ve been exploring it for a number of years trying to build up a toolbox of materials … from an exponential academic standpoint with an eye toward opportunities in medicine,” he told Medical Design & Outsourcing. In the last few years, clinicians approached Rogers and his team and asked for assistance. That’s how the transient pacemaker came to light. “It wasn’t us cooking up an idea, but us responding to a clinical need and leveraging a unique technological capability we developed over time,” Rogers said. “It was the interventional cardiologist downtown reaching out to us.” The technology used to create the transient pacemaker goes back about two and a half years and is something Rogers said they’ve been working on for a while. It began with some conversations with folks at the U.S. Defense Advanced Research Projects Agency (DARPA) amid military needs for sensitive proprietary electronics that would dissolve if they got into the wrong hands. “It got us thinking, and I think the sort of inﬂection point for us was identifying a semiconductor material that we can use,” Rogers said. That’s when he said they stumbled across an underappreciated application of materials chemistry — silicone. Silicone is itself water-soluble and has a slow rate of dissolution, and if left in the water for more than two to three weeks it’s gone, according to Rogers. “That was kind of an ‘ah ha’ moment for us,” he said. www.medicaldesignandoutsourcing.com

Rogers and his team were able to use very thin silicone — tiny amounts — but still enough to build transistors and diodes and functional electronic components. Lots of inbound interest from clinicians with various use cases followed. Researchers found the devices helped provide effective pacing in various size hearts in mice, rats, rabbits, canines and human cardiac models “with tailored geometries and operation timescales powered by wireless energy transfer.” George Washington University’s Igor Efimov co-led the study with Rogers and Dr. Rishi Arora, a cardiologist at Northwestern Medicine. “The transient electronics platform opens an entirely new chapter in medicine and biomedical research,” Efimov said in a press release. “The bioresorbable materials at the foundation of this technology make it possible to create a whole host of diagnostic and therapeutic transient devices for monitoring progression of diseases and therapies, delivering electrical, pharmacological, cell therapies, gene reprogramming and more.” The transient pacemaker isn’t the first bioabsorbable medical device from Rogers’ lab, which has been studying transient electronics for more than a decade. Three years ago they announced the development of an implantable, biodegradable, wireless device that speeds nerve regeneration and improves healing of damaged nerves. Liz Hughes is an award-winning digital media editor with more than two decades of experience in newspapers, magazines and online media. Hughes has produced content and offered editorial support for a variety of web publications, including Fast Company, NBC Boston, Street Fight, AOL/Patch Media, IoT World Today and Design News.

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PRODUCT DESIGN & DEVELOPMENT

How iRhythm sought to outdo the oldschool Holter monitor iRhythm is changing the game in a heart rhythm monitoring space that has been dominated for years by the Holter Monitor. Here’s how.

iRhythm’s Zio XT cardiac monitor

Image from iRhythm

Sean Whooley Associate Editor

bout 14 years ago, when Mark Day was interviewing at iRhythm, he could see the unmet needs that a project out of Stanford’s Biodesign program addressed. While that was a start, there was still a ways to go for what would become a massive disruptor in electrocardiograph monitoring and AFib detection. “While the design and idea was very compelling — and even 14 years later we’re doing very much what that idea was and have brought it to life and are changing the standard of care as a result — the reality was that it was a hockey puck that never would have adhered very long to the chest. It was very much a concept,” Day, who is now iRhythm’s EVP of R&D, told Medical Design & Outsourcing. “Our challenge as medical device professionals was to ﬁgure out how to take this concept that was a great idea but was not obviously directly useful and have it iterated into something that could be impactful.” By 2010, the company launched the ﬁrst generation of its Zio platform for cardiac monitoring. While Day said it

was effective, it remained that it was “very much” a first-generation offering with plenty of room to grow. These days, iRhythm is challenging the traditional Holter monitor with its next-gen Zio XT with a new and improved design of its flagship wearable Zio monitor and updated artificial intelligence (AI) capabilities. FDA cleared the changes in May. The idea behind the Zio XT is increased adherence and better patient comfort. The patient shouldn’t even know they’re wearing the miniaturized device, including during events like exercise, showering and sleeping, according to Day. On top of the size and weight — approximately 50% lighter than the previous iteration — the device includes a breathable, waterproof outer layer and a “stay-put” adhesive with a flexible design for secure attachment on the left side of the chest.

"Our challenge as medical device professionals was to figure out how to take this concept that was a great idea but was not obviously directly useful and have it iterated into something that could be impactful."

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PRODUCT DESIGN & DEVELOPMENT

A traditional Holter monitor can stay on a person for up to seven days, but it requires battery changing, electrode and wire removal and more. Day thinks the Zio XT offers something much more comfortable. “We’ve created a very patientcompliant form factor that can be worn continuously, and that’s the goal,” Day said. “The patient doesn’t need to interact with the device over the 14 days. They don’t need to recharge it, change batteries or otherwise. That is what the result of patient compliance is. For Holter monitors, it’s very much more a burden on the patient.” Zio XT yields 98% analyzable data over the two-week wear time, which Day says works out to approximately 1.5 million heartbeats for most patients. The next step — although it “doesn’t sound very digital health,” according to Day — is to mail the device back to iRhythm, where the company will analyze the data.

The recording amounts to about half of one gigabyte of data. The burden of transferring that data is not something the company wants to put on its customers, with a median age of 65 in the patient demographic. Day said the simplest thing, which demonstrates a “remarkably high” compliance, is putting the device in the mailbox. Holter monitors are delivered back to providers and cleaned before being passed on to the next patient. In contrast, the Zio XT’s patient-facing components are discarded, and the printed circuit board is reused. “Because [Holter monitors] are like capital assets that get lost, broken and are fairly expensive to replace — and we’ve done clinical studies on this — we’ve seen backlogs of up to months for patients waiting to get on what is 58

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essentially an asset,” Day said. “What we’ve created is more of a single-use diagnostic service where we stock the Zio XT product in the account more as a consignment type of model, and they just use it as they need it. That’s resulted in a pretty tremendous improvement in terms of the acknowledgment of the prescription or otherwise to the actual delivery of the report.” Day said the Holter monitor does hold the advantage over Zio XT in that it offers wider wire placement with more vectors to help with monitoring. However, the iRhythm executive likened the head-to-head between the platforms to a football game in which you can opt for three camera views for one quarter (Holter) or one camera for the entire game (Zio XT). The company says that, even in patients whose frequent symptoms might find a Holter more valuable in providing diagnostics, the two-week wear time gives a “much more diagnostically capable view” of what’s going on with a

patient’s heart rhythm. Day said that Zio often doesn’t just find one arrhythmia causing the symptom but multiple arrhythmias interacting with that symptom, leading to different treatments. “From the time it’s activated, either in the clinic or the home environment, [Zio] simply just records ECG,” Day said. “The Zio XT does not analyze in real-time; it just focuses on making sure we create a diagnostically complete and accurate recording of what happens over the patient’s electrophysiology experience over two weeks. In that, we’ve created a diagnostic service that really meets this unmet need.” www.medicaldesignandoutsourcing.com

"We've created a very patientcompliant form factor that can be worn continuously, and that's the goal."

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Here’s how you achieve proactive product development

TUESDAYS

Use strategic collaboration to overcome these ﬁve common medtech product development challenges. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

Here's how you achieve proactive product development Use strategic collaboration to overcome these ﬁve common medtech product development challenges.

Joe Jancsurak Contributing Writer

vercoming product-development barriers — the topic of a recent Device Talks Tuesdays webinar sponsored by Celestica — requires the elimination of design silos and the embracement of partnering opportunities. So how does this happen? Kevin Walsh, VP of Celestica’s HealthTech Division, and Kevin McFarlin, engineering director, had some answers. “It’s all about protecting and nurturing a company’s intellectual property in order to get to market as soon as possible,” Walsh said. As a service provider for OEMs and startups, “we’re looking to mistake-proof the manufacturing and assembly processes,” added McFarlin, who outlined ﬁve common product design challenges and strategies for overcoming them. 1. Usability engineering: Establish priorities Stressing the criticality of a medical device’s ease of use, Walsh emphasized that it is fundamental to widespread adoption and requires product developers to put forth a concerted effort to “design outside a vacuum” to understand the product’s application and use. “The best way to accomplish this is to conduct usability testing in a simulated environment in which users are observed interacting with the device, often revealing user-interface errors,” McFarlin said. Common

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user-interface errors include single multifunction buttons, such as an on/off that also dims or brightens the screen, leading to uncertainty in the operating room. Other user-interface errors can include improper use of high-alert colors (red and yellow) for situations not requiring surgeon or physician intervention. In addition, improper handling of print errors can result in pop-up windows that may cover the patient’s physiological information shown on the screen. To accomplish usability testing, Walsh advised listeners to consider partnering with a design and manufacturing services provider with ready access to healthcare professionals and observation rooms equipped with two-way mirrors. 2. Early-stage collaboration between design and manufacturing: Start early Another proactive measure in the productdevelopment process comes from assessing design for manufacturability (DFM). Even when a company has only a computer-aided design model, McFarlin said it’s not too early to engage a design and manufacturing services partner with a thorough knowledge of medical device manufacturing processes to evaluate such things as the efﬁcient orientation of components for assembly. “We can conduct design workshops, and we have specialized software for identifying design considerations,” he said. 3. Independent design reviews: Consider using a manufacturing partner as a reviewer When left to design products in a vacuum, design teams often focus exclusively on demonstrating the feasibility of the primary functions. The tunnel vision, said McFarlin, may cause them to overlook serious design issues, which is why FDA requires

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design reviews using independent reviewers with relevant technical experience or education. While McFarlin noted that a design team member can serve as a reviewer, he questioned whether such an individual could be a genuinely independent reviewer. Instead, a service provider acting as a manufacturing partner “could be a good option for countering your group’s bias,” he said. 4. Pre-compliance testing: Test early and often Once there is an early working prototype, it’s time for pre-compliance testing such as electromagnetic compatibility (EMC). In the case of EMC, the project team needs to measure emissions and evaluate frequencies as it “homes in on offending frequencies,” McFarlin said.

"We're looking to mistake-proof the manufacturing and assembly processes." Pre-compliance testing is a great tool, according to McFarlin, who advised its use early and often to ensure the product architecture conforms to safety standards and that there are no electromagnetic compatibility issues. “Fifty percent of devices, McFarlin noted, “will fail EMC testing on the ﬁrst try,” making the early-and-often mantra even more critical. 5. Eliminate manufacturing challenges by design: Incorporate design techniques to make products easier to test To achieve the elimination of manufacturing challenges, product developers and their service providers need to strive for comprehensive design

for testability to reduce test times while improving manufacturing time so that costs are lower, yields better and time to market faster, concluded McFarlin. Finally, from a quality perspective, Walsh said, understanding regulations is critical for ensuring that a product remains viable once it goes to market. “Document, document, document,” he proclaimed. “More than 50% of FDA recalls are documentation related. Do your companies have in place the necessary processes for ensuring robust documentation?” Since 1980, Cleveland-based writer-editor Joe Jancsurak has covered myriad medical, manufacturing and business topics for national publications and organizations.

The future of medtech is about connectivity and data

TUESDAYS

Here’s why medtech companies must embrace innovation, connectivity and disruption.. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

The future of medtech is about connectivity and data Here’s why medtech companies must embrace innovation, connectivity and disruption.

ealthcare must shift away from responding to acute episodes and focus on chronic and preventive care to provide better care, value and population health. Data will inform the transition. Key questions include: “What does this mean for medtech? What role does medtech play in the future?” The topic of innovation in healthcare — including devices, data and disruption — was the focus of a

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recent episode of DeviceTalks Tuesdays, sponsored by S3 Connected Health. Panelists included medical device experts Bill Betten, director of solutions – medtech for S3 Connected Health, and Michael Hill, Ph.D., retired VP of corporate science, technology and innovation at Medtronic and currently a partner at Science Innovation.

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Here are five takeaways on the growing importance of data and disruption in medtech: 1. Medical devices are becoming connected. Initially, “The device was the thing,” Betten said. A hospital laboratory or clinician used the medical device in isolation. But over time, Betten explained, “We’ve added connectivity to devices.” Connectivity provides the ability to extract data from a device such as a pacemaker. That data can be reviewed and interpreted to derive insights, influence therapy and eventually provide new types of services. Betten envisions a future of “truly connected health” and “hospitals without walls,” which eventually leads to ubiquitous personal care, with care delivered anywhere, anytime, on-demand. 2. Data is the lifeblood of healthcare. Realizing the vision of a connected health system — which provides better care, value and population health — requires a system driven by data. Betten said, “Data is the lifeblood of that system; without data, I can’t make decisions.” But deriving value from the data in the health system — and connected medical devices — is a massive challenge, illustrated by the 4 Vs of data: • The volume of data is overwhelming. • The velocity of data is incredibly high and is increasing, presenting challenges in using data for timely decision-making. • There is an enormous variety of data, with numerous data sources, including consumer data. • There are challenges in ensuring the veracity of the data. “How truthful is it, and can I trust it?” asked Betten. These Vs are prerequisites to generating value. “You turn data into information, and hopefully information into action. But really, action has to show up in outcomes and create a new value stream,” Betten said. 3. Medtech must overcome data connectivity barriers. The vision of a connected health system is exciting, but the reality is not yet there. “Data and analytics will create value,” Hill said. He added, “The problem is that it [the data] has to be shared. … The

shame,” Hill continued, is “it’s still in so many silos, in so many disparate places.” Betten advocated for industry-wide standards to drive data sharing. “I’m a big believer that we need to define standards for interoperability, standards that allow data to be taken, normalized and pulled together.” 4. Use data to create a holistic view and drive action. If these barriers can be addressed, silos broken and data shared, “We can have a holistic view of the patient,” Hill said. This holistic data-driven view provides the potential to fundamentally disrupt how healthcare is delivered. Instead of providing reactive and episodic care, care can be proactive, preventative, and personalized. This shift to prevention can involve predictive algorithms and decision support tools to assist clinicians. 5. Will medtech become more commoditized? Disrupted? Betten sees a future where medical devices become more commoditized, with similar core functionalities. He sees a future with smart homes, smart hospitals and smart devices — all driven by data. Hill isn’t so sure about the commoditization of devices. He sees device companies continuing to provide value by developing new therapies and increasing access to existing therapies.

"There's a lot of room for medtech device companies to disrupt our future." He also believes there are opportunities for medtech companies to improve efficiency and care delivery. The panelists agreed the disruption is an essential part of medtech’s future. “There’s a lot of room for medtech device companies to disrupt our future,” said Hill. Betten said, “The medical industry needs to disrupt itself.” If the medical industry and device companies don’t disrupt themselves, they leave opportunities for the Amazons and startups to be the ones driving change. Provided to Medical Design & Outsourcing by BullsEye Resources. www.medicaldesignandoutsourcing.com

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Medical Design & Outsourcing 63

PRODUCT DESIGN & DEVELOPMENT

Do your human factors drive design, or does your design drive human factors? A solid commitment to human factors in the design process can be critical to a medical device’s success. MaryBeth Privitera HS Design (HSD), a SteriPack company

n some early education circles, there is a philosophy that one can learn from testing. If you want a child to know vocabulary words, you can have them brieﬂy study, then give them a quiz, show them what they missed and do the quiz again — all in hopes for a better score without a concerted effort toward improvement. In medical devices, some may approach human factors as simply a test to meet a regulatory imperative. It’s a test that must get done but not one that truly informs design. The testing becomes the focus, the driving force viewed as another task rather than a powerful tool. Ultimately it is the device design that matters. Through innovative technology design, we have new opportunities to advance clinical care. Through advanced material exploration, we can improve manufacturing processes, device functionality, and potential clinical utilities and outcomes. Through industrial design, we can provide product embodiments which respect the user and their expectations. However, through applied human factors, we achieve designing the right product for the right person regarding their context. Applied human factors ultimately improves clinical outcomes, meets the regulatory requirement, but most importantly, it makes for happy customers. Thus, for ultimate success in the marketplace, a strong commitment to human factors in the design process can be critical to success. Applied human factors in design results in a total solution for the user. A better design can happen by taking a holistic approach and considering the physical interactions and the mental workload (perception and cognition) required to use a device. This includes understanding basic human skills and abilities that a user possesses; that anthropometry and biomechanics of users are clearly delineated regarding use interactions; that accessibility and/or cross-cultural/cross-national design implications be factored into the design. Technological advancement will always offer new opportunities for innovative design, and sound design is innovative. However, creative technology development must work with innovative design to be successful. Good design makes the product worthwhile. All these elements are true regardless of designing a consumer product or a medical device. The design must meet the functional criteria and the psychological and aesthetic criteria in the user’s viewpoint. In doing so, usefulness is emphasized.

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Designers have the responsibility to use the information provided inherent to their design processes — the principles found in the knowledge, skills and abilities (the human factors) of our users — to go beyond the demonstration of acceptability. They must go beyond the “don’t make me think” mantra of device users and into designed experiences involving artistry and elegance providing device users something they “want” to use, not just something they “need” to use. This full understanding of the user (capabilities, limitations, anthropometry, biomechanics, etc.) in consideration of the context of use (working and social environment) cohesively impacts safe and effective device use. Thus, ultimately the likelihood of regulatory approval but also success in the marketplace. For example, you design a medical device for an elderly market with some limited cognitive disabilities. In your human factors planning, you might ask: What defines the elderly? What does “limited cognitive ability” actually mean? Or you’re designing a combination device aimed at children, and in some instances, they may self-administer. In your human factors plan, you might ask: What’s the role of the caregiver or parent? What are the subgroups of pediatric patients, and how will this best be determined? Detailed questions can and will impact device design and the workflow of a device. If they are not clearly defined, how can design achieve desirability? How can risk assessments be thorough? Agencies require that devices be safe and effective, that they must be usable, and that there is evidence to back it up in the submissions. However, there are additional benefits to adopting a usercentric approach, wherein the design of the device user interface aligns with the user’s wants, needs and preferences. Let the human factors drive design and use the testing to prove it. You won’t be sorry. MaryBeth Privitera, master of design, PhD FIDSA, is a principal at HS Design, a Morristown, New Jersey– based product development firm, responsible for human factors and research. She’s also faculty and cochair of the Association for the Advancement of Medical Instrumentation’s Human Engineering Committee.

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PRODUCT DESIGN & DEVELOPMENT

Where are IoMTbased wearables going next? Here are three signiﬁcant trends shaping the Internet of Medical Things (IoMT) space.

Christopher Montalbano MIDI Medical Product Development

Image courtesy of MIDI Product Development

ome healthcare is an industry that has seen rapid growth in the past decade, with consumers taking more interest now than ever in understanding, maintaining and improving their health and wellbeing. As a result, there’s an outpouring of demand for telemedicine and telediagnostic solutions that are simpler, faster and internet-enabled. Internet of Medical Things (IoMT) technology has opened endless opportunities for serving these needs. Wearable IoMT biosensing lifestyle devices allow the collection of critical biometric in real-time, even outside medical facilities. Networked with smartphone and cloud-based apps, physiological and bio-sensing smart devices continuously measure and record essential metrics and contextual information, which are made easily accessible to users and medical providers. The devices have proven to be of great value, and their prevalence continues to grow, with many developers now looking to commercialize wearables of their own. Yet due to their unique components and related intricacies, creating wearables may prove more complicated than with your average medical product. Achieving success requires a clear understanding of these devices, their intended uses, and the processes necessary to make them both safe and maximally beneﬁcial. Here are three important trends in the space: 1. COVID-19 monitoring using wearables The COVID-19 pandemic created a huge need for digital health infrastructure, especially for remote patient monitoring. Don’t expect healthcare to return to its preCOVID way of doing things, either. Predictive analytics

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paired with wearables can offer early warnings of potential disease. In the case of COVID-19, there’s even the potential to collect anonymous health data across a population and pair it with people’s general location to help public health officials better track the virus’ spread. Wearable IoMT tech can potentially spot the virus early and help people recover. 2. Bioelectronic medicine using wearables The growing field of bioelectronic medicine has demonstrated that the human body is a biocircuit. Neuromodulation via electrical stimulus in appropriate locations in the body can induce a prescribed reaction to achieve a clinical outcome. When applicable, a “closed-loop” system that automatically adapts to a patient’s clinical state can enhance the efficacy of a therapy. A wearable with EEG can enable real-time observation of how the brain reacts, refining the stimulation through an algorithm. 3. Wearable bio-sensing vs. physiological sensing Wearable biosensory devices offer providers the opportunity to receive and monitor lab-quality data at any time, making possible higher quality and more personalized healthcare. This ability can be instrumental in preventing needless worsening of conditions when patients require around-theclock care, reducing waiting periods between when symptoms appear and when a patient may see their provider. Wearable physiological sensor devices differ from biosensory devices in that they do not utilize a biological body sample but instead continuously measure the user’s physiological parameters through non-invasive body sensors (think EEG, EKG, pulse oximetry, skin conductance, blood pressure, heart rate, body temperature, etc.), with non-invasive body sensors that collect vital signs continuously. This category of devices, like biosensory devices, can provide for disease monitoring, prevention and treatment.

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Importantly, it’s also possible to combine biosensor technology with physiological technology to produce a robust dataset that offers a more comprehensive picture of the patient’s condition. Heading toward commercialization With such initial concerns addressed, moving into development itself is a question of understanding and selecting the parts that will provide a device with its desired capabilities. In the case of wearable devices, the chosen sensor technology will heavily influence eventual functionality. Developers must determine whether the data provided by a device will be most helpful to providers if delivered short-term (daily/ weekly), mid-term (monthly/quarterly), or long-term (yearly/lifetime). In short-term delivery, physiological sensors are most often used, acquiring data in real-time, continuously and non-intrusively. Meanwhile, midterm applications typically employ biosensors, which collect data periodically to detect biomarkers in biological body samples. Some devices do so with minimally invasive techniques, while others are entirely non-invasive. In these cases, discrete periodic measurement of data is the preferred mode. It’s important to deploy a strategic device development approach under ISO-13485 to integrate and harmonize lifestyle, IoMT, biosensing and physiological sensing. There must be a value proposition between the device offering (paired to cloud services) and the external stakeholders such as doctors, patients, purchasing decision makers, insurance reimbursement and much more. If you’re exchanging value both ways, prepare for a successful journey. Christopher Montalbano is co-founder and CEO of MIDI Medical Product Development. For over 30 years, he copioneered the firm’s DevelopmentDNA quality process and methodology. Montalbano has implemented a comprehensive philosophy involving the fusion of reliable engineering tied to industrial design, cost effective manufacturing design and advanced HMI — utilizing the disciplines in harmonious concert. 9 • 2021

Medical Design & Outsourcing 67

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PRODUCT DESIGN & DEVELOPMENT

A new company called Katharos Labs is making and marketing the the Ultra Fit mask. Image courtesy of Katharos Labs

How bioengineers tackled the leaky mask problem Researchers from Harvard and MIT have formed a company to mass-produce a more eﬀective three-ply mask for everyday use.

Nancy Crotti Managing Editor Emeritus

nyone who wears glasses knows that the ubiquitous blue pleated mask leaks vapor upward, despite the wire designed to conform to the shape of the nose. Less obvious is the leakage from the mask’s sides and bottom, which a sneeze or cough can increase many times over. While three-ply disposable masks provide some protection for the wearer and those around them, they could be much safer for all. That’s the conclusion of a team of researchers from the Brigham and Women’s Hospital, Harvard University, Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital. They set out to develop a more practical everyday mask that could be mass-produced and sold at a comparable price. (They recently posted a non-peer-reviewed preprint of their research on medRxiv.) A pair of old friends, bioengineer Jeffrey Karp and physician-scientist Anthony Samir, took up the challenge. Karp heads an eponymous medical engineering lab at Brigham, while Samir runs a benchto-bedside bioengineering lab and research center at Mass General. The two Boston institutions formed the Mass General Brigham Center for COVID Innovation in March 2020. They tasked Karp and Samir with leading an N95 mask working group to solve the N95 shortage plaguing healthcare workers.

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Although scientists hadn’t yet proven it at the time, both men quickly realized that transmission of the SARS-CoV2 coronavirus was highly likely to be aerosol-based and that everyone would need to wear masks to control the virus’ spread. Their challenge was to provide that effective protection, at community scale, not only from minute viral particles but also from larger particles that people spread when they cough or sneeze. So they convened a group of U.S. and U.K. filtration experts to discuss materials that could provide N95-level filtration. They concluded that the types of polypropylene used in the everyday three-ply surgical mask are highly effective in filtering aerosols, and the materials are also plentiful and inexpensive. But regular surgical masks have a significant flaw — they just don’t fit properly, allowing in about 40% unfiltered outside air under the mask during inhalation. Similarly, about 40% of the wearer’s unfiltered exhalation can escape through gaps at the edges of the mask. So the team decided to focus on redesigning these masks using the same materials to drastically reduce that leakage. That meant extending the nose wire all around the mask and making the ear loops adjustable. Those changes make their new Ultra Fit mask conformable to anyone’s face, Samir recently told Medical Design & Outsourcing.

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The Ultra Fit mask’s creators added a ﬂap near the interior edges to capture aerosolized droplets before they can leak outside the mask. Image courtesy of Katharos Labs

“In doing that, we were able to drastically improve the performance of the mask, so leakage goes down on average by a factor of more than four in novice users,” Samir added. “So, from 40% leakage, we go down to less than 10% leakage in most people, and in experienced users we’re going down to less than 5% leakage in a lot of people. And that’s a really, really big improvement for a mask that leaks 40%.” The researchers — who also included Daryl Chulho Hyun, a former biodesign fellow at Oxford University, postdoctoral research fellow Martin Jensen, and others — made one more significant change. They added a flap near the interior edges to capture aerosolized droplets before they can leak outside the mask. A flange made of composite spunbond/meltblown polypropylene pushes the flap against the face when the wearer coughs or sneezes. They performed numerous tests using thermography and laserscatter droplet imaging to measure the flap’s performance. The tests showed a major reduction in leakage of unfiltered exhaled air around the mask. Hyun prototyped numerous mask iterations and tested them repeatedly to arrive at a high-performing, low-cost mask. Karp and Samir then recruited Hank Miller, CEO of Boston-based Harry Miller Co., a 100-year-old textile manufacturer, to develop a prototype and manufacturing plan. They also brought in Steven Gordon,

an MIT Ph.D. mechanical engineer and serial entrepreneur, to help work out how to mass-produce the new mask and run a company to manufacture and distribute it. Gordon had started a company called Intelligent Automation Systems in 1987 in Cambridge, Massachusetts, to develop automated manufacturing systems that would help keep manufacturing in the U.S. After Brooks Automation (NSDQ: BRKS) bought Intelligent Automation in 2002, Gordon co-founded Intelligent Bio-Systems, which developed DNA-sequencing instruments, reagents and software systems. Qiagen (NYSE: QGEN) bought Intelligent Bio-Systems in 2012. “I’ve been able to contribute to the design of the mask, which was rudimentary when I first got involved, to a place where it could be manufactured at high volume,” said Gordon, now CEO of Katharos Labs. “When they developed the mask, they had this long wire that was bent in all kinds of crazy shapes. … It kind of worked, but it would be a nightmare to manufacture it.” Gordon suggested using individual wires to span each side of the mask, corner to corner, and cinching it shut with the ear loops. Then, the wearer can press the wires against the face for a custom, close fit and finish sealing mask by adjusting the variable-length ear loops, he explained. “Our sense is that this could be used in schools, for events like concerts or weddings, in airports, on airplanes, public transportation and in the workplace,” added Karp. “I think that one of the really nice things about this mask is that because each person is fitting it to their face and it’s really personalized, once you have it in place, it doesn’t only have greater protection — you can actually feel it.” Gordon, Hyun, Karp, Miller and Samir formed Katharos Labs (“katharos” means “purity” in Greek) in October 2020 to make and market the Ultra Fit mask. Katharos’ leaders opted to start manufacturing in China because of its robust

surgical mask production infrastructure. However, their plan is to use Gordon’s expertise to modify and modernize existing mask-making equipment in the U.S. to automate domestic fabrication for mass production at a low cost. The researchers have also prepared a paper about how they developed and tested the Ultra Fit mask, including details about their efforts to validate the fit and field experiments by students wearing the masks in a classroom and mathematical modeling of infection spread on a subway. In both settings, the Ultra Fit mask approached the efficacy of N95 respirators to prevent the community spread of COVID-19, they reported. (They had not submitted the paper to any journals for publication at press time.) The researchers also ran experiments cleansing the mask by hand and in a washing machine to determine if it can retain its filtration properties. It has the potential to withstand multiple hand washes, but the experiments to determine how many will continue, according to Karp. They are also continuing to test the mask to determine compliance with new NIOSH and ASTM standards, he added. Katharos Labs’ leaders are confident they will find a market for their mask, even after mask mandates are lifted in the U.S. More than half of the U.S. population had received at least one vaccine dose by late June, according to the CDC. Many other countries, however, are much farther behind. Karp mentioned the threat of variants and seasonal outbreaks from COVID and other viruses like the flu. “We have to educate the general community that having a high-quality, wellfitting, high-performance mask is critical. A lot of people put a mask on because they’re required to,” he said. “But a mask that leaks a lot is not a mask that is working well.”

The Ultra Fit mask’s design improvements include extending the nose wire all around the mask and making the ear loops adjustable. Image courtesy of Katharos Labs

9 • 2021

Medical Design & Outsourcing

PRODUCT DESIGN & DEVELOPMENT

5 challenges Boston Scientific overcame to make single-use scopes work FDA wanted single-use scopes to reduce potentially deadly superbug infections. Here’s how Boston Scientiﬁc made it happen. The Exalt Model D

Image courtesy of Boston Scientiﬁc

That didn’t turn out to be the case. The result was that the FDA wanted to move away from fully reusable scopes.

Ray Marcano Contributing Writer

oston Scientific’s Exalt Model D single-use duodenoscope received FDA clearance in December 2019. It was the first device of its kind to hit the medical market. Just five months earlier, the FDA urged device manufacturers to move away from fully reusable duodenoscopes to scopes with disposable endcaps — or even fully disposable duodenoscopes. A culturing study had found an up to 5.4% contamination rate for high-concern bugs like E. coli and Pseudomonas aeruginosa. As it so happened, Boston Scientific was already working on a single-use scope. Now on the market, Exalt is making its way into physician’s offices, but it was a complicated journey. Dr. Brian Dunkin, chief medical officer of Boston Scientific’s Endoscopy division, recently told Medical Design & Outsourcing that the company overcame five challenges to make Exalt a reality: 1. Predicting the future “The whole impetus for developing this technology came out of the observation in the endoscopy community of some outbreaks of infections in patients,” Dunkin said. Researchers knew the outbreaks were from drug-resistant organisms, but they didn’t have the data to understand the gravity of the problem. “We had to predict the future a little because that data was coming in through different avenues, and it was entirely possible that it would say, ‘It’s not really a big problem.’“

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2. Design requirements Boston Scientific’s design process was daunting. Based on the feedback of some 150 doctors, the company designed a scope that went through about 9,000 iterations. When complete, the processor connected to the camera box contained 2,000 parts, and the scope itself had more than 150. It took six manufacturing facilities and a development team of 200 to build the device. In simplest terms, Dunkin put it like this: “We need to make this work like a state-of-the-art reusable scope, and turn it into a single-use device.” Boston Scientific also had to solve the intricacies of how the device navigates during endoscopic retrograde cholangiopancreatography (ERCP), a demanding procedure that requires a specialized scope that has different features. “It doesn’t look just front way, it looks sideways, so it has different lens angles. It has an elevator mechanism so that when we put tools through it, we can move those instruments in a much more refined fashion,” Dunkin said. Dunkin added that there was another important consideration. “If it changes my technique as an endoscopist, I’m not going to adopt it.” So Boston Scientific talked to experts, asking, “Is this right? Is that right? We had to make our own model of ERCP because nobody had one out there that you could use as,” Dunkin said. And then Boston Scientific tested in animal labs and eventually in humans to make sure the device performed as expected. 3. Cost Boston Scientific officials considered all the costs associated with reusable scopes — like cleaning, training and monitoring — and factored that into creating a singleuse device with a strong value proposition. “If cost is similar to what a reusable scope costs,

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that’s not going to help you necessarily — because I don’t throw that scope away every day,” Dunkin said. To strengthen that proposition, Boston Scientiﬁc worked with CMS so doctors get extra reimbursement for outpatient procedures. The company announced on Aug. 2 that it has also secured additional Medicare reimbursement for inpatient care. “You will actually get paid to use that scope,” Dunkin said. “You’ll get an additional payment to offset the cost of that scope. That is, to us, an indication that Medicare has made a decision that, ‘We think this is a signiﬁcant enough problem that we want our patients managed with this technology.’” 4. Performance In short, it’s got to work and work well. “You got to make the device that can do the job, not compromise the procedure and cause patient problems. And then you’ve got to convince people

"We had to predict the future a little because that data was coming in through different avenues, and it was entirely possible that it would say, 'It's not really a big problem.'" that it can do the job, and they have to see the value in that,” Dunkin said. 5. Professional development Boston Scientiﬁc quickly ﬁgured out it didn’t need to train people in ERCP; it needed to get health providers to understand the infection problem. “It’s very likely that I could have the impression that I’ve never seen a patient with an infection from a contaminated scope,” Dunkin said. But he noted the infections don’t present immediately and could take weeks or months to show up in patients. The infection might even show up in an area that has no immediate connection to ERCP. The healthcare community

needed to better understand the infection problem and the need to transition to new technology. For those looking to turn a device into a single-use model, Dunkin had this advice: “You’ve got to get those design requirements right and you got do that iteratively with the experts that you work with so that you don’t waste time going down false pathways that aren’t going to get you where you need to go. Ray Marcano is a longtime journalist who started his career covering health and medicine. He’s the former president of the Society of Professional Journalists, a twotime Pulitzer juror, and a Fulbright Fellow.

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9 • 2021

Medical Design & Outsourcing

PRODUCT DESIGN & DEVELOPMENT

Value analysis/value engineering can equal cost improvements Value analysis/value engineering (VAVE) is about boosting performance, efficiency and cost-effectiveness by improving the design of a finished product. Roger Lam MBX Systems

ost medical device manufacturers are familiar with the principles of design for manufacturing (DFM), a process utilized in the initial hardware development process to optimize product components and performance before production. But after launch, another critical step can trim the total cost of ownership (TCO) by 5–10% annually by fine-tuning design elements that usually get short shrift in the rush to get to market. Value analysis/value engineering (VAVE) involves engaging an engineering team to identify design improvements in the finished product and related processes that can increase performance, efficiency and cost-effectiveness. VAVE requires a comprehensive audit of areas ranging from the embedded system that runs and displays the diagnostics to the housing, assembly, shipment, installation and other functions. The goal is to optimize device operation as well as manufacturing, testing, logistics and support costs. Doing it right delivers competitive advantage and improved gross margins for the OEM. VAVE helps ensure reliable long-term device performance and assists healthcare organizations in meeting year-over-year cost reduction requirements to reduce the total cost of care delivery. VAVE in action Consider the case of a hematology analyzer, weighing in with price tags ranging from the low four figures to more than $100,000. The team engaged to perform a VAVE evaluation will examine every aspect of the product seeking ways to improve value to the OEM and the customer. The analysis will cover areas such as:

Medical Design & Outsourcing

9 • 2021

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The embedded system: Are the CPU, memory, hard drive and other components the best ﬁt for the application? How do they rank in reliability compared to alternatives? Do they adhere to regulatory requirements? Have they been tested for compliance and validated? Are there competing components or newer options that will deliver better performance or lower cost? Addressing these issues can maximize uptime, system longevity and cost efﬁciencies.

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Packaging and unpacking: Is the unit overpackaged? Can the packaging be streamlined to reduce logistics costs? Is it a larger machine like a CT scanner that can beneﬁt from adding wheels to the crate packaging to allow it to be rolled down a ramp by one person instead of needing three or four? All of these factors can reduce the cost of deployment and contribute to lower TCO.

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Cabling: Does the cabling scheme need to be simplified to reduce the time required to connect the embedded system to accessories such as barcode scanners, monitors and printers that come with their own cables? Would it be beneficial to create a cable harness with all cables bound together and color-coded to the appropriate ports for easier device setup? In some cases, this can save hours of installation time and thousands of dollars in labor costs per machine.

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• Functional testing: How are you harvesting and validating firmware and other components of the embedded system for quality control and traceability purposes? Is it a manual process that takes hours of staff time and drives up your TCO? VAVE partners who have the ability to write scripts that capture the information during production and flag validation problems can automate the procedure, again chipping away at product costs and helping improve OEM margins. • Circuitry testing: Your software is already validated to work on your hardware, but are all the cables, lights, timers and other circuitry elements working properly? Test fixtures built specifically for your device can simulate device operation on the production floor, reducing manual testing costs and failures in the field while also creating an electronic record verifying that all signals are being sent and received as designed.

market. It can optimize your product design, pinpoint failure points before they happen, minimize downtime, eliminate inefficiencies in areas ranging from testing to packaging and servicing, extend product life and prune unnecessary costs. This, in turn, can help improve competitiveness and the ability to achieve the price reductions demanded in the healthcare marketplace. Selecting the right VAVE partner is key to achieving these advantages. At MBX Systems, for example, our company’s proprietary Forge production infrastructure supports VAVE processes by providing fast, accurate imaging, testing and configuration during manufacturing of embedded systems. Forge also can automate scripting for functional testing and store the information for easy customer access in MBX Hatch, a toolset offering 24/7/365 visibility of real-time engineering, manufacturing and supply chain information.

The dollar impact of the changes recommended by the VAVE partner is dependent on which recommendations you decide to implement, but typically device manufacturers can achieve 5% cost reductions in the first year after product launch and 10% by the second. That’s why baking VAVE into your post-launch activities is so important. It’s an opportunity to perfect design and processes you didn’t have time for during upfront product development. Considering the intense competition among device companies and the intense price pressures in the healthcare space, VAVE is the doover that can make the difference between a mediocre product and an exceptional one. Roger Lam is director of engineering at MBX Systems, specialists in designing and manufacturing purposebuilt hardware devices for complex technologies.

• Serviceability: If a hard drive fails or needs upgrading to add capacity or next-generation capabilities, is there a way to quickly replace it without taking the machine offline? Device manufacturers rarely address this issue before launch because of time-to-market imperatives, but your VAVE partner can create removable drives that can be replaced in the field with hotswappable units that eliminate the need to power down the machine. The strategy — which can also be used for other components in the embedded system — significantly reduces support costs. Even seemingly inconsequential components such as brackets deserve analysis for their longterm value to a hardware system. When hundreds of platforms are deployed, the failure of a small bracket can spiral into significant cost ramifications. Post-launch problem-solving Overall, the value analysis/value engineering process provides a way to identify and implement mid-course corrections once your product is in the www.medicaldesignandoutsourcing.com

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4 pain points to avoid in medtech product design Reliability is crucial in medtech product design. Mitch Maiman Intelligent Product Solutions

edical technology product development combines the challenges of developing high-reliability commercial equipment with a regulatory landscape and discipline similar to defense/aerospace systems. The need for high reliability in medical technology products is obvious. Even in the lowest risk Class I devices, reliability is imperative. With Class III devices, the risk profile is so high that the highest standards of a rigorous design, verification and validation regimen are required. Here are four unique challenges embodied in the development of technology products with medical applications: 1. The supreme need for human factors considerations The issues around human factors reflect the criticality of risk reduction in medical devices. Mistakes from sub-optimal attention to human factors present the possibility of safety issues impacting treatment, data acquisition and treatment delays. Medically-oriented processes deal with people and the user interface and experience must consider the patient and the practitioner. Practitioners are busy people and not necessarily looking for the latest and greatest new technology, so critical functions need to be obvious. In “the heat of battle,” medical practitioners need to be able to work with the technology in a way that is not cumbersome or confusing. Many products in the medical technology space fail because the practitioners simply do not want to use them or find that the products interfere with their processes. If the device interfaces with the patient, it is important to pay care to comfort. Ease-of-use and ease-of-learning considerations are also important. Instructions need to be clear and concise, with little room for interpretive error.

Additionally, one should test human factors early and often to ensure the interfaces’ goals. It is one thing to build sophisticated computer models. It can be another thing to put actual prototypes in the hands or in front of those intended to interact with the technology. Often, one can discover subtle issues in this prototype phase that cannot be detected digitally. 2. Balancing process speed with requirements and risk management Most medical technology companies are working in a competitive environment. Capital can be scarce, and time is money. Project planning must always be cognizant of the timing required in commercialization, without compromising the relevant processes and achievement of the required goals in efficacy and safety (along with the regular trade-offs related to cost, size, weight, etc.). 3. Picking the right risk classification Risk classification is one of the most crucial decisions early in the project. Particularly when working with early-stage companies, there is not always a clear

Products designed by Intelligent Product Solutions include the AdhereTech smart pill bottle, according to IPS. Image courtesy of IPS

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understanding of the risk classification levels or the implications of avoiding this entirely by developing a process that is “health and wellness” oriented. In our experience working with startup companies, when the management team realizes the impact of a higher-risk product definition, they will sometimes flip to a consumer product standard with no medical claims. When they proceed down that path and then flip back to an FDA-certification goal, the cost can be substantial as the consumer product development process will not usually generate the artifacts necessary for an FDA certification. The result means going backward to create requirements, produce documentation (risk analysis and mitigation plans) and perform the verification and validation testing (along with reports) to prove efficacy, usage profiles and safety. Another issue often seen is use-case expansion. In an effort to secure a wider

market segment, changes of this nature can change the risk profile and, hence, the device classification. 4. Clearly defining requirements Both mature and early-stage companies face challenges around defining requirements. It is crucial to start medical technology product development with a clear definition of requirements. These include delineating the intended product claims, identifying the target practitioners for the use of the product, environmental constraints, and, of course, assessing the appropriate risk profile to drive the class designation. Even more critical than in commercial or consumer products, failure to define requirements early and clearly will burn capital and lose valuable time. Changes in requirements mid-stream on projects may impact the architecture, risk profile and validation/verification plans.

Medical technology product development boils down to paying careful attention to the requirements, which may be a bit more — or a lot more — rigorous than in most other industries. In the end, it’s about understanding the physics of the problem. If one abstracts the product to be designed and engineered, you need to apply the same skills related to the fundamentals. As in any industry, there are nuances related to development processes, regulatory requirements, and test methodologies. It is important to have an experienced medical product design partner and team to succeed. Mitch Maiman is the president and cofounder of Intelligent Product Solutions (IPS), a product design and development firm with a specialty in medical technology. Always espousing a hands-on approach to design, he holds a portfolio of numerous United States and international patents.

Keep the end in mind when choosing a medtech partner There are five general categories of medtech vendor partners. If the end is apparent in the beginning, the correct type of partner will be clearer. Jim Reed Minnetronix Medical

tephen Covey gave the business world this mantra in one of his bestsellers: “Start with the end in mind.” Whether they didn’t read the book or simply choose to ignore the advice, many companies enter into discussions with vendors without their end goal in mind. It sets the partnership on an inefficient course from the beginning. If the end results aren’t front and center from the beginning of the vendor selection process, the outcomes may include frustration and misunderstanding. When looking for a vendor partner to bring a product to life, the choices can be as widespread as a $12 billion global contract manufacturer with 50,000 employees that develops both industrial and consumer products; a mid-sized (roughly 500 employees) integrated developer, manufacturer and product lifecycle company focused on medtech; or a sharp, four-person consulting/engineering design company that’s never developed a medical device. This bewildering array of options and the complexity of the changing vendor landscape can be a challenge for many companies when selecting a partner. Yet it is also

an opportunity as this breadth of competing vendor solutions means there is an optimal partner type for almost any medical device company’s need. Therefore, the most important first step is clearly defining that need. Then companies can move to the selection process. Choosing the wrong type of partner can be the biggest fundamental mistake of the process. In other words, a company that is fantastic within its category but that also happens to be the wrong kind of partner for a particular project will foretell undesirable outcomes from the very beginning. Here are the five general categories of medtech vendor-partners, along with their respective features and trade-offs: 1. Individual design consultants • Best for quick and rough proof of concepts, early feasibility work, or prototyping when documentation, repeatability and technical continuity are not required.

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Individual consultants can build a great technical road to proof-ofconcept systems or prototypes, but aren’t equipped to drive the project to its destination.

2. Consulting groups •

Groups of consultants generally provide the same pros and cons as individual consultants, but with the ability to tackle projects of greater magnitude.

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3. Design and development companies •

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Appropriate for developing simpler products, often for clinical studies only, where manufacturing readiness or regulatory preparedness might be less important. They’re generally more systematic than consulting groups, with a greater diversity of technical experience and depth, with better continuity. Unbiased regarding the selection of the eventual manufacturer. Without in-house manufacturing, no tight post-development feedback loops exist. Design for manufacture (DFM) necessarily lacks in these ﬁrms, and resulting designs often require substantial redevelopment or remediation before full commercialization.

4. Contract manufacturers •

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5. Integrated design, development and manufacturing companies •

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Contract manufacturers (CMs) are a good ﬁt for products where manufacturing at high volumes is the paramount driver. Typically only do development work 9 • 2021

as a means to secure long-term manufacturing contracts. They’re generally uninterested in technically supporting customers over the long term unless they can drive short- or medium-term manufacturing volume. Sophisticated supply chains. Very solid and methodical if the product is refined and stable. Limited operational flexibility; generally with systems, organizations, and facilities optimized to specific volume levels and process flows. Products or customers that vary from that optimal situation may be problematic. Large CMs, therefore, have to shed customers that are not achieving the originally planned volume in the original time frame.

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Fit a fairly diverse range of projects and can accommodate customers across multiple phases of their business and product lifecycle and growth. Act as a single partner to take requirements and prototype early and potentially bring clinical units to commercialization. Offer the benefits of a design and development firm as well as those of a contract manufacturer. Tend to be DFM-oriented and systematic in their design and documentation approach. Customers can avoid fingerpointing between developers and manufacturers who may blame each other when issues arise. An integrated www.medicaldesignandoutsourcing.com

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partner is unavoidably accountable when issues inevitably arise. The best-integrated partners can also act as a virtual extension of a company’s internal team and quality management system (QMS), managing design history files and fielding topic-specific FDA, CE and diligence audits, are examples. Often poorly suited for very early proof of concept units and early prototyping.

It is common for companies to spend substantial time considering different vendor-partners scattered among the various option types and attempting to compare each to the other. A more successful approach is to first be very clear on the end goal: Quick prototype? Absolute lowest cost at high volume for products requiring extensive labor? An integrated lifecycle solution matched to the company’s strategy and current situation? If the end is clear in the beginning, the correct type of partner will be more apparent. As a result, the subsequent vendor selection process will be efficient, the vendor-partner appropriate, and the probability of success much higher. Jim Reed is VP and general manager of RF Stimulation and Wearables at Minnetronix Medical (St. Paul, Minnesota), which has developed dozens of RF-based medical devices over 25 years. Minnetronix has substantial electroporation-specific capabilities around designing, verifying and manufacturing different types of reversible and irreversible electroporation electrodes and pulse generators.

7 ways to ensure your medical device product design isn't biased Correcting unintentional biases in medical device product design is a big step toward improving equity in medtech. Liz Hughes Contributing Writer

chuta Kadambi, an assistant professor at the UCLA Samueli School of Engineering, says when looking at bias in medical devices, there’s often a lot of narrative in the media of what it is. However, it’s also important to address what it doesn’t show. “One that doesn’t show up is that it’s a really challenging technical problem and an exciting technical problem to address,” he said, citing an example of how light doesn’t play well with darker objects like darker skin tones. Kadambi, who recently published a column in the journal Science about achieving fairness in medical devices, says there has to be a technical passion for solving these problems. He adds that the social impact is equally crucial in making devices fair. “When inventing a life-saving medical device, it’s important to make sure it doesn’t disadvantage a certain class of people,” he said. “You want to invent for humanity, not subsets of humanity.” It’s possible to learn lessons from computer science, Kadambi said, and you can bring that methodology to medical device design as well. How can medical device product designers ensure their product design isn’t biased? Kadambi said there are several ways to avoid unintentional biases and improve equity in medical device design: 1. Include stakeholders as inventors. Kadambi said it may sound obvious, but designers should ensure their inventors include stakeholders. For example, if you are working on something for darker skin tones, don’t just rely on darker skin test subjects. He said to try to include them as co-inventors. 2. Include diverse groups. Make sure the inclusion criteria for your study includes diverse groups if you want to make a device. It’s vital to have minority populations and various demographics in clinical research studies and clinical trials, Kadambi said. 3. Quantify sample fairness. Once you have the study subjects and the technical authors on the paper lined up, the next thing to do to make a medical device fair is to quantify fairness mathematically, according to Kadambi. “What does it mean for a device to be fair?” he said. “You need some sort of numerical way to score bias or fairness.” www.medicaldesignandoutsourcing.com

In his column, he suggested medical device journals should require authors to quantify sample fairness in experiments. “Scientists are currently only required to provide statistics relating to a device’s performance without the human factor,” he said in that piece. 4. Start inventing fairly. Once you have a score for bias, you should have a diverse group to evaluate your fairness score. Then, report it as something as important as performance. “This is where the invention process begins — start to invent things that boost your fairness metric,” Kadambi said. “These could be inventions that take unconventional forms. For example, you realize light doesn’t reflect well off darker skin. Maybe you don’t use light. You use something else. So maybe combine light with another modality that makes the situation more fair.” 5. Read and cite other’s work. Read and cite work from other authors who have been working on algorithmic fairness. “Read these papers and, to an extent, be aware of them because they’ll help you design these metrics in a better way,” Kadambi said. He added that algorithmic fairness is a very popular area in computer science, and there’s some literature out there folks should read. 6. Weigh fairness appropriately. It’s also important to report your results in a way that gives fairness a similar kind of weight or importance to performance, he said. “Even if your device is not fair, report the shortcomings and let the community decide how they can improve that in future work,” he said. 7. Recalibrate measurement of performance. Kadambi also suggests recalibrating how medical device performance is measured, determining how existing devices perform when using a quantifiable metric, such as race or ethnicity, in evaluating equipment. Liz Hughes is an award-winning digital media editor with more than two decades of experience in newspapers, magazines and online media. Hughes has produced content and offered editorial support for a variety of web publications, including Fast Company, NBC Boston, Street Fight, AOL/Patch Media, IoT World Today and Design News. 9 • 2021

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How COVID-19 changed medical device clinical trials forever The success of remote clinical trial oversight opens the door to hybrid approaches and creates new possibilities for the future of trials.

ecause of the pandemic, virtually overnight, all players involved in medical device clinical trials had to pivot to virtual monitoring to keep trials going. What impact did remote trial oversight have on the quality, safety and costs of clinical trials? What are the implications for the future? A panel of experts from across the clinical trial ecosystem discussed these topics on a recent episode of DeviceTalks Tuesdays, sponsored by Avania. Panelists included Hamish Baird, clinical research president at Remington-Davis; Brandy Chittester, president of IMARC Research (now Avania); Xavier Lefebvre, global VP of medical and regulatory operations at Medtronic; and Dr. Eric Kolodziej, corporate VP and global head of quality

and regulatory affairs at Hologic. Four takeaways from the pivot to remote monitoring of trials are: 1. Virtual monitoring has not hurt quality or safety. The issue with trials during the pandemic was getting trial data because enrollment was down, Kolodziej said. But the panelists and most audience members participating in real-time polls agreed that remote trial oversight did not decrease the quality of clinical trials and was safe for study subjects. Medtronic’s Lefebvre said that in shifting to virtual monitoring, Medtronic carefully assessed the outcome of visits. “We have seen no difference in terms of the overall quality or the overall outcome of the visit with respect to the data quality,” Lefebvre said. Chittester from

How COVID-19 changed medical device clinical trials forever

TUESDAYS

The success of remote clinical trial oversight opens the door to hybrid approaches and creates new possibilities for the future of trials. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

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Avania and Baird from Remington-Davis agreed, seeing no negative impact and perhaps an increase in the quality of clinical trials because of the ability to monitor the trial in real-time. 2. Remote trial monitoring has decreased trial costs. Among DeviceTalks Tuesdays participants, 59% believe remote trial oversight has decreased the costs of clinical trials and 22% say remote trials have not impacted costs; only 19% believe costs have increased.

schedule than before.” The speciﬁc types of technologies embraced vary for every organization but include technologies to provide access to EMRs and to enable secure data sharing. “We’ve invested in technologies to help facilitate remote monitoring visits,” Kolodziej said. His organization implemented eSOURCE, a commercially available electronic source documents system. Sponsors want to know what technologies are in use and that these technologies are compliant with all applicable regulations.

"I don't think we're going back to where we were. At the same time, I don't think we're going to stay at the level we're at today in the U.S., where 95% of monitoring visits are done remotely." Preparation for a remote visit takes 1.5 to 2 times longer, Baird and Lefebvre said. But, according to Lefebvre, “the actual visit is shorter, more efficient, more effective. So, the additional prep time is offset by the time now gained during the monitoring visit. And the follow-up is also a little faster.” The other significant benefit is the elimination of travel time and expense. IMARC’s experience has been similar. “It seems an overall cost savings,” Chittester said. Spending extra time on visit prep and even paying sites a bit more for prep is more than offset by the reduction in travel time and expenses. 3. The adoption of various technologies has increased. “Technology is being embraced,” Chittester said. “We can have access to medical records on a different pace or

4. Remote monitoring and hybrid trials are here to stay. The panel believes that a sea change has occurred for all players in the clinical trials ecosystem. “I look at COVID as having enabled us to really have a tremendous transformation in clinical trial execution,” asserted Lefebvre, speaking from the perspective of a trial sponsor. “Remote monitoring is here to stay,” Kolodziej said. “If we want to play ball, then we’d better get in the game and make sure that we ﬁgure things out and make sure it’s efﬁcient and works for everyone.” The presence of remote monitoring creates more options for the future, including hybrid approaches that involve both on-site and remote oversight. “When we think of hybrid, it’s the mix of on-site and remote,” Chittester said. “There are so many places we can go

… deﬁnitely a lot of options for how we can run trials in the future using this combination of on-site and remote.” For Kolodziej, the concept of hybrid is not just for monitoring but also involves “data hybrids” where data comes from multiple sources, such as both prospective trials and real-world evidence. He believes data hybrids can help expedite regulatory approval. “I don’t think we’re going back to where we were,” Lefebvre said. “At the same time, I don’t think we’re going to stay at the level we’re at today in the U.S., where 95% of monitoring visits are done remotely.” For Medtronic, he predicted that over time, around 50% of visits in Europe will be remote and perhaps around 60% to 70% in the United States. Provided to Medical Design & Outsourcing by BullsEye Resources.

Keys to protecting your medtech AI from competitors

TUESDAYS

AI is a hot area in medtech. A panel of intellectual property experts had advice on protecting the IP. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

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Keys to protecting your medtech AI from competitors Artificial intelligence is a hot area in medtech. A panel of intellectual property experts had advice on protecting the IP.

etween 2002 and 2019, annual artificial intelligence (AI) patent applications more than doubled, and AI patent applications increased from 9% of all applications to 16%. AI is a white-hot area for investment and creation of valuable intellectual property (IP), including AI related to medical devices. Protecting medical device-related AI was the topic of a recent episode of MassDevice and Medical Design & Outsourcing’s DeviceTalks Tuesdays, sponsored by Finnegan, a law firm that handles all aspects of IP. The discussion involved Anthony Del Monaco and Cecilia Sanabria — partners at Finnegan — and two CEOs of healthcare companies that have developed exciting AI-related IP: Jan De Backer, CEO of Fluidda, a respiratory imaging company, and Todd Usen, CEO of Activ Surgical. In the case of Activ Surgical, the company makes a small device that attaches to any scope, a camera system that captures information that humans can’t see, a proprietary cloud platform that stores video data, and a proprietary annotation system. Both CEOs’ companies have IP related to AI. Four takeaways on protecting this IP are: 1. Companies that develop IP need to protect it or risk losing it. “Why do you need to protect this IP?” asked Del Monaco. The answer is simple. “The primary reason is because if you don’t protect it, you may lose it.” 2. Common ways to protect IP are patents and trade secrets. With a patent, the public can see the information, but the patent owner potentially obtains a monopoly on that idea for 20 years. Two ways to file patents are provisional and nonprovisional applications. A provisional application is easier and faster to file, and provides one year of protection for an idea, during which time a company can go to market and sell. The provision application route buys time to file a more comprehensive nonprovisional application. Trade secrets are different. With a trade secret, information that might not be patentable is kept secret (such as the formula for Coca-Cola). A company takes steps to protect the information. Trade secrets might include sales and marketing statistics, customer lists, proprietary tools, design concepts and more. www.medicaldesignandoutsourcing.com

Del Monaco emphasized, “The real takeaway is to make sure you get protection.” 3. When entering into agreements companies need to protect their IP. Companies that have developed AI-related IP often pursue business strategies such as licensing or entering into joint ventures. These activities require well-crafted agreements with several important terms. “The first thing to think about is what exactly is the AI that’s going to be the subject of the agreement?” Sanabria said. Also important, according to Sanabria, is “who is going to own the data and who has access to it?” Agreements should also specify rights and liabilities — a critical consideration if, for example, a party claims the AI harmed them. In a licensing agreement, joint venture, or a vendor/supplier agreement, who is going to be liable? Agreements must address liability. Because of the uniqueness and complexity of AI, agreements involving AI have more factors to consider. 4. CEOs who know better make protecting their IP a top strategic priority. As leaders of innovative healthcare companies, both CEOs view protecting their most crucial IP as a top priority and a CEO-level matter. Usen explained: “We see IP as an asset that provides a runway to commercialize our technology. If we are heavily investing in something, we want to make sure we have good IP.” Both CEOs described going through rigorous processes to think through the particular IP they want to protect. For example, Activ Surgical is interested in protecting its computer vision AI, algorithms, workflows and hardware. Fluidda is most interested in protecting its proprietary engine that generates insights and data. These companies are using multiple ways to protect their IP, including provisional patents and protection of trade secrets. For guidance in the process of protecting valuable IP, Usen acknowledged, “I think the No. 1 thing that we do — and it’s a credit to firms like Finnegan — is to partner with the best firms in the world when it comes to IP protection.” In addition, he suggested that other healthcare companies with valuable AI-related IP do the same. Provided to Medical Design & Outsourcing by BullsEye Resources 9 • 2021

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3 questions medical device manufacturers should ask before ISO 10993-17 updates The upcoming publication of ISO 10993-17 will support the latest ISO 10993 expectations already in place. Gain insights into what this standard will mean to the evaluation process and how to prepare in advance.

Sherry Parker W u X i A p p Te c Medical Device Te s t i n g

ollowing ISO 10993-1, the lens of medical device biological safety evaluation changed to a risk management process, impacting how manufacturers prepare their medical devices for submission. The newest version of ISO 10993-17 is approaching publication. These revisions expand current guidance on establishing limits for leachable substances to assess the toxicological risk of medical device chemical constituents. The changes allow for a more consistent evaluation and will likely lead to a more device-speciﬁc approach to subsequent biological safety evaluations. While the ISO 10993-17 guidance document is still in the draft stage, there are ways to begin preparing submissions to better satisfy future expectations. Based on a snapshot of the latest version of the guidance, medical device teams should ask themselves the following questions to vet their compliance strategies: 1. Has the team adjusted resource allocation to reﬂect new versions of ISO 10993? Medical device biological safety evaluations focus on risk and now prioritize identifying and understanding the device’s chemical constituents and the associated toxicological risk — before pursuing biocompatibility testing. Due to the changes instituted by ISO 10993-

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1, some manufacturers may need to shift how they approach biological safety testing to reflect this. Additionally, it is critical to reevaluate resource planning to ensure the company is prepared for necessary changes from a timing and budgetary standpoint. Now needing more thorough chemical information at the onset of biological safety assessments, toxicologists must evaluate vast amounts of chemical characterization data. However, this level of characterization can lead to more potential toxicological concerns identified than ever before. ISO 10993-17 updates will support more robust, consistent TRAs and help toxicologists avoid over or underestimating risks. Manufacturers should review their evaluation process and affirm it reflects the latest requirements and methods. An experienced laboratory partner can provide support to this effort. This review from the manufacturer should ensure the device submission meets the intended deadlines and stays within budget projections. 2. Where does the submission stand against the latest ISO 10993 guidance? ISO 10993-1:2018 was the driving force behind the significant changes to the methods used in biological safety evaluations. This standard forced the industry

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to move away from the traditional “checklist” approach to materials characterization, physical and/or chemical information, and risk assessment. Instead, this integrated approach helps inform the relevant biological endpoints that require further investigation. Following this change, ISO 1099318:2020 reinforced the requirements for adequate chemical characterization and established the basis for conducting toxicological risk assessments. With hundreds, if not thousands, of chemical results, it has created a challenge for toxicologists to assess every chemical in a medical device. The revisions to ISO 10993-17 will provide valuable tools for toxicologists when conducting toxicological risk assessments. Most notably, it will introduce new tools to estimate exposure and prioritize chemicals toxicologists need to assess, streamlining the currently cumbersome process.

3. What steps does the team need to take to establish a working relationship with an experienced laboratory? Toxicological risk assessments require knowledgeable and experienced individuals, and the revisions to ISO 10993-17 will further emphasize the importance of expert judgment in the process. Regulators are already requesting toxicology risk assessor CVs to verify qualiﬁcations. Because of this expectation, cultivating a relationship with an in-tune laboratory is crucial to success. Right now, companies may be intimidated by the mountain of data to sift through. Still, manufacturers who engage with testing partners early on can address this data head-on and strengthen their submissions. Testing laboratories with experts well-versed in ISO guidance will stress the importance of gathering relevant medical device information,

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including chemical characterization data, exposure, and background on the device use. These will be critical inputs to TRAs. Prepare While the updates to ISO 10993-17 come with major beneﬁts, the last time this standard was updated was in 2002. This change will likely create a paradigm shift in the performance of risk assessments. Considering the submission pathway and how the relevant regulator(s) typically implement ISO 10993 guidance can help gauge the urgency in adapting. Spend time exploring how TRAs can increase device understanding and risk evaluation. With the big picture in mind, the learning curve will ultimately increase submission efﬁciency and effectiveness. Sherry Parker has over 20 years of toxicology and medical device experience and is an expert in biological evaluation of medical devices and combination products. After receiving her Ph.D. in molecular and cellular pharmacology from the University of Miami, Parker worked as a toxicologist for the U.S. EPA, RTI International, OrbusNeich Medical, and Fresenius Medical Care. In her current position as WuXi AppTec’s senior director of regulatory toxicology, Parker provides manufacturers with guidance on global regulatory and technical requirements and testing program design. In May 2019, Parker was appointed to a three-year term as co-chair of the Biological Evaluation (AAMI/BE) Committee, the U.S. mirror committee for ISO 10993.

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SOFTWARE

Software as a medical device: Here's how the regulatory landscape is changing When it comes to software as a medical device, the regulatory landscape is quite complex.

Nach Davé Premier Research

oftware as a medical device (SaMD) has emerged as a class of devices for collecting, processing and analyzing healthcare data to manage disease. Powered by analytics, SaMD accelerates the diagnosis and treatment of a wide range of medical conditions and is automating certain aspects of patient care, saving time and improving health outcomes. Because the technology is relatively new, however, the regulatory environment is still evolving as regulators scramble to keep pace with innovation. Health providers are increasingly deploying SaMDs to facilitate patients’ pain management, arrhythmia management, and blood glucose monitoring. Some applications require daily use by the patient — sometimes multiple times a day — while remaining compliant with good clinical practice. The potential advantages include fewer ofﬁce visits, increased frequency of patient metrics, and real-time alerts if readings from the software suggest a risk to the patient. On the other hand, the use of SaMD may result in less face-to-face contact with patients, with potential ramiﬁcations for clinical trial operations and long-term care.

Medical Design & Outsourcing

9 • 2021

Navigating a complex regulatory environment The regulatory landscape for SaMD is quite complex, with multiple pathways and product development implications impacting the eventual regulatory determination. That complexity reflects the inherent challenges in classifying SaMD, as regulating this new class requires a basic understanding of what it is. The International Medical Device Regulators Forum (IMDRF) is a global working group comprising representatives of the U.S. Food and Drug Administration, European Medicines Agency, and other key regulators. It defines SaMD as “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device.” In other words, the software component must inform or enable a medical decision or outcome but must not principally drive a hardware device. For example, by that definition, the medical device software used to view images from a magnetic resonance imaging (MRI) scanner on one’s phone would be SaMD, but the software enabling an MRI machine to run the test would not be.

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SOFTWARE

However, suppose a device retrieves information, organizes data, and optimizes processes (see the farleft column in Figure 1) or enables a closed-loop intervention without a clinical intermediary (far-right column). In that case, it is not SaMD, according to the IMDRF. That leaves a vast gray area in the middle, underscoring the importance of early discussions with regulators to reach a consensus on the most appropriate category for a specific device. In our experience, the distinction matters because correct classification has profound implications for SaMD development and commercialization. Additionally, developers are increasingly making efficacy claims based on the use of SaMDs in clinical trials, in some cases before evaluating regulatory pathways or standards. For an SaMD with a low-risk application, a developer may assume it is a Class I medical device, implying a faster regulatory pathway and minimal scrutiny. Bridging gaps in knowledge and regulations Regulators in different regions have taken different views of the risks related to SaMD and are under pressure to harmonize their regulations as innovation continues at a breakneck pace. Additionally, SaMDs can be acquired online without medical oversight, and patients can use them while traveling abroad, where regulations may vary. Such gaps leave much to the interpretation of individuals with less than optimal regulatory knowledge. The challenge lies in striking an appropriate balance between encouraging innovation and ensuring patient safety. To meet that challenge, the FDA has initiated a pilot program — the Digital Health Software Precertification Program — to provide more streamlined and efficient regulatory oversight of softwarebased medical devices. Another key regulation, IEC 82304-2016, delineates general health software product safety and security requirements. The EMA similarly regulates software that drives or influences the use of a device; if the software is independent of any other device, it is classified in its own right. Seizing the opportunity In our estimation, the current regulatory environment presents a rare opportunity for SaMD developers to shape how these 88

Medical Design & Outsourcing

Figure 1. IMDRF Classiﬁcation Paradigm for Software as a Medical Device (SaMD)

products are regulated. That makes it vitally important to engage in early dialogue with regulators to ensure clarity and agreement on device classiﬁcation. It is also important to follow and contribute to IMDRF decisions, as all the major regulatory bodies recognize this forum. Additionally, following design controls can enable ﬂexibility across regulated regions and minimize any potential remediation efforts. Finally, these strategies can enable a comprehensive understanding of the appropriate regulatory pathways for SaMD and help ensure a successful market launch. Nach Davé is VP of development strategy at Premier Research.

Source: U.S. Food and Drug Administration. Software as a Medical Device (SAMD): Clinical Evaluation - Guidance.

9 • 2021

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STERILIZATION SERVICES

How to better clean fiber optics in medical devices When it comes to ﬁber optics in medical devices, cleaning is essential for reliability.

J a y To u r i g n y MicroCare

he use of fiber optics in the medical industry is steadily increasing. As the population continues to grow and age, healthcare providers are using fiber optic devices for better patient diagnosis, monitoring and treatment. Today, fiber optics are used for minimal invasive surgery (MIS), in sensors inside single-use catheters and endoscopes and for real-time diagnostic imaging with MRI, CT, PET and SPECT systems. Like many medical devices, cleanliness is crucial to the performance of fiber optic instruments. The device must perform without fault. One of the main causes of fiber optic instrument failure is the contamination of the fiber optic termini. Dirty fiber connections, also known as end faces, can cause a host of problems ranging from intermittent performance

to ruined instruments. That is why cleaning the end faces is crucial to ensure the reliability and performance of fiber optic medical devices. Identify and remove the contaminant One of the biggest challenges of end-face contamination is that it can’t be seen with the naked eye. Microscopic dust particles or fingerprint oils typically are only seen with a specialized 200x or 400x inspection scope. A close examination of the connectors is critical to confirm any particles or residue are completely eliminated, thereby ensuring that connections function properly. The best advice is to inspect, clean, and inspect again before making any fiber-optic instrument connections. Repeat this process until you are absolutely sure the instrument end faces are clear of all contaminants.

TOP: Fingerprint oils seen with a specialized 200x inspection scope Cleaning sticks or swabs are ideal for cleaning end face connectors.

BOTTOM: Inspect, clean and inspect end faces until they are clear of all contaminants.

Image courtesy of MicroCare

Images courtesy of MicroCare

Medical Design & Outsourcing

9 • 2021

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STERILIZATION SERVICES

Choose materials engineered for fiber cleaning The materials used to clean the end faces must be pristine; otherwise, it could make it worse by adding contamination. It may be intuitive to wipe the end face on a gown or a cloth, but under a typical fiber optic inspection scope, those items carry a large variety of contaminants that could soil the connector. Letting connectors touch the floor or even touching the termini with a finger can cause them to be significantly dirtied with dust or skin oil. To avoid further contamination, use products specifically engineered for cleaning fiber optics. Cleaning wipes and sticks There are two primary methods available to properly clean fiber optic end faces: a specialty wipe for plugs and a swab for sockets. Particulates, oils, and salts are the three basic types of contaminants found on the end faces, all of which require their own cleaning methods. Particulates are solids that are held on the end face by a static attraction. The best way to clean these types of contaminants is by dissipating the static charge that both attracts and holds them in place. This can usually be done with a specialty cleaning fluid. Cleaning fluid also dissolves the oils found on the fiber. Salts, on the other hand, are not necessarily fully removed by cleaning fluids alone. While cleaning fluids may quickly rinse away the oils, they tend to leave salt remains behind in the form of a white residue that can be very difficult to remove. The mechanical action that a wipe or a cleaning stick provides is usually combined with a cleaning fluid to fully eliminate oil and salt left on the termini end face. High-purity cleaning fluid When cleaning fiber end faces, be sure to use fluids engineered for fiber cleaning. Avoid using aqueous (water-based) cleaning solutions or pure isopropyl alcohol (IPA). Aqueous products are slow to dry and can leave moisture on end faces. If the moisture is not completely removed before the fiber is connected in the sleeve, the laser-energized fiber can instantly vaporize the remaining liquid into a gas, causing an explosion through the sudden expansion of the vapors. As with water-based cleaners, IPA may explode or catch on fire when left 92

Medical Design & Outsourcing

9 • 2021

Wet-to-dry cleaning dissolves oils and helps eliminate electrostatic charge. Image courtesy of MicroCare

on a highly energized fiber end face. IPA also frequently leaves a hazy film behind when it dries. Instead, use a fast-drying, high-purity fluid engineered specifically for cleaning fiber optics. Wet to dry cleaning High-purity cleaning fluids should be used with both wipe and swab applications. However, beware of presaturated cleaning materials. Presaturated wipes and swabs often contain microscopic contaminants drawn from the plastic packaging, which can transfer to the end face during the cleaning process and result in further contamination problems. Instead, carefully apply a small amount of high-purity cleaning fluid on the corner of a dry wipe or the tip of the swab and then apply to the fiber optic termini. A well-engineered cleaning fluid will not only dissolve oils found on the end face but will help to eliminate the electrostatic charge generated when the applicator is pulled out of its packaging. Be sure not to touch the wipe or swab area you will be using with your finger or clothing. Should you touch this area or drop it on the ground, discard the wipe or swab and start over. Once the cleaning process is complete, discard the wipe or swab and inspect the end face to ensure all contaminants have been eliminated. www.medicaldesignandoutsourcing.com

Fiber cleaning means better patient care The use of thin, small, flexible fiber optics inside catheters and surgical scopes makes it easier for healthcare providers to see and work inside the human body with better comfort for the patient. These fiber optic medical devices help provide better diagnostics, improved medical treatment and better surgical outcomes. It is imperative to clean the termini end faces properly to ensure reliable performance. Medical providers can’t afford to have a faulty connection, a fire or a fiber optic shut down when there is a patient on the table. To help safeguard device reliability, use specially-engineered fiber optic cleaning products and closely inspect the end faces before connecting. This helps ensure the fiber optic medical devices operate as intended without fault. For those looking for help in selecting fiber optic cleaning tools and fluids, it’s best to partner with a supplier that specializes in fiber optic cleaning. They can provide advice on the best cleaning solutions and methods to use. Jay Tourigny is SVP at MicroCare, which offers Sticklers brand fiber cleaning solutions. He has been in the industry for more than 30 years. He holds numerous U.S. patents for cleaning-related products that are used on a daily basis in fiber optic, medical and precision cleaning applications.

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TUBING

Image courtesy of Resonetics

The advantages of laser-cut tube (LCT) catheters Here’s how laser-cut tube (LCT) catheters compare to traditional catheters: the design process, functional advantages, test methods and cost comparisons.

he medical device community has a long history of using braided and coil-based catheter constructs. But these traditional constructs present multiple performancebased issues. “With the advent of the laser-cut tube capability we have at Resonetics, it’s opened up a lot of options for catheter manufacturing,” said Dave Rezac, VP of design and development services at the company, in a recent DeviceTalks Tuesdays webinar. Kevin Hartke, Resonetics’ chief technical ofﬁcer, joined Rezac in the Resonetics-sponsored webinar to discuss how their company studied the comparative performance of LCT versus traditional catheter constructs. Here are four takeaways on how LCT compares to the traditional catheter construct: 94

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1. Different catheter construction The catheter construction process consists of layering individual components — the mandrel, liner, reinforcement layer, and jacket — and turning them into a composite-reinforced catheter by fusing them through heat and pressure. Rezac termed it “like a slow-motion molding process.” The traditional construct contains these layers as well as a tie layer and classic braid or coil. 2. A different design process Customers often ask Resonetics, “What information do we need to develop an LCT?” Rezac said. “It’s surprisingly little. We can work with functional requirements and target speciﬁcations.”

TUBING

Resonetics asks questions like: “What does it have to do? How much load does it have to carry? Where is it going?” “We translate those functional requirements into the pattern,” Hartke said. “That’s one of our offerings as a business. We have a nice library of patterns and a full understanding of how those patterns affect the functional output of the device or the part.”

• Jacket: The jacket deﬁnes the catheter’s interaction with the outside world. It helps deﬁne and amplify or offset the mechanical properties of the underlying layers.

ﬂexibility, improved kink resistance, no ovality, and comparable tensile strength.” He added, “You’re not sacriﬁcing a lot of integrity and tensile and compression to get these advantages.”

4. Different test methods and results Resonetics tested bending stiffness, kink resistance/ovality,

• Torque transfer: Catheter shafts exhibit superior torque transmission with LCT as compared to conventional braid construction. “This is where LCT really blows the conventional methods out of the water,” Rezac said. “This is a huge differentiator for the applications space.”

"The LCT component might be a larger portion of your cost; however, you're saving headaches downstream. ... By and large you're moving some costs around." 3. Different components Key components for LCT are the liner, reinforcement layer and jacket:

tensile strength, and torque transfer in comparing catheter constructs. Here’s what Resonetics found:

• Liner: The liner is placed over a core material to deﬁne the lubricious inner lumen. Liner options include PTFE, HDPE, FEP and PVDF and ePTFE. In deciding on the liner, essential considerations are performance requirements and cost.

• Bending stiffness: There was parity between LCT and traditional construct. It’s possible to design LCT for a variety of bending stiffnesses across typical values seen with braid and coil.

• Reinforcement layer: Traditional braids and coils can be cumbersome. Manufacturers can experience processing challenges when using both on the same catheter. LCT can be game-changing, especially with high-end novel applications, because LCT decouples traditional torque, column strength and ﬂexibility relationships. In addition, it is highly tunable and continuously variable. “The reinforcement layer was really the star of our study,” Rezac said.

• Kink resistance/ovality: Kink resistance and lumen integrity are paramount in many interventional applications. LCT reinforced shafts maintain excellent kink resistance and lumen integrity through bends, demonstrating extreme resistance to ovalization. “This is where LCT started to differentiate itself and pull away,” Rezac said. • Tensile strength: LCT reinforced catheter shafts exhibit acceptable tensile and compressive strength. Rezac reported “comparable or similar

LCT has multiple advantages, according to Resonetics. Monolithic design can achieve the mechanical performance of braid, coil, or a combination of the two. It is highly tunable and stable. It eliminates the need for braid and coil wire termination and transitions. It provides superior hoop strength and lumen integrity, ensuring smooth passage and actuation of devices through the inner lumen while operating in tortuous anatomy. And it is compatible with conventional liners, jackets and layup manufacturing processes. “Generally speaking, you can achieve cost parity in a lot of these constructions,” Rezac said. “The LCT component might be a larger portion of your cost; however, you’re saving headaches downstream. … By and large you’re moving some costs around.” Hartke noted that Resonetics “is able to manufacture [LCT] parts that are price competitive to a standard catheter construct.” Provided to Medical Design & Outsourcing by BullsEye Resources.

The advantages of laser-cut tube (LCT) catheters

TUESDAYS

Here’s how laser-cut tube (LCT) catheters compare to traditional catheters: the design process, functional advantages, test methods and cost comparisons. Watch the DeviceTalks Tuesdays On Demand presentation. https://www.devicetalks.com/devicetalks-tuesdays-agenda/

Medical Design & Outsourcing

9 • 2021

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TUBING

Design considerations you need to know when making ablation catheters to treat AFib Catheters are increasingly deploying heart devices in minimally invasive procedures. CardioFocus VP of Engineering Jerry Melsky describes the components and design considerations that go into making successful ablation catheters to treat AFib.

CardioFocus’s HeartLight X3 ablation catheter and balloon Image courtesy CardioFocus

Danielle Kirsh Senior Editor

trial fibrillation (AFib) is the most common irregular heart rhythm disorder. If the atria of the heart beats rapidly and irregularly, blood does not flow through the heart as quickly, according to the Cleveland Clinic. The irregular heartbeat makes the blood more likely to clot, and if the clot leaves the heart, it can travel to the brain and cause a stroke or to the coronary arteries and cause a heart attack. There are several ways to treat AFib, including various medications, procedures such as electrical cardioversion and pulmonary vein ablation, and devices like pacemakers and left atrial appendage occluders. Ablation procedures introduce a catheter into the left side of the heart and create circles of scar tissue around the pulmonary veins to isolate the veins from the rest of the atrium. The most common catheter-based technology in treating AFib is radiofrequency (RF) ablation, Jerry Melsky, VP of engineering at CardioFocus, told Medical Design & Outsourcing. In RF procedures, the physician typically repositions the catheter each time to make a lesion. The doctor may need to circle the pulmonary vein to make 50 to 100 lesions. An alternative method is endoscopic laser ablation. In balloon technologies, the balloon goes in the vein, and once it’s stable, the physician can manipulate its energy source to make circles of lesions in as little as three minutes. How to make an ablation catheter There are five elements in an endoscopic laser ablation catheter, such as CardioFocus’s HeartLight X3 system, www.medicaldesignandoutsourcing.com

allowing it to quickly ablate the pulmonary veins: the balloon, endoscope, sheath, laser energy source and motorized system. The balloon is a compliant balloon that has an adjustable diameter. The physician places it right at the pulmonary vein entrance in the left atrium, feeding it through the body on the end of a catheter using a deflectable sheath. A sheath guides the catheter and its device to the desired location. The HeartLight X3 ablation catheter, in fact, uses a sheath to deliver the balloon to the heart. Endoscopes give physicians a real-time view of balloon deployment to ensure accuracy. They insert the fiber optic device into a catheter at the beginning of the procedure and remove it at the end. It is a small compact device that gives doctors a good visualization inside the vein, Melsky told MDO. The laser energy in an ablation catheter like the HeartLight X3 makes permanent and durable lesions on the pulmonary vein to treat AFib. It’s possible to change laser energy dosing depending on where it is delivered to ensure that the vein is not over treated or under treated in any location. A motorized system enables laser energy delivery in an automated fashion to make a continuous ring of lesions around the pulmonary vein “very quickly” in less than three minutes, according to Melsky. The full ablation procedure starts with an ablation catheter inserted in the femoral vein and fed through a deflectable sheath that runs up the complete length 9 • 2021

Medical Design & Outsourcing

TUBING TUBING TALKS

of the inferior cava. The balloon threads through the inferior vena cava to the right atrium, where electrophysiologists do a transseptal procedure. They make a small puncture in the membrane that separates the left atrium from the right atrium. The catheter goes into the left atrium through the small puncture, with the balloon then deployed. Laser energy then ablates the afﬂicted pulmonary veins on the left side of the heart, creating circles of scar tissue to electrically isolate the pulmonary veins from the rest of the atrium. Melsky said that the laser ablation technique is less time-consuming than other methods of ablation like RF. “That takes a procedure that requires hundreds and hundreds of difﬁcult maneuvers to make many lesions and turns it into a procedure where you only have to make a small number of maneuvers,” Melsky told MDO. “That small number of maneuvers is getting the balloon into each of the pulmonary veins.”

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Overcoming technological the design, PVC may not bechallenges the best in making catheters option. ablation For industries where high purity Ittubing is important to to understand the is critical typical applications, anatomy of the vasculature system, other materials such as silicones or TPEs according to Melsky. are more typically seen. “We started out a while back trying to come up with a system that would Silicone make it very for thepure user material to create Silicone is aneasy extremely lesions around the vein, that processes intopulmonary very flexible, softbut there were a lot itofless unknowns atkinking the tubing, making prone to beginning the project,” Melsky said. than other of materials. It handles a wide “Probably the biggest unknown ‘What range of temperatures – from asis, low as does theup anatomy of –the vein looksilicone like, -100 °F to 500 °F and many and what meet does the interface between the products regulatory compliances balloon and the veinNSF lookand like?’” related to the FDA, USP. Silicone When prototyping the HeartLight is non-toxic, naturally translucent andX3 catheter, engineers started with such a catheter free of substances of concern as system thatand didn’t have endoscopic BPA, latex phthalates. The tubing visualization. As aand result, the device is also odorless tasteless and can didn’t workrepeated as well assterilization. the CardioFocus withstand Certain engineers hadofhoped. Without the imaging formulations silicone also perform very capabilities of theinendoscope, couldn’t well when used a peristalticthey pump. see how the balloon contacting the Silicone tubing was is typically broken tissue around pulmonary vein and into two mainthe categories, peroxide-cured where it delivered the laser energy. silicone and platinum-cured silicone.

the most tubing "Wedetermine started tosuitable make solution for an application, the best ideaprogress is to discuss yourreally needs with a supplier that has a wide breadth of rapidly. You start to product offerings, an understanding of and compliance requirements, thinkregulatory that really doing and a knowledgeable staff that can this complicated help recommend the most suitable tubing product to meet your individual ablation procedure in application needs. the pulmonary veins Alex Kakad until recently was a product is somanager much easier and at NewAge Industries (Southampton, Pa.). so much better and faster if you can get direct visualization of what you're doing."

the CardioFocus engineers elongation values and virtually unlimited BothOnce are widely used in medical device incorporated theoffer fiber-optic endoscope, flexural abilities. Polyurethane offers good applications and a high level of they see how the catheter system chemical resistance, and like silicone, its puritycould compared to other material types. was working. raw materials conform to FDA standards. However, peroxide-cured silicone does started make acid progress have“We low levels of to benzylic as a really rapidly,” said. “You Ifstart to Fluoropolymers byproductMelsky of its processing. the highest think that really doing this complicated level of purity is required, platinum-cured Another set of tubing products ablation inbest the pulmonary historically used in the medical device silicone isprocedure typically the option. veins is so much easier and so much industry is fluoropolymers, including better FEP, PFA and PTFE. These products TPE and faster if you can get direct visualization what you’re have a very high level of purity but Thermoplasticofelastomer (TPE)doing.” tubing are not as flexible or kink-resistant products are another good option if a The evolving catheter device high-purity, flexible tubedelivery is required. A compared with the other materials market discussed in this article. Fluoropolymer unique advantage to TPE tubing is that it The evolution ofor catheter ongoing, tubing products do have a set of very can be welded sealeddevices to itselfis using a Melsky said. for Balloon angioplasties, which involveunique properties, including extremely heat sealer use in sterile applications. a specialized catheter delivers a stent high tensile strength and burst pressure, Many versions of thisthat material also meetto blocked arteries, kick-started the as transformation, USP Class VI standards as well FDA a wide range of chemical resistance, and the continues to innovate. NSFspace requirements. and a high spectrum of continuous “It’s more evolutionary than operating temperatures (up to 500 °F). Combining properties of plastic revolutionary,” Melsky said.polyurethane “Whenever Choosing the right tubing for an and rubber, phthalate-free you have a speciﬁ problem that you have application can be a daunting task, tubing offers morec resistance to pressure to or ifthan yourcorresponding focus is makingsizes atrial as there are almost limitless options andsolve, vacuum ﬁ safe, fast and effective, it will have available, but very few candidates will ofbrillation PVC or rubber. It provides abrasion a lottear of value for thehigh patient.” meet all the requirements. In order to and resistance, tensile and

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Medical MedicalDesign Design&&Outsourcing Outsourcing 101 37

TUBING

3 pitfalls to consider when creating catheter delivery systems Multiple components go into a catheter delivery system, with several ways to combine them. An Edwards Lifesciences senior R&D director goes over potential pitfalls. Danielle Kirsh Senior Editor

catheter is a tube that can deliver devices or pharmaceuticals into the body. It is also commonly used for diagnostic purposes. A catheter has a hub or a handle on its end that can connect to a syringe or something that actuates a device. There are a number of catheter delivery systems currently on the market that deploy devices such as heart pumps, balloons, stents and other clot-busting products. The catheters need to be small enough to ﬁt through the blood vessels and ﬂexible enough to navigate the human body’s complex cardiovascular system. Sean Chow, a senior director of R&D at Edwards Lifesciences, told Medical Design & Outsourcing about three pitfalls that creators of catheter-based delivery systems should avoid: 1. Tangible prototypes are better than a computer screen. Computer programs can make every catheter design possibility seem easy — but the real innovation starts with building an actual model and testing prototypes.

Having a tangible prototype of a catheter delivery system allows an engineer to see the device’s shortcomings and feel what they can do, according to Chow. From there, an engineer can create new iterations of the device and improve. “If you can detect 95% of the failures in a model, then you won’t have a failure in humans. As you continue to iterate, it sparks more and more ideas,” Chow said. “You go from 95% confidence to 97% confidence to 98% confidence, 99.9% confidence. You just become more and more confident the more you use models.” You will eventually end up designing what your model has shown you. 2. Rigidity from guide catheters is essential for delivering devices through catheters. One can compare a catheter by itself to a rope, Chow said. Without any constraints, a rope won’t push toward the direction it needs to because it’s soft. The easiest way to push the rope is to create a tunnel. For catheter delivery systems, a guide catheter facilitates the movement of the soft catheters. Guide catheters are stiff and provide support for devices like balloons or stents to move into the complex anatomy of the human vasculature system. “A guiding catheter can really help you push something,” Chow said. “It doesn’t flop around as much when you have a guiding catheter. It’s unable to bow when it’s constrained on the outside.”

Edwards Lifesciences created its Commander delivery system for its Sapien 3 TAVI. Image courtesy of Edwards

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3. Follow the wire. Catheters need to be soft to get to distant structures of the body, but the softness makes the catheter more difficult to control. As a result, almost everything done in catheter delivery systems is about following the wire because variable stiffness is a very important part of catheter design, Chow said. “Imagine your catheter as a rope with a hole inside of it, like a coaxial hole that runs the whole way down. What you want to do is run that rope over a wire.” The torquability and variable flexibility of a guidewire allows a physician to maneuver the catheter into tortuous anatomies and control the direction in which it goes. When you have a catheter following that wire, the closer to the hand the catheter is, the stiffer it needs to be. The distal end of the catheter needs to be soft and the proximal end needs to be stiff. It is also important that the transitions between the stiff and soft areas are gradual in nature. “To follow the wire, design things that are soft on the part where it needs to go to be tracked,” Chow said. “As you go further and further back and closer to your hand, it needs to get stiffer and stiffer because you need something to push on.”

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SEAN WHOOLEY ASSOCI AT E EDI TOR

hen Abbott CMO and divisional VP of global medical affairs for its vascular business Dr. Nick West looks back at his use of drug-eluting stents in the early 2000s, all he sees is innovation. As a practicing interventional cardiologist, West remembers an earlier time in which the stents were barely deliverable. Each available platform had marked differences and each had its beneﬁts and drawbacks. “It’s fair to say that, if you look at the world of drugeluting stents, they’ve evolved enormously,” West told Drug Delivery Business News. “They’ve just changed hugely.” That evolution has led to Abbott’s latest version of its drug-eluting stent platform. The Xience Skypoint — which last month received FDA approval and the CE mark — is touted as easier to place while allowing physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively. Additionally, Abbott recently received FDA approval for one-month dual antiplatelet therapy (DAPT) labeling using the Xience family of stents, with the FDA’s approval for one-month (as short as 28 days) DAPT labeling applying to high bleeding risk (HBR) patients in the U.S. The major difference, West says, comes in the form of more than 15 million implants of the stent platform over the years, plus more than 120 clinical trials to back it up.

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Image courtesy of Dexcom

Abbott’s Xience Skypoint stent Image from Abbott

DRUG-ELUTING STENT

“The Xience drug-eluting stent platform is probably the class-leading, best-in-class drug-eluting stent,” West said. “It has an unrivaled quantity and quality of data behind it. “Compared to any other platform — and I’m not just saying this as a promotional thing — we have an unrivaled quantity of data. More than that, we have up to the minute data.” West said the early days of drugeluting stents saw dual antiplatelet therapy periods vary from platform to platform, with decisions made less on evidence and more on the original trials conducted. Six months and four months were early DAPT ranges, while around 15 years ago, concern over higher rates of stent thrombosis was put down to patients not continuing antiplatelet therapy for long enough, so the knee-jerk reaction was to set DAPT time at 12 months with indeﬁnite aspirin treatment after that.

A dichotomy of schools of thought soon came, with one side pushing for longer antiplatelet therapy to reduce the risk of the stent clotting and heart attack, with a downside of a higher risk of a bleeding event. West pointed out

With this in mind, Abbott sought a solution for providing this necessary therapy without keeping the risk of bleeding beyond a month. The company with Xience managed to shorten the duration

"We're saying that, for those patients with HBR, where a bleed can be catastrophic, you can have the security of knowing that you can stop [antiplatelet therapy] as early as 28 days without penalty." that the HBR group of patients, who take a combination of blood thinners for antiplatelet therapy — a large population, given that anyone over the age of 75 is considered a bleeding risk — demonstrate the need for a different avenue with DAPT.

of dual antiplatelet therapy, ﬁrst to 90 days and now 28 days, with patients staying on aspirin beyond those time periods. Studies of both ranges of time showed similar outcomes, with no penalties in ischemic outcome, stents

DRUG-ELUTING STENT

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Medical Design & Outsourcing

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cutting off, heart attacks and the need for revascularization, while the risk of bleeding was lowered. “We’re not saying everyone should necessarily shorten their antiplatelet therapy,” West said. “We’re saying that for those patients with HBR, where a bleed can be catastrophic, you can have the security of knowing that you can stop as early as 28 days without penalty.” Part of the Xience platform’s success, West said, comes from the fact that the platform, rather than undergoing wholesale changes, has remained similar over the years with only slight deviations, meaning the FDA has not required additional investigational device trials for validation. The platform uses the same ﬂuorinated copolymer with proven antithrombotic qualities, plus everolimus, a cytostatic drug designed to stop cells from reproducing, thus stopping vascular renarrowing or restenosis. Changes for Xience Skypoint came in the form of better stent retention on the balloon, ensuring that the stent does not come off the balloon during deployment, as West said some stents shorten after deployment. Xience Skypoint was designed not to shorten in any way. “We’ve now got the whole package,” West said. “We’ve not only got an up-tothe-minute stent platform with all of these great features that make a clinician’s job easier when they’re putting it in, but it’s backed by a vast quantity of clinical data both in terms of safety and efﬁcacy.” As always, West expects more evolution to come with the Xience platform, although focus may shift from the stent itself — which he said is “about as optimal as it can be” — to the pharmacology and the use of other technologies, including intracoronary imaging with Abbott’s AI-based optical coherence tomography (OCT) platform for guiding the implant. West said there’s not necessarily nowhere to go with the stent, but changes can still come down the line. “We never stand still in terms of innovation,” West said. “We’re always interested in innovating to generate devices that can meaningfully impact patients’ lives. That’s desperately important.”

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Dexcom CEO says G7 will be

SEAN WHOO LEY ASSOCI AT E ED I TO R

D As we enter what may be the “new normal,” Dexcom’s CEO bets the company can pave the way in continuous glucose monitoring.

excom, like any company seeking to innovate, remains in a state of perpetual forward motion. That’s the way Dexcom Chair, President and CEO Kevin Sayer views it, anyway. As the company looks toward the future, the G7 continuous glucose monitor is the next big thing. San Diego–based Dexcom’s latest iteration of its CGM system — building on the G6, which ﬁrst won FDA approval in 2018 — has inspired plenty of optimism, both within the ranks of Dexcom and likely among customers, too. “The enthusiasm here is at an all-time high for a new product,” Sayer told Drug Delivery Business News. “We’re ready to go. It’s really going to be wonderful.” Data presented during the 14th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) highlighted the accuracy and timein-range capabilities of the G7. Sayer said that the data presented at ATTD was “better than any G6 data” the company presented before.

"The enthusiasm here is at an all-time high for a new product. We're ready to go. It's really going to be wonderful." The G7 wearable CGM — which is roughly the size of a coin — measures 60% smaller than the G6. It contains a smaller all-in-one sensor applicator and transmitter with a 30-minute warm-up time before use, according to Dexcom. It also possesses interoperability with insulin delivery devices as it maintains accuracy. 108

Medical Design & Outsourcing

9 • 2021

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Image courtesy of Dexcom

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