MPN NA Issue 6

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N AMERIC AN EDITION

MEDICAL PLASTICS news

D R ES S ED FO R SUCC E SS

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Accumold explains how micro molding became the perfect accessory for wearable manufacture

DIGITAL HEALTH: WHY THE SMART MONEY’S ON FEMTECH THE LATEST ON IMPLANT TECHNOLOGY

ISSUE 6

Apr/May/Jun 2018

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CONTENTS MPN North America | Issue 6

Regulars

Features

3 Comment Lu Rahman looks why standards are high in the medical device sector

19 Why the smart money’s on femtech A new report stresses the value of this sector

5 News focus Why AR and VR are set to transform the medical device sector

22 For what it’s worth How in the value-based medicine race, Xenco Medical has emerged with a novel way to win

13 Opinion Aaron Johnson, Accumold and the ABHI offer industry insight 16 Cover story Accumold highlights the value of micro molding in the manufacture of sensors 32 Back to the Future

25 Smart objectives Renishaw discusses how smart implants are changing the way bone diseases and injuries are treated 27 The future of medical implants AMSilk and NuSil outline some of the latest developments in implant technology

30 The future is here Lu Rahman explains how 3D printing is still having a marked effect on medical device manufacture 33 Inside information Cikautxo Medical OEM explains the benefits of integrated sensors in catheters 34 It’s the little things that mean a lot Raumedic explains how the company is focussing on a complete systems approach to micro molding 39 What’s on offer at NPE 2018

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CREDITS

EDITOR’S

comment

head of content | lu rahman deputy group editor | dave gray reporter | reece armstrong advertising | gaurav avasthi art | sam hamlyn graphic design | matt clarke publisher | duncan wood Medical Plastics News is available on free subscription to readers qualifying under the publisher’s terms of control. Those outside the criteria may subscribe at the following annual rates: North America: FREE UK and Europe: $249 Rest of the world: $249 subscription enquiries to subscriptions@rapidnews.com

Medical Plastics News is published by: Rapid Life Sciences Ltd, Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE T: +44(0)1244 680222 F: +44(0)1244 671074 © 2018 Rapid Life Sciences Ltd While every attempt has been made to ensure that the information contained within this publication is accurate the publisher accepts no liability for information published in error, or for views expressed. All rights for Medical Plastics News are reserved. Reproduction in whole or in part without prior written permission from the publisher is strictly prohibited. ISSN No:

2047 - 4741 (Print) 2047 - 475X (Digital)

Why the standards are high in the medical device sector

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e’re getting ready for the Med-Tech Innovation Expo here at MPN – we’ll be back at our desks by the time you read this! Run by our sister team and publication Med-Tech Innovation News, the event offers some of the best solutions for the healthtech and medtech supply chains and allows medical device manufacturers to partner with some of the most innovative companies in the UK and Ireland. Take Blue Frog Design for example, which has made use of 3D printing to help a patient with an ongoing skin condition. The patient was suffering from paraesthesia, a skin condition that causes tingling, tickling, numbness and burning sensations for no apparent physical reason. Blue Frog Design was able to 3D print a structure that stopped the patient’s clothes from touching his upper body, removing the irritation and improving his quality of life. It’s a great example of the way the medtech sector innovates in response to medical need. Long gone are the days of devices like the Mallam Scarificator. This four-bladed device was dipped into the pustules of someone carrying small pox, and was then stabbed into the arm of a child. Or what about the Ecraseur which was used in the nineteenth century to strangle hemmorhoids, uterine and ovarian tumors by placing a wire around the unwanted growth? Thankfully we’ve definitely

come a long way. Take the team of researchers at Leicester University as an example – they’ve been looking at how clinicians and scientists have been using near-patient and remote sensing technologies to analyse breath samples to better diagnose cardiorespiratory disease. Medtech now is designed to benefit the patient without hurting them, which has to be a good thing. It’s this kind of innovation that makes this sector a pleasure to work in. On a daily basis we hear about devices and technological advances that are designed to safeguard our health and boost our well-being. I have to admit it’s not always the case. I recently received information about a vaginal speaker designed to communicate with a foetus. I’m sure there’ll be many people out there that might think this is a useful product. Unfortunately I’m not one of them. Or what about the bracelet that produces negative ions to counteract the effects of positive ions we may encounter? Scientifically the jury’s out as to the harmful effects of positive ions but my question is, just how effective can a bracelet be at doing this if they are a danger to our health?

On a daily basis we hear about devices and technological advances that are designed to safeguard our health and boost our well-being.

Possibly I’m a sceptic but I guess when you work in a sector that’s filled with groundbreaking innovation, the bar is well and truly raised. Keep the innovation coming.

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NEWS FOCUS

WHY AR AND VR ARE SET TO TRANSFORM THE MEDICAL DEVICE SECTOR

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Tim Jennings, Custom Case Group explains how these technologies could impact medtech

ugmented reality (AR) and virtual reality (VR) have seen tremendous growth in the last several years, and the hype surrounding them is only increasing as their possibilities continue to make themselves apparent. But AR and VR aren’t new. In fact, people have been using and improving them for quite some time. From early audiovisual flight simulators in the 1950s to the first VR headsets in the 1990s, devices that layer analytics or data onto the real world or create a new reality entirely have been in use for both entertainment and training purposes for decades. The concept of manipulating reality might not be novel, but how it’s being executed is. Modern high-definition screens can render rich images that are nearly indistinguishable from in-person visuals, and the sheer power and ubiquity of today’s devices would have rendered users 20 years ago dumbstruck. Blazing-fast smartphones with expandable memory would put the computers of the early 2000s to shame, and they’re in almost every hand. Consumers and enterprises have access to a level of power that makes AR and VR more feasible and effective than ever before.

storm in 2016) aren’t novel anymore – they’re commonplace. Virtual reality headsets, once heavy and often burdened with a range of peripheral accessories and sensors, are now far more selfcontained, and continue to get lighter and even more portable. Clinical skills training that would have previously taken place in a full simulation room covered floor to ceiling in specialized hardware can now happen with a headset paired with wearable connected devices to sense motion. Portable vital-signs-monitoring devices and automated diagnostic programs using smartphonecaptured visuals are making practicing medicine possible anywhere.

hefty sum, more mundane items like headsets and wearables continue to become more affordable. Richly detailed VR headsets that would have been under lock and key at a government facility 10 years ago are on sale for several hundred dollars to interested consumers – and the price is dropping every day, even as the technology becomes more sophisticated.

Lightweight but durable plastics and polymers are vital to the comfort and usability of many of these devices, and materials innovation should pay off in coming years.

Versatility From facility-sized systems that project a digital layer onto connected mannequins and simulated surgical devices to lightweight wearables that provide medical insights based on vital-signs monitoring, AR and VR devices vary widely in where and how they’re used. For the most part, the only true limitation of AR and VR is human creativity. Any medical scenario could potentially be simulated for learners, provided that someone is willing to program its functionality. Pediatric cancer patients who are confined during chemo can travel anywhere with a headset, provided that someone is able to render visuals rich enough to carry the patient away. These technologies can do so much if innovators are willing to reach out and take the opportunity.

Accessibility Accessibility can mean two things, and one is price. While the most sophisticated AR and VR technologies – like those that are used in detailed surgical simulations, for example – may cost a

While the most publicized inroads into the potential of AR and VR technologies have taken place in entertainment, things have gotten serious, too. AR and VR are making waves in the medical industry – and making a transformation of the entire medical device industry more and more likely. Here are three key areas of potential that will make AR and VR a monolithic presence in the medical device industry in the coming years:

As manufacturers respond to rising demand and get smart with lighter materials and more economical designs, AR and VR technologies have the potential to be remarkably affordable (and thus, accessible).

The more that these technologies do, the more refined they become. The more refined they become, the more willing health care organizations will become to adopt them. This cycle is already underway, and staying aware of how AR and VR are evolving will be a crucial part of participating in the new reality that they’ll undoubtedly create in the coming years.

Portability AR is already living on phones and in wearables. Connected devices add a digital layer to the world around us through wireless networks, GPS data and image capture. AR apps (like a famous monster-catching game that took the world by

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DIGITAL

MATERIAL UPDATE

spy

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Covestro develops versatile plastic for glasses

TECHNOLOGY UPDATE

Team spirit ONTARIO PARTNERS WITH MEDICAL DEVICE COMPANY

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ntario, Canada is partnering with Baylis Medical Company to build a new facility and expand its product development.

that will be produced for the first time, anywhere in the world. It will also help the company expand into new international markets in Europe and Asia.

Steven Del Duca, minister of economic development and growth, made the announcement at Canada’s MedTech Conference in Toronto.

“Ontario is becoming a global magnet for medtech innovation thanks to homegrown companies like Baylis. Together, we are transforming Ontario’s health system by accelerating the development and adoption of new health technologies that can improve the lives of patients and create jobs,” William Charnetski, chief health innovation strategist for Ontario.

Baylis Medical develops and manufactures medical devices that are used in cardiology, radiology and spinal procedures. It is one of the few medtech companies with both research and development (R&D) and manufacturing operations in Canada. With support from Ontario’s Jobs and Prosperity Fund, the company is expanding its footprint in Mississauga with a new Baylis Medical Innovation Center that will centralize the company’s R&D activities. This expansion will allow Baylis Medical to develop a number of new product lines, including four technologies

“We are pleased to partner with the Ontario government on this expansion, which marks a significant next chapter in the development of our company. The Baylis Medical Innovation Centre will sharpen our competitive edge as we continue to expand our international reach and position our company as a global leader in the medtech sector,” Kris Shah, president, Baylis Medical Company.

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olycarbonate is an ideal lens material for corrective eyeglasses and sunglasses: It is lightweight, impact resistant, durable and comfortable. Covestro has developed special lens-quality grades of its Makrolon polycarbonate designed to offer excellent optical properties, high mechanical strength, toughness and comfort. Jiangsu Sigo Optical Co upgraded the polycarbonate material used for its corrective and sunglass lenses, and turned to Covestro Makrolon

High optical purity grade For corrective lenses, Jiangsu Sigo Optical utilizes Makrolon DP1-1821 polycarbonate, which is formulated specifically for the ophthalmic market. Available in clear tints, the material offers high optical purity, transmission and scatter resistance and UV stabilization. In processing, the material is distinguished by its high viscosity and easy release from the mold.

EVENT UPDATE

NPE 2018 promises commitment to waste

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www.npe.org

he Plastics Industry Association (PLASTICS), producer of NPE2018: The Plastics Show, has announced a 100% waste diversion goal for this year’s NPE, which will welcome more than 65,000 plastics professionals to the Orange County Convention Center (OCCC) in Orlando from May 7-11. The goal demonstrates the association’s commitment to sustainability and aims to exceed the 87% of waste that was diverted from NPE2015.

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polycarbonate resins for improved optical purity and production yield.

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“Plastics are a valuable resource that should always be recovered for their highest and best use,” said PLASTICS president & CEO, William Carteaux. “At NPE2018, we’re practicing what we preach, putting sustainability and recycling at the center of the event, from the forward-thinking educational programming of the co-located Re|focus Sustainability & Recycling Summit, to our ambitious goal of diverting 100 percent of the waste from the show.”


DIGITAL SPY

DIGITAL LISTENING

www.soundcloud.com/medtalkpodcast

Sound you out Latest MedTalk podcast out

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f you haven’t already listened to the Medtalk podcast, where have you been?! Episode 9 is now out and the MPN team along with sister publications, EPM, MTI and DigitalHealthAge.com discuss some of the key issues in the sector. In this episode find out why doctors have been protesting about an online app in the UK and how it links to the CQC’s recent investigation into the safety of online pharmacies.

Fliss Thomas, editor of EPM, talks about Martin Skhreli’s sentencing and gives some more insight into the scandal surrounding #Pharmabro. Finally the team gets their geek on and talks about what the bionic body of the future looks like and imagined what it would be like to make exact copies of our brain – essentially becoming immortal.

talking

POINT

Can this medical device help tackle the US opioid epidemic A MEDICAL DEVICE USED TO TREAT CHRONIC PAIN THROUGH LOW-LEVEL ULTRASOUND COULD HELP FIGHT THE OPIOID CRISIS IN THE US. What’s the device? The PainShield device, developed by medical device company NanoVibronix, is a drug free wearable that emits a slow release ultrasound that targets the cause of nerve and soft tissue pain.

EVENT UPDATE

Two become one New event for medtech set for Nuremberg

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edtecLive is set to launch in 2019 and will replace the organisers’ previous exhibitions, Medtec Europe, Stuttgart, and MT-Connect, Nuremberg.

Does it work? It would seem so. The product is being backed by former Major League Baseball professional, Mariano Rivera, who became interested in the device after his wife began suffering from back pain. Speaking to Fox News, Rivera said that his wife’s symptoms began to improve when she started using the device. So what next? After this, Rivera pitched PainShield to president Trump as a new way to fight the opioid addiction in the US.

The show will provide a new platform that champions networking with industry experts and showcases cutting edge medical innovations.

“We’re fighting opioids, but we don’t know what we’re going to do after that. The best thing is using our product, [which] is safe and handy. We have to move toward alternatives,” Rivera said.

About the new partnership, John van der Valk, managing director of UBM EMEA Amsterdam, said: “As per current proposal, the advantage of MedtecLive will be that all important national and international players in the medical technology industry will come together in one place. This will save time and money for our customers and provide a 360-degree view of the entire industry.”

The device could be used to combat pain, potentially negating the need for opioids and reducing the number of potential addictions,

Dr Roland Fleck, CEO of the NürnbergMesse Group said: “It makes us

proud that MedtecLive shall take place in Nuremberg as of 2019. Conveniently located in the heart of two of the strongest medical device manufacturing hubs in Europe and Germany, Baden Wurttemberg and Bavaria, MedtecLive is set to provide the European platform for the medical device industry.”

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In 2017, the opioid crisis was announced as a public health emergency by the US Department of Health and Human Services. In 2016 there were over 63,000 drug overdose deaths in the US, according to the National Centre for Health Statistics

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NEWS FOCUS

MD&M East sits within Advanced Manufacturing New York, the East Coast’s advanced design Taking place in New and manufacturing event. York on 12-14 June, This year its organisers this year’s event have announced the introduction of three promises to offer the new education hubs that medtech visitor high bring conference-level quality and unrivalled education to the expo expertis floor. With a full schedule of content across all three days of the event, the education hubs are, focused on medtech, smart manufacturing, and packaging. The event takes place 12-14 June at Javits Convention Center. “The education hubs are an exciting development for us as it’s the first time we’re bringing a complete and robust line-up of conference-quality content to the expo, free of charge for all attendees. Not only will this give all our attendees the opportunity to experience high-level presentations on the latest industry trends, but it will also bring more action to an already lively expo floor,” said Nina Brown, vice president of events, UBM. “We encourage all of our attendees to take full advantage of this unique opportunity to learn from industry leaders.”

Medtech Education Hub:

Smart Manufacturing Education Hub:

Developed for medical device engineers working in R&D, design and product development, the Medtech Education Hub offers top-notch education from industry experts. Attendees will have the opportunity to learn about the latest innovations and breakthroughs affecting the medical device industry today. Highlights Include:

Advancements in technology are rapidly changing the way we manufacture, and the Smart Manufacturing Education Hub will drill-down on the key innovations and solutions that are transforming the manufacturing industry. Presentations will cover important topics such as big data, robotics, artificial intelligence, the Internet of Things, IIoT, machine learning, smart sensors, and the digital twin. Highlights Include:

• How artificial intelligence (AI) is moving the needle in medtech This panel discussion will cover AI and medical devices, and its potential impact on the industry landscape. This session will also focus on challenges surrounding AI applications in imaging, surgical robotics, neurological disorders and other use cases. • Top trends to watch in medtech: Innovation and consolidation Medtech is at the crossroads of healthcare and technology, and, through innovation, new technologies can change how healthcare is delivered through medical devices. Learn about the latest trends and what’s coming down the pike in this ever-evolving industry.

• Learning from nature: The mechanics behind the robotic zoo Leading automation companies have been creating a menagerie of bionic animals and insects; this presentation will demonstrate how these robotic creatures help audit current trends in R&D, test new technologies and manufacturing methods, and encourage creativity in product development. • Mobility: The driving force behind the growth in collaborative robotics This session will look at the growth in demand for collaborative robotics, mobility’s significant role in this growth, and whether robots will ever fully take over manufacturing jobs. Packaging Education Hub: Professionals across a variety from industry including medical devices and pharmaceuticals will benefit from the Packaging Education Hub to stay on top of the latest packaging trends, technologies, and materials, and will learn from best practices in the business. Highlights Include: • Just How hard is it to open a medical package aseptically? Medical device packaging contains a sterile barrier system to lock out microorganisms, making it nearly impossible to open packages without instant contamination. In this live demonstration, attendees will see how medical packages can be opened aseptically.

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NEWS FOCUS

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Trade mission helps US companies do business in UK

leading health technology trade association in the UK, the ABHI, is hosting an inward trade mission to help US companies accelerate the speed at which they enter the UK. The weeklong Pathfinder Program will connect UK healthtech businesses to hospital systems in key cities, as well as a comprehensive overview association of the UK market, remuneration systems, launches regulation and guidance on navigating pathfinder Brexit.

program

Mission participants will also have access to ABHI’s International Membership scheme, providing companies with year-round support and access to the association’s network of connections. ABHI coordinates several outbound missions to the United States each year, which has seen significant partnerships in some of the nation’s largest states, as well as the establishment of an Innovation Hub at Austin’s Dell Medical School. The Pathfinder Program, running from 18 – 22 June 2018, now sees the association extend its deep UK market knowledge to US companies. Paul Benton, ABHI’s managing director of international said: “We are a country steeped in academic excellence, and in the NHS, we have the biggest single-payer health system in the world. By actively developing a sustainable two-way trading bridge, we can connect pioneering US companies with the right UK partners. ABHI’s Pathfinder Program is a terrific opportunity for those looking to collaborate, learn and accelerate their business this side of the Atlantic”.

Commencing at the new US Embassy, the mission will take in visits to healthcare hubs, including London, Cambridge and Birmingham. Commenting on the Program, Verena Kallhoff, manager of the Health CoLab at University of Texas Dell Medical School said: “ABHI has demonstrated a strong commitment to transatlantic partnerships and collaboration. For US companies looking to access the highly dynamic UK market, ABHI is uniquely positioned to provide expert levels of guidance, insight and support. No other trade association has the knowledge, credibility, and connections to the UK health system like ABHI.” Tony Davis, commercial director of West Midlands Academic Health Science Network added: “The Academic Health Science Network is delighted to support ABHI’s inward mission which will build on the UK’s strengths in health technology.” Supporting partners of the Pathfinder Program include: the US Commercial Service, AdvaMed, the UK’s Department of International Trade, the Academic Health Science Network, National Institute for Health and Care Excellence (NICE), Medicines and Healthcare products Regulatory Agency (MHRA) and National Institute for Health Research (NIHR). For more information on the UK Pathfinder Program, contact david.phillips@abhi.org.uk.

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NORTH AMERICA EVENT CALENDAR

MAR 7–8, 2018 // CLEVELAND, OH

OCT 31–NOV 1, 2018 // MINNEAPOLIS, MN

Advanced Design & Manufacturing Expo featuring ATX, Design & Manufacturing, MD&M, Pack, PLASTEC

ATX Minneapolis, Design & Manufacturing Minneapolis, ESC, MD&M Minneapolis, MinnPack, PLASTEC Minneapolis

APR 18–19, 2018 // BOSTON, MA

NOV 14–15, 2018 // MONTRÉAL, QUÉBEC

BIOMEDevice Boston, Design & Manufacturing New England, ESC

Advanced Design & Manufacturing Expo featuring ATX Montréal, Design & Manufacturing Montréal, Expoplast, Montréal Powder & Bulk Solids, PACKEX Montréal

HUNTINGTON CONVENTION CENTER OF CLEVELAND

BOSTON CONVENTION & EXHIBITION CENTER

APR 24–26, 2018 // ROSEMONT, IL

MINNEAPOLIS CONVENTION CENTER

PALAIS DES CONGRÈS DE MONTRÉAL

DONALD E. STEPHENS CONVENTION CENTER

International Powder & Bulk Solids

DEC 5–6, 2018 // SAN JOSE, CA SAN JOSE CONVENTION CENTER

JUN 12–14, 2018 // NEW YORK, NY

BIOMEDevice San Jose

Atlantic Design & Manufacturing, ATX East, EastPack, MD&M East, PLASTEC East, Quality Expo

JANUARY 29-31, 2019 // SANTA CLARA, CA

SEP 11–13, 2018 // NOVI, MI

FEB 5-7, 2019 // ANAHEIM, CA

The Battery Show, Electric & Hybrid Vehicle Technology Expo, Critical Power Expo

ATX West, MD&M West, Pacific Design & Manufacturing, PLASTEC West, WestPack

JACOB K. JAVITS CONVENTION CENTER

SUBURBAN COLLECTION SHOWPLACE

SANTA CLARA CONVENTION CENTER

DesignCon

ANAHEIM CONVENTION CENTER

348345 AS18_NA

For more information please e-mail us at: amgpartners@ubm.com 12

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ALL IN A DAY’S WORK

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hen it comes to supply chain management, finding and adding new suppliers can be daunting. The traditional costs and risks associated with bringing on a new supplier can be real and for those of us trying to get things done, this can stifle progress. Thankfully, it doesn’t have to be this way. Over the years, we’ve collected three big keys to make this process smooth and to leverage it as a competitive advantage. 1. LEVERING SUPPLIER KNOWLEDGE

This issue, Aaron Johnson, Accumold, explains how to maintain a competitive edge while adding new vendors

In most large organizations there is a concentrated effort to reduce the numbers of suppliers in their system. Your team has likely gone back and forth on what makes one vendor more valuable than another, making decisions cloudy and uncertain. We’ve discovered a great strategy is simply to leverage the most knowledgeable person on your team – the potential supplier! It might sound unorthodox, but most suppliers would jump at the chance to visit a potential customer. They are fully capable of giving everyone deeper understanding giving the purchasing managers an opportunity to see the value too. You’d be hard pressed to find a supplier that wouldn’t

One step AHEAD

travel to close a big project. Some organizations even have a structure where R&D or engineering can source their own suppliers, especially if it’s something specialized. This can be a fantastic opportunity for all involved as long as you are up front and honest on expectations with this potential supplier. Assuming the seller’s business isn’t just prototyping, make sure to help your potential new supplier understand how to navigate your organization for the longterm of the project. Establishing a trustworthy relationship at the points is key, which leads us to the second key. 2. LEVERAGE THE FIRST IMPRESSION Every supplier wants to steer the conversation about capability and, of course, your buying team will want to obsess about price, leaving engineers stuck in the middle. Avoid your price obsession as much as possible however. If you are looking to add a supplier, chances are this means the service is not already in your database and that there is a special nature to this purchase, therefore the deal will eventually be less about price and more about capability. Our experience indicates the most important aspect in these arrangements is trust, which comes through relationships. Sure, if you’re buying commodity widgets from the lowest supplier, order online and be done. However, if you’re looking for a special partner for a critical component that will be the next generation life of the company… get to know the supplier and avoid souring the relationship you will need, which leads us to the third and most important key… 3. LEVERAGE THE RELATIONSHIP The most obvious factor when bringing on a new supplier is to

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ensure they have the capability, scalability and sustainably your company needs for the future, but what is often overlooked is to ensure you want to be around them in the first place! Make sure to walk them through your plant and see if they work well with your team. The lone seller and buyer scenarios are rare these days. Today it’s about team selling and team buying. Every sales seminar that teaches supplier sellers how to penetrate organization buying structures is juxtaposed with a seminar for purchasing managers on how to avoid the traps of a good salesman. It’s a reality of business. Each one must work in the best interests of their own company, yet somehow, you need each other to survive. Both the buyers and sellers need to remember a new relationship is like a first date. Pushy suppliers, drowning in their organizations Kool-Aid aren’t shy about how wonderful their product or service might be, but you won’t share that view, at first. Trust however, will ensure that time comes as the process flourishes. And buyers will need to remember they’re probably not going to get the price they want out of the gate either. Deals like this have two sides and beating up someone on price is a great way to lose a great partner. New relationships come with a measure of risk and as the relationship strengthens so will the understanding, At the end of the day we all have tasks to accomplish, but we need each other to be successful. Finding that right supplier can be difficult, but it can be very rewarding in the long run when you leverage supplier knowledge and nurture a real authentic relationship. Win-win does exist and it’s in the form of suppliers who become an extension of your team. 13


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Playing by the rules What you need to know about EU regulation

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or a product to be placed on the European market, it must meet the requirements outlined in the relevant regulation and be affixed with a CE Mark. The current EU regulation for health With many technologies is undergoing North American change, with the existing companies looking Medical Device Directive (MDD) to do business being replaced by the new Medical Device Regulation in the European (MDR), first published in 2017.

market, Phil Brown, ABHI director, technical and regulatory, outlines some of the regulatory considerations that need to be taken into account

The culmination of eight years’ work, the MDR will ensure that European regulation for devices is considered the ‘gold standard’ globally. For our industry, this new regulation modernises the original MDD rules, bringing together best practices from existing Commission guidance whilst covering newer technologies such as nano-materials and human tissue derivatives. The updated requirements demand a more robust compliance with elements of quality management, risk management, distribution control, transparency, post-marketing surveillance and training. These elements are now ingrained within the business process, ensuring that CE Marking has a more holistic feel.

OPINION In conjunction with the transition timelines, there are several aspects that companies need to address to allow for the future CE Marking of their products. However, until May 2020, either the new MDR or the old MDD can be applied to medical devices being placed on the European market. Beyond May 2020, all new products must comply with the new MDR. This all sounds reasonable and logical of course, but there are caveats and nuances that impact on these timeframes and that will influence company strategies surrounding their product portfolio. For example, a notified body that will certify ‘conformity assessment’ of a product or quality system, must apply to be accredited under the new scheme. Only accredited bodies can issue certificates against the new MDR. This application and accreditation period is underway, with the first notified body accreditation expected towards the beginning of 2019 at the earliest. This does not leave a great deal of time for companies to organise certification and CE Marking against the MDR and requires early dialogue with their notified body. This, before we consider the overall capacity of notified bodies. One standard of the ‘new legislative framework’ is EN ISO 13485, which controls the quality management system of a manufacturer. Quality management considers all aspects of the manufacturers activities, from product conformity to management responsibilities and actions. Unlike the MDD, the new regulation includes aspects of quality management within its legal text. The regulation demands details of quality objectives, organisation of the business, design and development, as well as details on post-marketing plans and activities. The ‘declaration of conformity’ therefore, which is the legal document stating that a given product is compliant with the regulation, demands that aspects of management review and business practice are carried out, and that these aspects are audited by the notified body. The signatory to the ‘declaration’ must be cognisant of such processes to be assured that compliance requirements are met.

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The MDR also requires manufacturers to have greater control over the distribution of their products. All ‘economic operators’, which includes the manufacturer, authorised representative, warehouses, importers and distributors, have defined roles and responsibilities. Indeed, all have a responsibility for ensuring that only products that are MDR compliant are placed on the EU market. Manufacturers must have complete transparency of their distribution network, including sub-distributors. In addition, the authorised representatives must have a ‘person responsible for regulatory compliance’, who effectively releases only conforming products onto the EU market. Post marketing surveillance is considered as both reactive and pro-active, in that it covers vigilance and adverse effects, as well as continual monitoring of products in use. Both are critical to understanding how a product performs and how product ‘risk’ changes. The MDR requires that these processes are audited by the notified body, as they form part of the legal text rather than part of European guidelines. A company must also have plans for conducting post-marketing clinical followups either to verify or enhance product performance. These activities are then used to update risk management documentation, drive product development processes and determine lifecycle needs. In addition, the MDR mandates the development of a database called EUDAMED, which when fully implemented will house data on vigilance, clinical performance, clinical investigations and product literature. Certain parts of this data will have to be made publicly available, which will certainly help to debunk the mystery of medical devices!

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COVER STORY

ith an increase in media attention, and reports indicating the wearable market could double by 2021, big questions are being raised that the medical industry hasn’t had to consider in the past. Does this affect medical devices and should we be paying attention? Where are the opportunities? Which designs and materials are best? Fortunately, as an enabling technology micro injection molders have a unique perspective you aren’t likely to find from your R&D department. Most of us have a daily, hourly, or by-the minute interaction with at least one wearable device. Asking how this affects the medical device industry and the supply chain as a whole is certainly an important question, but if you’re smugly reading these words, thinking you were just left overlooked in this sweeping generalization, this raises the first question. Are you even sure you know what a wearable is? Big Question 1: What is a wearable? No, really… There is a notion that wearable technology is a modern construct, but this is only partially true. Smartwatches and fitness trackers have hit the market in a big way. And in recent years their popularity has given prominence to this sector, paving the way for new connected device. However, they don’t exclusively make up the wearable category. Wearable technology has been around for a long time. A pedometer is perhaps the oldest wearable we think of, and in the medical space the humble hearing aid is certainly a wearable piece of tech that is often overlooked. Even insulin pumps and

pace makers are technically considered a ‘wearable’ and they have been on the market for decades. Your cell phone, with its accelerometer meant to monitor your activity is also a wearable. We just didn’t call these devices wearables. So, where’s the line? When looking at the modern offerings there are a couple of common traits that seem to get us closer to understanding how we might draw the wearable line today. First, there is a measure of “smartness” to the device. While the term “smart” is somewhat overused, it does at least tell us there is more than a passive element to some devices. In some way wearing this device will provide real-time feedback that it can interpret, alert and/or react in a way that goes completely unnoticed. Another common trait is connectivity. Most devices are either collecting data for analysis or connecting to another device, like your phone, for enhanced features, or it’s doing both. Connectivity takes a smart device that can interpret on its own and allows it to share its smarts with the user, a doctor and perhaps the world. It doesn’t necessarily have to be a wireless, continuous connection, but in some fashion, provide on-going benefit to the user. Big Question 2: Where are the challenges and opportunities in these markets? Some of the biggest challenges for the industry also create some of the biggest opportunities. From a market driven point of view the challenge lies in the question, ‘what else does the device do?’ Start with notion that if a device is already going to be on our body, what else can it do for us? For example, if a hearing aid is already

Aaron Johnson, VP marketing & customer strategy, Accumold takes an in-depth look at the wearable market, its rise in popularity and the knock-on effect it has had on the micro molding sector

DRESSED FOR SU How micro molding became the perfect accessory for wearable manufacture

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COVER STORY giving us hearing, why not have it count steps, check our heart, take our temperature, etc. Some of these features and more are already in these devices. The challenge lies in the ‘so what’ factor. How many devices do we already own that can provide the same data? Consumers will not need, or even want six different ways to count their steps and therein lies the rub. The competition for which device does what will be strong in the coming years and the most elegant solution will win the game. The phone in your pocket is currently your TV, radio, computer, camera, fitness tracker and your…. oh yeah, phone. The second big challenge and opportunity will be in manufacturing. Consumers want more benefit in smaller devices and this stands to put added strain on your supply chain. The opportunity will come when you find partners, that fit more detail it tighter spaces. This is the world we live in and we know partners that can help you push the limits of design for manufacturability to give you that competitive edge are more valuable than ever. This will be a gating factor. The concepts and technology exist in many cases, getting it all to fit is the challenge we continue to chase. Big Question 3: Is the sector under any threat from overseas competition or regulation? The world of manufacturing seems to be in a form of paradigm shift when it comes to where and how things are made. There is no real distinction when it comes to medical devices or wearables that overseas competition isn’t already tackling. Those factors will continue to face the industry and it will evolve along with it. The bigger threat is regulation. It’s not that regulations are changing at an increasing pace – consumer demand is – and that’s the challenge. It comes down to what defines a medical regulated device. Most smartwatches or fitness tracker have built in heart rate monitors that are not technically ‘healthcare devices’ yet consumers are using them without considering the technical status of the component. Indeed, some consumer tech companies are partnering with medical institutions. Studies have shown that some consumer grade components are very accurate and most consumers don’t care if they are ‘real’ or regulated by a healthcare entity. They work and perform as needed. The pinchpoint is many other medical device technologies are riding this same line with consumer-grade products. Which device, with what diagnose, will win? The consumer grade product is much cheaper and more flexible to make, so this will continue to make it difficult for medical device makers to compete, especially when technologies are associated with other consumer tech, like smartwatches. Consumers will continue to fight complexity and additional devices in favor of one elegant solution. Big Question 4: How has the rise in smartphone technology and wearable tech affected the micro molding market? Size of the wearable tech or smart device is key. Pressures on manufacturing will grow with the need for smaller components. Accumold, which specializes in micro mold technologies, has been around for over 30 years, but it’s the last decade that the demand has spiked. Smart technology is a big factor in demand. Big Question 5: What are the main design considerations for these type of devices? The biggest factor affecting the design is the relationship you have with your supply chain partners, especially micro molding, micro machining

SUCCESS

and companies you need to push the limits. There are many factors involved in determining what can be done from a micro molding standpoint, that there is no way to cover all the considerations. Don’t assume you can’t make something smaller or thinner before you talk with your micro molder. There are text book rules, and then there are micro molding rules, and we even find ourselves breaking our own micro molding rules from time to time. The best way to understand the rules are open and honest conversations about your needs and goals with your micro molding supplier. To be sure, your other suppliers that are helping you push will feel the same way. Big Question 6: Which materials work best for these type of components? As a micro molder who works with thermoplastics, the biggest micro molding rule we can define is not so much the design, but the material. Often the biggest challenge is finding a material that will fill mold completely and fulfill the desired form factor. The first two questions in any project here at Accumold are: ‘Is it a shape that is moldable?’ and ‘What’s the material?’ Not all micro geometries that can be molded with one material will work with another, therefore material selection has a profound affect on modality when it comes to micro injection molding. Materials like LCP do well in long thin sections, but PEEK does not. This is again where a textbook or even a materials datasheet may not provide the right clues. Talk to your supplier. Their expertise will give insights, but sometimes you just to need try it. We surprise customers all the time and it isn’t uncommon to hear “I didn’t know you could do that with plastic.” Big Question 7: What should OEMS look for in a manufacturing partner? There are three components to any supply chain evaluation. Capability, scalability, and sustainability. Of course, most device makers are not looking to check off just one box, in their efforts to find new and competitive ways to drive value. It’s for this reason, these decisions end up being less about finding a commodity supplier and more about finding a strategic partner. Navigating the relationship beyond the, ‘I just need to get it done’ phase, facing most development projects, is critical. The correct partner will be able to grow with the demands of the project and have the wherewithal to be a long-term. Critical components of any project shouldn’t just be ‘jobshopped’ but seen as extensions of your own manufacturing teams. This can be a huge competitive edge. Big Question 8: How much of a threat is 3D printing to micro molding in this sector? There may be only one other sector that’s attracted more buzz than wearables in recent days, and that’s 3D printing. There is real potential for 3D printing to expedite the design and creativity process and advancements in this technology have opened new markets and new business models. It’s exciting to guess where this tech can take modern manufacturing, but from a micro molding perspective, the technology has not arrived at a level of precision that competes. For high volume, high-precision micro molding, 3D printing is not a replacement, at least not for some time to come. The bottom-line when looking at wearables or any smart device for medical device manufacturing is finding the ‘where’ and ‘what’. With strong competition for space on the human body not every component is going to win. Find where your company can bring the most advantage to the marketplace then choose the right supply chain partners carefully. Who knows, you could set the next standard for medical wearable/smart tech!

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DIGITAL HEALTH

Why the smart money’s on femtech Harriet Forsyth is an analyst at ClearViewIP. Her report, Femtech & IP, outlines how insights into the market prove that the femtech trend isn’t a fad and is definitely worth the hype

Give it a few years and I think that people will start understanding that having this longitude dataset of your health is going to be an incredibly valuable thing to have — almost like life insurance. Because we will learn to pick up early signals of disease that currently we have no ways to detect early enough — ovarian cancer would be one of them. Which is totally treatable if you catch it early, but it’s hard to catch it early. And I think there will be many more things like this where people will learn to know that collecting data for your health is just a really, really smart thing to do,

While femtech includes more than health monitoring technology, this shift towards women’s health aligns well with the next phase of wearable technology applications. The landscape for wearables is changing. In recent years, use of wearables has been on a decline with one study showing that a third of people stop using a wearable within six months of receiving it. Jawbone was liquidated in 2017 and Fitbit also reported a financial loss and announced it would be laying off 6% of its staff. Arguably, the first phase of wearables is ending, and the next phase of data discovery through the use of wearables is taking place. Simply tracking activity is not enough for users anymore, devices that just track activity may get people moving, but they don’t lead to any discovery about what is happening within the body.

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Wearable makers are currently creating integrated wearables for trainers, clothes and even beds. There are a lot of health data applications that exist within this technology space. For example, Fitbit’s Ionic sport watch has a new oxygen sensor that they hope will enable them to gather data in order to address sleep apnea. This next phase of wearables is proving to be an ideal opportunity for women’s health tracking products like the Clue app and Bellabeat’s leaf.

In the current age of apps and wearables, tracking and monitoring menstrual cycles seems like an obvious application for health tracking technology. Interestingly, this hasn’t been the case. For example, as recently as 2015, Apple was heavily criticised for not including a period tracking feature in its HealthKit app, something it has since rectified.

A new collaboration between Clue and Fitbit announced in late February 2018 will allow women to start collecting their health data on their wrists. The availability of Clue on Fitbit’s Ionic sport watch is the first period tracking app to be compatible with the Fitbit OS. Based on the internal pilot study, Clue has already been able to spot a correlation with spikes in heart rate and ovulation.

Ida Tin, CEO of Clue 2017 TechCrunch event in Berlin

hen products have the potential to impact roughly 51% of the world’s population can they really be considered niche? For trailblazing innovators and entrepreneurs in the femtech space, designing and developing products and apps for women has until very recently, been considered fringe. They have had to fight against the notion that women aren’t interested in technology, or eager to track and monitor their personal health data to live more comfortable and fulfilling lives. These notions are fortunately changing and a new technology space, as well as innovation opportunities, are emerging.

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This is highly relevant when you consider the historical context and the lack of femalespecific health data available to researchers and medical professionals. Women were not included in medical trials until 1993 as it was thought they may get pregnant during a study and drugs testing could harm a fetus. Even once the ban had been lifted, many studies continued to use all male participants. We, therefore, have far more information on how drugs and diseases affect men than we do for women. The data currently being collected by femtech products could start to address this data void. As many of the discoveries in femtech revolve around tracking and monitoring female health, the data collected could be used to aid medical research. There would be a need to ensure that the data is accurate and reliable, so there is further space for developments in data processing and data science.

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DIGITAL HEALTH

NOW YOU SEE IT Sensor monitors pressure and then disappears

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angle so that its internal molecular structure was altered and it adopted piezoelectric properties. Curry then connected the sensor to electronic circuits so the material’s force-sensing capabilities could be tested.

Conn engineers have created a biodegradable pressure sensor that could help doctors monitor chronic lung disease, swelling of the brain, and other medical Colin Poitras, conditions before UConn Today, dissolving harmlessly in outlines how a a patient’s body.

biodegradable pressure sensor could have huge implications for monitoring disease

When put together, the UConn sensor is made of two layers of piezoelectric PLLA film sandwiched between tiny molybdenum electrodes and then encapsulated with layers of polylactic acid or PLA, a biodegradable product commonly used for bone screws and tissue scaffolds. Molybdenum is used for cardiovascular stents and hip implants.

The UConn research is featured in an online issue of the Proceedings of the National Academy of Sciences.

The small, flexible sensor is made of FDAapproved, medically safe materials for use in surgical sutures, bone grafts, and medical implants. It is designed to replace existing implantable pressure sensors that have potentially toxic components. Those sensors must be removed after use, subjecting patients to an additional invasive procedure, extending their recovery time, and increasing the risk of infection. Because the UConn sensor emits a small electrical charge when pressure is applied against it, the device also could be used to provide electrical stimulation for tissue regeneration, researchers say. Other potential applications include monitoring patients with glaucoma, heart disease, and bladder cancer.

A prototype sensor made by the lab consisted of a thin polymer film. The sensor was implanted in the abdomen of a mouse to monitor its respiratory rate. It emitted reliable readings of contractions in the mouse’s diaphragm for four days before breaking down into its individual organic components. To make sure the sensor was also medically safe, the researchers implanted it in the back of a mouse and then watched for a response from the mouse’s immune system. The results showed only minor inflammation after the sensor was inserted, and the surrounding tissue returned to normal after four weeks.

“We are very excited because this is the first time these biocompatible materials have been used in this way,” says Thanh Duc Nguyen, the paper’s senior author and an assistant professor of mechanical and biomedical engineering in the Institute of Regenerative Engineering at UConn Health and the Institute of Materials Science at the Storrs campus.

One of the project’s biggest challenges was getting the biodegradable material to produce an electrical charge when it was subjected to pressure or squeezed, a process known as the piezoelectric effect. In its usual state, the medically safe polymer used for the sensor – a product known as Poly(L-lactide) or PLLA – is neutral and doesn’t emit an electrical charge under pressure.

“Medical sensors are often implanted directly into soft tissues and organs,” Nguyen notes. “Taking them out can cause additional damage. We knew that if we could develop a sensor that didn’t require surgery to take it out, that would be really significant.”

Eli Curry, a graduate student in Nguyen’s lab and the paper’s lead author, provided the project’s key breakthrough when he successfully transformed the PLLA into a piezoelectric material by carefully heating it, stretching it, and cutting it at just the right

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The piezoelectric PLLA film emits a small electrical charge when even the most minute pressure is applied against it. Those small electrical signals can be captured and transmitted to another device for review by a doctor. As part of their proof of concept test for the new sensor, the research team hardwired an implanted sensor to a signal amplifier placed outside of a mouse’s body. The amplifier then transmitted the enhanced electrical signals to an oscilloscope where the sensor’s readings could be easily viewed. The sensor’s readings during testing were equal to those of existing commercial devices and just as reliable, the researchers say. The new sensor is capable of capturing a range of physiological pressures, such as those found in the brain, behind the eye, and in the abdomen. “Let’s say the sensor is implanted in the brain. We can use biodegradable wires and put the accompanying non-degradable electronics far away from the delicate brain tissue, such as under the skin behind the ear, similar to a cochlear implant. Then it would just require a minor treatment to remove the electronics without worrying about the sensor being in direct contact with soft brain tissue,” says Nguyen. This article originally appeared in UConn Today

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INNOVATION

Jared Lewis, freelance healthcare contributor, explains how in the value-based medicine race, Xenco Medical has emerged with a novel way to win

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ith the unsustainability of health system costs reaching boiling point and the pressure to boost costeffectiveness increasing significantly, healthcare providers have found themselves scrambling to reduce their costs while maintaining their current patient outcomes. According to An Investigation of the Healthcare Supply Chain: Literature Review, “healthcare costs are expected to grow at a rate greater than that of the GDP, reaching almost $4.6 trillion and accounting for 19.6% of the GDP by 2019”. Companies like Athenahealth and Xenex have used big data and UV-emitting technology to position themselves in this new era of healthcare. Noted for being one of the largest segments of the healthcare industry by the US Department of Commerce, the medical device sector especially has been targeted by the cost-saving efforts of Centers for Medicare and Medicaid Services. One of the most visible examples of this trend is Stanford University’s shift of its hospital acquisition process to one that prioritizes cost-savings over surgeon preference. In an article on Stanford Medicine, Healthcare Finance reported on the university’s new, tight-fisted, medical acquisition strategy and its emphasis on cost-effectiveness. The article notes: “It’s part of a shift from a physician-centric culture to more of a cost, quality and outcomes-based approach.” Being disruptive Among medical device companies, Xenco Medical has emerged as one of the most disruptive by approaching medical device design with a novel strategy. The company has managed to incorporate materials science in a new way: the entire system, from instrument to implant. Describing the challenges presented by current metal-based products, Jason Haider, Xenco Medical’s founder and CEO, notes: “As the inefficiencies of traditional metal implant systems have required repeated sterilization and the costly transport of heavy trays after each surgery, healthcare facilities have had to compromise on the cost-effectiveness of their care.”

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Haider continues by explaining that, “beyond the stresses that these systems have had on the internal logistics and profit margins of healthcare facilities, their nature as reused devices has exposed patients to aging instruments that deteriorate over time, some of which inevitably fail during surgery.” Asked how the company has addressed these problems, Haider notes, “Xenco Medical has created a bridge between materials science and device design to transform the performance, manufacturing process, and logistics of implant systems.” The use of materials science Haider refers to has been central to the company’s position in the value-based medicine race. Companies across the country have been competing to prove the value proposition of their products to healthcare facilities who, in turn, are accountable to payers like the Centers for Medicare and Medicaid. Using their process to injection mold their polymer-based product lines, the company has argued that the unique approach has both upfront and indirect savings to the hospital supply chain. Haider notes: “Beyond the direct savings of 850 to 950 dollars per case through elimination of the autoclave process, we’ve found that Xenco Medical’s single-use systems have had a dramatic impact on turnover rates at both hospitals and ambulatory surgery centers, allowing centers to increase their surgical volume and maximize their impact.” According to the Centers for Medicare and Medicaid, the Hospital Value-Based Purchasing Program “encourages hospitals to improve the quality and safety of acute inpatient care for Medicare beneficiaries and all patients by eliminating healthcare errors resulting in patient harm, adopting evidence-based care standards and protocols that make the best outcomes for the most patients, changing hospital processes to make patients’ care experiences better, increasing care transparency for consumers, and recognizing hospitals that give high-quality care at a lower cost.” As the healthcare landscape has shifted, medical device companies with a value-oriented thrust have found success across both major

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INNOVATION

of polymer science in healthcare. The emergence of value-based medicine has accelerated this search to develop and incorporate high-performing materials for use in medical devices. By streamlining the internal logistics of healthcare facilities, providers can increase the value of their care instead of expending time and resources on processes required for setup. Haider calls attention to one of the most common spinal surgery procedures to demonstrate the efficiencies gained by circumventing the sterilization process.

health systems and small outpatient surgery centers. It’s within this emerging framework that companies like Xenco Medical have thrived. Identifying surgical tray sterilization and processing as a primary culprit for soaring costs on healthcare systems, the company has garnered considerable buzz for engineering every product around healthcare costs and infection reduction. There may be a lesson about the future of healthcare in Xenco Medical’s model. Seeing a significant discrepancy between the cost-constraints of healthcare providers and medical device design, the company has set its focus on what it sees to be responsible for a lion’s share of hospital processing costs, depreciating metal instruments that require sterilization after every use. Asked what allows Xenco Medical to develop easily disposable products that retain the strength of metal instruments, Haider says: “This is attributable to the unique strength of the interfacial bond in our composite polymer systems.” He continues by noting that “the extremely rare bond strength makes it possible to combine semi-crystalline nylon, with its high impact strength and low internal tension, and uniquely oriented fibers in a way that produces a remarkable strengthto-weight ratio.” Making use of injection molding, the company has expanded the applications of medical plastics and pushed its industry to think differently about systems as a whole. Medical device companies are now seeing that they must innovate at every step, beyond only that which is reimbursed. Market research reports have predicted that polymer-based technologies would boom in the healthcare industry in the coming years. We’ve seen a shift away from metal and glass-based medical devices as polymer science allows for materials with high strength, durability, and flexibility while significantly lower costs. Noting the role an intensifying marketplace is playing in pushing companies to find novel ways to manufacture products, findings suggest that we will continue to see radically new uses

Haider notes: “Research on operating times has found that the average time for a two-level Anterior Cervical discectomy and Fusion, including anesthesia, is 2.3 hours. With instrument tray sterilization times averaging 3.5 hours, a sterile-packaged, singleuse system enables smaller centers to perform an additional procedure each day”. The study he is referencing is Safety and feasibility of outpatient ACDF in an ambulatory setting: A retrospective chart review. Perhaps what’s most interesting about the point he makes is that there is a hidden cost to the inefficiencies at hospitals. Through the Value-Based Purchasing program brought forth through the Affordable Care Act, hospitals are judged on five metrics: mortality and complications, healthcare-associated infections, patient safety, patient experience, process, and efficiency and cost reduction. Though the company has highlighted the costs and inefficiencies of the autoclave process to drive its implant systems forward, Xenco has also called attention to other VBP metrics that its single-use devices address. Haider tells us: “Beyond the gained efficiencies and cost reduction, we’ve leveraged materials science to reduce hospitalacquired infections. Replacing reused metal systems, which are used countlessly from patient to patient, the Xenco Medical implant systems eliminate the risk for pathogen transfer from patient to patient through improperly sterilized instruments.” This polymer-based approach to healthcare-related infections adds to the list of technologies, such as pulsating UV light, aimed at tackling this problem. Contextualizing Xenco Medical’s positioning within the current state of healthcare, Haider notes: “It’s clear that we’ve reached an inflection point and that decades of stress on our healthcare system has created a need for implant systems that offer just as much value to the hospital supply chain as they do to the patient.” As Value-Based Medicine becomes an increasingly important part of healthcare, the race to innovate will undoubtedly give way to many solutions. We will see how these innovations streamline care and, inevitably, revamp the system.

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SMART OBJECTIVES

INJECTION MOLDING

Matt Parkes, Renishaw, currently working on a collaborative project with Western University in Ontario, Canada, discusses how smart implants are changing the way bone diseases and injuries are treated

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etal implants have been since the 1900s, typically to treat bone diseases including osteoarthritis and inflammatory rheumatoid arthritis, as well as in reconstruction therapy. Though longestablished, traditional implants often cause challenges for patients and surgeons. One area currently being developed is smart implants, which improve patient outcomes. Implants can be smart by either being additively manufactured to produce patient specific implants (PSIs) from computed tomography (CT) data, or by incorporating sensors. Still in early development, inbuilt sensors could collect patient-specific data, enabling surgeons and healthcare professionals to tailor treatment. THE CHALLENGES WITH TRADITIONAL IMPLANTS One of the key challenges that traditional implants present is loosening. This can be a result of poor osseointegration — the structural and functional connection of the implant with the patient’s bone. This can occur due to wearing over time and is exacerbated by factors including infection and poor compliance with physiotherapy regimes. Another limitation of traditional metal implants is that they are only manufactured in a number of shapes and sizes, making it unlikely patients will receive an implant that fits them accurately. This can cause poor physical function and contribute to loosening. Poor physical function can also occur because of stress shielding — the process where metal implants remove stress from the patient’s bone. The bone responds by reducing in density and becoming weaker. The increasing incidence of obesity is one reason joint replacements are becoming more common in young people. This poses longevity issues as implants can reach their maximum lifespan and need replacing several times during the patient’s lifetime.

To combat these issues, researchers and engineers have been developing implants using techniques such as additive manufacturing (AM) to improve the form, fit and function of implants. ADDITIVE MANUFACTURING Because AM builds an implant layer by layer, it’s possible to produce PSIs that are a more accurate fit for the patient. The manufacturing method also has fewer geometric constraints than subtractive manufacturing. PSIs designed and manufactured according to a patient’s CT scan encourages the implant to integrate with the patient’s bone, reducing the risk of loosening. As a result, patients are less likely to suffer pain or require revision surgeries. AM also enables surgeons to design implants that mimic the patient’s bone stiffness, density and trabecular structure, which can reduce stress shielding and improve osseointegration and physical function further. SENSORS Adding sensors to imnplants allows clinicians to accurately measure patient data — the key to evidence-based medicine. They can also measure temperature to spot infection before symptoms appear. Sensors can also be incorporated into bone reinforcement implants, to help fractures heal. They can measure the strain exerted on the implant, which indicates the extent the fracture has healed. Surgeons can then determine when to progress the patient to the next stage of therapy and identify healing problems earlier than currently possible. There is currently a collaboration between Renishaw and Western University in Ontario, Canada, who have set up the Additive Design in Surgical Solutions (ADEISS) Centre to bring together clinicians and academics to generate

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novel 3D printed medical devices. ADEISS recently showcased the smart hip concept, which uses temperature sensors and accelerometers to collect patient data that can be communicated to a remote device. There is now potential for the development of implants that can detect an infection and subsequently secrete the appropriate dose of antibiotic to treat it before it becomes symptomatic. This could reduce the number of patients admitted to hospital. CHANGING THE FACE OF MEDICINE Smart implants can potentially improve patient outcomes. AM offers several benefits, one being that the fit time schedule is reduced. Patients are likely to suffer less pain and discomfort, will be less likely to become seriously ill due to infection and could be at lower risk of needing revision surgeries, critical for younger patients. For widespread clinical adoption of smart implants, there are still challenges to overcome. Clinicians must run clinical studies to collect data on the safety and performance the implants offer to patients. This must be done in line with regulations such as the EU Regulations on Medical Devices. A further consideration is the processing of personal data in smart implants and how it is used by the industry and clinicians.

Implants can be smart by being additively manufactured to produce PSIs from computed tomography data, or by incorporating sensors

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IMPLANTS

The future of medical implants Bioengineered silk for better biocompatibility

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very year, millions of people receive implants for medical and cosmetic procedures. While Lin Römer, the majority of these co-founder of operations have no long–term side effects, AMSilk, discusses a portion of them how a silk protein result in complications coating could change that require follow implants and the up surgeries and safety of medical expensive post-op devices everywhere treatments. As demand for medical implants has grown over the past years, finding a way to make implants safe and effective has been a key priority for the medical implants market. At AMSilk, we have created a thin coating from bioengineered silk to make medical implants – beginning with silicone breast implants – safer for the human body.

The longstanding challenge Most medical implants today are made of crude oil-derived polymers or metals. Once placed inside the human body, these implants are registered as a foreign object and generate a physiological response from the immune system. This response – which occurs any time a foreign object enters the body – can in extreme cases result in complications ranging from painful inflammation to capsular fibrosis, necessitating further operations to fix or remove the implant. To address this challenge, the industry has sometimes turned to animalderived materials for implants, which are primarily composed of proteins and are recognized by the body as natural. Unfortunately, many animal materials

currently in use, such as collagen, are not easy to handle and are generally not desired due to their animal origin. Moreover, they are often not robust enough to withstand the sterilization processes needed for them to be used in surgery. In contrast, AMSilk’s silk proteins can be used as a coating for almost any material and any implant size to give traditional implants a natural shell. Real spider silk, the model for AMSilk’s silk proteins, had been used for centuries in the form of cobwebs to stop bleeding and promote wound healing, but aside from the difficulty of finding enough cobwebs to supply a hospital, the quality of naturally occurring spider silk is too inconsistent for serious medical applications.

A silk solution At AMSilk, we use the tools of industrial biotechnology to produce synthetic spider silk proteins from engineered e.coli bacteria. These proteins possess many of the extraordinary properties of spider silk – a material known for its strength, flexibility and lightness – but in a form that makes them available for various applications. For the medical industry, we have created a highly biocompatible silk coating for medical implants designed to further reduce post-operative complications such as inflammation, capsular fibrosis and biofilm production, one that we’re proud to introduce alongside our corporate partner Polytech Health and Aesthetics.

Once inside the body, the silk coating acts as a thin protein barrier between the silicone of a typical breast implant and the body’s surrounding tissue, allowing it to be better integrated into the body. Currently, we are conducting human trials for the silk-coated silicone breast implants throughout Europe with Polytech Health & Aesthetics. Following successful results in the studies, our goal is to expand the use of this innovative silk coating to a broad range of medical devices, ranging from other soft tissue implants to sensors and hernia meshes, as the silk coating layer we have created is adherent to almost any material, be it metal, plastic, Teflon or stainless steel. As the silk coating can be applied through traditional production methods (e.g. through dip- or spray-coating), it can fit easily into already existing manufacturing processes and is built to scale. We expect to see the implant community transition to using this technology in order to prevent many postoperative complications. With very little impact on the physical implant, we will be able to render it nearly invisible to the human immune system, resulting in less operations, less side effects, and longer-lasting products. POLYTECH-AMSILK: SILKline silicone breast implants by POLYTECH and AMSilk

With the support of our partner, we have developed a coating for silicone breast implants as the first demonstration of the technology.

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DON’T MISS THE EAST COAST’S

BIGGEST MEDTECH EVENT

JUNE 12-14, 2018 // NEW YORK, NY JACOB K. JAVITS CONVENTION CENTER

MD&M East—now in its 34th year—is the largest medtech event on the East Coast, connecting you with thousands of engineers and executives, as well as hundreds of leading suppliers. Find the medtech solutions, innovations, and inspiration you need to solve your toughest challenges, while staying on top of the latest advancements across the industry. This year the show floor spotlights two industry mega-trends—3D printing and smart manufacturing—with a dedicated 3D Printing Zone, plus the latest in collaborative robots and robotics on display from the world’s top suppliers.

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IMPLANTS

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ilicones entered into orthopedic medical applications in the 1960s. Manufacturers often choose silicone Julie Cameron, for their medical devices due to its established pedigree NuSil, discusses of biocompatibility, unique the possibilities a physical properties and the new innovation in ability to be altered at the sterilizable silicone polymer level.

dispensing systems can provide for medical device manufacturing

Silicone provides a diverse range of properties that make it useful in multiple ways. Its properties can range from very sticky to very slippery, from soft and pliable to stiff or rigid. This has made it very attractive for multiple medical applications, from soft silicone adhesives to lubricious coatings, or from soft tissue implants to high modulus tubing. Silicones can also accommodate a range of performance characteristics to match an equally diverse range of applications. More specifically, liquid silicone rubber (LSRs) can provide various solutions for device designers. Common examples include: • Cardiovascular: Components manufactured from LSRs used to assemble pacing devices • Neurological: LSRs used for the assembly of shunts, valves and seals • Ophthalmic: Optically clear LSRs used to produce intraocular lenses • Otological: LSRs used for the assembly of cochlear implants • Urological: Foley catheters composed of several types of LSRs Medical grade LSRs are used for a range of implantable medical devices. For long-term medical implants, design options were often limited to preformed materials that may have required invasive implantation procedures. Until recently, most medical devices made with LSRs were formed or molded externally to the body, then ‘cured’ to lock their properties in place and make them chemically stable before implantation. The device would then be assembled, packaged, sterilized and later surgically implanted.

The patented, NuSil double-cartridge dispensing system enables LSRs to be sterilized in the uncured form, opening new opportunities for LSR-based medical devices. Curing in the body creates the ability to customize the fit of implanted devices. For example, in vertebral repair, it is conceivable that this could enable a custom-fit device. This also opens possibilities for less invasive implantation procedures. In addition, LSRs themselves can be customized to tune properties such as work time, cure time and physical properties to support desired performance characteristics. New packaging enables sterilization Implanted medical devices fabricated with LSRs must be sterilized—so an efficient and fully verifiable sterilization solution is necessary. Traditional methods for sterilizing cured silicones can negatively affect the desired properties when used to sterilize uncured silicones. For example, gamma irradiation and electron-beam irradiation may increase cross-linking, thereby reducing flexibility. Exposure to dry heat and autoclave conditions may damage the packaging or impact workability. Ethylene Oxide (EtO) exposure is a widely used medical device sterilization method. With this new patented design, the prefilled dispensing system can be EtO sterilized, thereby maintaining the integrity of both the uncured implantable silicone and its packaging. This allows for implantation of presterilized materials for in-situ cure and forming within the body. Now, medical device manufacturers can offer novel solutions using a unique package that enables sterilization in the uncured form. Patented two-part LSR dispensing solution

packaging solution for in-situ curable LSRs features a double-cartridge prefilled dispensing system. Each cartridge has a gas-permeable plunger seal, designed to allow EtO sterilant gas to permeate through the plunger seal to sterilize the contents of the cartridge. Key features of the packaging system include: • Disposable syringes available in a variety of sizes—2.5, 5.0, 10, 25, 50 and 75 mL • One-step sterilization of LSR components and packaging • Adaptable to a variety of injection technologies • Engineered for use in complete surgical kits With the two-part dispensing design, sterilization verification demonstrated: • Effective sterilization • No residual EtO, post-sterilization • Minimal change to key LSR physical properties such as rheology, durometer, modulus, work time and cure rate Medical grade silicones specific for healthcare NuSil medical grade silicones used with the in-situ cure dispensing system are specifically designed, manufactured and purified to meet the strictest requirements of the healthcare industry. Master Files can be submitted to the US Food and Drug Administration (FDA) in support of these products. All raw materials, intermediates and finished products for NuSil medical grade silicones are manufactured under applicable Current Good Manufacturing Practices (cGMP) and NuSil’s ISO 9001 certified Quality Management system. 1 Gas Sterilizable Two-Part Polymer Delivery System, U.S. Patent No. 8,435,217 B2, May 7, 2013.

Designed specifically to allow sterilization of the uncured medical grade LSR, the innovative new

However, a new innovation in LSR dispensing systems from Avantor’s NuSil brand has been designed to make it possible for medical device manufacturers to create devices that can be in-situ cured in the body rather than cured outside the body and implanted.

Designed to allow sterilization of uncured medical grade LSR, new packaging for in-situ curable LSRs features a double-cartridge prefilled dispensing system

What lies within WWW.MEDICALPLASTICSNEWS.COM

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The future is here 3D PRINTING

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he merits of 3D printing in the medical manufacturing space are well documented. For anyone working in medical device sector, this technology is growing in strength for the development of new healthcare products, offering cost-efficiencies and the creation of products that allow surgeons to perform procedures with increased accuracy and precision. It has helped improve surgical experience for both the healthcare professional and the patient, allowing the production of more precise and personalised implants which in turn improves patient outcomes. For the design engineer and device manufacturer, the benefits of the technology are wide. It allows manufacturers to tailor-make devices to suit the individual as opposed to a ‘one size fits all’ approach, and the nature of the process means that changes to production can be made quickly and easily. The noise around 3D printing remains positive. According to ProfShareMarketResearch the 3D printing medical devices market is estimated to reach $2.77 billion by 2025; growing at a CAGR of 16.8% between 2017 and 2025.

and have expanded their offering to customers keen to exploit the potential of the technology. Last year MPN sister title, TCT magazine, reported that three leading 3D printing companies had announced new products and partnerships at the 2017 Radiological Society of North America (RSNA) annual meeting. Samuel Davies revealed that 3D Systems had launched Volume Virtual Reality software as well as embarking on a partnership with Philips Healthcare; Stratasys launched its BioMimics 3D printed medical models solution, while Materialise announced a partnership with Siemens Healthineers. “3D Systems continues to deliver on the growing need of the medical community for innovative and adaptive tools designed to provide better insights, better processes and better outcomes,” Kevin McAlea, executive vice president, metals and healthcare, 3D Systems, told the magazine. According to Stratasys, its BioMimics release, which has been developed

Many of the industry’s major players have realized the advantages of 3D printing

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through collaboration with researchers and manufacturers, provides realistic and accurate 3D printed replicas of anatomical structures. It’s hoped that this will help with both training and advanced medical device testing. The company has shown an ongoing commitment to growing the use of 3D printing in the medical field. Last year it teamed up with SSM Health Cardinal Glennon Children’s Hospital in St Louis, Missouri, to open a 3D printing ‘center of excellence’. The center is designed to accelerate advancements in pre-surgical preparedness, medical research and patient treatment. By using Stratasys’ 3D printing technology, the center is able to develop and share best-practices throughout a range of specialties such as neurosurgery, orthopedics, and cardiac treatment. SLUCare – the physician practice at Cardinal Glennon Children’s Hospital – is encouraged to utilise 3D printing technology to explore new approaches for patient care.


3D PRINTING

While no longer considered an emerging technology, the effect of 3D printing on medical device manufacture, is still having a marked effect on innovation and medical advancement, says Lu Rahman Steven Burghart, president of SSM Health Cardinal Glennon Children’s Hospital, said: “As a leading pediatric care and academic research facility, we’re committed to continuous improvement by harnessing cuttingedge tools like 3D printing.” “Our Center of Excellence stems from a long-standing partnership with Stratasys, working together to raise the bar in all that’s possible in patient care.” Burghart continued In addition to its tie-up with Siemens Healthineers, Materialise became the first company to provide software which follows new regulations and can be used in US hospitals alongside a 3D printer – as of August 2017 software used to print 3D patient-specific anatomical models for diagnostic purposes are considered class II medical devices and require regulatory clearance. Frank Rybicki, chief of medical

imaging at Ottawa Hospital, said: “510k clearance is an essential component to ensure quality and safety in the practice of anatomical modelling in hospitals. This milestone for Materialise serves as a benchmark for the clinical implementation of 3D printing for physicians creating 3D models at the point-of-care.” Materialise CEO, Wilfried Vancraen, added: “Materialise has nearly three decades of experience in developing certified medical solutions that create a better and healthier world. The FDA clearance for our Mimics inPrint software will support the adoption of 3D planning and printing in US hospitals and the creation of point-of-care 3D printing facilities.” Elsewhere in the medical space 3D printing in being used to innovate and advance medical care. A student at the University of Canterbury, UK, Logan Williams, has used the technology to create polarised contact lenses for sufferers of photosensitive epilepsy.

Williams says he was inspired by the lack of non-medical prevention available to address the condition with the special lenses he calls Polar Optics. According to the university website Polar Optics mitigates environmental threats, enabling sufferers to go about their daily lives without fear of a seizure. It has the potential to make a difference to people all over the world with photosensitive epilepsy, and will also help anyone who suffers from headaches and migraines from bright light. An interesting use of the technology has come out of Massachusetts Institute of Technology (MIT) where engineers have cut kirigami-style (an Asian folk art) slits into stretchy films to make bandages, heat pads and wearable electronics that adhere to flexible surfaces. Made by pouring liquid elastomer into 3D printed molds, the thin and lightweight rubberlike film can stick to areas of the body such as knees and elbows and maintain hold even after 100 bending cycles. According to MIT: “The key to the film’s clinginess is a pattern of slits that the researchers have cut into the film, similar to the cuts made in a paper-folding artform known as kirigami”. This is just one of many uses of 3D printing taking place at MIT. Last year engineers came up with a printing technique that uses a new kind of ink made from genetically programmed living cells. MIT described how the cells are “engineered to light up in response to a variety of stimuli. When mixed with a slurry of hydrogel and nutrients, the cells can be printed, layer by layer, to form three-dimensional, interactive structures and devices.” The product has been dubbed a “living tattoo” and by using genetically programmed bacteria, the team hopes it could develop this wearable chemical sensor, and drug delivery systems to deliver pharmaceuticals etc into the body.

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CATHETERS

Inside INFORMATION Cikautxo Medical OEM explains the benefits of integrated sensors in catheters

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bout 10% of the western population will, at a certain stage in their life, be taken to a catheterisation laboratory for angioplasty surgery (stent placement), treatment of an arrhythmia or a heart valve replacement. This percentage is increasing with an aging population. Fortunately, most of these interventions can be carried out using minimally invasive procedures that are assisted by smart imaging and sensing catheters that are the ‘eyes and ears’ of the surgeon directly at the point of intervention.

Customers are increasingly demanding sensor integration in our OEM catheter manufacturing activity, says Iker Principe, Cikautxo Medical OEM

The growing number of cables in the cath lab is rapidly becoming a problem. The interventionist increasingly has to deal with instruments that have electrical cables connected to them. These cables hamper the workflow, and can result in dangerous situations eg, when a cable hooks behind the rotating X-ray C-arm, or during an electrical cardioversion. Sensing smart catheters are consequently more and more demanded in the cath lab. ‘SENSING’ TRENDS IN CATHETERS To improve the success rate of the most important cardiovascular diseases but also for other type of surgeries, catheter manufacturers have started to add electronic sensing functionality to the instruments resulting in what is referred to as ‘sensing’ catheters. Here, different examples of catheters are distinguished based on their application disease. Some of the ongoing applications today are: Urology: Foley Catheter Temperature Sensors enable clinicians to accurately monitor urinary output and bladder temperature in addition to facilitating urine drainage. Commonly used also to monitor a patient’s body temperature during surgery. Vascular: Vascular catheters with blood glucose measurement have the potential to become a standard of care for the management of blood glucose levels in the critical care units of the hospital. The near-continuous glucose measurements automatically transfer whole blood from a radial artery, peripheral vein, or central venous catheter to an external flow-through glucose sensor. A vascular catheter with this type of sensor acquires a fresh blood sample every five to 15 minutes, measures the concentration of blood glucose, and then flushes the sample back into the bloodstream using flush solution. Standardisation of blood sample acquisition, analysis, and calibration will increase the accuracy SUCCESS STORIES: To improve the success rate of many cardiovascular diseases, catheter manufacturers have started to add electronic sensing functionality

The US market for smart catheters used in the treatment of cardiovascular diseases. The European market prediction follows the same trend at approximately half the market value.

and precision of the blood glucose measurement, a major advantage of those catheters compared to routine clinical methods. On-going therapy: A whole new class of implantable devices is being developed with the purpose of delivering local and on-going therapy. These ‘electroceuticals’ stimulate or block nerves directly addressing organs. The ‘sensing’ catheters are contributing to Industry 4.0, where the Internet of Things (IOT) will also conquer the Internet of Medical Devices (IMD). MANUFACTURING ‘SENSING’ CATHETERS “Customers are increasingly demanding sensor integration in our OEM catheter manufacturing activity. We are embedding different types of sensors, from the most common ones like temperature or pressure sensors, up to the most difficult ones, like position systems. “Sensors are very fragile components that need to be carefully manipulated during the assembly in the catheter. Intensive tests are also made to validate the correct sensing functionality after the product final assembly. “Our sensor R&D centre, IKERLAN, located only a few miles from our cleanroom facilities, mean we stay on top of the latest technologies in sensors, so we can help our customers to select the most appropriate solution for their needs,” says Iker Principe, CEO, Cikautxo Medical OEM.

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INJECTION MOLDING

IT’S THE LITTLE THINGS

THAT MEAN A LOT

Jared Sunday, Raumedic explains how the company focusses on a complete systems approach to micro molding

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he continually evolving demands of the medical industry drive suppliers and manufacturers to expand their technical competencies into areas that they may have feared to tread. Doctors and surgeons are demanding instruments for less invasive procedures with quicker turnovers. Devices are becoming smaller and more complicated. Industry designers and procurement specialists are demanding smaller, higher precision components with exotic materials and tolerances that may not have been possible years ago. This trend in micro-molding processes and components advertised or written about in technical articles and industry publications has often led to confusion and to missed opportunities when it comes to supplier selections. How to define micro molding Raumedic defines true micro molding in several ways. One is part weight, with a typical range from 1 gram to smaller than 0.004 grams. Tolerances required are often much tighter than 0.001”. But more importantly micro molding can be defined as components with sizes or tolerances so small that they are not able to be manufactured correctly, robustly, or with a high degree of precision using traditional injection molding equipment and standard thought processes. Raumedic also applies the micro molding thought processes to extrusion and tubing manufacturing. Defining the specifics of micro-extrusion as inner diameters of 0.004” with wall thicknesses of 0.002”. This can even apply to coating technology with micro-layers as thin as 0.0002”.

Solve the manufacturer early The specific type and grade of resin should be selected with careful input from the material supplier and the manufacturers engineering resources. Semi-crystalline or amorphous resins, fillers and fibers, and even colorants can all have an impact on the product consistency required to meet critical dimensional requirements. Selecting the material appropriately is the foundation for the longterm manufacturability. Use consistent amorphous engineering grade resins for tight tolerances. Apply fillers for added dimensional stability where necessary. Following general part design principals are recommended for any successful part design. In micro molding, not just meeting these guidelines but exceeding them is a hard requirement. Slight areas of sink in ribs, slight warpage in sharp corners, or

Think small To be successful with micro molding takes more than simply purchasing a small injection molding press and a microscope. All levels of the organization must make the decision to commit to success, at all levels of the manufacturing process. This must translate to a passion for problem solving, and thinking small, in the micro molding world. All phases of the process should be engineered to manage the specific subset of problems that comes with making micro components. Careful resin selection, component design, equipment and molding processes, tooling construction, measuring equipment and even component handling and packaging are all critical. These may seem standard in today’s injection molding industry but micro requires specialized solutions to ensure success and a happy customer.

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To be successful with micro molding takes more than simply purchasing a small injection molding press and a microscope.

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INJECTION MOLDING flowing thin to thick may cause problems in a large part. In a small part they can be disastrous and result in deformation that can exceed the allowable tolerance. Get your suppliers involved early in the design phase to ensure success and a robust design. Tool construction is of the utmost importance as well. Traditional time-tested tool construction methods can cause problems when tolerances and geometries are microscopic and critical. In fact this may even be the most important phase of the development project. It is critical to manufacture the tooling using processes that are able to create fine sharp corners, extremely flat surfaces, tricky geometries, and everything in the perfect detail required. The standard end mill and EDM need not apply!

Communication is the route to success Micro molding is a challenging venture. But it can be done successfully. All interacting systems should be designed concurrently with careful thought to how all components interact within the manufacturing process. Positive communication between engineers, project managers, equipment suppliers, designers, molders, and quality inspectors is required for success. Designers and engineers should contact their supplier of choice early in the project. This will lay the roadmap required with there is little room for error in the micro molding world.

Equipment selection is the next step in the development process. Many manufacturers now offer packages that are almost off the shelf for specialization in micro molding manufacturing. Make sure to involve the manufacturer early in the process. Be prepared to disclose shot weights, material selections, part size, and critical features. Shot control may exceed what is possible for a check ring screw. A plunger or ram may best fit your application. Consistency is the key to long term success. 100 % control of quality and quantity Now that you have molded a component, how do you know it is acceptable? Careful selection and possible investment in

metrology and measurement systems processes will give you the data you need to know for sure. Equipment must be able to measure small dimensions, with small tolerances, and demand Gage R&R results better than 10%. Calipers and micrometers will not lead to positive results. Each component offers different challenges for measurement. But technology has come a long way in this area in the past five years. Laser scanners, CT scanning, non-contact optical vision systems are more readily available and all offer packages that can be customized and programmed for your specific need.

Successful micro molding takes more than purchasing a small injection molding press and a microscope, says Raumedic’s Jared Sunday.

An area that may be often overlooked is packaging. It may almost be an afterthought for standard injection molding but can cause many problems when trying to control delivery of micro molding components. Ensuring part counts are correct can be difficult when a month’s worth of production demand can fit into the palm of your hand. Traditional weigh scale verification certainly will not get the job done here. Certain automated systems can help with this as they tie directly into the press interface and rely on camera controls to verify count and quality. Rely on optics and on technology. Use small sealable bags or vails where appropriate. Segregate into small quantities when you can.

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STANDARDS & REGULATIONS

Setting the standard CHEMICAL REACTION: The changes of ISO standards will impact medical device manufacturers by putting more emphasis on chemical characterisations, says Dr Albrecht Pot

Dr Albrecht Poth, Dr Knoell Consult, examines biological evaluation and the challenges and consequences for the medical device industry

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he important standards for biological evaluation and risk analysis of medical devices are explained in three parts. ISO 10993-1 provides the framework and describes the general principles of the biological evaluation; ISO 1099318 provides information on the qualitative and quantitative characteristics and finally ISO 10993-17 gives guidance on the derivation of the allowable limits for the leachable components of the medical devices. All the three major standards are going to be revised substantially. For ISO 10993-1 “Evaluation and testing within a risk management process” the final draft international standard (F-DIS) has been published in January 2018. The revision will include a change in the flow-chart describing the systematic approach of the biological evaluation including as an initial step the chemical characterisation. As a consequence Annex A 1 “Evaluation tests for consideration” of ISO 10993-1 has been revised by adding a new column including chemical characterization as a test parameter. It will further include additional test parameters for certain device categories and additional toxicological endpoints for evaluation based on the US-

FDA modified matrix as outlined in the US-FDA guidance document “ISO International Standard ISO 10993, Biological evaluation of medical devices Part 1: Evaluation and Testing” (2016). By including additional requirements it was discussed that chemical characterisation is the only mandatory testing requirement and all other toxicological endpoints will be evaluated on a case-by-case basis within a toxicological risk assessment. A major revision of ISO 10993-17 on allowable limits for leachable substances is in works. The experts of TC 194 are discussing risk assessment approaches to use the concept of Threshold of Toxicological Concern (TTC), a concept which is already established and accepted for genotoxic pharmaceutic impurities. If it can be shown that an impurity is below the TTC, then it is assumed that the level of the chemical substance is of no significant risk and no further evaluation is required with regard to that impurity. The TTC allows definition of threshold values for substances below which there is insufficient material available to cause a toxicological hazard and thus no further evaluation is required. The concept may also be applied more generally to unidentified contaminants.

The inclusion of TTC in Part 17 would be a significant advance which will allow avoidance of unnecessary animal testing if chemical characterisation can demonstrate that leachables are below the TTC. This concept is planned to be implemented in the revisions of ISO 10993-17. A major revision will also be made to ISO 10993-18 “Chemical characterization of materials” including the technical and scientific experience made during the last 10 years since its publication in 2005. A second Committee Draft (CD) was published in January 2018, including the choice of extraction types (exaggerated versus simulated-use extraction) and a better definition of the experimental requirements for investigating extractables and leachables. It will further include a description on the stepwise chemical characterisation process and the revisions needed to the associated flowchart. The revision will include approaches for setting analytical evaluation thresholds (AETs), recognizing that this will have to be developed in alignment with thresholds of toxicological concern (TTCs). It can be foreseen, that the proposed step-wise chemical characterisation will be of more complexity especially for high

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risk devices, including more complex chemical analytical methods for structure elucidation of unknown chemical substances released but also the evaluation of release kinetics of chemical compounds from medical devices. Based on the proposed revisions it can be foreseen that in future the chemical characterisation will be a key parameter in the assessment of the biological evaluation of medical devices within a risk management system. Toxicological hazard and risk assessments will also be key aspects not only for the evaluation of extractables and leachables but also for the evaluation of raw materials and their impurities. Overall, the changes and adaptations of the ISO standards will impact the biological evaluation strategies of manufacturers of medical devices by putting more emphasis on chemical characterisations and sound toxicological evaluations. Thus, the era of the ‘tick-the-box of the flowchart’ mentality for animal studies in the medical device business is to be replaced by systematic evaluation approaches taking into account the chemical composition of the devices.

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NEWS FOCUS

New medical zone to feature at NPE The organiser of NPE2018 says this year’s event – which takes place on 7-11 May in Orlando, Florida – will allow visitors to track trends, innovation, new products and connect with industry leaders NPE2018 brings together all industry sectors, including vertical and peripheral markets, end markets, brand owners and recyclers. Held every three years, it attracts more than 65,000 plastics professionals and features industry-focussed education and leading suppliers of emerging technologies, equipment and materials for every phase of plastics processing – all in more than 1.1 million square feet of exhibit space. Building on its most successful show in 2015, held in Orlando, Florida, NPE2018 anticipates even greater participation from up and down the global plastics supply chain when it returns this year. NPE is produced by Plastics Industry Association (PLASTICS) which has announced that this year’s event debuts a new Medical Parts Processing Zone among the Technology Zones on the show floor located in the South Building. This new sector-specific zone focuses on plastics materials, processes and technology advances for medical devices and diagnostics in healthcare industries. Propelling the demand for this specialised zone is the forecasted

3% growth in revenue from medical device manufacturing anticipated by 2023. This growth is centred around the emerging trend for using plastics in the medical and healthcare industries to create pioneering medical devices, equipment and treatment items. “Breakthroughs in the use of plastics will drive future medical care efficiencies and bring life-saving advances to hospitals globally,” says Glenn Anderson, NPE2018 executive committee chair. “The Medical Parts Processing Zone will connect new technology providers with equipment manufacturers to source medical innovations and support the business initiatives of vertical market attendees.” The use of plastics in cleanroom technology is providing costeffective and environmentally friendly innovations to the medical industry. It is imperative that sterile medical equipment is manufactured in a modern controlled environment. The equipment, supplies and solutions making this possible will be among the highlights in the zone and will give attendees the opportunity to explore options that meet the medical industry’s high business standards.

From barrier technology to 3D-printed prosthetics to new treatment methods, medical manufacturers can find the robotics, automation and supplies for tomorrow’s healthcare not only in the Medical Parts Processing Zone, but throughout the Technology Zones in the Material Science, Flexible Vinyl, 3D/4D Printing, Thermoforming and Processors zones. NPE2018 will feature 11 Technology Zones to help to create discussions between the attendee and suppliers on the newest equipment, processes and education opportunities transforming the plastics industry. Some of the highlights include the expanded Re|focus Zone and 3D/4D Printing Zone, all designed to address the growing market demands, highlight innovations and technologies and provide customised education. NPE is a globally-recoignised trade show and conference serving the plastics industry, its verticals and enduser markets. This year’s event will provide access to industry-leading and emerging suppliers from over 2,000 companies showcasing the latest products, processes and technology. With 65,000+ attendees from over 100 countries on the show floor, the event organisers says it is the best place for plastics industry attendees to boost their production and efficiencies.

MEDICAL MANUFACTURING COMPANIES THAT ATTEND NPE INCLUDE:

The medical breakthroughs of today would not be possible without plastics.

3M | Alcon |B Braun Medical Bausch + Lomb | Bayer Healthcare Bemis Manufacturing | Boston Scientific | Bristol-Myers Squibb Cardinal Health | Colgate | Conair Johnson & Johnson | Kimberly Clark | Newell Rubbermaid Philips Healthcare | Siemens

$42.6 million - medical device manufacturing industry revenue 2.9% annual growth of medical device manufacturing industry projected to 2022 Medical supplies wholesalers account for an estimated 27% of the total industry market

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Say cheese:

Sensor can measure what we eat and drink

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esearchers at the Tufts University School of Engineering have developed a miniaturised sensor which sits on the tooth and measures glucose, salt and alcohol intake. The sensor, which is a mere 2mm in length and width, can flexibly bond to the irregular surface of a tooth. It has been designed to monitor in real time how our bodies react to glucose, salt and alcohol and the researchers state that it could be invaluable in the context of healthcare of clinical studies. The sensor works by transmitting data wirelessly in response to an incoming radiofrequency signal. When a radio wave hits the sensor, part of it is cancelled out and the rest is transmitted back. However, the sensor is able to absorb and transmit a different spectrum of radiofrequency waves with varying intensity by changing its electrical properties, enabling it to detect and measure other nutrients.

Can this polymer read your mind?

PROBABLY NOT BUT RESEARCHERS IN SOUTHERN CALIFORNIA HAVE DEVELOPED A POLYMER-BASED MATERIAL TO HELP RECORD ACTIVITY MORE DEEPLY IN THE BRAIN

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he thin, flexible polymerbased material, called Parylene C, was developed by a team at the USC Viterbi School of Engineering. The materials are used in microelectrode arrays that record activity in more subregions of the brain and with more specific placement. The electrodes can record from a total of 64 subregions of the brain at once. Each microelectrode array is made up of eight “tinies”, each with eight microelectrodes which record brain activity. The researchers hope that their work will produce insight into the interconnectivity which occurs between thousands of microscopic entities, such as neurons, in the brain. Scientists’ major goal in this

devices get recordings of neuronal communication over long periods of time.” The arrays have so far been used to record synaptic responses of individual neurons within the hippocampus. The polymerbased material is able to conform to a specific location in the hippocampus and “listen in on a conversation” between neurons, Meng said.

Professor Ellis Meng of the USC Viterbi department of biomedical engineering said: “The information that we can get out is equivalent, but the damage is much less. Polymers are gentler on the brain, and because of that, these

“I can pick where I want my electrodes to be, so I can match up to the anatomy of the brain” Meng said. “Along the length of a tine, I can put a group of electrodes here and a group of electrodes there, so if we plant to a certain depth, it’s going to be near the neurons I want to record from.”

The future of medical devices from Medtec Europe…

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mart health was the name of the game at this year’s Medtec Europe, which took place in Stuttgart. Patrick von Meiss, head of sales at Swiss contract manufacturer Valtronic explored the many evolving challenges of using electronics in medical devices.

competitive”, said von Meiss.

In an industry which has been disrupted at scale by connected technologies, electronics are driving new waves of innovation in medical devices.

But challenges like miniaturisation of the device are compounded by the need to retain standard costs - and this can hold manufacturers back. Other obstacles include optimized security, efficient power management and supply chain

“Companies need to completely redesign their products in order to stay

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area is to develop complete brain mapping, something of which could unlock great therapeutic potential.

The trends driving the need for electronics in medical devices include minimising patient trauma, more cost-effective therapy, more functionality, reduced size, portability, ease of use and connectivity.

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management (including the risk of components becoming obsolete over time).


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