MPN EU Issue 17 by MPN Magazine

MPN

MEDICAL PLASTICS NEWS

Custom CNC machined and micro moulded parts for the medical industry ALSO IN THIS ISSUE: Antimicrobials 3D Printing for the Medical Industry Plasma Polymerisation Wearable Medical Devices Potential Leachables for Packaging Systems

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MPN

All Medical, All Plastics

Contents

Cover Story—Page 10

5. Editor’s Letter: Growth and Change Gareth Pickering discusses the current economic climate and shares his predictions for 2014. 6. On the Pulse: Aerogen Beats Stiff Competition to Secure the Irish Medical Technology Company of the Year Award A report from the Irish Medical Technology Industry Excellence Awards, which were held in Galway, Ireland, in December.

3D Printing—page 18

Wearable Devices—page 23

Plasma—page 35

10. Cover story: Custom CNC Machined and Micro Moulded Parts for the Medical Industry Proto Labs presents new opportunities for the medical industry. 13. Antimicrobials: Plastics with Antimicrobial Capabilities against Microorganisms Zhen Zhu of Evonik Cyro LLC discusses hospital-aquired infections and antimicrobial materials that can help prevent them. 18. 3D Printing: All Aboard: The 3D Revolution is Spreading Like Wildfire The Düsseldorf trade show and VDMA announce launch of the 3D fab+print brand. A report by Andrea Köhn, Bötel Graphic Communication. 23. Wearable Devices: Developing a Better Wearable Medical Device — Critical Issues to Consider Kyle Jarger, Program Manager of Farm presents important advice for the wearable medical devices manufacturers.

26. Regulation Review: Risk-Based ‘Three Loops in One’ CAPA Process is Critical to Ensuring Product Quality Ken Peterson of MasterControl Inc. discusses successful implementation of CAPA processes. 29. Automation: Making Medical Sector Automation Better Sam Anson makes a visit to the ATM facility in the UK. 35. Plasma: Functional Nanocoating with Millimeter Precision Inès A. Melamies discusses atmospheric plasma polymerisation in medical engineering. 39. Extractables & Leachables: Total Organic Carbon (TOC): A Viable Analytical Endpoint for Assessing Potential Leachables from Packaging Systems An article by Roger Pearson of Aspen Research Corporation and Shayne Spence, MACtac North America. 44. Orthopaedics: Breaking the Mould: A New Generation of Orthopaedic Implants through OsteoFab Technology A feature by Jim Porteus, OPM. 52. Intellectual Property: Protecting Your Innovation Jackie Maguire of Coller IP on how to effectively use and protect your IP. 50. Medtech Innovation

Online and in digital Orthopaedics—page 44 Disclosure: Medical Plastics News charges an undisclosed fee to place a contibutor’s image and headline on the front cover.

Medical Plastics News is available online at our website www.medicalplasticsnews.com and via a digital edition. JANUARY-FEBRUARY 2014 / MPN /3

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EDITOR’S LETTER

PREDICTIONS FOR 2014:

Growth and Change

anuary seems to have started with a bang here at the MPN offices. So, as this is the first issue of the year, here’s a roundup of what we can all expect in 2014. My predictions are clear: 2014 means growth and change. I won’t be the first to talk about growth; but it’s the change that looks the most interesting; let me explain. Growth In general, the vital signs for the industry as a whole are healthy, as manufacturing sectors in the US and Europe are moving into growth. The recession, I’m convinced, is genuinely behind us. There is increasing confidence in Europe, largely led by the German and UK economies. Sure, we are not out of the woods just yet but there are real signs that the northern European economies are witnessing a sincere and sustained recovery. The debacle that dogged the Euro from 2010 onwards, which hampered growth and business confidence, now feels in the past. In the US we are a long way from fiscal cliffs (remember that damp squib) and the Q3 Government shutdowns that have stalled so much investment. All welcome news indeed. Growth will continue, albeit at a slower pace; it will be more sustained and infinitely more controlled. Change So, what are the changes we can expect? 2014 will be a monumental year for the Medtech sector. It will see EU-wide regulations take shape, changing the landscape of Europe’s device market. The US market will get to grips with Obamacare, there will be a bedding in of the sales tax and a potential seismic shift in pricing expected across the entire healthcare sector. We’ll wait to see how these exogenous pressures will be played out over the next 12 months. This year will also see the continuing of a major trend to outsourcing and moving locally as the healthcare industries grow and develop in the BRIC (and now MINT) economies. China will be a major influencing factor as multinational medical device makers moving there want locally marketed products made to European standards.

The economics of the industry will also continue to change. Here at MPN we believe the pace of big mergers and acquisitions will not let up. To the little guys, now’s the time to make yourselves look pretty if you are looking for an exit strategy! Pressures 2014 may well see the return of some old pressures. The resurgence of other sectors (automotive, consumer etc.) may put a real pressure on many venture capitalists to reinvest in these industries and venture out from under the safe ‘medical’ haven that has sheltered many from the worst of the troubles over the last few years. Globally, national governments’ constraint on public spending will remain through the year forcing the industry to continue to product price as keenly as possible as healthcare procurement remains tight. But the opportunities are there. We’re seeing a globally ageing population and an explosion of the Chinese middle classes who will want higher standards of healthcare. Match these facts to the growth in the number of new registered clinical studies (up 28% since 2000) and it’s easy to see brighter times ahead for the global medtech sector.

In January MPN said farewell to its editor Sam Anson. Sam will be taking up a new role as product manager for a global polymer and raw material distributor, where his wealth of knowledge in the medical plastics industry will be put to use. I’d like to offer a personal note of thanks to Sam. You take the best wishes of me and the industry with you to your new role. Gareth Pickering, Medical Plastics News

CREDITS

acting editor | aleksandra wisniewska advertising | gareth pickering art | sam hamlyn production | peter bartley production | tracey roberts 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: UK: £80 Europe and rest of the world: £115 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

© 2014 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.

BPA Worldwide Membership ISSN No: 2047 - 4741 (Print) 2047 - 475X (Digital)

JANUARY-FEBRUARY 2014 / MPN /5

AEROGEN BEATS STIFF COMPETITION TO SECURE the Irish Medical Technology Company of the Year Award

he very best of Irish medical technology companies was showcased at the Irish Medical Technology Industry Excellence Awards, which were held in Galway in December. Jointly hosted by Enterprise Ireland, IDA Ireland and the Irish Medical Devices Association, a business sector within Ibec, the awards are a prominent feature in the European med tech events calendar, are very highly regarded and attract both global and indigenous Irish companies all vying to secure the top awards. The overall winner of the Irish Medical Technology Company of the Year Award 2013 was Aerogen Ltd. Aerogen is no stranger to scooping top awards, having also recently secured the 2013 Zenith Award from the American Association of Respiratory Care (AARC) in recognition of its breakthrough nebuliser technology. Also recognised on the night was The University of Limerick, which won the Irish Medical Technology Academic, encompassing the Emerging Medical Technology Award. Silver Awards went to Abbott (Longford), which secured the Silver Medical Technology Company of the Year Award, and NUIG, which scooped the Silver Medical Technology Academic, encompassing the Emerging Medical Technology Award. Congratulating award winners, Colm MacFhionnlaoich, Manager Life Sciences Department at Enterprise Ireland, said: “Congratulations to both Aerogen and the University of Limerick on their wins. I’m delighted that Aerogen, an indigenous Enterprise Ireland client, won this award against such stiff competition from both home grown and international companies. Likewise, the University of Limerick stood out for its exceptionally successful collaboration with Cook Medical.” The remaining shortlisted organisations including Medtronic, Nypro Healthcare Ireland, Arann Technologies, BioInnovate Ireland and Galway-Mayo Institute of Technology (GMIT) were all highly commended for their excellence. “These awards really showcase the very best that the medical technology sector in Ireland has to offer. All those who entered, be they indigenous or multinational companies,

6/ MPN / JANUARY-FEBRUARY 2014

“The Irish medical technology sector is very strong, with many of the world’s top medical technology companies investing significantly in Ireland, and a number of exciting, researchbased, indigenous companies are emerging and competing internationally.” demonstrated that they were operating at the very highest levels of best practice and each exemplified the world class innovation that is taking place here in Ireland,” according to Sinead Keogh, IMDA Director. The Irish medical technology sector is very strong, with many of the world’s top medical technology companies investing significantly in Ireland, and a number of exciting, researchbased, indigenous companies are emerging and competing internationally. The industry in Ireland is changing from being predominantly manufacturing to being more complex and driven by R&D. Furthermore, the Irish government has identified the medical technology sector as one of the key drivers of industrial growth for the future and provides a wide range of support to encourage and foster this growth. Commenting on the medical technology sector, Andrew Vogelaar, Head of Medical Technologies, IDA Ireland, said: “The sector is of key importance to the Irish economy and has continued to grow year on year. Exports in 2012 rose by 10% to €7.9billion compared to

2011 and Ireland is one of the largest exporters of medical technologies in Europe. The sector employs 25,000 people in 250 companies, half of which are indigenous. The future looks bright for the med tech sector in Ireland and I’m very much looking forward to an equally successful 2014.” Medical Technology Company of the Year Award Aerogen is an innovative medical device and drug delivery company specialising in the design, manufacture and commercialisation of aerosol drug delivery systems. It was recognised for its project entitled ‘Clear Vision and bold strategies: Aerogen’s key to success’. From Aerogen’s MBO in 2008 it has implemented successful strategies to drive global business growth from the Galway base (30% CAGR). Aerogen has developed a worldleading aerosol technology enabling critical drugs to be delivered directly to the lungs. Through a successful R&D and manufacturing strategy, along with a targeted and focused commercialisation plan the company has delivered best-in-class medical device nebuliser solutions. Through its high performance team the company has created a holistic approach to medical device business development encompassing sales, marketing, engineering, manufacturing and customer care. Aerogen’s products are now used in Intensive Care Units in more than 60 countries around the globe, providing optimum care to the most critical patients from pre-term babies to adults. As the company continues to grow and prosper, the impact of Aerogen’s success can be seen from the one million patients who have benefited from the superior performance of Aerogen products. Commenting on winning the Company of the Year Award, John Power, CEO & Managing Director at Aerogen, said: “It is a great honour for Aerogen to be recognised as the Medical Technology Company of the Year 2013. As an Irish owned company we are immensely proud of the fact that our life saving products are sold in over 60 countries around the world and that today Aerogen is a recognised global brand leader in acute-care aerosol drug delivery.”

ON THE PULSE

Medical Technology Academic, encompassing the Emerging Medical Technology Award The University of Limerick (UL) has a long tradition of close collaboration with industry and business across many of the manufacturing sectors in Ireland including medical devices, pharmaceuticals, ICT and engineering. Its award winning project involved an innovative partnership between UL and international medical devices company COOK Medical, which was supported through the Enterprise Ireland Innovation Partnership Programme. The project resulted in scientists and engineers from the University of Limerick and COOK Medical inventing a new metal that will make medical devices inside the body more visible under X-ray. This project is a successful case of industry-academia collaboration in implementing breakthrough innovation into commercial products that benefit patients worldwide. Commenting on winning the Medical Technology Academic, Dr Mary Shire, VP Research, University of Limerick, said: “This award endorses the University of Limerick’s

focus on translation of research to affect the real world. This project is an example of where Irish research is cutting edge, has significant commercial value and ensures better therapy for patients. The success of this project can be attributed to a real team effort between COOK and UL.” Medical Technology Outstanding Contribution Award The prestigious Medical Technology Outstanding Contribution Award was given to Dr Jim Browne, President of NUIG. For over 25 years, Jim has been a key driver in the promotion of a strategic and integrated approach to the development of the med tech sector in Ireland. An industrial engineer by background, he is passionate about the need for industry and higher education to work together. Universities are the means of generating the human capital which the med tech sector requires: a welleducated and trained workforce; a strong culture of research; and an ecosystem of innovation. During his tenure as Dean of Engineering, up to 2001 at NUI Galway he

<< ABOVE: Aerogen Ltd was named Medical Technology Company of the Year at this year’s Medical Technology Industry Excellence Awards, which took place in Galway last night. Pictured at the awards are Tom Kelly, Divisional Manager, Cleantech, Electronics and Life Sciences at Enterprise Ireland; Sinead Keogh, Director IMDA; and John Power, CEO and Managing Director, Aerogen. >>

established the first accredited undergraduate degree programme in Biomedical Engineering in Ireland. Since then, as Registrar, Deputy President and now as President, he has continued to lead a prioritised research agenda in the area of Biomedical Engineering Science. Jim has led the development of a complementary range of interdisciplinary research centres and programmes at NUI Galway, including the National Centre for Biomedical Engineering Science (NCBES), Regenerative Medicine Institute (REMEDI) and Network of Excellence in Functional Biomaterials (NFB) to name just a few. These initiatives have resulted in a world-class clinical, research and people infrastructure at NUI Galway.

JANUARY-FEBRUARY 2014 / MPN /7

ON THE PULSE DuPont Named Strongest Global Biocompatible Brand BY MEDICAL PLASTIC PROCESSORS

uPont has been named the strongest biocompatible brand in a survey of global medical plastic processors concluded by Medical Plastics News in October 2013. Invibio Biomaterial Solutions is the second strongest brand, while BASF is third and Bayer MaterialScience is fourth. The results have been gathered after survey respondents were asked to select which single polymer manufacturer they believed had the strongest brand. The respondents were given a list of selected manufacturers to choose from. DuPont was chosen by 16% of all respondents with Invibio being chosen by 15%, BASF by 10% and Bayer MaterialScience by 8%. The survey identified a fairly positive outlook about the future. On a scale of one to 10, where 10 is very positive and one is very pessimistic, the average score was 7.2. Respondents in Asia were the most optimistic with a mean score of 7.8 while those in the

8/ MPN /JANUARY-FEBRUARY 2014

Americas gave a mean of 6.5 and those in Europe answered with a mean of 7.4. People who bought TPEs were most optimistic across all regions giving a mean score of 7.5. By contrast, buyers of polyolefins were least positive, giving a mean score of 6.7. Just over half of medical plastic processors use a distributor for some or all of their polymer requirements. Half of respondents purchased materials for injection moulding, a third bought for extrusion and a fifth for compounding. The most common application was surgical devices, followed by long term implantable â&#x20AC;&#x201D; orthopaedic, minimally invasive devices, long term implantable â&#x20AC;&#x201D; other, drug delivery and non-engineered drug packaging, and syringes. In terms of challenges, most respondents (43%) said that cuts to spending on healthcare were the biggest issue they faced. Overregulation (36%) and progress in research and development in new materials (29%) were second and third respectively. Looking at the

results from North American processors only, the biggest issue was over-regulation (49%) followed by cuts to healthcare spending (44%) and progress in research and development in new materials (29%). The exercise was part of an independent poll designed by Medical Plastics News to identify how well known and well liked the range of biocompatible polymer brands are by the medical plastic processing community. The results are available for purchase from Medical Plastics News. Polymer brands are divided into categories that allow meaningful comparisons to be made from one brand to the next. The main categories are: polyolefins, engineering polymers, polyketones, high performance polymers, resorbable polymers, TPUs, TPEs, silicone rubbers and PVC compounds. For more information about the survey please contact Gareth Pickering on gareth.pickering@rapidnews.com.

INTERPLAS The Boys Are Back in Town

estament to this, over 75% of the show floor has already been sold and allocated to exhibitors, with some of the biggest 2014 is set to be an names in the exciting year. Not only is industry it the year of the horse, signed up for the World Cup in Brazil what is and Glasgow’s turn to predicted to host the Commonwealth be a sell-out Games, crucially, it is an event. Interplas year. What “I am that means for the delighted plastics industry is the that opportunity to do big ARBURG are business. Thanks to the returning to recent resurgence in the Interplas fortune of the UK’s show. After manufacturing industry, some years, some of the world’s we felt it was biggest companies in the right plastics are choosing time to be Interplas as the perfect included in platform to target a the growing and lucrative exhibition,” market. Colin Tirel, Managing Director of ARBURG UK, commented. “As a leading supplier of

moulding technology it is important for us to demonstrate innovative and relevant technology to our market. The UK and Irish markets have been key markets for us for many years and so we believe we are supporting the market by being there.” ARBURG will be one of over 400 exhibitors taking their place in the hall at the event, which will run from 30thSeptember to 2nd October 2014 at the NEC in Birmingham. Exhibiting alongside them will be a whole host of companies in the machinery and equipment sector, including Engel, Sumitomo Demag, Summit Systems, Romi Sandretto, Ferromatik and Milacron Extrusion. The materials sector will be equally well represented, with confirmed exhibitors including Gabriel-Chemie, Distrupol, Plastribution, Resin Trade, Ultrapolymers and Albis, amongst others. The show, which was revived to industry acclaim after being taken over by current organisers, Rapid News Communications Group, in 2009, is expecting a steady increase in visitor numbers, with the total number attending likely to exceed 12,000 over the course of the three-day event.

“We are delighted by the progress we have made since taking the event over,” commented Duncan Wood, Interplas COO and Event Director. “An extremely encouraging 2011 — which saw Interplas back in growth across the key metrics of space sold, number of exhibitors and of course visitors — is set to be exceeded spectacularly by the 2014 edition. The momentum and appetite for the show is palpable across the industry.” Interplas will co-locate in 2014 with a range of complementary design and manufacturing events including the TCT Show + Personalize, Sensing & Instrumentation, Micro Nano MEMS and the PPMA Show. These shows make up an essential visit for anyone interested in the latest design and manufacturing technology, and every visitor will have access to all the shows on one ticket, enabling them to move seamlessly between the events. For more information about the show, visit the website: www.interplasuk.com

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Bespoke CNC Machined and Rapid Injection Moulded Parts

FOR THE MEDICAL INDUSTRY

roto Labs was founded as The ProtoMold Company in 1999 by Larry Lukis, a successful entrepreneur and computer geek. Larry previously was co-founder of a successful $100 million company that wanted to design a better printer — and was floored at the time and money it took to get injection moulded parts. His answer was to develop an automated process for producing injection-moulded parts in a fraction of the time and cost it had taken before. With a stated mission “to radically reduce the time it takes to get prototype injection moulded plastic parts” and “to make plastic injection moulding a practical option for products not requiring large quantities of parts” Protomold was off and running.

<< Figure 1: Proto Labs' European head office and manufacturing facility in Shropshire, UK. >>

With a rapidly growing customer base demanding more, the company pushed the technology envelope to produce bigger and more complex parts, introduced the Firstcut CNC machining service, opened up manufacturing facilities in Europe and Asia, and changed the name of the company to Proto Labs to reflect its growing capabilities. The two services offered by Proto Labs have different capabilities: Firstcut can be used for one to 10 CNC machined parts and Protomold for 10 or more rapid-injection-moulded parts. Medical-device designers wanting injection-moulded parts can submit their 3D CAD model using the Protomold webbased quoting system, Protoquote, to receive a detailed manufacturability analysis and an all-in production price within a day. Finished parts can be made from hundreds of medical-grade resins, including polycarbonate, polypropylene and TPE. In addition to the injection-moulding service, Firstcut is dedicated to producing CNC machined prototype parts as quickly and easily as they can be made using traditional rapidprototype (RP) processes. CNC machined parts are claimed to be far superior to RP produced parts due to their greater strength, better surface-finish and more accurate dimensions. Firstcut allows designers and engineers to make fully functional prototypes of products earlier in the development cycle. Choosing from over 30 different materials, including medical grade resins, aluminium, copper, brass and four grades of steel, the parts produced do not compromise any of the component’s physical attributes. Firstcut customers can upload a 3D CAD model to receive a FirstQuote, which includes a detailed cost and manufacturing analysis. Once the model is finalised, Firstcut’s software — running on Proto Labs’ ultra-fast compute cluster — automatically produces the cutting paths and then programmes the CNC machines. This eliminates the upfront programming costs and delays typically associated with CNC machining, and makes it a fast and affordable process for quantities of one to 10. Choosing between Firstcut and Protomold services. Before making the investment to have injection mould tooling made or high volume machining processes, Proto Labs’ customers will likely want to test a part that is as close to the production part 10/ MPN /JANUARY-FEBRUARY 2014

<< Figure 2: John Tumelty, Managing Director of Proto Labs in Europe. >>

as possible. Firstcut CNC Machining is the best option for this situation. Product designers often need just one or maybe a few parts for testing. Machining is the best option here as well, but traditional machine shops will often charge a significant nonrecurring engineering (NRE) charge for programming and fixturing. It’s this NRE charge that often makes getting very small quantities unaffordable. The automated Firstcut process eliminates the upfront NRE costs and hence reduces the overall cost of a project. Protomold rapid-injection-moulding is better suited to support prototyping that needs larger amounts of samples for functional or market testing, bridge tooling or low-volume production If engineers need parts before a tool can be made (typically 6-10 weeks with other moulders) or the volume requirements don’t justify expensive steel production tooling, Protomold can supply production parts to meet the customer’s full requirements in just 15 days, less if needed. Protomold’s process gives design engineers a fast and affordable way to get real injection moulded parts in prototype or lowvolume quantities. Working with advanced aluminium alloys and high-speed CNC machining the process features an unprecedented degree of standardisation and automation, which is how it delivers injection moulded parts so quickly.

COVER STORY

Case study PROTO LABS REINFORCES THE WAR ON CANCER

ermany-based Zellwerk GmbH is using single-use bioreactors provided by Protomold, the rapid injection moulded parts service from Proto Labs, to help combat cancer in patients where vital immune cells are deficient. Made from special plastic resin with carefully controlled surface finish properties, this groundbreaking system has opened up completely new perspectives in the world of regenerative medicine. When it comes to the war on cancer, the body has its own front guard: ‘natural killer cells’ are able to destroy their cancer cell rivals and prevent viral infections from spreading. Unfortunately, the immune system in many patients is already weakened to such an extent that it cannot produce enough of these precious cells. Now, however, Zellwerk GmbH of Eichstaedt, some 25 km northwest of Berlin, has succeeded in cultivating cells outside the human body in greater quantities than ever previously achieved. Zellwerk, a specialist in cell culture and tissue engineering, performs the task using single-use bioreactors manufactured using injection moulded components supplied by Proto Labs. Prof. Dr. Hans Hoffmeister, CEO of Zell GmbH, described the system while holding an inconspicuous, transparent plastic part with a lid in his hands. “What you see here is the core of our bioreactors. It meets all the requirements necessary to produce the body’s own cells in the same quantity as drugs, in a standardised and repeatable process,” he said. “This patented system is both a revelation in regenerative medicine and the dream of biomedical scientists. It takes a sample from the patient such as blood, isolates the immune cells, cultures them outside the body in large quantities and leads them back to fight tumour cells.” The Zell system is called Z RP Technology and comprises an incubator, located in the sterile work chamber of the bioreactor, and a special adapter. An external control unit monitors, controls and documents all of the parameters. “It is critical that ‘laminar flow’ is created in the plastic reactor,” said Prof. Dr. Hoffmeister. “The cells are placed on the bottom of the reactor and flushed evenly without creating turbulence. Simultaneously, cells with oxygen and fresh medium are supplied, while spent media is transported and a constant pH maintained.” To ensure the repeatability of the process, the vital element of the challenge was to create a special surface in the reactor offering the optimum amount of friction — not too smooth and not too rough. Construction Manager Rainer Mausolf summarised the requirements for the reactor resin and its surface condition: “The choice of plastic was crucial because we needed to provide constant chemical and physical conditions in the reactor. We tried several common plastics but had difficulty in finding a material that was resistant to sterilisation by gamma-rays. Finally, with the help of Proto Labs, we found the optimum resin for our system,” he said.

“Proto Labs also helped extensively with the implementation of our surface requirements. In Z RP Technology systems the cells must not be free to be rinsed around and therefore require a finely grained surface on which they find support. Only this makes it possible to have a standard, repeatable process. To keep the conditions uniform throughout the system we have a probe upstream of the reactor adapter that continuously measures the pH, temperature and oxygen, and relays this data to an external control unit.” All the bioreactors and probe adapters (in different versions) used in Z RP Technology are manufactured using the Protomold rapid injection-moulded parts service. “At first we could not believe the speed and reliability of the service,” said Mr. Mausolf. “We knew of no other suppliers who could deliver finished parts within 10 days of transferring the 3D model. Sometimes we would even receive components within five days, if we had opted for this. The process was so simple: I just uploaded my 3D SolidWorks model to the Protomold website. Almost immediately my quote arrived and shortly after I was contacted with valuable tips on implementation. Within days we had received the first reactors and adapters made using our special plastic.” Prof. Dr. Hoffmeister added: “For Zellwerk this is both the most ideal and least expensive solution. We absolutely rely on parts made of ‘real’ material. Substitute materials, such as those offered by traditional prototype methods are useless for us. Without Proto Labs, we would have never made as quickly and inexpensively a fully functional bioreactor for growth of the body’s own immune cells that meets the stringent requirements of regulatory agencies.” Z RP Technology bioreactors from Zellwerk now represent the most advanced cultivation technology commercially available for adherent cell types and tissue engineering purposes. www.protolabs.co.uk

JANUARY-FEBRUARY 2014 / MPN /11

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<< Table 3: Chemical Resistance of CYROLITE Protect 2. >> Chemical

Tensile Strength at Yield (kpsi)

% Elong. at Yield

Modulus (kpsi)

Lipid

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236

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3.8

247

IPA

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245

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5.53

3.8

252

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Modulus

Lipid Resistance

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100

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IPA Resistance

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100

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for FDA regulated Class 1 or Class 11 medical devices covered by 510(k) submission. They also comply with RoHS and do not contain heavy metals, phthalates, natural latex or conflict minerals. The typical application for those products include but are not limited to luer connectors, IV spikes, needle hubs, adapters, fittings, filter housings, Y-sites, valve assemblies, protection caps and covers and sharp needle dispenser receptacles. Other favourable attributes in the Protect family include easy processing, resistance to gamma, e-beam and ETO sterilisation, free of bisphenol A (BPA) for both CYROLITE Protect and CYROLITE Protect 2, bondability to PVC tubing and easy welding. The antimicrobial capabilities are incorporated within the polymer structure so that there is no need of a secondary process step. Besides antimicrobial capabilities, CYROLITE Protect acrylicbased multipolymer compounds provide excellent processibility. CYREX Protect alloys offer outstanding impact resistance, toughness and high heat resistance. The newest addition to the

Protect family, CYROLITE Protect 2 acrylic-based multipolymer compounds focus on superior resistance to lipids and to alcohol. Evonik has been continuously working to expand the product portfolio to match market trends and meet customers’ needs. Due to significant concern and growing financial burden, the healthcare industry implemented many infection control methods including swabbing devices with alcohol before use to prevent HAIs. Lipid and alcohol contact can cause devices made from other plastics to fail and CYROLITE Protect 2 has been designed to address this challenge. The products retain antimicrobial efficacy after Gamma and ETO sterilisation, as shown in table 2. Table 3 shows chemical resistance of CYROLITE Protect 2. Both CYROLITE Protect and CYREX Protect have already been commercialised in the last two years. Evonik will launch CYROLITE Protect 2 at the MD&M West Exhibition, 11-13 References: 1. February 2014 at the Anaheim Convention Center, CA, USA. BCC Research, 2011: HEALTHCARE-ACQUIRED INFECTION: DEVICES, HARMACEUTICALS, AND ENVIRONMENTAL PRODUCTS (HLC092A) 2. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 4. Department of Medicine, Ralph H. Johnson VA Medical Center, Charleston, South Carolina 5. L.A. Herwaldt, J.J. Cullen, D. Scholz, P. French, M.B. Zimmerman, M.A. Pfaller, R.P.Wenzel, T.M. Perl, Infect. Control Hosp. Epidemiol. 27 (2006) 1291. 6. K. Page, M. Wilson, I.P. Parkin, J. Mater. Chem. 19 (2009) 3819. 7. From Wikipedia, the free encyclopedia 8. A. Peleg, D. Hooper, N Engl J Med. 2010 May 13; 362(19): 1804–1813. 9. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005; 41:848–854. 10. Pollack, Andrew. “Rising Threat of Infections Unfazed by Antibiotics” New York Times, Feb. 27, 2010 11. A. Bhalla, N.J. Pultz, D.M. Gries, A.J. Ray, E.C. Eckstein, D.C. Aron, C.J. Donskey, Infect. Control Hosp. Epidemiol. 25 (2004) 164. 12. J.M. Boyce, G. Potter-Bynoe, C. Chenevert, T. King, Infect. Control Hosp. Epidemiol. 18 (1997) 622. 13. D. Talon, J. Hosp. Infect. 43 (1999) 13. Disclaimer In so far as forecasts or expectations are expressed in this press release or where our statements concern the future, these forecasts, expectations or statements may involve known or unknown risks and uncertainties. Actual results or developments may vary, depending on changes in the operating environment. Neither Evonik Industries AG nor its group companies assume an obligation to update the forecasts, expectations or statements contained in this release.

Dr. Zhen Zhu is the Director, Business Development, Innovation & Technology, Acrylic Polymers at Evonik Cyro LLC. She received her Ph.D in Polymer Science and Engineering in 1988. She has 14 years’ academic experience in polymer structureproperty relationship and characterization of different polymers. Her area of expertise of the last 18 years in industry is new product development from concept to commercialisation, including idea generation, feasibility assessment, intellectual property analysis, formulation development, design of experiment and scale up. Dr. Zhen Zhu has held noteworthy positions at various universities in Asia, Europe and North America as well as prestigious positions at Polyone, GE, Honeywell and SaintGobain before joining Evonik. With great business insight and strong technical skills, she guided her team at Evonik Cyro to focus on customer and market needs and perform research, business development, product/process development and technical service for the medical, optical, automotive and architecture applications. JANUARY-FEBRUARY 2014 / MPN /17

3D PRINTING

ALL ABOARD: The 3D Revolution is Spreading Like Wildfire

<< Figure 1: The 3D printer Replicator 2 by MakerBot currently sells for about 1,890 Euros and as model 2X for ABS plastics, 2,290 Euros. >>

Andrea Köhn, Bötel Graphic Communication

lmost unnoticed, revolutionary production technologies have emerged without any meaningful input from big players. Instead, the initiatives came from researchers, small start-ups and in their garages THE DÜSSELDORF TRADE tinkerers who experimented with SHOW AND VDMA (GERMAN printing threeINDUSTRY FEDERATION) dimensional stuff. As is with all technical ANNOUNCE LAUNCH OF THE common revolutions, the 3D FAB+PRINT BRAND ‘movement’ thrives on its early protagonists’ enthusiasm, which in our case happens to be mostly made up of middle-aged, male tech aficionados working in tandem with a complementary open-source community. These so-called ‘makers’ espouse the trend toward personal production and the networking of things. Social utopians entertain dreams of repossessing the means of production by the ‘masses’, tech enthusiasts the triumph of self-replicating machinery. The elation of a new age, together with goldrush-like optimism is palpable, notwithstanding that many young businesses will soon join the corporate world, fairly quickly abandoning their open-source ideals en route.

Still, 3D printing is not without history. Long before the internet changed the world, laser-based processes for industrial applications had been developed, e.g. for the manufacture of prototypes and models to be used in the production of limited numbers of work pieces and building components. Other than is the case with standard injection moulding processes, 3D printing bypasses the labour-intensive set-up of jigs, together with the various processes of cutting, lathing and drilling. As an undeniable fact, the 3D revolution’s social and economic repercussions are making themselves felt. In times where the life cycle of products continues to compress while the number and variety of products inexorably expands, the printing robots that work tirelessly producing complex objects at precision levels unmatched by mere mortals, are just what the doctor ordered. Especially in the field of tool system technology, construction component production, medical device technology and the consumer goods industry, 3D print technology occupies an immensely important place. For those reasons and on the occasion of K 2013 (the international trade show for plastics and rubber), the Düsseldorf trade show and VDMA decided to launch the 3D fab+print in October 2013. Under its umbrella, all

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3D PRINTING

<< Figure 2: The design engineer and mathematician Adrian Bowyer (born 1951) teaches mechanical engineering at Bath University. His manifesto “Wealth without money“ dating from 2004, gave rise to the RepRap movement. >>

Continued from page 19 relevant Düsseldorf trade shows will in the future bring together their respective exhibitors with the goal of moving the entire subject into the focus of industry observers. Related shows featuring 3D fab+print include COMPAMED (12-14 November 2014), taking place simultaneously with MEDICA (12-15 November 2014), the four standbys GIFA, METEC, THERMPROCESS and NEWCAST (16-20 June 2015), in addition to drupa (31 May to 10 June 2016).

<< Figure 4: The Cube by 3D Systems can print with two materials in a single print operation and sells for $1,600. >>

<< Figure 3: The version 1.0 of RepRap called Darwin replicated for the first time all its own plastic building components in May 2008. >> Consequences of the 3D revolution 3D printing not only supplants, reconfigures and leverages traditional processes, but accelerates innovation by virtue of the fact that an instant creation of solid prototypes and tangible templates has numerous benefits. In the consumer space, unit costs of mass-produced articles will always stay below those of customised manufacture, yet at the very margins, some share of the manufacturing process may well be taken over by the consuming public itself. It would hardly be a detriment to the economy, since these unaffiliated manufacturers still need 3D technology besides materials and support, at the same time creating brand new lines of business, e.g. printing services for those who are reluctant to invest in a 3D printer themselves. We all recall the unreal rates a square foot of digital printing on fabrics commanded back in its early years. Birth pangs Hewlett Packard was the first of the large press manufacturers to enter the 3D printer business. Between 2010 and 2012, the US American IT company had struck an alliance with Israeli-American Stratasys. The result: devices with the names HP Designjet 3D and HP Designjet Color 3D, that are no longer on the market. Now, HP is about to embark on a second attempt. Meg Whitman, HP’s CEO, made it a point to personally announce the initiative: “3D printers are still in their infancy,” stated Whitman. “It’s a great opportunity and we are very much committed. By the middle of next year, we will have something to show.” The strength of HP’s conviction may be somewhat debatable, though, since Ms Whitman stressed that actual revenue flow from the sector to the bottom line is a long way off. Indeed, patience is the order of the day, not the least because the costs of efficient 3D printers mean they remain out of reach for many, as does the raw printing

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3D PRINTING

<< Figure 5: The FDM 3D printer Mojo by Stratasys is currently thought to be the smallest 3D printer in the professional space. >>

material, the variety and selection of which still leaves much to be desired. In addition, the machines currently available run at an agonizingly slow pace. Meg Whitman described it thus: “To print a bottle may take eight to 10 hours. All quite interesting, but it feels like watching grass grow.” The hope for these birth pangs to be soon a thing of the past seems to be justified, however. 3D printing is more than hyping some pipe dream, but a veritable revolution of production technology. Right now, 3D printing is mostly limited to CAD supported laser cutters, lathes or injection moulding machines, yet new ideas have benefitted all industries over time. Incorporating 3D printing into the canon of printing technologies as a fourth pillar next to letterpress, offset and digital print is the right thing to do; no half-way measures, please. Sing its praises in high schools, vocational training classes, professional associations, and especially, companies. Online print shops print on the strangest objects like Christmas baubles and coffee mugs. It only makes sense to also create certain objects according to customer instructions as the infrastructure and skilled labour is already in place. A realistic prospect to profit handsomely is certainly there. The time is now to define and hone business models, for as you sow, so you shall reap. The potential of it all is reflected when taking a look at the shares of Stratasys. 10 years ago, they sold for $7.58. Today, they change hands for $114 and an end to the rally is nowhere in sight. Market survey Getting your feet wet in 3D printing is relatively easy. Building sets and apparatuses for beginners can be had for around 300 Euros. Professional machines sell for 3,000 Euros and up. But these machines, being used in industrial applications, are under a great deal of pricing pressure. Analogous to 2D printing equipment, three categories of machinery have also emerged in the 3D sector: for home use, for professionals, and for industrial application. Two dozen manufacturers from all over the world are currently offering solutions for the press floor. Most of them were inspired by the RepRap project, originally conceived by Adrian Bowyer, a professor for evolutionary research at Bath University in England.

RepRap stands for Replicating Rapid-Prototyper and is a 3D printing press, the blueprint of which Bowyer had published under a GNU general public licence with the goal to achieve rapid proliferation. Vendors like Ultimaker and Makibox follow in its footsteps. The best-known American maker of 3Dprinters, Makerbot in New York, used to be a non-profit organisation. Since 2013, it has been a subsidiary of Stratasys and the current 3D printer model Replicator 2, unlike previous models, no longer bears any resemblance to the open source matrix. The English manufacturer Bits from Bytes was also bought out. The company started with the 3D printer RapMan, a commercial version of the open source hardware RepRap Darwin. In October 2010, the enterprise was taken over by the leader in the consumer sector, the American company 3D Systems. The South Carolina based organisation is currently firing on all cylinders. Resources for research and production at their main plant in Waterford Business Park of Rock Hill are at the limit of their capacities; for those reasons, 3D Systems plans an additional site creating up to 133 new jobs. In the professional sector, Stratasys is the undisputed worldwide leader. The concern has two head offices in Eden Prairie (Minnesota, USA) and Rehovot (Israel) in addition to six branch offices, one of them in Rheinmünster near Baden-Baden, Germany. Stratasys’ product range extends from popular-priced desktop 3D printers all the way to large state-of-the-art 3D production systems. With 150 photo polymers and thermo plastics, it also features the largest assortment of special materials. World leader for industrial applications in the Laser Sintering sector is EOS GmbH in Krailling near Munich/Bavaria. Dr. Hans J. Langer and Dr. Hans Steinbichler founded the company in 1989. It supplies customers like MTU, EADS, Daimler and BMW with 3D printers for their production sites. China supports its 3D printer industry through TierTime Technology Co. Ltd., founded 2003 in Peking. Their devices are marketed under the name Inspire. In short: whether high-end products, one of a kind, or small-scale series — the capabilities of 3D printers are advanced enough right now to perform many conceivable and as yet inconceivable tasks.

Continued on page 22

JANUARY-FEBRUARY 2014 / MPN /21

3D PRINTING << Figure 6: Platforms like Thingiverse offer thousands of CAD data with print templates for downloading and individual printing. >>

Continued from page 21 One principle, many processes 3D printing, also known as Rapid Prototyping or Additive Manufacturing, is based on the layering principle, an additive process by which the objects to be printed are built layer upon layer from several liquid or powder-like substances. In the course of printing, chemical and/or physical processes precipitating curing and/or melting take place. For those reasons, the typical materials used are artificial resins, plastics, metals, ceramics and paper. Manufacturers currently use a number of 3D print processes, which in their application are fundamentally alike except for a few patented variations. Among the most notable processes employed are selective laser melting, electron beam melting for metals, selective laser sintering for plastics, stereo lithography, digital light processing, polyjet modelling for photopolymers, and fused deposition modelling for thermoplastics. Most 3D printers at this time process only a single type of material or some kind of blend. There have been tests, though, to use plastics with different degrees of hardness and

colour in a combined printing process. Industry giant Stratasys took out a patent on a variation of layering by melting, or FDM technology (fused deposition modelling). The FDM process melts delicate, semi-liquid strands of the thermoplastic acrylnitrilbutadiene-styrol (ABS) with a spray nozzle, piling layer upon layer to eventually assume the final objectâ&#x20AC;&#x2122;s shape. The PolyJet technology deploys photopolymers that are instantly cured under UV light and indistinguishable from products made by injection moulding. www.drupa.de

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WEARABLE DEVICES

Developing a Better Wearable Medical Device — Critical Issues to Consider

WORDS | Kyle Jarger, Program Manager, Farm

ure, your firm has designed and developed a lot of medical equipment. You’ve developed a solid understanding of the requirements and pitfalls of designing medical equipment that will be used in a hospital, in an ambulance, and maybe even in a patient’s home. But while you were busy, a confluence of technical breakthroughs and regulatory updates have awakened the wearable medical device industry. It’s not just about hearing aids and Holter monitors any more, and now your marketing people have asked your engineering group to specify and design your company’s first product to be worn by a patient directly on their body. Now what are you going to do? The following is an attempt to illustrate how several hardware-focused electrical and mechanical considerations are prompting developers to adopt an approach to wearables design that may differ greatly from that of desktop or portable medical devices, along with suggestions on how to adapt the wearable product development process.

reveal problems with early prototypes and help the product developer arrive at the most effective solution for the target enduser.

Consider your intended user population. Is there a certain patient age, weight or size that represents your typical user? Ideally your product could be designed so that one model of the device — perhaps with an adjustable feature — could work for your entire end-user population. Should it appear that two or more versions/sizes of the device are required to satisfy your user population, you’ll need to consider the trade-offs between excluding users at the extremes of the target population versus the complexity and sales/support implications of releasing multiple devices. A programme of usability testing can often

Avoid small, easily-removable parts if possible. Your device will be exposed to all of the activities and chaos of daily life. Any small parts that can intentionally or unintentionally become disconnected from your device will get dislodged and lost, and possibly render your device useless. If a small, easily-removable part is required for the functionality of the product, consider providing the healthcare professional and/or the user with spare parts as appropriate to allow your wearable device to continue functioning. Continued on page 24

Another important consideration is the user’s ability to operate small electronic devices. Some patient populations may not have the experience, eyesight, or hearing acuity required to operate small controls or react appropriately to status indicators or alarms. For wearable devices, giving the patient a simple user interface is always preferable. Leave the complex device setups and interactions to the medical professional who is caring for the patient. If the patient is required to use a smartphone, tablet PC, or custom device to interact with the wearable device despite your best attempts to avoid it, be sure that the user interface is clear, simple and intuitive. This is another aspect of product development that can benefit from usability testing.

JANUARY-FEBRUARY 2014 / MPN /23

WEARABLE DEVICES

Biocompatibility evaluation according to ISO 10993 - Biological evaluation of medical devices may be new to you if this is your first wearable product. The acceptability of materials intended for patient contact is classified based on the amount of time that the material is expected to remain in contact with the patient. Ideally, a material that has already been validated for biocompatibility by the manufacturer can be located for use in the patient-contacting areas of your device. If not, ISO 10993 requires the manufacturer of the device to perform biocompatibility testing on the material in question, generally using the services of a third-party vendor. Since the wearable device will be used in the patient’s home, two guidance documents apply: the IEC standard 60601-1-11 Requirements for Medical Electrical Equipment and Medical Electrical Systems Used in Home Care Applications and the FDA document Draft Guidance for Industry and Food and Drug Administration Staff, Design Considerations for Devices Intended for Home Use. These address many of the safety and usability requirements that a wearable device or a system that includes a wearable device will need to meet. Regarding electromagnetic compatibility (EMC), wearable medical devices fall into the same category as other devices intended for use at home, and are generally subject to tighter EMC regulations than equipment intended for use in a healthcare facility. The governing standard is IEC 60601-1-2 - General requirements for basic safety and essential performance Collateral standard: Electromagnetic compatibility Requirements and tests. If there is an IEC particular standard (IEC 60601-2-X) for the type of device you are planning, you may find that there are clauses of the standard that cannot be applied to a wearable version of the device. Be aware of these details before claiming that your device meets the particular standard. Discuss the implications with your Marketing department if you find that you will be unable to claim compliance to the particular standard. If your company has already released non-wearable devices with functions and features similar to your planned wearable device, take advantage of the product history and records available to you. You may find areas where problems or failure modes will be exacerbated when the device becomes a wearable. Similarly, opportunities may arise to further mitigate failures, improve performance or reduce costs. An example might be an electrode cable for an Electrocardiogram (ECG) device. Much effort is spent ensuring acceptability of ECG cables for a particular application, for example flexibility, triboelectric effects and EMC. If the ECG electrode can be integrated into the device itself, the ECG cable and its associated functional requirements, failure modes and costs no longer need to be considered. If at all possible, your wearable design should be wireless and self-contained within a single housing. Device components that are wired together to create a system when the device is worn will inevitably cause patient discomfort or disconnect as the wires tug on the device components or become tangled in the patient’s clothing. The connections between components also create possible failure points. Consider the environment in which your wearable device will be expected to operate, as well as environments where a failure to

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Carefully consider the scheme that will be used to provide power to the wearable device. To optimise your patient’s experience, consider how to best integrate the charging or replacing of batteries into the workflow, use requirements, and allowable ‘down-time’ of your particular device’s functionality. operate under a specific condition is acceptable. As a wearable product, the device will be exposed to sweat regularly, and perhaps to other bodily fluids or rain. The device will be squeezed, dropped and mechanically shocked constantly. Where a failure to operate in a specific environment is found to be acceptable, ensure that the device fails in a safe manner. Have a clear understanding of how the patient will be expected to deal with the wearable device during showering or bathing. Ensure that this information is clearly communicated to the patient. If necessary, consider how the wearable device will be cleaned by the patient or healthcare professional. In the event that the device or part of the device is to be washed by the user or healthcare professional, ensure that the instructions for use are clear regarding device preparation, water temperatures, detergent or cleaner types and drying methods. Should disassembly and re-assembly of the device be required for cleaning, simplify these actions as much as possible. Carefully consider the scheme that will be used to provide power to the wearable device. To optimise your patient’s experience, consider how to best integrate the charging or replacing of batteries into the workflow, use requirements, and allowable ‘down-time’ of your particular device’s functionality. This information will help to optimise design trade-offs such as device size/weight vs. battery run-time. Ideally, this familiarity with your target patient’s abilities or limitations, the requirements of the device, and the optimum use scenario will allow you to determine if your device is best designed with the battery permanently enclosed within the device or user-replaceable. Consider the use of wireless charging methods, as this technology has the potential to greatly simplify ease of use. Of course, battery safety and regulatory requirements must be strictly followed in all cases. Your wearable device may require active accessories to provide for data display, data storage, communications or recharging. Carefully consider how best to allow for the transfer of data or power between system components, while minimising the quantity and complexity of the tasks your user is required to perform. Ideally these connections and communication between system components should be implemented using wireless technology and occur automatically, with no patient involvement. The medical device industry is entering a ‘Golden Age’ of wearable product development that is being supported by both regulatory progress and significant innovation in battery technology, materials science and wireless communication. This article has touched on a few of the many critical issues to be considered in the design and production of a safe, usable and successful wearable medical device.

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REGULATION REVIEW

Risk-Based ‘Three Loops in One’ CAPA Process IS CRITICAL TO ENSURING PRODUCT QUALITY Ken Peterson, Director of Business Development, Quality and Compliance Consulting Team, MasterControl Inc.

n regulated environments, corrective action and preventive action (CAPA) is inherently tied to the concept of product quality. The assumption is that somewhere along the line of developing and manufacturing a product, something is likely to go wrong that could affect quality. An effective CAPA process is, therefore, critical in addressing and minimising the impact of deviations and nonconformances and making sure that they don’t recur. Companies regulated by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other regulatory entities, as well as companies that adhere to ISO quality standards, ICH quality guidelines, and similar international standards should maintain a CAPA process as part of their quality system. These companies must pass quality audits and regulatory inspections as part of their compliance efforts. A CAPA process in a regulated environment must be ‘closed loop.’ The newer risk-based processes utilise a ‘three loops in one’ methodology that uses a gateway for determining what type of action is needed to solve the situation. What is ‘three loops in one’ and why is it important? ‘Three Loops in One’ CAPA Regulations such as 21 CFR Part 8201 and international quality standards such as ISO 13485 and ISO 9000 series have specific CAPA requirements2. As required by these regulations and standards, CAPA is necessarily a solution-driven process that sometimes appears like a ‘maze’ to quality teams. ‘Three loops in one’ is meant to help the quality team and other CAPA professionals come up with the right solution that resolves the issue in a compliant way. In my recent CAPA webinar, I talked about the ‘three loops in one’ CAPA methodology, which consists of: First Loop: A quality issue begins with the quality event, which means that something has gone wrong (e.g. customer complaint, deviation, audit findings, etc.) and your organisation needs to find out why it happened. For example, an issue that comes in as a customer complaint should be resolved quickly. If the problem is minor and there’s a solution that can be performed immediately and sufficiently, then you can often close the complaint at this stage with an effective containment or correction. Second Loop: If the issue (e.g. customer complaint) is significant, it moves to the second phase. Typically, the quality team conducts a risk-based review process (also known as risk-based filtering process) to determine if the problem needs to be escalated to CAPA. If the issue can be resolved with some

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containment and some trending and tracking so it can be monitored, then you can close it at this stage with the focus still on containment or correction. Third Loop: If the quality team decides that the customer complaint warrants a full-fledged CAPA, then a CAPA is initiated, followed by a root-cause investigation. Once the root cause is determined, a corrective action can be performed, and sometimes it might also require a preventive action. The team will then proceed to verify and validate the corrective action to make sure that it resolves the problem. This includes performing trending, tracking and monitoring to obtain measurements for assurance that the quality issue has indeed been resolved. In summary, ‘three loops in one’ refers to a quality event system that has three stages, and each stage with decision points based upon risk assessment to ensure an effective and compliant action for issue resolution. How do you arrive at the right solution? Your organisation needs a sound methodology or process that’s replicable and reliable and will lead to critical thinking, which in turn will lead to the right solution. You need a CAPA process and framework that will help you ask the right questions. If you do that, you will arrive at the right solution each and every time. View my webinar and learn more about what questions to ask during a closed-loop CAPA process. It is available to watch free of charge at www.mastercontrol.com/capawebinar. References: 1 Code of Federal Regulations Title 21 Part 820, also known as Quality System Regulation, is an FDA-enforced regulation for medical device companies and manufacturers. Subpart J is devoted specifically to CAPA requirements. 2 ISO 13485 is a set of quality standards for medical device firms and manufacturers, while ISO 9000 series is broader and applies to almost any type of business.

Ken Peterson is MasterControl Inc.’s director of business development, Quality and Compliance Consulting Team. He has helped many organisations (including Abbott Laboratories, Kodak, and IBM) come up with new quality management solutions that allow them to achieve enhanced and breakthrough results. MasterControl provides software and comprehensive services (consulting, education and training, validation, implementation and project management) to regulated companies worldwide. The company has corporate headquarters in Salt Lake City, Utah, and offices in both Europe and Asia.

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<< ABOVE | Figure 1: A gripper at the ATM facility. >> << RIGHT | Figure 2: A welding cell. >>

W Making Medical Sector Automation Better Sam Anson, Medical Plastics News

ith a history spanning over 40 years, ATM has come to be recognised as a leading supplier of robotics and automation within the UK. The company’s excellent reputation for quality and reliability has also spread beyond these shores with exports to Europe, Asia and the USA, fast becoming a major part of ATM’s business. The company continues to see expansion and diversification across its customer base, with the medical sector currently representing around 30% of the company’s turnover, and growing year on year. Supplying automation into the medical sector brings with it its own set of challenges, not least the stringent regulatory standards and procedures which must be adhered to, but there are often other obstacles which need to be overcome before an automation solution can be deemed feasible and cost effective. ATM’s longstanding experience within equally demanding

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AUTOMATION

<< Figures 3 and 4: Sam Anson, Medical Plastics News, and Sabir Hirji, Director of ATM, at the company’s facility in the UK. >>

Continued from page 29 sectors, such as automotive, allows the company to apply its wealth of information to develop what are often innovative and sometimes unique solutions to medical sector automation applications. During the initial stages of a project it is not uncommon for the automation supplier to be presented with little more than a series of component drawings and perhaps some representative prototype parts. The manufacturer at this stage is often looking for an outline concept and budgetary pricing to determine if automation will be financially justifiable. From the point of view of ATM however it is essential that the application is reviewed in detail, not only to decide on the best approach for automation, but to identify any potential issues or technical risks associated with each specific operation. ATM Director Sabir Hirji explained: “Even what might on the face of it appear to be a simple task, can sometimes pose significant challenges for us at the early stages of a project. Just removing a component from the mould tool requires consideration in terms of: How can we hold the part? Will vacuum cups leave unacceptable marks or contaminate the part? We need to repeat this process for each and every proposed operation to maintain the integrity of the component. This in turn leads us then to consider the different technologies that we may use to for handling, assembly, joining and inspection etc. Although at the outset, the customer may only be able to provide us with basic information, we need to be certain that our

concepts are technically robust, as at the end of the day the customer expects productivity, efficiency, quality and reliability from their system.” Whilst this requires a significant investment in time on the part of the automation supplier, it is often the only way to fully understand the customers’ requirements and assess risks. This process, however, is also highly beneficial for the end user as it will usually identify any pre-requisites that may need to be in place to maximise the benefits which automation will bring. This can range from ensuring individual piece part consistency through appropriate tolerances, to having the right calibre of individuals in place for operation and ongoing maintenance. Proof of Principle — Getting it Right Ahead of Time The use of proof of principle helps to establish that the chosen concept is appropriate for the application, ahead of a commitment by the end user to purchase a production system. The extent of the proof of principle process varies from application to application and can be as simple as assessing or testing the repeatability of a particular component, process or operation, right through to building a fully functioning but off line version of an element of the proposed machine or system. This is especially useful when seeking to evaluate complex assembly operations or to determine the capabilities of a new process. Sabir Hirji explained further: “Whilst this may often require an up front investment by the customer to fund the

Continued on page 32 JANUARY-FEBRUARY 2014 / MPN /31

Continued from page 31 purchase of proprietary equipment and the manufacture and build of the station in question, the benefits to all parties can be significant. From the point of view of ATM, the information generated from these trials allows concepts to be refined and technical risk reduced, whilst the customer will benefit from increased confidence in the process or application and also recoup the up front costs through savings in development time, which is reflected in the machine or system price.” Examples of how proof of principle works in practice were evident during the recent tour of the ATM facility. A system used to produce disposable tonometer optical lenses uses a clever lighting arrangement combined with a machine vision system to measure the flatness of an optical surface to micron level. Light passes through a filter arrangement and then through a prism to produce a series of parallel lines on the optical surface of the component. Defects on the surface, either convex or concave, result in a deviation in the parallel lines, which is measured by the vision system to determine whether the component is within the required specification. Sabir Hirji explained: ”At the end of the day, although this solution is quite innovative it is not particularly complicated, but it was far better to establish this well ahead of the final machine design through proof of principle trials. This measurement is one of the key features of this system and proceeding to build without confirming the concept for this station would have been foolhardy.”

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Future Proofing Through Diverse Technologies The continual development of new medical devices, drug delivery and diagnostic test systems has influenced the types of technologies used within medical sector automation. As some of these products become more complex, the number of individual operations needed to complete an assembly often increases. In some cases there is a requirement for the part for be manipulated or orientated several times between processes and in these instances robots — especially the SCARA and 6 axis varieties — are finding their way in increasing numbers into production systems. Sabir Hirji commented: “If you look back at our business some 10 years ago you would find that Cartesian robots were the mainstay for de-moulding and some post moulding operations. You would also find many more dedicated machines, configured to perform a number of operations on just one part type. Today however, the ongoing drive by our customers for flexibility and future-proofing means that we are using greater numbers of 6 axis and SCARA robots, some of which are also vision guided, to provide the flexibility needed. We also find ourselves using servo operated linear motions systems as opposed to simple pneumatic devices in many cases as this also provides the option of re-programming to accommodate product changes or indeed new variants of product.” Hirji continued: “Fulfilling the requirements for traceability and process monitoring has also had an influence on the types of technologies used within our medical sector systems. In joining applications for example, the use of ultrasonic or laser welding technology not only allows precise control of the process but also enables us to record and store the parameters used on the part. The more traditional technologies such as hot air cold staking (HACS), whilst perfectly capable of producing a good joint, do not offer the levels of control and traceability needed in many instances. Part identification and traceability, through the use of 2D matrix codes, has also become a technology with which we have become familiar in recent years.” What became clear from this visit is the fact that medical sector automation here in the UK is in good health and being driven by a passion, evident within ATM, to seek out and apply new and innovative ideas and technologies.

AUTOMATION

STARTING A NEW ERA in Pipette Tip Manufacturing Bettina Leibold, Waldorf Technik GmbH & Co. KG

o you believe that 32 cavities for high-quality pipette tip manufacturing in a 6-second cycle time is very demanding? This productivity level might become history soon, if the trend in this sector keeps heading in the same direction. Waldorf Technik THE SPEED OF TECHNICAL recently exhibited a DEVELOPMENT IN THE AREA 64-cavity system with OF PIPETTE TIP OR REACTION 4.3 second cycle time at a VESSEL MANUFACTURING trade show, and is now in ENTERS A NEW LEVEL. THE regular industrial operation SPREAD OF EFFICIENCIES AND with this performance at a customer’s facility.

QUALITY LEVELS BETWEEN TRADITIONAL AND MORE AUTOMATED PRODUCTION ENVIRONMENTS REACH A NEW PEAK AND IS BOUND TO REVOLUTIONISE THE INDUSTRY. ONE OF THE MAJOR DRIVERS OF THIS TREND IS THE GERMANY-BASED COMPANY WALDORF TECHNIK.

In North America today more than 60 injection moulders produce pipette tips, some as brand owners of high-tech dispensing instruments or automated diagnostic systems, some as suppliers of OEM lab consumables, others as suppliers of generic disposables. The majority of these manufacturers have been in this specific market for many years, and take strict care of the quality of their tips. “Patient’s safety first” is the clear message. The majority of these North American injection moulders of pipette tips run their production with 16 cavities mould, a few still with eight cavities only, a couple of companies already work with 32 cavities and few run 64 cavity processes. These days the first 96 cavity systems are coming into production. The traditional processes run with cycle times of 12 seconds and above, the big automated systems frequently run cycle times of 5.5 – 6.0 seconds instead. Some of the North American injection moulders employ their own local staff for quality control, semi-automatic filter assembly or packaging; some deliver bulk pipette tips to Mexico to perform those steps there and ship back the filled racks or packs. Compared to Europe, where you can hardly survive with highly automated 32 cavities systems anymore due to the severe price and quality pressure, the wide spread of cavitation used in North America is remarkable. “We are actually in a transition phase: the number of high cavitation systems with integrated quality control, filter assembly or individual packaging solutions is significantly growing. The early adaptors with automated processes substitute the traditional producers,“ Anja Schopp, Business Development Mgr. North and South America at Waldorf Technik, said: “The productivity of a 64 cavity automation with 5.5 sec cycle time for

instance is so significantly higher than a process of 16 cavities with, let’s say, 12 seconds, that this naturally causes changes in the branch.” But not only the costs improvement, also the quality improvement at the same time is a growing expectation of the market. This is exactly the field that Waldorf Technik worked on the recent past years, developing the Vario TIP automation systems for pipette tip manufacturers. „We continuously improve our patented Vario TIP systems, that’s what our customers want us to do and that’s our passion,” proudly reports Wolfgang Czizegg, CEO of the company. Both 96 cavities or 4.3 second cycle time on big moulds for such applications are definitely world records, which change the rules for the entire branch.“ Today a catalogue of standardised modules for three different levels of requested automation, all dedicated to fast cycle times and cavitation from 32 to 96 cavities, is available. All of these standard concepts deliver cavity sorted racks filled with 96, 384 or even 1536 tips. In order to reduce labour cost also the quality control (e.g. for horizontal or vertical flash on the orifice, broken cores which close the orifice or geometric failures on the upper end of the pipette tip) can be integrated as a standard module. The same with filter assembly, which is also available as standard module. Importantly the Vario TIP systems are flexible enough to run three or four different products on the same production cell, so many individual demands can be collected on one cell. Aside the performance also floor space in the cleanroom got a focus of the developments. As a new option Waldorf Technik offers a floor space saving package for its Vario TIP range, which reduces the floor space required for removal, cavity sorting, vision control, rejection of false parts and replacement by good ones, inclusive rack filling to less than 80 square feet. A very important quality feature of a pipette tip is the run out, the coaxial straightness of the tip in order to meet the absolute exact geometric point for releasing the fluid. Waldorf Technik developed a system which now allows the moulder to forecast weeks before when exactly the individual cavity will have to be maintained or replaced. This reduces unnecessary stops, allows the moulder to organise the required spare parts and increases productivity for the moulder again. All in all, last year was a very innovative year for Waldorf Technik and its customers again.

Anja Schopp

www.waldorf-technik.de

JANUARY-FEBRUARY 2014 / MPN /33

PLASMA

Plasma Surface Activation of PEEK — CASE STUDY

ention Medical is a globally integrated solutions partner for the design, engineering and manufacturing of complex medical devices and components. ANSAmed, a Vention Medical Company, provides advanced extrusions and catheter solutions to the global medical device industry. With a focus on continuous product innovation and process improvement, ANSAmed provides a comprehensive design, development and manufacturing services. Operating under stringent quality standards, ANSAmed’s extrusion products and components conform to the tightest possible tolerances. ANSAmed’s range of extrusions include single-lumen, multilumen and over the wire extrusion, tapered bump and multilayer extrusion, balloon tubing, co-extrusion and braided tubing, along with contract medical device design and manufacture. ANSAmed’s custom extrusions and contract medical devices are supplied to the cardiology, peripheral vascular, neurovascular, CVC, urology, respiratory and other clinical markets. PAD Print Ink Adhesion ANSAmed sought Henniker Plasma’s advice after discovering issues with the PAD printing of certain medical devices. The medical devices in question required regular, intricate printing and depth marks using the PAD Printing technique, which places a very thin layer of ink onto the surface. In this instance the medical devices were made of PEEK and included Catheters and Microcatheters, Nasogastric Feeding Tubes & Endotracheal Tubes, among others. Polyetheretherketone (PEEK) is an engineering thermoplastic with outstanding heat resistance. The glass transition temperature is 144°C, the melting point 335°C and it is typically melt processed at 370°C. These properties, although advantageous to the design engineer, often result in secondary assembly and decorating issues — bonding, printing, coating and painting. Henniker worked closely with ANSAmed’s Technology Team to identify a solution to these problems. A basic requirement for successful ink adhesion is spreading of the ink on substrate. Spreading will occur if the surface tension of the ink is lower than the surface free energy of the part. After confirming that there were no underlying contamination issues, the Henniker team first of all determined the surface free energy of several PEEK devices using a range of in-house surface test methods, a common step in the process development method.

Surface Energy Surface energy is defined as the excess energy at the surface of a material compared with the bulk material itself. If the molecules of the liquid are attracted to each other more strongly than to the surface then the liquid won’t wet the surface very well, instead forming beads. Conversely, if there is a larger attraction to the surface then the liquid will spread out more. It follows that if a particular surface has a higher surface energy, it will wet more easily and, since the ability to wet a surface is in turn a simple definition of the adhesion characteristics of the surface, it will be easier to glue/print/paint or bond to that surface. Values of surface energy of between 30-35 dynes were found for untreated PEEK, whereas typical inks used in the process have surface tension values approximately 25% higher than this. Plasma Surface Treatment A range of plasma treatments were then investigated to determine the quickest and most cost-effective process to improve the surface wettability of the PEEK devices. After the initial trials were completed the company was able to demonstrate a simple and effective process which was able to increase the PEEK surface energy to greater than 72 dynes with a total process cycle time of less than two minutes. Contract Plasma Treatment Henniker Plasma was also able to provide ANSAmed with a contract treatment solution offering a quick turnaround contract plasma treatment service for both its small one-off requests and ongoing production. Contract plasma treatment is a costeffective way of tapping into the unique benefits of plasma treatment where the cost of capital equipment isn’t justifiable, for example where one-off or short-term contracts have been awarded. Complete Satisfaction A combination of Henniker Plasma’s experience and knowledge relating to low surface energy materials, coupled with its ability to perform rapid testing and quickly develop a suitable process were invaluable to ANSAmed’s Technology Team. The process was quickly transferred to Henniker’s in-house contract treatment team and continues to serve the client with a rapid, cost-effective solution to its specific printing problem. Henniker Plasma plasmatreatment.co.uk

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PLASMA

<< Figure 1: Photo courtesy of Plasmatreat. At the heart of the process is a plasma nozzle, which conceals a complex coating system allowing the deposition of locally selective nano-coatings. >>

<< Figure 2: Graph courtesy of Fraunhofer IFAM. Structure of an antimicrobial plasma coating from the APASI project. >>

A Functional Nanocoating with Millimeter Precision Atmospheric Plasma Polymerisation in Medical Engineering InĂ¨s A. Melamies, Journalist, Bad Honnef, Germany

special atmospheric plasma coating process can bring about micro fine cleaning, disinfection and sterilisation, and apply functional coatings. Diffusion barriers and antifrictional coatings can be produced, or antimicrobial layers deposited. Manufacturing processes in medical engineering demand extremely high standards. Surfaces must be absolutely clean, or even sterile, before they can be further processed or used. Furthermore, pre-treatment processes in medical technology must be very reliable and precisely reproducible. A special plasma process meets these requirements. PlasmaPlus is a plasma process that for the first time enables functional nanocoating to be applied to material surfaces under normal air conditions in a fully automated and continuous inline process. Until recently, plasma polymerisation could only be carried out under low pressure in a vacuum chamber. Together with the Fraunhofer Institute for Manufacturing Technology and Advanced Materials (IFAM) in Bremen, market leader Plasmatreat GmbH in Steinhagen, Germany has spent the last few years developing and patenting a much simpler, quicker and more cost-effective process using atmospheric pressure plasma. The nanofine functional coatings allow a variety of new applications in medical engineering, such as self-cleaning or antimicrobial surfaces. In 2012 the process was awarded with the German Industry Award 2012 in the category â&#x20AC;&#x153;Production and Mechanical Engineeringâ&#x20AC;?. Atmospheric plasma coating At the heart of the process is a plasma nozzle, which conceals a complex coating system (figure 1). The process is environmentally friendly, needing nothing other than compressed air, electricity and the so-called precursor, which is added to the plasma. A variety of different materials including metal, glass, plastics and

Continued on page 36 JANUARY-FEBRUARY 2014 / MPN /35

PLASMA Continued from page 35 ceramics can be coated by varying the chemical composition of the precursor and delivering it directly to the plasma. The precursor is exited within the plasma or respectively fragmented and is deposited on the material, where it forms a cross-linked layer. Apart from the inline-use, the main advantage of this technology compared with other systems is the locally selective coating technique. The use of a plasma nozzle enables locally selective coatings to be applied in a highly targeted manner, which makes efficient use of resources. Processes can be so accurately controlled that layers, which confer different functions, such as corrosion protection, adhesion, or even anti-adhesion, can be applied using the same nozzle. Furthermore, only very small quantities of coating material are required. A big advantage also is the extremely high speed by which a coating can be created. While the low-pressure plasma technology, already frequently used in medicine, takes one to two minutes to form a 100 nm coating thickness, a deposition layer can be achieved in milliseconds with the new coating technology. This process can be used in different medical fields. Self-cleaning coatings This process can already be used to deposit photocatalyticallyactive titanium-dioxide coatings. When exposed to sunlight and moisture, these coatings have a self-cleaning and germicidal effect. This application is used to prevent the formation of biofilms on all surfaces that come in contact with light or are light conducting surfaces. The process is therefore of particular interest for coating medical and sanitary products since it allows manual cleaning intervals to be extended or omitted altogether.

Antimicrobial coatings A further focus of research is the deposition of antimicrobial coatings containing silver (figure 2). Within APASI, a joint project funded by the German Federal Ministry of Education and Research, the Fraunhofer IFAM and Plasmatreat have set themselves the task of producing antimicrobial plasma coatings. The aim is to bind silver nano particles to an organosilicon layer. Germs on the surface are killed by the continuous release of silver ions. The silver nano particles are not added externally, as with other coating processes, but generated directly in the nozzle and deposited in situ, where they bind to the surface of the layer (figure 3). The new nozzle design enables layers containing silver, and even copper, to be deposited in a simple and cost-effective single-step process. Coatings of the kind are not new. The innovative aspect of this research project is the deposition process. Until lately such coatings could only be created in costly chemical or low-pressure plasma processes. The new atmospheric plasma polymerisation offers an environmentally friendly and efficient solution, which is easy to integrate inline. Anti-friction coatings The rubber seals of syringe plungers are often subject to the ‘stick-slip’ effect, the jerky motion that occurs when two surfaces slide over each other. To prevent this and make it easier to eject the syringe, the new plasma polymer anti-friction coating has already been successfully applied to seals. The new coating ensures that the rubber surface glides smoothly (figure 4). Barrier layers Barrier or diffusion layers produced with AP plasma are an important research goal of the plasma company. Barrier layers can be applied to various plastics and constitute an effective barrier against carbon dioxide, oxygen and water. In medical packaging barrier layers protect the active ingredients and flavourings, and preserve the quality and integrity of the contents. With the aid of highly cross-linked plasma polymer

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<< Figure 4: A frictionreducing plasma coating on the rubber seal is applied in order to prevent the slip-stick effect and to make it easier to push out the syringe. >>

layers, the process can already create oxygen diffusion barriers, which achieve a BIF (Barrier Improvement Factor) of up to 5. Typical materials include polyethylene (PE), polypropylene (PP) and polyethylene terephthalate (PET). Adhesion promoting layers for hybrid components The plasma process has also improved adhesion between rubber-to-metal and plastic-to-metal bonding in hybrid injection moulding. This involves applying nano-coatings with active adhesion to the metal surface, then moulding the plastic components onto the surface. The deposition of adhesionpromoting coatings with this plasma process is a technique that will allow solvent-based primers to be entirely replaced in the future.

PLASMA

M. y of Fraunhofer IFA articles << Figure 3: Courtes ) shows silver nano-p on ati ific gn ma x 00 . >> 0,0 (20 co e antimicrobial ating The SEM imag c plasma to create an eri ph os atm by d sputtere Nanocoating with atmospheric pressure plasma enables substances tailored specifically to the application to be deposited deep into the nanostructure of the material surface. This technique creates a highly effective functional coating, which confers completely new surface characteristics on the materials. Manufacturing products with selectively functionalised surfaces opens up a completely new dimension in innovation capability for companies working in the field of medical engineering. www.plasmatreat.co.uk

JANUARY-FEBRUARY 2014 / MPN /37

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EXTRACTABLES & LEACHABLES Total Organic Carbon (TOC): A Viable Analytical Endpoint for Assessing Potential Leachables from Packaging Systems Roger Pearson, Ph.D., Vice President Research and Development, Aspen Research Corporation, and Shayne Spence, Lead Senior Research Associate, MACtac North America

here is a growing amount of pressure from regulatory agencies on suppliers of medical devices and pharmaceuticals to provide information on chemical compounds that could or do leach from devices into the body or from packaging into pharmaceuticals. With that comes the subsequent request that suppliers furnish more information on the extractables and/or leachables profiles of their materials to allow the end user to evaluate their potential for use in finished products. Thus there is impetus for suppliers to test for potential leachables as they develop new products. However, that testing in its entirety can be quite expensive and there exists a need for a screening tool that allows for judicious choice of what final materials to test in a more comprehensive manner. In systems where aqueous carriers provide a reasonable surrogate for the final drug product, measurement of total organic carbon (TOC) provides just such a screening tool. Extractables Screening Experiments The point of an extractables screening experiment is to try and identify what compounds are likely to migrate from a material in direct contact with a pharmaceutical (or body) to the pharmaceutical or body (leachables). Typically these studies are conducted by extracting the material in question with polar (often water), modified polar (ca. 20% ethanol in water) and nonpolar (ca. hexane) solvents. The extractions are usually carried out under elevated temperature (perhaps 50oC - 70oC) and times. The extracts are then analySed by a number of analytical techniques which usually include at least gas chromatography with mass spectrometry (GCMS) and high pressure liquid chromatography usually with some type of mass spectrometry (LCMS) for organics, often inductively coupled plasma (ICP) for metals, and sometimes infrared (FTIR) and gravimetric analyses for polymeric degradants and possibly ion chromatography (IC) for anions of interest. It is not difficult to see how the cost of the full suite of analyses can become significant in short order. However, for certain drug and device products, it is also not difficult to see why the rigorous extractions are needed to identify potential leachables prior to going into a full scale stability study. There exist other suppliers into the market whose products are not in direct primary contact with the drug product or << Figure 1: TOC Experimental Design for 7 Test Systems and 1 Blank. >>

device, but where there is some precedent that migration can occur. One primary example of such a products are labels. Typically the labels are comprised of a base substrate to which a pressure sensitive adhesive (PSA) is applied to one side and the outer most side is then printed with an ink system of some type. The pressure sensitive adhesive side is the side closest in contact with the primary barrier and thus the pressure sensitive adhesive manufacturer gets requests from the final product manufacturer to supply information on potential leachables. Given that there is a primary barrier through which a compound would have to migrate to get into a drug product (or perhaps onto a device) a screening methodology mitigating the extensive analytical protocol for direct contact materials to evaluate possible migration would be considered appropriate. The use of TOC as a screening tool MACtac, a leading manufacturer of pressure sensitive adhesive products worldwide, contracted Aspen Research Corporation to assist the company in assessing potential leachables from PSA backed labels. In most cases (MACtacâ&#x20AC;&#x2122;s included) labels are affixed to containers that hold aqueous-based drug formulations. The test systems chosen for the study were typical of the industry and consisted of a labelled linear low density polyethylene (LLDPE) bottle holding a nominal volume of 100 mL of HPLC-grade water (surrogate for an aqueous based drug product). For the label system to be a problem, compounds from the label would have to migrate through the polyethylene and into the water within the expiry lifetime of the drug. In almost 100% of the cases, compounds that could leach from the labels through the plastic barrier into the water have organic carbon. Generally that carbon will comprise 20% or more of the total weight of the compound. Thus, by monitoring the TOC in the contained aqueous phase, one can get an idea if any significant event in accumulation of organic compounds has occurred. At the point in time that the TOC increases to a level of concern, more specific and stringent analyses can be performed. Of course, all data must be compared to a blank as most plastic containers will leach some organic carbon with time. One question that remains is to assess for how long and at what temperature should the exposure be carried out. Since typical storage conditions might be ambient temperature (~23oC) for two years, the use of 40oC for six months (typical of the pharmaceutical industry for accelerated stability studies) was used to provide a reasonable exposure scenario. A TOC Screening Experimental Design The final experimental design as agreed to (figure 1) included performing TOC measurements at nine time points across 180 days. More complete chemical analyses were performed early on at day 2 and at the end of the 180 day exposure. It was left up to MACtac to decide, based on the TOC results, whether to have additional analyses done earlier in the exposure cycle. Since MACtac wished to test seven formulations (and the requisite blank), the design called for a minimum of 72 TOC analyses but far fewer of the more costly analyses. JANUARY-FEBRUARY 2014 / MPN /39

indicates analytical result after exposure for two days. * CAS is best match but confidence is only 56%. ! Concentrations are estimated assuming the response of Unknown 4 in the blank is equal to 1 ppm and uses that response to estimate all other LC TOF data. The LC TOF concentrations should be considered order of magnitude estimates only.

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Results from the TOC Screening Experiment MACtac affixed 20 of each of the seven formulated labels to the LLDPE bottles and shipped them to Aspen Research Corporation, along with blank bottles. Prior to beginning the experiment, the TOC in seven blank bottles was assessed after two hours exposure at 40oC. The blank bottles were filled with 100 mL of HPLC-grade water without prior rinsing of the shipped bottles. The average TOC in the seven bottles was determined to be 0.125 ppm ± 0.007 ppm. Thus it appeared that the background TOC in the bottles was low and consistent and validated the design of experiment. The 20 bottles of each label type were filled with 100 mL of HPLC grade water and placed into an oven held at 40oC ± 2oC. TOC was measured from one bottle at each time point (figure 2) with the exception of day 32 where TOC was measured in each of three bottles from each formulation and the blank. Results of the triplicate analyses suggested the rsd of the TOC measurement from individual bottles was 15% or less. More complete analytical characterisation was carried out at day 2 and day 180. At day 2, GCMS and HS-GCMS (headspace GCMS) were conducted following Aspen Research ISO17025 SOPs for determination of volatile organics in extractables screening experiments. Gravimetric residual and FTIR were also conducted at day 2. No measurable gravimetric residual above the blank was determined and only very trace levels of organics were found (<0.1 ppm). By day 180 the TOC had increased by 10 to 20 fold over the initial measurements in all the samples, including the blank, indicating that the bottle itself was contributing the most significant amounts of leachables. However, even though TOC does provide a

EXTRACTABLES & LEACHABLES

<< Figure 2: TOC Results. Table: Summary of Analytical Findings by GCMS and LC-TOF. Concentrations in μg/mL. >>

great deal of information about the trend in organic leaching with time, it does not provide identification of what is leaching. That identification requires more specific analytical testing, the most common of which is GC/MS and LC/MS (or LC-TOF, time of flight mass spectrometry). The mass spectrometric techniques are preferred because they afford the opportunity to identify unknowns from the compound mass spectrums. This has a good chance for success in GCMS where large libraries of known mass spectrums exist. The same does not hold for LCMS. The use of high mass resolution (to < 5 ppm) time of flight (TOF) MS helps because the possible empirical formulas are narrowed substantially. Aspen has developed a TOF library of over 5000 compounds common to polymeric systems that can be searched for potential TOF match of unknowns. Even with the use of the GCMS and LC-TOF techniques, unknowns remained in the final analyses. There was consistency with the TOC data in that all of the samples had the same major contributor in each of the GCMS 180 day samples and a common major contributor in the LC-TOF samples. Unfortunately, the major LC-TOF common compound remains an unknown although Aspen continues to try and elucidate its structure using LC-MS/MS techniques and continues to add to its TOF library. Without the unknown identity, it is difficult to estimate concentrations, particularly in the LC-TOF as responses can vary greatly. That said, we applied a generic response factor based on an external standard to estimate concentrations. That done, the

GC/MS and LC-TOF data might account for about 50% of the total TOC measured. TOC is a useful tool for monitoring the migration of organic chemicals into water. As shown in this example, it provides a nice time course map of migration and can also be used to indicate the major source of leaching chemicals (in this case, the bottle itself). For this particular study, MACtac now has defensible data showing that their PSA formulations are very unlikely to contribute leachables in any appreciable amount to an aqueousbased pharmaceutical. www.aspenresearch.com www.mactac.com Dr. Roger Pearson (VP of R&D) joined Aspen Research in 1997 from a post-doctoral position with the University of Minnesota’s School of Public Health where he received an M.S. and Ph.D. in Environmental Chemistry. Prior to pursuing his graduate degrees he held positions as a Research Chemist and Production Superintendent for Celanese Chemical Corporation (1977 – 1983). Shayne Spence, Lead Senior Research Associate for MACtac, has 15 years of experience in the adhesive research industry, 10 of which include extensive work in the research and development department at MACtac. Shayne is responsible for developing, implementing and managing new market initiatives. JANUARY-FEBRUARY 2014 / MPN /41

Injection Moulding Rotational Moulding Extrusion Blow Moulding Thermoforming Vacuum Forming Film Extrusion Recycling Materials Design

30 September-2 October 2014

NEC, BIRMINGHAM, UK

www.interplasuk.com

DOCTOR’S NOTE

Simultaneous Direct Writing and Rheology Andrea Tallis and Roy Carter, Aptifirst Instruments and Technology

printing, or to give it its formal title, Additive Manufacturing (AM) is one of the most exciting and fast moving manufacturing technologies to emerge over the last few decades. One method of AM of particular interest to the plastics industry is Direct Writing, a technique based on the extrusion of a filament of material through fine capillaries, enabling the layer by layer manufacture of customised items with minimal energy usage and low wastage. The material dispenser is guided along pre-programmed paths to create a single ‘slice’ of the finished product, including the external and internal geometry. Subsequent slices or layers are overlain in the correct order to create final three-dimensional objects with unprecedented levels of design freedom. The materials used for such an operation may be thermoplastic or thermosetting polymers, or a ceramic paste, but whatever the type of material their flow properties or rheology will be of paramount importance in determining the efficacy and efficiency of the process. The experimental rig described here was built as a collaboration between De Montfort University and Aptifirst Ltd for a PhD project, and has the benefit of inline measurement of rheological properties during the Direct Writing operation, so that other properties such as tensile strength and tendency to slump could be correlated to the rheology. A commonly used instrument for developing direct writing materials and processes is a syringe pump. Adapted from medical technology, it is basically a holder for a hypodermic syringe with a mechanism driven by a computer-controlled stepper motor to allow the syringe plunger to be depressed at a controlled speed. It was realised after several trials that knowledge of the extrusion characteristics of the build material and the extent of batch-to-batch variation was required in order to optimise processing conditions and material formulation. An instrumented device was therefore designed to fit the existing syringe pump equipment. The designed device, designated the FSR (Flexible Syringe Rheometer) was, in, fact, a miniature capillary extrusion rheometer. These precision instruments are, indeed, similar to large syringes, with a piston being driven down a cylindrical sample chamber at a series of controlled speeds in order to force the test material through an orifice or die of known dimensions and geometry. The force needed to drive the piston at each speed, or, of preference, the pressure in the test chamber immediately before the entrance to the die, is measured. From these parameters, the shear stress, б, and shear rate, γ, and thus the viscosity, η, may be calculated:

б = ΔPr 2L γ = 4Q π r3 η = б γ

(1) (2) (3)

where ΔP is the pressure drop across the die, Q is the volume flow rate through the die, r is the radius of the die orifice, and L is the length of the orifice. Please note that the parameters derived from equations (1), (2) and (3) are termed ‘apparent’, and need corrections to be applied to arrive at the ‘true’, instrumentindependent values. However, apparent values are often used for batch-to-batch comparisons, etc.

<< Figure 2: Diagram of the FSR Rheometer. >>

<< Figure 1: 3D writing rig with FSR rheometer fitted. >>

<< Figure 3: FSR in action, building a cylindrical test piece. >>

The stainless steel FSR body was designed to fit the existing driven 3-axis test rig and the syringe pump drive. It was fitted with a replaceable nylon piston tip (bronze would be used for materials such as polymer melts), and a fitting for Luer-type hypodermic needles. The hypodermic needles, in a variety of calibres, were cut to a range of lengths in order to provide a series of ‘dies’ for experimentation. A miniature pressure transducer was mounted with its sensing diaphragm in the wall of the bore of the barrel, and pressure transducers of different sensitivities were procured to optimise precision for different materials and conditions. Additionally, a thermometer pocket was machined so that a temperature sensor could be located in the barrel wall at the same radial point as the pressure sensor. Substantial testing was carried out to prove both the accuracy and repeatability of measurements using calibration standards over a wide range of extrusion rates and orifice diameters. The system went on to be used to characterise the rheological properties necessary for a successful Direct Write material. These include the ability to ‘freeze’ the material in place very soon after deposition which is achieved either through a steep temperature gradient in the case of thermoplastics or a so called ‘yield point’ in the feedstock material, whereby below a critical level of applied stress the material does not flow. In conclusion, the FSR proved to be a valuable tool for measuring in real time the rheological properties of materials as they were being extruded for the Additive Manufacturing technology of Direct Writing. This inline measurement of properties allows the rheological characterisation of material that exhibits superior properties for the Direct Write process whilst eradicating the uncertainty of batch-to-batch variation or material degradation. This particular instrument proved the concept, and can easily be adapted with, for example, controlled heating, inline extrudate swell and surface temperature measurement, and with a purpose-built piston drive module with a wider range of speed control. JANUARY-FEBRUARY 2014 / MPN /43

BREAKING THE MOULD: A New Generation of Orthopaedic Implants through OsteoFab Technology WORDS | Jim Porteus, Oxford Performance Materials

xford Performance Materials (OPM) was founded with a specific purpose: to exploit the molecule PolyEtherKetoneKetone (PEKK), a high-performance thermoplastic polymer in the family of PolyArylEtherKetones (PAEKs). OPM’s founding mission focuses on the development of PEKK products for use in a wide array of biomedical applications, including extruded products in rod and pellet form, injection moulded parts, and most recently 3D printed implants. In addition to supplying raw material for biomedical applications, OPM produces finished parts for the industrial and medical markets as both an established contract manufacturer and a medical device OEM. OPM is a leader in the development of additively manufactured medical devices and was the first company to receive US FDA clearance for a 3D printed patient specific polymeric implant. The development of biocompatible OXPEKK-IG polymer, Oxford Performance Materials’ proprietary, high-purity formulation of PEKK, enabled a vast array of business opportunities, beginning with the manufacture and sale of extruded products in rod and pellet form for orthopaedic medical applications. This arm of the business is still prosperous today and its success is evidenced by the extensive implantation of OXPEKK-IG polymer worldwide. Regulatory approvals of devices manufactured from OXPEKK-IG material first occurred in Europe and South America for spinal cages; devices that effectively treat a range of spinal conditions including degenerative disc disease, lower back pain, and spondylolisthesis. The OSD Squale spinal implant is one such device and is used for intervertebral body fusion in the cervical spine. OPM continues to develop the biomaterials business by advancing new materials compositions that are enabling for medical applications, to include barium sulfate, titanium dioxide and carbon filled OXPEKK pellet and rod. The development of a biocompatible, implant-grade PEKK polymer also spurred the launch of OPM’s own medical device division. OPM’s product development strategy pledges the use of cutting edge technology to manufacture products that deliver the maximum clinical benefit at optimal cost to the patient. This includes a continual effort to provide contract manufacturing services and to develop OEM products. The venture into medical device development included the purchase of an EOSINT P800 high temperature laser sintering system (P800) and the development of the OsteoFab manufacturing process technology. OsteoFab devices are additively manufactured using the P800, which selectively melts successive layers of OXPEKK-IG powder. This process effectively

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<< Figure 1: The OSD

al spinal cage. >> Squale anterior cervic

transforms two dimensional layer ‘slices’ from a design file into a three dimensional part. One of the major benefits of this process is that it confers the ability to make each medical device patient specific. For these cases, the design file is created using anatomical dimensions derived from a patient’s CT or MRI scan and is made to perfectly fit a bony void or to replace sections of bone. OPM operates a cGMP compliant facility certified to ISO 9001: 2008, AS9100/C, and ISO 13485: 2003 by TUV-USA. Extensive development work led to a milestone year in 2013. In February, OPM was granted 510(k) clearance by the US FDA to market the OsteoFab Patient Specific Cranial Device (OPSCD), a long-term implant intended for use in the replacement of bony voids in the cranial skeleton resulting from trauma or disease. This was a historic achievement as it was the first additively manufactured polymer implant to receive 510(k) clearance in the United States. The first US implantation of the device took place weeks later and the implant successfully replaced a large section of a patient’s skull in New York. OPM has exclusively partnered with global medical device company Biomet for worldwide distribution of the OPSCD. Countries shipped to include the US, Argentina, Germany, South Africa and Israel.

ORTHOPAEDICS

<< LEFT | Figure 3: An example OPSFD. >> << BELOW | Figure 2: STL design file of an OPSCD. >>

When asked to comment on the success of the OPSCD, OPM President and CEO Scott DeFelice stated: “We have sought our first approval within cranial implants because the need was most compelling; however, this is just the beginning. We will now move systematically throughout the body in an effort to deliver improved outcomes at lower overall cost to the patient and healthcare provider.” The fourth quarter of 2013 saw a fulfillment of Scott DeFelice’s promise with the submission of OPM’s second 510(k) for the OsteoFab Patient Specific Facial Device (OPSFD). This device is designed individually for each patient for aesthetic enhancement, to correct trauma, and/or to correct defects in facial bone. It is also indicated for non-load bearing enhancement of mandibular bone. The recent opening of a new production facility will allow OPM to separate industrial manufacturing activities and undertake device development in a purely medical focused environment. Orthopaedic implants under active development include load bearing areas of the foot, ankle and spine. After extensive design verification and validation studies, 510(k) submissions for those indications for use will be prepared and sent to the FDA this year.

The future will bring continued advances from OPM’s medical device division in the form of novel orthopaedic implants that enable a solution not currently available through traditional manufacturing techniques or with conventional materials. It is the intersection of reproducible material properties with cutting edge technology that allows OPM to offer innovative medical devices. As always, OPM will continue to support client needs through contract manufacturing capabilities and will continue to be an industry leader in the pursuit of its mission. “We see no part of the orthopaedic industry being untouched by our OsteoFab technology,” said OPM COO Severine Zygmont. Jim Porteus is the Regulatory Affairs Specialist at OPM. He earned a BS degree in Biomedical Engineering from the University of Connecticut and has been with OPM for one year.

JANUARY-FEBRUARY 2014 / MPN /45

INTELLECTUAL PROPERTY

Protecting Your Innovation Jackie Maguire, CEO, Coller IP

nnovative uses for plastics have revolutionised healthcare in the past few decades and this demand is set to continue. With innovation, however, come challenges, not least of which is ensuring that ideas are not stolen or counterfeited — the latter has clear dangers for the medical market in particular, as well as depriving an inventing company of income and causing damage to its reputation. The development of new products and processes in a dynamic industry such as medical plastics requires a substantial combination of technical legal and commercial expertise. This includes an understanding of how to effectively use and protect Intellectual property (IP). IP refers to a range of creations of the mind for which specific legal protection may be available. This includes patents, trademarks, registered design rights and copyright. With up to 80% of a company’s value now typically deriving directly from intangible assets, including intellectual property, it is vital that companies not only ensure they are not infringing the IP rights of another, but also that they have adequate protection around their own designs, products and processes. In an innovative industry it is not always easy to identify areas of key technological advance and also avoid infringement of third party rights. In order to make good business decisions relating to investment in innovation, or development of a new product, for example, an understanding of the relative position of products, processes and machinery to the patents held by competitors is necessary. One way of acquiring this understanding of i.e. ‘competitive position’ is through the generation of a patent landscape. Such a landscape is formed through an analysis of the most frequent words and phrases within a focused set of documents. In general, patent families positioned closely on a landscape can be considered to be related technically and the contours show areas of high patenting activity.

Medical plastics are developing areas and ripe for further IP protection. In IP terms, a novel medical plastic device is a device that has not been publicly disclosed before the date of the patent application filing. Such devices are part of the creator’s IP and can form part of a coherent IP strategy going forward. A good IP strategy includes a clear understanding of the value of the IP in the invention, as well as full legal protection in the jurisdictions in which the invention is to be marketed. It also includes an understanding of how to commercialise the IP going forward. Inventions in medical plastics can include: l new polymers with specific properties such as biocompatibility and porosity; l additives which enhance the characteristics of existing compositions; l the formation of surface coatings for implants and drugrelease devices; l the functional design of medical devices; l methods of moulding and prototyping. Organisations in this field often make use in their products of components already built and tested as that leads to faster and more cost-effective development cycles. Such components can be considered as IP assets, and as such, their use should be optimised and protected, whether developed internally or by a third party. Instead of purchasing a component outright, the company may acquire a license to use the component for a specific purpose, or negotiate a contract where a royalty is paid for each shipped product in which the component is integrated. A combination of commercial judgment (the cost-effectiveness and viability of the chosen model) and IP skills are required, the latter to ensure that contracts between an organisation and any third-party supplier are watertight and do not lead to problems in the future. Particular problems can occur in using products manufactured overseas in countries such as China, where the same IP constraints do not always apply.

<< Figure 1: Filing rate for medical plastic patents. The figures for 2012/2013 are not yet fully published (output from Thomson Innovation). >>

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JANUARY-FEBRUARY 2014 / MPN /47

INTELLECTUAL PROPERTY

<< Figure 2: Patent landscape for 5685 families relating to medical plastics (output from Thomson Innovation). >> << Table 1: Studies of patent literature highlight many active players from the chemical and medical device industries. >>

them through this maze and review their IP on a regular basis. Some of the patents on the landscape will be of significant value, and understanding the relative position of the new development to existing patents is important for business decisions that may relate to investment in an enterprise, development of a product or the complete sale of a business.

We strongly recommend that prior to any external disclosure whatsoever, organisations take professional advice on precisely when they should patent their inventions and how they should go about it. Otherwise, there is a serious risk that they may not be able to claim ownership in the future. The following questions should be asked when trying to understand IP in the field of medical plastics: l Who are the major patent holders and what are their activities? l Which players occupy niche technology areas? l Is this a growing or shrinking field of technical activity? l Are there core technologies common to the product offerings of patent holders? l How is the technical field changing over time? l Are my activities novel or are they used by my competitors? l Who are my nearest competitors in terms of technology? l Will my activities result in infringement of third-party patents? l How valuable is my IP? Patent searches relating to medical plastics identify nearly 5,700 patent families that have been filed over the past 20 years. Analysis of the patent filing dates shows that medical plastics is an area of growing activity (figure 1). Studies of patent literature highlight the many active players, as shown in table 1. The patent landscape provides an indication of where competitors might be active and there are specific features of the landscape that can affect the success of product offerings for medical plastics. In a patent landscape as crowded as the medical plastics field (figure 2), there is always a possibility of a new entrant infringing patents belonging to a third party. Anyone coming into this complex field, as well as existing players, should ensure that they have professional advisors who can help to steer 48/ MPN /JANUARY-FEBRUARY 2014

Anyone who has business interests in the field of medical plastics will want to know who their nearest competitors are and what patents they hold. The landscape for the set of 5685 patent families used for figure 2 is generated through an analysis of the most frequent words and phrases (referred to as themes) in the set of documents and allows us to see the active parties in a specific area of development. In general, topics that lie close together on the landscape can be considered to be related technically, and the snow-covered peaks are around subject areas of high patenting activity. Figure 2 has been annotated to show the location of broad technical areas within the landscape. We have also shown in figure 2 the position of the seven top patent family holders in the landscape, which are further detailed in table 1. In some cases, patents for a particular player are dispersed across the landscape activity in various technical areas. Where patents are clustered for a player in a specific region of the landscape, there is an indication that that player has focused on a specific technology or application for the technology, for example an emphasis on surface coatings. In summary, the medical plastics area has seen growing patent activity over the last 20 years. Assessment of the wider patent landscape reveals the intellectual property held by both existing players and new entrants in the medical plastics market, essential information in todayâ&#x20AC;&#x2122;s world of business. A full understanding of where a new invention lies on the patent landscape is vital, as is ensuring that all contracts with third-party suppliers are watertight. An IP audit, review or health check should be undertaken on a regular basis to ensure the organisation is aligning its business strategy with its IP â&#x20AC;&#x201D; the so-called crown jewels of a company â&#x20AC;&#x201D; to achieve maximum competitiveness.

Distrupol is proud to be working with Wells Plastics offering BACTIglas™ antimicrobial masterbatch. Antimicrobial performance can be delivered to anything, any part, any application, from medical equipment to floor and wall coverings to lighting to footwear to soap and towel dispensers. Key benefits of BACTIglas™ include: Reduction in spread of healthcare acquired infections Protection against cross contamination Accelerated healing from wound dressings Increased product lifespan and durability Reduction in odour formation in synthetic fibres and sportswear Superior consistency delivered by unique microscopic glass delivery system unique to BACTIglas™

info@distrupol.com www.distrupol.com

Silicones l The experts on silicone rubber for medical devices l Cost saving advice on product design l Material, tooling, manufacturing and approvals expertise l ISO 7 cleanroom l ISO13485 certififed

Contact: Caroline Herdman +44 (0)1544 312660 carolineh@primasil.com Primasil Silicones Ltd | Kington Road | Weobley United Kingdom | HR4 8QU

www.primasil.com JANUARY-FEBRUARY 2014 / MPN /49

MEDTECH INNOVATION

TOP 10 TIPS for Designing with Medical Silicone Materials

n inert, biocompatible and customisable material — the benefits of silicone rubber as a manufacturing material in the healthcare sector are now well known. For product designers and engineers though, there remain the same old questions. These top ten tips will help you get to grips with designing components that require silicone rubber. As with all manufacturing, a top quality industry partner will provide hand holding and design insights for your particular product. Top tip 1: Get the experts involved early. Talk to your supplier as early as you can. Unlike plastics, working with silicone rubber is not an exact science. Split lines, shrinkage and manufacturing options should be discussed at the earliest possible opportunity to prevent costly mistakes and re-work. Top tip 2: How many hoops? Before the pen hits the paper (or the fingers hit the keyboard) it is essential to be aware of, and understand, any regulatory requirements for your product. Material approvals, manufacturing environments, packaging and sterilisation can all scupper the timely release of a medical product. Understand what hoops you have to jump through and discuss these with your supplier. Top tip 3: Don’t over engineer year after year. Do you really understand the function of the part? Designers are creative people, we all know that. There is a real skill in optimising the design so that it is sufficient for its function but no more. Over engineered designs are more expensive, take longer to develop, and are more prone to failure. Stay on brief and deliver the part for the job. Top tip 4: All materials are not created equal. The choice of the silicone rubber cannot be separated from the manufacturing process. Do you need liquid silicone rubber (LSR) or high consistency rubber (HCR)? What is your tooling budget? Are parts particularly price sensitive? Does the material have the appropriate approvals and certifications? There are many variations, such as high strength, self-bonding, oil leaching, conductive, antimicrobial as well as post surface treatments that provide further properties to improve component performance. It is essential that your supplier can provide expert material advice. If they can’t, walk away. Top tip 5: High quality tooling is a price worth paying. Don’t be tempted to cut corners with tooling. A component is only as good as the tool from which it is made, and a tool is only as good as the design from which it was cut. Your supplier must have extensive tooling design knowledge for compression, injection and LSR moulding. They should also be using the latest 3D modelling software. A poor tool design will result in substandard parts, re-work, and a delay in getting your product to market. If you don’t have the funds available for top quality tooling, ask your supplier if they provide alternative financing options. This is one area where you really can’t afford to cut corners, or you risk re-cutting tools. Note that although LSR flows like water, it can be abrasive and will wear tools over a period of time. Proper mould maintenance leads to longer tool life.

Top tip 6: When is a cleanroom not a cleanroom? The properties of silicone rubber create challenges for cleanliness and packaging. Silicone should be moulded in a controlled environment, whether in a cleanroom or in a more standardised manufacturing area. Operators should wear proper attire including gloves, when required. Will your components be further assembled? If so, how will they be shipped? When packaging parts, if bulk packed, product should be double-poly bagged. Tip 7: Control is everything. Up to date machinery enables precise control over the manufacturing process. Injection and temperature controls, cold runner systems (or decks), and automated de-moulding combine to provide consistent, top quality parts time after time. Whilst the initial investment is often higher for automated production, the unit cost is frequently much cheaper. Tip 8: Two materials can be better than one. When designing the product, think hard about the functionality. Is the product a subcomponent? Would combining silicone with another material remove the need for another component? Would this reduce costs and/or achieve better results? If so, evaluate how they would function together in the finished device. To reduce part count, silicone can be over-moulded to many plastic, metal and fabric substrates and therefore benefit from the properties of both materials. This can help not only minimise part count but maximise assembly efficiencies. Tip 9: Plan your programme carefully, with contingency. Thermoplastic tooling is quicker to develop and more likely to produce exact parts first time. Silicone rubber mould tools take an additional 50% development time and often need modifications. Take advantage of programme management services offered by your supplier and ensure you understand any potential issues that could delay the project. Again, more thought and planning at the outset leads to components being delivered on time, to budget. Tip 10: Prototype to perfection. Rapid prototypes are much easier to create using modern technology. This allows the design and dimensions to be assessed before costly production tooling is commissioned. Whilst en vogue 3D printing technique can provide useful insights into the optimum design of the product, prototypes manufactured using a more appropriate material in a traditional mould are more useful with numerous samples being more easily produced. Silicone rubber is the perfect material for many medical products. With these tips in mind, go and talk to an expert who will work closely with you to get your product to market in the most efficient manner. Just make sure they are certified to the acknowledged benchmark for medical suppliers – ISO13485. www.primasil.com

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Confirmed exhibitors as of July 23, 2013. For the latest list visit www.mediplasuk.com/sessions.html.