MPN EU Issue 15 by MPN Magazine

MPN

MEDICAL PLASTICS NEWS

RIWISA Completes Flextronics Capabilities

ALSO IN THIS ISSUE: Switzerland: The Heart of Innovation Evidence Suggests Bisphenol A is Safe Next Generation Regenerative Biomedical Textiles Hydroxyapatite Enhanced OPTIMA PEEK from Invibio Preview of Medica and Compamed

ISSUE 14 September-October 2013 WWW.MEDICALPLASTICSNEWS.COM

MPN BPA is Safe—Page 6

All Medical, All Plastics

Contents 5. Editor’s Letter: Plastics litter Sam Anson discusses with British Plastics Federation president Mike Boswell how we can press governments to take a tougher approach to litter. 6. On the Pulse: Industry news Ahead of an investigation into bisphenol A (BPA) by the EU’s Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), the latest evidence suggests BPA is safe.

Switzerland—page 13

10. Cover: RIWISA acquisition Sam Anson interviews the head of medical of Flextronics, the new owner of RIWISA, subject to closing. 13. Switzerland: Heart of innovation In August Sam Anson toured a host of medical plastics companies in the ZürichBasel region.

Medical textiles—page 24

22. Product Focus: Medical textiles Josh Simon and Ryan Heniford of Secant Medical present the next generation of regenerative biomedical textiles and new polymer poly(glycerol sebacate). 31. Sterilisation: NO2 and scCO2 Interview with CEO of new kid on the block Noxilizer and technical update on supercritical CO2.

Implantable medical drones—page 39

46. Doctor’s Note: Product lifecycles Crystal Densmore of RJ Lee gives some simple steps to mapping a polymer product’s lifecycle. 50. Regulation: 510k modifications Rhonda Thompson provides a guide to proposed changes to 510k and the FDA’s modifications policy. 54. New Materials: Polymer hybrids Dr Xiang Zhang of Ceram looks at polymer-collagen hybrids and forecasts that moulded load bearing bioresorbable implants may not be too far away, technologically speaking. Also, Invibio’s new hydroxyapatite enhanced PEEK-OPTIMA. 56. Extrusion: Rheology Roy Carter of Aptifirst explains why rheology is an essential tool for successful extrusion. Also, continuous fibre thermoset composite tubing for medical applications. 60. Design 4 Life: Design for manufacture Bill Welch, CTO at Phillips-Medisize, introduces design for manufacture as a guiding philosophy.

36. Folio: Catheters Interface announces availability of new catheter catalogue.

63. Compamed and Medica: Preview As official UK media associate for the Medica exhibition, Medical Plastics News interviews Shah Fayyaz, CEO of leading laryngoscope maker Timesco, about replacing metal with plastics.

39. Product Focus: Plastic electronics Miniaturisation, implantable drones and plastic electronics at K.

66. Events: E&L and Chicago Exctractables and leachables 2013 and MiniTec and MD&M Chicago report.

Online and in digital Plastic electronics—page 57 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 brand new website www.medicalplasticsnews.com and via a digital edition. SEPTEMBER-OCTOBER 2013 / MPN /3

CREDITS

Plastics and Litter: How can we take responsibility?

editor | sam anson

Sam Anson

EDITOR’S LETTER

lastic packaging gets a bad press among environmentalists. They see the material as the main cause of marine litter. Plastic packaging tends to float in water and blow in the wind, so it collects in hedgerows and runs off in rainwater into rivers and lakes, and eventually finds its way into the sea. Reports of plastic soups—which are collections of partly degraded plastic molecules in oceans and lakes—provide ammunition for activists to take easy pot shots at plastic manufacturers. But other materials contribute to the problem, including processed metal (meshes and wires), cardboard and glass, especially drinks containers. None of these degrade quickly. This week I watched a video about a cameraman who spent some time living on an island inhabited by albatrosses. He captured shocking footage of carcasses with excessive waste rigid litter in their stomachs. Watching this video made me ask myself a reel of questions. Is it reasonable for the plastics industry to be expected to clean up after consumers? What happened to penalties and fines for littering and the nationwide Keep Britain Tidy campaign? Has the plastics industry become a scapegoat for litter in general? Has litter become socially acceptable? Can manufacturers of plastic packaging do more to protect themselves from criticism and bad press by lobbying governments to take better control of litter? How can stakeholders come together and work on a coordinated and long term solution to the problems? I posed these questions to the newly elected president of the British Plastics Federation (BPF), Mike Boswell. Mike is managing director of UK polymer distributor Plastribution, whose customers include a wide range of plastic packaging manufacturers. Commenting, Mike said: “Litter is a serious issue of massive environmental concern. The fact that the plastics industry is sometimes forced to accept a degree of blame from environmentalists is unfair, and a real shame. UK manufacturers are some of the most environmentally conscious processors I know. But they have no control over what happens to plastic parts once the products they contain have been consumed. Recycling of plastics packaging has moved ahead fast while the amount of plastic being used is being reduced through lightweighting.” Emulating the point that not all litter is caused by plastic materials, Mike said: “Walking around my local park I regularly see empty soft

advertising | gareth pickering drink cans, cigarette packets, alcohol containers and crisp and sweet wrappers—these are not direct products of the plastics industry, more of big manufacturers of fast moving consumer goods and their retailers.” To solve the problem of litter on land, and the run off of this litter into rivers, lakes and ultimately the oceans, Mike says we need more effort from the government in terms of education, infrastructure and law enforcement. He adds: “It’s not good enough insisting that fast food companies install bins on their own land. I live 6 miles from the nearest fast food restaurant and I regularly pick up litter with the restaurant’s logo on it from outside my house.” I asked Mike whether he thought enough was being done at government level to tackle littering. “Not at all,” he responded. “We need more momentum for campaigns like Keep Britain Tidy, TV ads, more litter bins and joined up thinking across manufacturers, environmentalists and local and national government to help manage litter on land and prevent it flowing into the sea.” For me, litter is a real problem in the UK, especially compared to Germany and Scandinavia. It’s a sensible guess that rubbish which ends up in the sea was discarded on land. The point is that if, as an industry, the plastics industry attempts to solve it on its own, it is inadvertently taking responsibility for the problem without much hope of success—it’s too big for us to handle on our own. And, more importantly, litter is the responsibility of the government and the general public. Closing, Mike said: “Plastics are essential for sustaining human life. All stakeholders— including society, governments, NGOs, producers, processors, users, retailers and consumers—must work together to solve the issues relating to plastics litter and the problems that are caused in the environment. The solutions exist; it is more a case of the will to engage them. And it is not a task that the plastics industry should be left to tackle on its own as this would inevitably result in failure.” The British Plastics Federation is a supporter of Keep Britain Tidy. It also operates a loss prevention initiative called Operation Clean Sweep, the goal of which is to help the plastics industry reduce the loss of plastic pellets to the environment. The initiative includes a manual with guidelines to help manufacturers and a pledge signed by companies who have made a commitment to a clean environment.

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

© 2013 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.

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SEPTEMBER-OCTOBER 2013 / MPN /5

Polycarbonate Crucial for Medical Devices | OUTLOOK SAFE DESPITE SCAREMONGERING AND FRENCH BAN

Latest Review of Evidence Suggests Bisphenol A is Safe PLASTICS HAVE BECOME AN INDISPENSABLE ELEMENT OF MEDICAL TECHNOLOGY. ONE OF THE MOST WIDESPREAD MATERIALS HERE IS POLYCARBONATE, USED IN A RANGE OF CRUCIAL DEVICES. HOWEVER, AN IMPORTANT CHEMICAL PRECURSOR FOR IT HAS BECOME THE SUBJECT OF A HEATED POLITICAL DEBATE. FOR THEIR PART, PLASTICS MANUFACTURERS AND REGULATORY AUTHORITIES ACROSS THE WORLD ARE CONVINCED: THE BUILDING BLOCK OF POLYCARBONATE, BISPHENOL A, WHICH HAS BEEN UTILISED AND UNDER STUDY FOR OVER FIFTY YEARS, CAN BE USED SAFELY—AND THE SAME HOLDS TRUE FOR THE NUMEROUS MEDICAL PRODUCTS BASED ON IT. Many ill people dream of being able to live in familiar surroundings and not be forced to frequently visit the doctor or stay in hospital. Yet many medicines have to be taken regularly and with high accuracy. In order to apply them at home or on the way, small devices that patients can wear on their body or in their clothing have been developed. One innovation is a small injection pump that fits comfortably into one’s breast pocket, enabling patients to administer their own medicines very precisely. The device, which has regulatory

July 26, 2013 Phillips-Medisize Makes Acquisitions in Mexico and China

<< Injection pump for onthe-go usage with housing made from polycarbonate. >> approval pending, is to be shown at the K 2013, the world’s largest plastics fair being held in Düsseldorf, Germany in mid-October. And it is a good example of how useful hightech plastics are for the medical technology industry: all housing components of the mechanical pump are made of polycarbonate. A combination of good properties make the material the preferred choice for this application, according to Bayer, one of the world’s leading polycarbonate producers. It was at Bayer where this kind of plastic was invented in 1953—exactly six decades ago. The transparent, light and easy to shape polycarbonate was put on the market only a few years later. Since then global consumption has reached 3.7 million metric tonnes and is expected to grow further. Part of Daily Life The high-performance plastic has become part of daily life and is used in many key industries—in the automotive business and in consumer electronics as well as in the construction sector. As the producers—represented by the Polycarbonate/Bisphenol A Group under the industry association Plastics Europe—point out, polycarbonate makes big roof constructions and razor-thin laptop shells possible, or it helps making

cars lighter by replacing components from glass and steel, so reducing fuel consumption. And, of course, polycarbonate is commonplace in medical technology, particularly when other materials are unable to meet all the stringent requirements for the devices. So far, so good. But now a political discussion casts a shadow over the success story. The reason is that the chemical Bisphenol A (BPA), the essential building block for polycarbonate, is becoming increasingly prominent in a public debate on suspected hormone-like substances. The controversy is focused on the substance’s use in materials in contact with food. And many are concerned of a possible spill-over to other areas—such as medical technology. At the time of going to press, stakeholders are waiting for another milestone in the debate. In the European Union, the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) is expected to issue a draft opinion on

<< US-company Cannuflow has chosen polycarbonate for its new access cannula body. >>

August 6, 2013 BD and College of American Pathologists Announce Alliance to Support Pathology in India and China “This historic initiative brings together two of the leading global organisations that are ideally positioned to support laboratory improvement efforts around the world, particularly in China and India,” said John Ledek (right), president, BD Diagnostics— Preanalytical Systems.

Matt Jennings, president and CEO of Phillips-Medisize Corporation, says the manufacturing sites to be acquired are “to Switzerland standards” and so operations will be integrated “rapidly and seamlessly” into PhillipsMedisize.

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August 16, 2013 Australian Dental Industry Calls for Medical Device Regulatory Framework Overhaul

“The TGA’s regulatory framework is designed to deal with one individual importing ten thousand products, not ten thousand people importing one product,” said Troy Williams, ADIA's chief executive officer.

August 29, 2013 Flextronics Acquires RIWISA “The addition of RIWISA’s precision plastics and automation capabilities to Flextronics Medical is a tremendous complement to the broad range of healthcare solutions we can offer our customers globally and underscores the strategic commitment we have made to expand our services in this market,” said Mark Kemp, president of Flextronics Medical.

ON THE PULSE

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Continued from page 7 Florida, USA uses sensors and wireless technology to provide real-time, evidence-based data to the surgeon to optimise the positioning and balance of implants. OrthoSensor had several criteria for choosing a material for this innovative product, including biocompatibility, lubricity and superior strength. They chose a special polycarbonate grade which is available in various translucent << Granulate mix partly made from colours. “The OrthoSensor Knee Balancer is a polycarbonate for medical technology. >> revolutionary, intelligent orthopaedic device, so using a high quality, reliable material was of Safety confirmed paramount importance to us,” said Erik Herrmann, “Numerous other authorities, including those in the company’s Director of Product Development, Germany, Switzerland, the United Kingdom, Surgical Balancing. Japan and Australia, share the view that BPA The use of polycarbonate is not limited to poses no health risk when used as intended in hospitals and doctors’ offices, however. It is also materials in contact with food,” says Jasmin Bird utilised in rehabilitation—for example for the from Plastics Europe. In addition, the Food and housing of HAL®, a “robot suit” developed in Drug Administration (FDA) in the United States Japan. Its artificial arms and legs help patients to has confirmed the safety of the chemical in the move and rebuild muscles. currently approved uses in food containers and packaging. Polycarbonate: Meeting strict requirements However, a ban on baby bottles made with To put it in a nutshell: polycarbonate helps bring polycarbonate has been in place in the European innovative devices to the healthcare market. And Union since June 2011. Through this step the its resins and blends are especially able to meet European Commission had wanted to create a the rigorous challenges and requirements these uniform legal position in the Union following applications and the medical authorities demand. corresponding ventures in the member states But in spite of the repeated safety Denmark and France. “It sees the ban as strictly a confirmations from authorities around the world precautionary measure and has continuously and the obvious benefits of the material, the underscored that there is no scientifically sound polycarbonate market is threatened with erosion basis for broader restrictions,” says Bird. by the debate on Bisphenol A, its essential The driving factor behind such measures is component. The debate is occurring within the fear that BPA could interfere with hormone levels European Union and focused on applications in the human body. But humans are exposed to with food contacts, for example water bottles and only extremely low quantities of BPA. And these cans with synthetic resin coatings. trace amounts are not only well below the safety In Belgium, for example, a law has been in thresholds defined “AN AVERAGE by the regulatory force since the beginning of 2013 that no longer permits BPA-based food packaging for children ADULT CONSUMER authorities and under the age of three. A similar ban was applied WOULD HAVE TO scientific at the same time in France. In addition, products INGEST MORE THAN committees of this type are to be subject to a general ban in 600 KILOGRAMS OF around the world, the country beginning in January 2015. they are also FOOD AND excreted from the In contrast, the European Food Safety Authority (EFSA), one of the organisations BEVERAGES IN body very rapidly. responsible for the risk assessment of BPA, has CONTACT WITH repeatedly confirmed that products based on POLYCARBONATE Threshold for this intermediate—which is firmly bound in the intake CONTAINERS EVERY In the European plastic matrix—can be used safely in food contact. Its most recent opinion on this subject DAY TO EXCEED Union the daily came in late 2011. THAT LEVEL— intake limit is 0.05 According to the EFSA, an official French WHICH IS milligrams BPA per report on BPA failed to consider several key IMPOSSIBLE,” kilogram of body points required for a comprehensive and scientific weight. “An assessment. Currently, the authority is undertaking average adult a full re-evaluation of the human risks associated consumer would have to ingest more than 600 with exposure to BPA through the diet. It considers kilograms of food and beverages in contact with also the contribution of non-dietary sources to the polycarbonate containers every day to exceed overall exposure to Bisphenol A. that level—which is impossible,” says Bird. The first part of this re-evaluation has been However, some researchers maintain that the made available as draft in July—it reconfirmed that chemical can produce harmful effects in humans in diet is the main source of BPA exposure. Exposure small quantities and not at higher doses. This is is extremely low and was even found to be far referred to as the low-dose hypothesis. But lower than previously estimated by the EFSA. multiple studies conducted according to

8/ MPN /SEPTEMBER-OCTOBER 2013

protocols established for human health assessment by regulatory agencies have not confirmed these low dose observations. So this hypothesis remains unproven. Multiple studies have already been published on BPA, and there is a constant stream of new ones. “Yet it is not the number of studies that is decisive, but rather their quality,” says Dr Melanie Möthrath, a chemist and BPA expert at Bayer MaterialScience. Scientific studies often arrive at different conclusions, and the reasons often lie far back at the study's concept phase. Möthrath explains: “For example, there are differences in the test system selected—cell culture or live animal. Or the studies differ in the uptake pathway for the substance being examined. They can be applied via the food, injected into tissue or via small pumps under the skin.” Robust science is key, not scaremongering Another important factor is the amount of a substance to which a test animal is exposed. The question is whether the dose of the substance reflects normal human exposure or is so high that it is not realistic. In addition to the validity of each individual study, the consistency of all data from various studies plays a major role. “The key concept here which looks into the consistency of the data across multiple studies is the so-called weight of scientific evidence,” Möthrath explains. Another measure of quality is the use of Good Laboratory Practices (GLP). This is a system of research management practice guidelines designed to ensure the generation of high quality reliable data. These guidelines, recognised by authorities and scientists the world over, stipulate that all recordkeeping must be complete, the data and methodology transparent and the conclusions are expected to be replicable. Nevertheless, according to the experts, results from small exploratory studies often dominate the media headlines. “This fuels public fear, which is then picked up and reinforced by politicians,” Plastics Europe’s Jasmin Bird says. But stakeholders hope that scientific principles and reason eventually gain the upper hand in the debate. Not least because any other intermediate than BPA would of course have to be as well safetytested and the medical end use application would have to prove to be as reliable as a device made of polycarbonate. But such a precursor is not in sight. With the help of polycarbonate however, innovative products can be created which are the size of a credit card and thinner than a typical cell phone. For example, an auto-injector for people who are at risk from allergic shocks was introduced last year by US-based pharmaceutical company Intelliject. "As someone who has suffered severe allergic reactions myself, I know it is critical to have an epinephrine auto-injector that can be taken anywhere and cope with rough and tumble situations and still perform,” says Evan Edwards, the company’s co-founder. Its novel device e-cue (trademarked) meets these requirements—thanks to polycarbonate.

RIWISA Completes Flextronics Capabilities Sam Anson: RIWISA has a firm and excellent reputation throughout Europe as one of the best manufacturers of plastic parts and finished drug delivery devices with high levels of expertise in precision injection moulding and highly efficient FAMILY-OWNED SWISS INJECTION assembly. How does MOULDING AND AUTOMATED this fit with Flextronics’s ASSEMBLY FIRM RIWISA AND capabilities? GLOBAL SUPPLY CHAIN SOLUTIONS Mark Kemp: I would definitely agree with COMPANY FLEXTRONICS HAVE your statement about SIGNED AN AGREEMENT WHEREBY RIWISA and their FLEXTRONICS WILL ACQUIRE outstanding capabilities. We RIWISA. SUBJECT TO FINAL conducted an APPROVALS, THE DEAL REPRESENTS extensive search of over 100 plastic A MAJOR STEP FORWARD FOR THE companies during our INDUSTRY. SAM ANSON SPOKE acquisition due WITH HEAD OF MEDICAL AT diligence and RIWISA quickly emerged as FLEXTRONICS MARK KEMP TO FIND one of the top three OUT HOW CUSTOMERS OF BOTH companies on our target list. We are very COMPANIES WILL BENEFIT. excited about this acquisition as RIWISA is a perfect complement to our medical growth strategy at Flextronics. Specifically, RIWISA strengthens our precision moulding and automation capabilities in drug delivery and IVD consumables while broadening our healthcare solutions footprint in Europe. RIWISA also brings precision moulding and automation capabilities to our industrial and consumer packaging segments. Additionally, we are very impressed with RIWISA’s engineering capabilities and their innovative problem solving skills. Sam Anson: What benefits will Flextronics ownership bring for RIWISA’s customers? Mark Kemp: We have spoken with several of RIWISA’s customers and received extremely positive feedback about this acquisition. Essentially, the customers are excited about the global scale that Flextronics will bring to their supply chain. Many of RIWISA’s Switzerland-based customers want to expand to other regions, such as the USA and Asia, and Flextronics affords them solutions in these and other regions. The customers and RIWISA’s management views the acquisition as the clear and logical succession plan for the company moving forward. Sam Anson: And what benefits will Flextronics customers gain? Mark Kemp: Many of our existing customers require RIWISA’s precision moulding and automation capabilities. Several of these customers also require RIWISA’s cleanroom moulding and regulatory expertise. The acquisition also increases our healthcare footprint in Europe and compliments our existing design, industrialisation, tooling, manufacturing and logistics solutions. Additionally, Flextronics gains access to additional precision moulding solutions for the dental, consumer/food packaging and industrial markets.

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Sam Anson: Tell me a bit about Flextronics’s history in medical? Mark Kemp: Flextronics has been servicing top healthcare customers for over 20 years. The business started with Flextronics providing printed circuit board assemblies (PCBAs) to the top tier diabetes companies and gradually developed into a business providing full device manufacturing and logistics services. In 2006 our CEO, Mike McNamara, formed a separate business unit focused solely on the needs of our healthcare customers. At that time, we created our dedicated healthcare team and developed a proprietary healthcare Quality Management System called “FlexQ”. These investments along with the commitment from Flextronics leadership team enabled us to strengthen our capabilities, assemble a world class team and grow to become the number one outsourcing partner in the healthcare space today. wder inhaler, nents in a dry po po m co tic as Pl << automated d assembled by manufactured an ISA. >> machinery at RIW

<< A double barrel syringe system manufactured at RIWISA’s cleanroom moulding and assembly plant. >>

Sam Anson: And which particular segments of this market are you strongest? Mark Kemp: Our medical business units span across lab diagnostics and life sciences, imaging and patient monitoring, patient mobility, drug delivery, consumer health, implantables and single use disposables. By design, we built a global footprint with the broadest portfolio of medical business in the healthcare outsourcing space. We are currently expanding into orthopaedics and dentistry soon so the portfolio is becoming even broader as we speak. Sam Anson: Tell me more about the expertise you offer for pharmaceutical and medical device companies? Mark Kemp: Our customers increasingly want a single supplier solution for their medical devices and disposables. Many of the devices we are working on today include a consumable or disposable with integrated electronics and wireless capabilities to monitor and relay compliance, dose accuracy and patient conditions. These device and consumable products require a partner with industry leading electro-mechanical design and

COVER STORY and device connectivity is accelerating the need for a very flexible supply chain as products are succeeding or failing at a much faster pace due to customer/patient interactions on social media. Medical OEMs need a global supply chain that is less complex, more cost effective and one that provides flexibility and visibility throughout the supply chain. We are advancing our solutions on all of these fronts. It is an interesting time to be in medical devices. The industry is changing in many ways.

Sam Anson: Global outsourcing partners are extremely important for medical OEMs today. Please comment on this from the viewpoint of Flextronics. Mark Kemp: Medical OEMs are under cost pressures and industry dynamics that they’ve not experienced before. Additionally, they need to reduce risk, streamline their supply chains and expand into emerging markets. Consequently, our customers need a strategic partner that can provide global supply chain solutions and innovative business models. Flextronics is in a unique position to provide these solutions on an unmatched scale. << RIWISA’s medical building in Hägglingen, Switzerland, where the precision high-cavitation injection moulding and assembly takes place. >> industrialisation engineering expertise. Over the past ten years we have assembled one of the best such teams in the world. RIWISA is a perfect complement to this team adding industry leading high-cavitation, precision moulding and automation expertise. This combined team will be a powerful solution for our customers to leverage.

Sam Anson: How does Flextronics approach R&D? Mark Kemp: The Flextronics Product Innovation Centers play a big role in helping our customers develop and commercialise new technologies. We have six of these centres around the world and they contain innovation labs that focus on developing new technologies like “wearables” for consumer, automotive and medical applications. Another example would be our lab focused on developing the technology of 3D printing applications for consumer and medical devices. These Product Innovation Centers work with startups in the earliest stage to solve technical challenges and industrialise new technologies to make them scalable from a high volume manufacturing perspective. We also have a dedicated R&D team in the medical group working on a half a dozen technology projects every year. Today this group is working on projects such as smart patches, device specific sensors and smart pharma packaging applications. In addition, we are collaborating with the R&D teams across the Flextronics organisation to cross-pollinate technology from one business segment to another. Sam Anson: I see from your biography that your experience is wide ranging. What are the most important trends you are seeing in the industry right now? Mark Kemp: In the United States, there are big changes with Obama Care, the device tax and the shift of purchasing control from the physicians to the payers. Also, the US regulatory landscape has become more stringent and is challenging the industry with additional compliance requirements. Consequently, Europe has become more attractive as a regulatory pathway for companies as it is easier to bring products through the process in Europe. Globally, there is more of a focus on technology that improves patient outcomes, hospital processes and efficiencies. Additionally, we see a shift towards more regional manufacturing

Sam Anson: Please provide a short snapshot of your global footprint in medical. Mark Kemp: Flextronics has an experienced and compliant footprint in all of the major regions around the globe. In Asia, we have large operations in north and south China, Singapore and a fast growing operation in Malaysia. In Europe, we have operations in Romania, Austria and Italy— and of course Switzerland now with RIWISA. In the Americas, we have three large operations in Mexico and three in the USA. Sam Anson: Is there anything else you would like to add you feel is important for my readers? Mark Kemp: The addition of RIWISA’s precision plastics and automation capabilities to Flextronics Medical is a tremendous complement to the broad range of healthcare solutions we can offer our customers globally and underscores the strategic commitment Flextronics has to expanding the services we provide to the healthcare industry. We are very excited about bringing RIWISA’s highly talented team into the Flextronics family and look forward to creating a European Center of Excellence for precision plastics in Switzerland. The medical group at RIWISA is an important part of our medical growth strategy but RIWISA also brings industry leading precision moulding and automation solutions to our industrial and consumer packaging segments at Flextronics. We plan to work with RIWISA to continue their great efforts in these markets and to grow these business segments as well. RIWISA will be on hand to answer questions about the deal at D01 in hall 8b at Compamed in Düsseldorf, Germany, on November 20-22, 2013. For more information please contact Christian Classen at RIWISA (c.classen@riwisa.ch). About Mark Kemp Mark Kemp is president of Medical, a segment of the High Reliability business group at Flextronics. Flextronics is a US$24 bn Fortune Global 500 end-to-end supply chain solutions company with a global workforce of 200,000 and operations in over 30 countries.

SEPTEMBER-OCTOBER 2013 / MPN /11

SWITZERLAND QUALITY AND PRECISION I The Heart of Innovation?

Plastics in Switzerland’s Medtech Industry: Thoughts of Eight Industry Leaders by Sam Anson

<< The roots of Switzerland’s expertise in automation lie in watchmaking. >>

Introduction I arrived at Swiss medical injection moulding specialist RIWISA on the morning of August 28, 2013. Prior to visiting RIWISA I had heard rumours that the familyowned company was for sale. The rumours were confirmed that afternoon. The company was to be sold to USA-based Flextronics, a leading end-toend supply chain solutions company that delivers design, engineering, manufacturing and logistics services to a range of industries and end markets with a specialism in electronics, metals and plastics. My visit to RIWISA was the first stop on a tour of six leading advanced technology companies, who provide manufacturing services and products for international producers of healthcare goods, including medical devices, diagnostic equipment and drug delivery products.

THE SWISS ARE EXPERTS IN MANUFACTURING—IN UNDERSTANDING HOW THINGS CAN BE MADE, AND MADE WELL. BUT THEY ALSO KNOW HOW TO DO THIS EFFICIENTLY, AUTOMATICALLY AND IN A WAY WHICH IS SCALABLE AND HIGHLY REPRODUCIBLE WITH PRECISE DIMENSIONAL ACCURACY. FOLLOWING A TOUR OF SELECTED MANUFACTURERS IN AUGUST, SAM ANSON LOOKS AT THE ROOTS OF THESE CHARACTERISTICS, EXAMINES RECENT ACQUISITIONS, AND PICKS UP SOME OF THE CHALLENGES THE INDUSTRY FACES GOING FORWARD.

The other manufacturers are Weidmann Plastics Technology (injection moulding and automated assembly), Phillips-Medisize (injection moulding, injection blow moulding and assembly), Cicor (electronics and injection moulding), Gsell (machined and injection moulded medical plastics) and Netstal, a Swiss manufacturer of high precision, high speed injection moulding machines with a strong position in medical and packaging markets, especially bottle preforms and caps and closures. The idea for the tour came after Christian Classen, director of sales and marketing at RIWISA, invited me to see his company’s manufacturing operations, saying: “I really want you to see our operations here, Sam. I know you’ll be impressed.” RIWISA And impressed I was. I can see why Flextronics want ownership of the company. RIWISA is located just 40 km (25 miles) from Zürich Airport. As much as half its sales are to the healthcare sector. Its main products in this realm, all injection moulded, are: disposable plastic products for in vitro diagnostic (IVD) test equipment and drug delivery devices like dry powder inhalers and

Continued on page 15 SEPTEMBER-OCTOBER 2013 / MPN /13

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SWITZERLAND << Left: Sam Anson at one of RIWISA’s class cGMP cleanrooms Right: RIWISA’s cleanrooms are housed in a building dedicated to precise and highly automated medical plastic manufacturing. >>

Continued from page 13 double-syringe bone cement mixing injectors. The parts are manufactured and assembled in highly controlled and professionally organised class cGMP cleanrooms, including a temperature- and humidity-controlled, fully automated warehouse that is able to store moulded parts in cleanroom conditions while they are waiting to be assembled. The company has been owned by the same family since 1946 and, according to Classen, has always focused on “advanced” manufacturing of “high demanding” products. Classen says: “Our competent team, a high degree of flexibility, and our state-of-the-art infrastructure assure tailormade solutions, which consider all quality, regulatory, and economic aspects.” In the 1990s RIWISA entered the healthcare market initially through a dry powder inhaler project and later followed by IVD disposables. Today, the company boasts advanced expertise in high cavity injection moulding and fully automated assembly operations, as well as design and regulatory support with a speciality on part producibility. Christian explains: “Our expertise is on producibility—we are able to turn challenging ideas from our customers into a product design which is manufacturable in terms of high volume production and consistent in terms of high quality of each single part.” Industry “Big pharma” and medical technology drive medical plastics processing in the Zürich-Basel region in the north of the country. According to official industry statistics1, the five biggest medical device manufacturers by number of employees in the country are Johnson & Johnson—whose importance in the country grew significantly since the take over of Swiss orthopaedic device maker Synthes—Roche (Basel), Medtronic (near Lausanne), Sonova (Zürich), and Zimmer (Winterthur). Other selected relevant multinational healthcare manufacturers with operations in the country include Abbott Vascular, who produce the Fox angio-plast catheter, Actelion (Basel), B Braun (near Lucerne), Doetsch Grether (Basel), Ferring (west Switzerland), Galderma (Lausanne), Gerresheimer (Lucerne), Hamilton (Chur), Novartis (Basel), Nycomed (Zürich), Roche Diabetes (Basel), Stratec (Schaffhausen), Straumann (Basel), Synthes (half way between Basel and Berne), Tecan (Zürich) and Ypsomed (near Berne). Switzerland is among the world’s top ten medical technology manufacturing industries in

absolute terms. Patrick Dümmler, managing director of industry association Medtech Switzerland, explains: “We have the highest relative share of medical device sector in the world with as many as 1,600 companies in the medtech field alone. We define medical technology as follows: Medical technology includes non-metabolic products, instruments and equipment that serve diagnostic purposes or improve general well-being, life expectancy or the quality of life of patients. Products range from wheelchairs to high-tech band aids, inhalers, injector pens, implants, and even diagnostic devices and disposables.” << Christian Classen is director of sales and marketing at RIWISA. >>

<< Patrick Dümmler is the managing director of Medtech Switzerland. >> Roots The industry’s roots lie in watchmaking and machining and engineering. This, according to Mr Dümmler, is what gives the country its world renowned capabilities for highly precise, high quality products, particularly in medical devices. “The watchmaking industry requires highly precise small parts made by engineers who know about new and innovative materials,” he says. “Our machining and mechanical engineering skills are driven by innovation, and this has laid the foundation for our reputation for quality highly engineered technologies.” Echoing this is Tilo Callenbach, managing director of Gsell, a manufacturer of plastic components for medical devices with a specialism in machining of high performance polymers: “We have a watchmaking mentality mindset here. This spirit means we are highly innovative. Half of all Swiss medtech companies generate half their sales revenues from products which are no more than three years old. I find this statistic impressive given the fact that medical

projects take a long time to become commercialised, especially in implants.” Gsell works with a range of polymers, like PEEK, PPSU and PEI (including carbon fibre reinforced polymer—CFRP), and those for load bearing implants such as PE. The company has recently acquired an advanced automated machining centre from Swiss milling machine maker Fehlmann (see images on page 16). It uses this to manufacture machined plastics for implantable and non-implantable medical applications. The machining centre is highly automated in terms of part handling and the tool exchanger. It enables Gsell to economically machine smaller lot sizes, which is a popular trend in the medical industry these days. The company also has in-house injection moulding expertise in carbon fibre reinforced PEEK blanks—which it then processes through machining into spine cages. Additional knowhow is an innovative catheter finishing procedure which uses thermoforming to create, for example, a flare at the end of a piece of plastic tubing. Fritz Stein, head of the medical division at Weidmann Plastics Technology, reinforces the theme of innovation. “We are highly innovative in manufacturing. Our advanced techniques allow us to guarantee quality and reliability. There is a good image of Switzerland’s exports throughout the world—in all products.” Looking further back, historically speaking, Dr Patrick Blessing, head of the medical business unit for the brands Netstal and KraussMaffei said: “Switzerland has never had its own natural resources like gold or oil. So our economy has developed through negotiating with other countries. We have always had a strong import sector. We add value to these imports and then sell them on as exports. Value-added exports are a big area for the Swiss.” KraussMaffei is a brand of plastics processing machinery consisting of injection moulding, reaction processing and automation equipment. Automation For me, advanced and highly efficient automation is, very clearly, a key winning capability for manufacturers here. It seems to come naturally to companies to set up automation systems. Indeed there are lines running for blood lancet devices which in the USA might have up to a dozen people working on them. In Switzerland these

Continued on page 16 SEPTEMBER-OCTOBER 2013 / MPN /15

SWITZERLAND Continued from page 15

<< Tilo Callenbach (left), managing director of Gsell, and Sam Anson discuss a fibre reinforced plastic part in front of the company’s new machining centre. >>

<< Wolfgang Czizegg confirms the high services like FMEAs productivity level of (failure mode effect Swiss manufacturers of analyses) and GAMP lab consumables (good automated through automation. >> manufacturing practice) 5 qualifications are key for our customers,” Wolfgang explains. With many patented technologies, the company says it is the global leader in automation for products like lab consumables (pipette tips and reaction vessels), contact lenses and drug delivery devices. In countries where there are high labour costs (Switzerland being one of them), an important benefit of investing in automated technology is that it allows you to strip out labour costs. The cost of the investment can be spread out over the expected lifetime of the machinery in the profit and loss account as a depreciating asset. Wofgang Czizegg reaffirms that these high labour costs are a major driver for Switzerland’s fast process development activities and high innovation levels. “Working in automated processes with low manual work involved enables Swiss medical injection moulders to successfully compete with low labour cost countries,” he states. “In fact, continuous and significant process innovations make them global leaders.” He adds: “Working closely with our Swiss customers we can achieve cleanroom productivity improvements by factors of 4-8 in pipette

manufacturing within two years. While in other countries, where manufacturers may be working with 8-16 cavities and cycle times above ten seconds, using our systems the Swiss are already using 64 cavities and more, in cycle times below five seconds.” Waldorf Technik’s automation systems have enabled new plastic technologies in low cost manufacturing. Wolfgang explains: “Besides innovation for productivity benefits, Waldorf Technik has also reached a breakthrough on low cost technologies to provide migration barriers to medical plastic parts (as a substitute to glass), which again opens unique market segments for customers.”

lines are fully automated in a highly innovative and, frankly, mesmerising way. Exchange rates Patrick Blessing has a good deal of expertise The cost of labour is not the only thing which is in automation. As a mechanical engineer he expensive in Switzerland. The Swiss Franc is supplies machines which are to be used with currently regarded as being extremely strong, multi-cavity moulds in highly automated lines in trading at a much higher rate than in recent years medical cleanrooms. His company specifically compared with the Euro and the US dollar, both focuses on turnkey solutions for medical plastic of which have fallen in value since the credit crisis manufacturers. Patrick points out that by of 2007-08. Every single person I spoke to raised automating, you can improve productivity and this as the number one challenge the Swiss reduce scrap rates. “Automation allows you to medtech industry must overcome. One be efficient, you can strip out human error in explanation for the high rate is that since the manufacturing. The financial crash investors have deposited funds in result is quality and Swiss bank accounts, seeing it as tax efficient safe reliability, so you can haven for capital until international markets be much more recover. Added to this, the Swiss economy has comfortable in not suffered the same extremes as the likes of the guaranteeing the UK, the USA and the Eurozone, which are only required quality of just beginning to recover. parts so that The exchange rate issue affects all export customers who use industries. Swiss exports have been relatively these parts in their more expensive than products sourced from own manufacturing comparable Western countries for nearly five years now. << Patrick Blessing is will return to you to maintain their own Commenting, Patrick Dümmler said: “The head of medical at productivity rates. ” exchange rate pressure is the same for everyone, KraussMaffei Group, The Netstal no matter what industry you’re in. But the the company which brand is known for medtech sector is highly innovative, and the owns the Netstal offering machines strong Franc forced exporters to focus on even brand of high more efficient and lean operations, and it is precision, high speed which are fast, precise, reliable, user-friendly something we have done well.” injection moulding and cost-effective in Fritz Stein adds: “We compete with cheaper machines. >> terms of operation. suppliers in the Euro zone. Our strong currency The range includes has forced us to invest in operational excellence. the all-electric ELION (pictured). Added to this, upcoming regulatory changes A well known automation company, bringing additional hurdles makes us an industry Germany-based Waldorf Technik, is located which is able to withstand forceful market directly on the Swiss border. At the pressure. Our core competences are to manage manufacturing sites I visited, I noticed a regulatory affairs and optimise our << Netstal’s ELION 1750 with medical specification. >> significant number of machines from this resources.” company. According to company CEO Despite this overarching cost Wolfgang Czizegg, his machines pressure, the industry is poised for contribute to the success of Swiss growth. Patrick Dümmler states: “Our manufacturers of medical consumables. outlook is promising, at 6% a year the “Being in this particular field of automation projected growth is substantially for more than 20 years allows us to deliver higher than expected GDP increases, more than just reliable automation systems albeit lower than the double digit to our customers. The expertise of our rises we were enjoying ten years ago.” employees, the focus on patient and Employment in the sector is also product safety as well as dedicated growing at a steady 3%. 16/ MPN /SEPTEMBER-OCTOBER 2013

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SWITZERLAND Continued from page 16 Industry consolidation International investors have an optimistic outlook for the Swiss industry. One of the sector’s strengths is its high concentration of small to medium sized companies operating in highly specialised niches. Patrick Dümmler highlights that this allows an entire medical device to be designed and manufactured in the country: “Every aspect of the supply chain is well represented by a large concentration of highly specialised small to medium sized companies.” Fritz Stein reinforces this: “It is easy to find a specific manufacturing technology in Switzerland. We can match needs to an individual solution.” The strong Franc has not put off global investors. On the contrary, many international players see smaller Swiss firms as prime takeover targets to help them acquire highly efficient and technologically advanced manufacturing techniques which have the potential for being “exported” overseas. There is a clear trend towards consolidation in the Swiss sector. As previously mentioned, the acquisition of RIWISA was announced the day I arrived in the country. Just two weeks earlier, St Jude announced it had bought defibrillator and pacemaker manufacturer Endosense for US$171 mn. The theme of consolidation is clear on a global basis. Small to medium sized medical device companies are being bought and sold everyday. Commenting on the situation in Switzerland, Phillips-Medisize’s director of sales and marketing for Europe, Christof Plätzer, said: “There is definitely a trend of consolidation in the medical device and pharmaceutical packaging sectors in Switzerland, and more broadly all over the world. Customers are looking for contract manufacturers who have a global footprint— especially in international manufacturing locations—so they can call on local companies who have European quality standards. Prior to our merger with Phillips, Medisize was a European manufacturer with high levels of expertise mainly in Europe. When we became Phillips-Medisize this was married with Phillips’s US focus and we now offer a global contract manufacturing option—which is very popular with our customers all over the world.” Reflecting the advantages of Switzerland’s automated approach to manufacturing in the context of industry consolidation, Christof said: “Switzerland’s capabilities in advanced engineering and manufacturing, through highly automated equipment and vision inspection systems, attract large international companies.” But there is a double-edged sword to the trend of consolidation. Patrick Dümmler explains: “Acquisitions of Swiss companies create jobs for the sector as the buyers invest in the technological expertise found here. The production sites set up by international companies have healthy output and are creating jobs.” In 2012 more than half of the ten biggest Swiss medical technology companies were foreign owned. The downside is a leakage of decision making to the buying companies’ overseas headquarters. Patrick goes on to say: “Decisions 18/ MPN /SEPTEMBER-OCTOBER 2013

<< Christof Plätzer is PhillipsMedisize’s director of sales and marketing for Europe. >> are sometimes made without the innovation systems available in Switzerland being fully taken into account.” Consolidation is apparent at a higher level in the Swiss industry, and in Europe as a whole. Patrick Dümmler explains: “There are plans for the three major medtech associations in Switzerland—Fasmed, Medical Cluster and Medtech Switzerland—to merge together. We are already highly complementary and not in competition. We have a responsibility to react to market dynamics and provide networks abroad. This helps to secure jobs in export-led industries like medical technology. One industry association is much easier for people to work with. Swiss manufacturers only need to be a member of one association and there are clear synergies across the associations. Furthermore, a single organisation gives us the opportunity for a single voice, making us better heard and giving us more influence in national Parliament.” In Europe, there has been consolidation recently too. Eucomed and the European Diagnostic Manufacturers Association have merged and a new umbrella association, MedTech Europe, has been formed. Education Switzerland’s education levels are a key strength. This is clear as a visitor to the country. The Swiss system has a strong emphasis on vocation and practical experience, even more so than in Germany. State schools are the norm and are of a very high standard. Everyone I spoke to on the streets are clearly highly intelligent and most spoke at least three or four languages. Unlike parts of Germany I have visited, where some workers in cafes and restaurants, and sometimes in hotels, speak very little English, every person I conversed with had excellent English—most with a fluent accent that sounded like it was their mother tongue. Erich Trinkler, executive vice president at Cicor Electronic Solutions, summarises: “For us, an excellent level of education in Switzerland— especially in engineering, but also in terms of good workmanship—provides us with wideranging know-how, which in turn leads to a high degree of innovation.” Erich believes that within the medical technology sector, the country is home to many highly innovative companies that play an important part in advancing the sector as a whole. He adds: “The focus is always on trends and innovations that serve to further develop all branches of the healthcare sector (medication, therapies, new surgical techniques, and so on).” With a core specialism on electronics—in terms of printed circuit boards and customised electronic solutions—Cicor is a contract

manufacturer with a global presence. The company also has knowhow in injection moulding, including 3D moulded interconnect devices (MIDs)—which are advanced injection laser activated moulded electronic circuits. The company has 11 production sites across the globe, in Western Europe, Eastern Europe and Asia. “A global base positions us perfectly to meet the needs and requirements of our customers, with some sites being certified according to ISO13485.” Global outsourcing Global outsourcing is a hugely important aspect of modern day manufacturing for healthcare markets. A key strategy of global OEMs is to have facilities fed by reliable supply chains which are close to their main markets (for example, USA, Europe, China and Brazil) and which are capable of delivering locally while finely tuning quality to the demands of buyers in these markets. Phillips-Medisize positions itself as a company which is at the forefront of this phenomenon. The company operates injection moulding, injection blow moulding and automated assembly operations in Switzerland and has seven plants in the USA and five in Europe—including a highly advanced automated production and assembly plant near Helsinki in Finland. It has recently acquired plants in Mexico and China. Christof Plätzer explains: “We are a global provider with our own design and development capabilities in the USA and Europe. We are extremely flexible—we can produce from a small scale up to more than 100 million units per year of a finished device. Our design capabilities combined with manufacturing close to our customers allows us to offer some of the fastest time to market for new devices.” EU independence The most important markets for Switzerland’s medical technology are those in the EU, especially Germany, followed by the USA and China. But non-membership of the EU doesn’t appear to be a hinderance to success—ignoring the challenges presented by the high value of the Franc compared with the Euro and the US Dollar. Erich Trinkler adds: “Advantages are that we benefit through little bureaucracy and low taxes—both favourable characteristics for entrepreneurs. We also have a free trade agreement with China, which is helping our exports to that country.” Patrick Blessing adds the thought that even without EU membership Switzerland has never been isolated. “We have always been very good negotiators thanks to our historical roots as a trading location, so working across borders comes naturally to us.” “On the other hand, there is the issue of the soaring Swiss Franc, and some customs-related problems can cause delays in the flow of goods between Switzerland and the EU,” he adds. Switzerland’s geographical location— nextdoor to German speaking Austria, Germany and Leichtenstein, as well as Italy and France— gives it enviable access to other advanced suppliers and technology partners in these

Continued on page 21

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<< Erich Trinkler is executive vice president at Cicor Electronic Solutions. >>

countries. Tilo Callenbach underlines this: “We foster cooperation throughout Europe but especially in our neighbouring countries. The infrastructure connecting these markets is excellent, and cooperation and sophisticated services are essential, especially in complex device supply chains.” Christof Plätzer underlines the importance of partnerships in the industry for medical devices: “In order to allow the medtech companies to focus on their core competences they need a CMO [contract manufacturing outsourcing] partner to develop and manufacture the medical device or disposable. A characteristic of the medical device market is the particularly long engineering, development, and clinical testing— which for a new generation product can take up to seven years, or even longer. As such, partnering with another company who can provide expertise often leads to reduced costs and better efficiency.” There is strong alignment with regulatory aspects in the rest of Europe. Patrick Dümmler explains reassuringly: “Bilateral treaties with the EU in healthcare markets allow Swiss companies to register products in Switzerland and these registrations are good for the European Union. Similarly, German companies can register in Germany and that product is good for the Swiss market.” When looking at pricing structures, Patrick helpfully points out that companies must still assess each market on its individual merits, but this would be the same for all member states. Industry associations and trade shows There are three major industry associations in Switzerland—Fasmed, Medtech Switzerland and Medical Cluster. And as Patrick Dümmler pointed out before, all three are complementary. Fasmed is the main lobbying group for industry issues at government level. It participates in EU decision making with respect to the EU healthcare industry regulations, and is a member of the European association Eucomed. Medical Cluster is a network of Swiss manufacturers, suppliers, service providers, and research and development institutions working in the value-added chain of medical technology. Medical Cluster organises events, conferences, forums and services and helps companies and experts to meet and exchange information in order to foster new cooperations. The needs of its members are always at the focus of its activities. The Medical Cluster is not politically active. Medtech Switzerland is a non-profit group focused on the promotion of exports from the medical technology industry in Switzerland to key

world markets. As part of its work it looks to build good networks abroad for its members. Within the liquid handling and lab automation sector in Switzerland, which is an important market for manufacturers of pipette tips like Weidmann and RIWISA, a useful industry association is Toolpoint for Lab Science. The group is a vertically integrated cluster, which combines the know-how and ability of the lab automation industry in Europe. The cluster was founded ten years ago by companies of the Greater Zürich area, and combines industry, universities, institutions and partners, which share the same goal of making processes in and around the laboratory more efficient and effective. The Swiss Technology Network (SwissT.net) is an umbrella organisation of technology sub-sectors in Switzerland. IG Exact is a trade association for the Swiss electronics comminity. Swissmem is a members association which unites the mechanical and electrical engineering industries and associated technology-oriented sectors. The Swiss plastics association is KVS. The World Medtech Forum was held for the first time in Lucerne in 2012. At the time of going to press the event was taking place for the second time on September 17-19, 2013. Swiss Plastics is a trade show for plastics processors. The next event will be held in Lucerne on January 21-23, 2014. Technological research institutions Three noteworthy research institutions are: the Swiss Centre for Electronics and Microtechnology (CSEM—Centre Suisse d'Electronique et de Microtechnique; the Swiss Federal Laboratories for Materials Science and Technology (Empa— Eidgenössische Materialprüfungs- und Forschungsanstalt; and ETH Zürich— (Eidgenössische Technische Hochschule Zürich). CSEM is a Swiss research and development company with expertise in micro and nano technologies, microelectronics, systems engineering and communication technologies. Empa is an interdisciplinary research and services institution for material sciences and technology development. The institution plays a key role in the Swiss educational, research and innovation scene. Its research and development activities are oriented to meeting the requirements of industry and the needs of society. The institution offers its partners solutions tailored to meet their specific needs. This encourages companies to think and act in innovative ways. ETH Zürich is an engineering, science, technology, mathematics and management university in the city of Zürich, Switzerland. In plastics, points of interest are the Plastics Training and Technology Center (KATZ), the Institute of Polymer Engineering IKT, and the Institute of Polymer Nanotechnology INKA. Industry relations As Tilo Callenbach points out, medical technology exports accounted for 5.5% of all exports in 2011. The general consensus among my interviewees was that relationships with the government are good. But there are concerns

about the exchange rate. Putting that to one side, Patrick Dümmler sums it up well: “As an industry we have a growing influence but it could be better. More work could be done to build relationships with our government. Our industry associations are always working hard to develop good connections in governmental networks and we are increasing our influence, but it is from a very small base.” In terms of reciprocation, Fritz Stein feels the government supports the industry well: “Overall, help from the government is on a good level, we get assistance with booths at international trade shows and it presents our values accurately in the public eye.” The interface between manufacturers, research institutions and clinicians is very close. Patrick Dümmler believes this is one of the main success factors of the industry. He says: “There are excellent relations with doctors and they provide feedback into new products.” He adds: “The CTI [Commission for Technology and Innovation] makes funding available for universities to develop new ideas. The universities are expected to work with industry to find a commercial partner who can match the public funds made available. These initiatives have led to ten or more relevant new commercial products being developed every year—and these are not just ideas on paper. Endosense, sold to St Jude in August, was a start-up once supported by this initiative.” The government also supports medical technology industry engagement with universities and healthcare associations. Christof Plätzer explains: “The Swiss medtech industry exploits its intellectual resources to produce maximum innovation potential by building active collaborations across multiple disciplines. For example, many innovations happen at the interface between engineering, medicine and biology where natural scientists and engineers work together to create solution-driven products and techniques in the medical technologies sector.” Healthcare provision Despite being one of the world’s smaller countries, both in terms of population and land mass, Switzerland is known around the world to have one of the best healthcare sectors. Health insurance is a mandatory requirement for all residents. In return, they enjoy the world’s higest ratio of doctors to patients. References 1 The Swiss Medical Technology Industry 2012 “In the Wake of the Storm”, Medical Cluster, Medtech Switzerland, IMS Consulting Group and Innovation Promotion Agency CTI. Credits Patrick Blessing, Netstal and KraussMaffei. Tilo Callenbach, Gsell Medical Plastics. Christian Classen, RIWISA. Wolfgang Czizegg, Waldorf Technik. Steve Duckworth, Clariant. Patrick Dümmler, Medtech Switzerland. Christof Plätzer, Phillips-Medisize. Fritz Stein, Weidmann. Erich Tinkler, Cicor. SEPTEMBER-OCTOBER 2013 / MPN /21

TEXTILES

Regenerative Biomedical Textiles of the Next Generation by Josh Simon, PhD, and Ryan Heniford, Secant Medical Cutting costs while improving patient recovery are predominant pressures faced by the medical device industry. Manufacturers that work with biomaterials must be prepared to address this challenge by introducing technology that effectively returns the patient to normal activity while also restoring the body to its native state from a long-term perspective. In the context of biomedical textiles and their use in medical devices, it is important to understand the evolution of textiles and how the next generation will enable the body to heal itself. The historical use of textiles in surgical procedures and wound healing closely parallels the greater story of biomaterials. In broad terms, there are three generations of biomaterials and biomedical textiles, with the first two generations focused primarily on repairing and recovering from an injury, defect or condition. However, the first and second generations elicit a chronic immune response; the body sees these materials as foreign and tries to eliminate them. This can cause a host of issues, from excess inflammation and scarring to outright implant rejection. The third-generation biomedical textile, which will be made possible with the adoption of advanced biomaterials, discourages this harmful inflammatory response and encourages regenerative healing. To explore the recent trends and the future direction of biomedical textiles in regenerative medicine, it is necessary to look at some areas in which their uses are increasingly being developed. This article discusses how current biomedical textiles are transitioning into enabling the body to heal itself, and a material that could launch textile platforms into a wholly regenerative system. Textile Evolution Since the times of the ancient Egyptians and Aztecs, sutures composed of various natural materials have been used to close wounds, and by the 1930s, synthetic polymers became available for use in medical applications. In that first generation of medical textile materials, lasting from the beginning of recorded history to the early twentieth century, the idea was simply to create a material that held the injury in place and allowed it time to heal. There was little consideration as to the nature of breakdown products formed from degradation of the suture, if it degraded at all. In fact, many of the animalbased sutures did degrade, while most synthetics did not. It was not until the second generation of biomaterials, which emerged in the 1960s and 70s with the widespread use of polyglycolic acid (PGA) and polylactic acid (PLA), that developers gave consideration to what happens to degradation products. This was a significant

<< A knitted scaffold can be designed with varying pore size to elicit tissue in-growth in applications such as a hernia mesh. >> improvement over the first generation of biomedical textile materials. However, in both the first and second generations there were, and still are, problems with biological integration. Namely, these biomaterials are considered to be invaders by the natural immune system, which reacts accordingly based on the location of the implanted material and its geometry. In the case of resorbables, the reaction can resolve. Devices made from resorbable materials generally do not need to be removed post-healing, as compared with many first-generation materials, which can elicit a chronic inflammatory response and thus may require removal. Second-generation biomaterials interact meekly with the body’s natural biological processes; they are designed to interfere as little as possible, and then disappear. It is the third generation of biomaterials that promises to raise biomaterial interactions to the next level: the repair, recovery, and regeneration of damaged tissue by enabling the natural biological processes for healing. Modern Biomedical Textile Formation An important aspect in all generations of medical textiles is their ability to be formed into scaffolds for tissue growth. Since textiles are porous by nature, the manipulation of pore size has been a central feature in medical textile development, primarily to optimise the

conditions necessary for a specific application. For any given biomedical textile design, it is important to tune the material’s structure for the application. In instances in which in-growth is desired, the appropriate pore size must be present. Conversely, in situations in which ingrowth is detrimental, the material must be able to act as a barrier. Although there are conflicting reports in the literature regarding optimal pore sizes as well as the methodology for determining pore size for specific cell types, pores in textiles can be controlled. The density of a textile can also be increased to the point in which pores are too small to allow the passage of cells, and even liquids such as blood. “Blood-tight” woven fabrics are a common component in vascular prostheses and cardiovascular devices, such as heart valves, which contain at least one biomedical textile component (usually the skirt around the implant that acts as the interface between the edge of the valve and the tissue). Knitted fabrics can also have complex networks of interconnected pores of various sizes to accommodate the flow of nutrients and the movement of cells through the matrix. From a generational perspective, these parameters serve to maximise the repair and recovery of tissue by directly replacing structures in the body in a semi-permanent fashion. This puts them squarely in the first generation.

Continued on page 24 22/ MPN /SEPTEMBER-OCTOBER 2013

TEXTILES Continued from page 22

<< This braided PGA tubular structure uses a second-generation resorbable biomaterial that is designed to have minimal interference with the immune system before degrading within the body. >>

Creating Regenerative Textiles The leap from a tailored scaffold that minimises interference with the natural healing process to a functional scaffold that actively participates in tissue regeneration is the critical element that elevates a medical textile structure into this third generation. This tissue regeneration capability can become part of the design in several ways, including through the use of biofunctionalised coatings. By coating the porous scaffold material with an agent that produces a known biological effect, the overall textile product becomes an active participant in healing. Covalent or ionic attachment of growth factors that can be released from the device and into the surrounding tissue in a controlled manner would serve as one such platform for active healing. One early example is collagen scaffolds that contain bone morphogenetic protein-2 (BMP-2). Newer materials, such as poly(glycerol sebacate) (PGS), are in the early stages of commercialisation and can be used both for the purpose of minimising the release of acidic chemistry that can negatively affect local healing and for possible use as a basecoat to attach some other active agent. Active agents attached to a PGS coating should possess a sterically accessible and reactive hydroxyl, carboxyl or amine group that can be released over the desired time period to acutely modulate the body’s response and enable more effective healing. Aside from growth factors, these agents could be

antimicrobials, pharmaceutical ingredients or even components of extracellular matrix that play important roles in wound healing. Many engineers tend to gravitate toward materials that are tried and true. This can be partially attributed to regulatory hurdles, but it is also due to the relatively small number of commercial partners that have taken materials out of academia and into the commercial arena. These two challenges are not mutually exclusive and are in fact related. Use of regenerative materials in the form of coatings could be an effective way to slowly introduce the regenerative concept to the market while providing enough time to meet regulatory requirements. These coatings add value to the medical devices they adorn—value that comes in the form of increased capabilities for new and established devices, and a more coherent method for tackling a specific injury or application, such as an upgraded treatment that causes fewer biomaterials-related complications or problems with tissue healing. Picture a coated wound dressing that overcomes the inhibition of wound healing seen in diabetic patients. Potentially, a pre-existing device that has already been cleared or approved can be retroactively coated with third-generation regenerative properties without some of the high barriers to entry needed if starting from an entirely new device concept.

The Transition to a Wholly Regenerative Device How will the healthcare landscape look when biomedical textile components and their devices are wholly regenerative? The use of first- and second-generation materials will diminish, particularly once third-generation materials capable of handling the mechanical loads emerge and gain acceptance. The entire structure will be made from fibres drawn from these materials, instead of being coated with a bioactive agent. PGS is one material that will help facilitate regeneration within the body. As a surface eroding material its degradation profile can be controlled so the material does not experience a sudden breakdown, as seen with PGA or PLA. When working with bulk eroding materials such as PGA or PLA, loss of strength occurs as water molecules penetrate deeper into the structure. For example, when creating a scaffold with PLA, as the material degrades, the pH can drop too low to elicit cell attachment and natural tissue development. The goal is to control the degradation such that the cell load can be transferred in a manner that does not cause sudden failure of the scaffold. Using a material such as PGS—that degrades in a predictable manner, that does not abruptly lose strength, and that has a reduced acid burst—will encourage the body to heal itself without promoting excessive inflammation. PGS has considerable

Continued on page 26 24/ MPN /SEPTEMBER-OCTOBER 2013

SEPTEMBER-OCTOBER 2013 / MPN /25

TEXTILES Continued from page 24 potential in a range of medical device applications, including surgical meshes, heart valves, tendon and ligament repair, and nerve regeneration. New fibres made from materials such as PGS have interesting properties. Core-sheath techniques can be used to form fibres with dual, tri, or quad functionality depending on how many layers are built into the fibre. A multi-layer fibre can have a quickly degrading outer layer designed to address inflammation and an inner layer with a slower degradation profile that contains agents important in the middle and later stages of healing. For bone tissue, this could be an outer layer with a type of PolyAspirin, a polymer created from salicylic acid (the principal metabolite of aspirin), set above an inner layer that contains osteocalcin or another growth factor involved in mid-to-late bone formation. The fibre shape could also be tailored toward cell migration, and its shape could change depending on when and where the cells must migrate. By creating a smooth fibre, some cell types would react by quickly moving and proliferating along the length in a non-directional fashion. At a later point, the fibre would partially resorb to leave a purposely roughened surface that would promote cell differentiation once the cells arrived at the intended location and proliferated. Alternatively, fibres could contain grooves designed to directionally guide certain

cell types to different parts of the device. Furthermore, with overall control of the design and porosity of a textile, the mechanical forces within the device could be tailored. Since mechanical forces are critically important for tissue development, the appropriate kind of forces can be applied for the specific application to achieve tissue growth in a three-dimensional space. Currently adopted biomaterials can address certain health issues acutely. However, fixing problems acutely is not the solution, because it often involves revision surgery and leads to higher healthcare costs in the long run. Multiple new second-generation materials (besides the well-trodden lactide-glycolide permutations) are entering the market each year. Some of these materials are being used in neurosurgical devices like nerve cuffs, and others are in the form of hernia meshes made from tyrosine-derived polyarylates. Other examples abound.

<< PGS (material shown in image) can be used as a basecoat of a textile, upon which active agents can be attached to acutely modulate the body’s response and enable more effective healing. >>

The third generation of biomedical textile structures is taking shape from a convergence of second-generation material development and bioactive agent exploration. By enabling the creation of structures that improve the long-term chronic response by reducing inflammation, preventing secondary procedures (thereby cutting costs), and enabling the body to regenerate on its own, this new generation of biomaterials presents a value proposition that cannot be ignored in today’s healthcare environment.

About the authors Josh Simon, PhD Josh Simon, PhD, is business development manager at Secant Medical, based in Perkasie, Pennsylvania, USA. Josh joined Secant Medical in July 2013. Focusing on orthopaedic and neurovascular applications, Simon works with Secant Medical’s partners to bring their biomaterial visions to life in products. Simon began his career as a research scientist at Biomet, the fourth-largest orthopaedics company in the world at the time. In addition to his role at Secant Medical, Simon is also an adjunct professor at the New Jersey Institute of Technology (NJIT), USA, where he teaches courses on medical device development, project management, and orthopaedics. Simon holds a Bachelor of Science degree in chemical engineering, a Master’s of Science degree in biomedical engineering, an MBA in general business, and a PhD in biomedical engineering, which focuses on biomaterial interactions and bone healing.

26/ MPN /SEPTEMBER-OCTOBER 2013

Ryan Heniford Ryan Heniford is business development director at Secant Medical. He joined the company in January 2006 as a research and development engineer after completing his Master’s degree at North Carolina State University, USA. Heniford assumed the role of Senior R&D Engineer in August 2008 and became the company’s development engineering manager in October 2010. In February of 2012 Heniford assumed his current role as director, business development. Heniford’s Master’s degree is in textile engineering. He also holds a Bachelor of Science degree in mechanical engineering.

Simon and Heniford will be at Compamed in Dusseldorf, Germany, November 20-22, 2013. Secant Medical’s stand is Hall B, Booth G20-2.

SEPTEMBER-OCTOBER 2013 / MPN /27

MEDICAL TEXTILES Electrospun Nanomaterials in Woundcare and Other Biomedical Applications by Dr Ramesh Babu and Dr Murugan Rajendiran, CRANN & School of Physics, Trinity College, Dublin, Ireland, on behalf of the Society of Plastics Engineers European Medical Polymers Division. Introduction Electrospinning has attracted increased attention as a versatile technique, applicable to numerous organic and inorganic systems which can result in a tightly controlled size distribution of nanomaterials1. The resulting nano-system can be described as a highly porous network structure, with a large surface area to volume ratio, the dimensions of which can be easily tailored and optimised during production. Itâ&#x20AC;&#x2122;s probably the most researched top-down method to form nanofibres from a remarkable range of organic and inorganic materials. The process Electrospinning is a process that produces nanofibres through an electrically charged jet of polymer solution or polymer melt (see figure 1). The polymer drop from the needle tip is drawn into a fibre due to the high voltage. The jet is electrically charged and the charge causes the fibres to bend in such a way that every time the polymer fibre loops, its diameter is reduced. The fibre is collected as a web of nonwoven fibres on the surface of a grounded collector. The process is versatile: fibres can be spun onto any shape using a wide range of polymers. Properties of the fibres can be designed in advance and controlled to a high degree. The fibres are very thin and have a high length to diameter ratio, thereby providing a very large surface area per unit mass. It allows for the creation of nanofibres that can be collected to form a non-woven fabric. Biomedcial applications Electrospun nanomaterial has great potential in various biomedical applications, such as tissue engineering, cardiac batches, drug delivery, nerve regeneration, biosensors, enzyme immobilisation, wound dressing, biological protective clothing, regenerative medicines, stem cells, artificial organs, vascular grafts, ex-vivo models, antimicrobials, diagnostics, medical devices, prosthetics and fabrication of scaffolds. It has recently emerged as a versatile method for generating biomimetic materials made of synthetic and natural polymers for tissue engineering applications. Electrospun fibres with a high surface area and a nano-sized diameter can be used to mimic a natural extra-cellular matrixâ&#x20AC;&#x201D;which acts as scaffolding that allows cells to attach, proliferate, differentiate, and develop essential functions within tissue. Providing cells with an artificial extra-cellular matrix encourages tissue growth and therefore promotes healing. Polyurethanes Polyurethanes are often-used polymers in biomedical applications, particularly those in 28/ MPN /SEPTEMBER-OCTOBER 2013

<< Dr Ramesh Babu has written for Medical Plastics News on behalf of the Society of Plastics Engineers (SPE) European Medical Polymers Division (EMPD). For information on how to join the EMPD please contact the current chair and councillor Austin Coffey at austincoffey@gmail.com. >> contact with blood. Polyurethane fibres have shown great promise in the area of wound dressing application. While earlier use of polyurethane occlusive dressings on the healing of wound has the difficulty of significant fluid accumulation after a few days of use, electrospun nanofibrous polyurethane membranes promote fluid drainage. This is because of the high porosity of the nanofibrous membrane which also allows excellent oxygen permeability. Natural polymers For most of the biomedical applications, the materials used have to be biocompatible, thus natural polymers have distinct benefits compared with synthetic materials. Since many natural polymers can be decomposed by naturally occurring enzymes, it can be used in applications where temporary implants are desired or in drug delivery. Natural polymers such as cellulose acetate, alginate and aloe vera are used in biomolecule immobilisation, tissue engineering and biosensor applications. Most polymers that have been electrospun are proteins and polysaccharides. Proteins that have been electrospun include collagen, silk and gelatin. Collagen is one of the most commonly used natural polymers and naturally occurrs in connective tissues where it provides mechanical support. There are many different forms of collagens dominant in specific tissue. However, most of the collagens share the fundamental triple helix structure. As collagen presents naturally in fibre form, electrospun collagen fibres are able to mimic an extracellular matrix in the body. Normally, collagen is relatively strong and forms stable fibres, particularly after cross-linking. However, at present, only collagen types I, II and III have been successfully electrospun together with their blends. A cheaper alternative to collagen would be gelatine, which can also be electrospun. Another protein that is electrospun for use in tissue engineering is fibrinogen. As this protein plays a key role in blood clotting and wound healing, electrospun fibrinogen has been explored for possible usage in wound dressings. Due to its unique biological properties, chitosan is used as a component in the extracellular matrix to promote healing. Chitosan

is biocompatible, biodegradable, nontoxic, a haemostatic, and a natural antibacterial agent. By incorporating an electrospun layer of chitosan onto film, film placement could potentially be permanently established in the suitable location within the body, due to chitosan’s haemostatic nature potentially increasing adhesion to the wound site, until the film is resorbed into the body. The addition of chitosan also induces wound healing, and helps prevent infection within the surgical site further reducing the opportunity for adhesions to occur. Ceramics Ceramics have found uses as biomaterials like calcium carbonate based ceramics and hydroxyapatite ceramics. Ceramics including glasses have been widely used in many biomedical applications such as diagnostic instruments, porous glasses as carriers for antibodies and restorative dental materials. Because of their excellent wear resistance, corrosion resistance and good biocompatibility, ceramics are also commonly used in load bearing prosthesis. Aluminium oxide has been used in orthopaedic surgery for more than two decades and zirconium dioxide is used as the articulating ball in total hip prostheses. A ceramic implant is used to encourage bone growth within the interconnecting pore channels with pore size exceeding 100 μm. Bioresorbable ceramics have also been broadly tested as artificial bone substitute. Hydroxyapatite ceramic is found in natural bones and its most commonly used bioresorbable ceramics. Nanoscale alumina borate oxide fibres have successfully been electrospun to form a random mesh which may have the potential for use as ceramic filters. Nanostructured ceramics are also desirable in other applications such as microelectronic devices, chemical and biological sensing and diagnosis, energy conversion, catalysis and drug delivery. Tissue engineering Nanofibres and nonwovens composed of them are unique nanostructures with an extraordinary potential both in technical areas and in medical applications. Approved electrospun materials in tissue engineered products for human use or in clinical trials are skin, cartilage, blood vessels, corneas, urinary structures, main stem bronchus, bone and kidney dialysis. Devices approved by the FDA which include synthetic polymers have incorporated drugs using the electrospinning process. These are used for multipurpose prevention against HIV, HIV-2, and sperm. Electrospinning and nanofibres prepared by this technique will without any doubt lead to major scientific and technical advances in nanotechnology. It has become a widely appreciated nanostructuring technique in academia and industry and, in fact, this technique has indeed a lot to offer. Based on current studies it is no surprise that electrospun nanofibres are expected to play a critically important role in many important application areas in addition to medical devices—like water purification, renewable energy and environmental protection in coming years. References: 1 Z. M. Huang, Y. Z. Zhang, M. Kotai, S. Ramakrishna, Compos. Sci. Technol., 2003, 63, 2223. 2 M. Neves Nuno, Electrospinning for Advanced Biomedical Applications and Therapies, iSmithers Rapra Publishing, 2012. 3 A. Greiner, J. H. Wendorff, Angew. Chem. Int. Ed., 2007, 119, 5750. 4 D. Li, Y. Xia, Adv. Mater., 2004, 16, 1151.

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STERILISATION Nitrogen Dioxide Sterilisation:

The CEO’s View In March 2013, US developer of nitrogen dioxide (NO2) sterilisation equipment Noxilizer acquired Japan-based Saian Corporation. Both companies have been involved in developing nitrogen dioxide as a sterilisation solution for pharmaceutical, biotech and medical device companies, as well as hospitals. The strategic acquisition is intended to strengthen the global effort to promote acceptance and growth of nitrogen dioxide sterilisation as a powerful and less-expensive alternative to current sterilisation methods. Sam Anson spoke to Noxilizer’s president and CEO Lawrence Bruder to find out more about the company’s growth trajectory and some of the challenges which come with being a new small player in a vast market. SA: Can you provide some background on Noxilizer? LB: Founded in 2004, Noxilizer pioneered the development of nitrogen dioxide as a sterilant. We are focused on two large markets: life science manufacturing and hospitals. Today, Noxilizer is at the commercial stage, already servicing a number of pharmaceutical, biotech and medical device companies. We offer customers contract sterilisation services and sell sterilisation units to companies interested in bringing sterilisation inhouse. Noxilizer is based in Baltimore, Maryland, USA, with an office in Japan. SA: What attracted you to join the company? LB: In a professional career, there are very few opportunities to bring a new technology to market, not to mention a technology that addresses real unmet market needs. Noxilizer has a safe, proven technology, all the key patents issued for major markets including the United States, Europe, Canada, Australia, and India and a very strong team. From my experience, all the key elements were in place for our success. SA: NO2 sterilisation is new and not well recognised yet. How do you plan to overcome that? LB: The short answer is by focusing on customer needs. From my conversations with customers, there is a clear market need for a truly room temperature sterilisation process and all the benefits that delivers. Medical device, pharmaceutical and biotechnology companies are developing new drugs and devices that can’t be sterilised using the existing sterilisation methods. While no sterilisation method can do everything, at Noxilizer, we are very focused on the unique benefits nitrogen dioxide sterilisation delivers. SA: Tell me about the technology. LB: NO2 sterilisation is a room temperature process, leaves no cytotoxic residuals, can scale to

larger units, operates with or without a vacuum, and is safe to bring in-house. For many applications, it is a superior sterilisation method. Not to mention, there is a real financial advantage. If a company uses contract sterilisation today, their product is typically out of their control for 2-4 weeks. At a minimum, they are paying for transportation and inventory carrying costs. And, they are limited in their ability to respond to their customer needs. The typical Noxilizer sterilisation cycle is about two hours (including aeration). It does not take long to do the cost/benefit analysis to understand the benefits of bringing nitrogen dioxide sterilisation in-house. This is the message we take to the key industry meetings: Medical Design & Manufacturing (MD&M, USA), Parenteral Drug Association (PDA), and the ISPE (International Society for Pharmaceutical Engineering). We have been invited to present at these meetings and have had a number of articles published in the USA and Europe. The word is getting out. Companies are enthusiastic, and are now coming to us. SA: NO2 sterilisation is a new player in a well-established market and Noxilizer is a very small company with big competition, how can you compete? LB: Well, that is always the challenge as the new player in an established market. But, that challenge is part of the fun. Noxilizer’s early success has come from identifying companies who are “early adopters” to new technology or have a sterilisation challenge with an existing or new product. By partnering with those types of companies, demonstrating success with NO2 sterilisation, alongside the financial advantages of NO2, we have been successful in selling the RTS 360 Industrial NO2 Steriliser. In addition, we have a number of contract sterilisation customers in the United States and Europe that we serve from our new facility in Baltimore. SA: What type of products is Noxilizer sterilising and how were they sterilised in the past? LB: We have focused on the types of products that are not really compatible with ethylene oxide (EO), gamma radiation or hydrogen dioxide, like prefilled syringes and other drug delivery devices, as well as bioresorbable implants. These are ideally suited for room temperature nitrogen dioxide and they are growing markets. NO2 sterilisation compares favourably to traditional methods for a wide range of products. While a company may be using EO, gamma or hydrogen peroxide today, the results are not satisfactory. With EO, there are concerns about a range of issues, including contamination of the drug, temperature, vacuum, long aeration times and the high hurdles to bring sterilisation in-house. With gamma, changes in the mechanical properties of the implant are troublesome, or simply

unacceptable. The capital investment required makes it impossible to bring this method in house. And finally, hydrogen peroxide also operates at a somewhat elevated temperature, requires a vacuum, and is not scalable. This becomes a big challenge as product volumes increase. In addition, Advanced Sterilization Products (ASP, a J&J company) has announced that they are exiting the life science market. There will always be a place for all these sterilisation methods. Today at Noxilizer, we are focused on the products that will realise benefit from the nitrogen dioxide sterilisation process. SA: In February, Noxilizer acquired SAIAN Corporation in Japan. What attracted you to SAIAN? LB: SAIAN was founded shortly after Noxilizer. They were also working with nitrogen dioxide for use in life science and hospital markets; however, the SAIAN team took a very different approach to sterilisation. I saw the opportunity to combine the expertise in NO2 and leverage both companies’ products to form a stronger organisation versus the competition in the established market. That has already paid off. The company in Japan has been renamed to Noxilizer Japan KK. SA: Can you speak a bit about their technology and how you plan to leverage it? LB: The acquisition of SAIAN Corporation immediately brought us an expanded product line. In fact, we have already collaborated on a joint development project with a well-known pharmaceutical equipment manufacturer. The unit is complete and testing will begin in September. We view much of the SAIAN technology as our next generation offering that includes: onboard sterilant generation, recycling and abatement capabilities. This approach offers real promise for our customers in the next 3-5 years. SA: What are your plans for Asian markets and how does the acquisition complement these plans? LB: Now that Noxilizer has a facility in Japan, we have a base of operations as the gateway to other Asian markets. Today, Noxilizer Japan KK is focused on product development. We have plans to add commercial staff next year. SA: What about other areas outside the USA—Europe for instance? What are your plans there? LB: We are on schedule to submit the CE package this year for the RTS 360 Industrial NO2 Sterilizer. That will allow us to sell the unit in

Continued on page 30 SEPTEMBER-OCTOBER 2013 / MPN /31

STERILISATION Continued from page 31 Europe. I have already identified a commercial leader who will oversee European operations. Noxilizer recognises the need to move into Europe and Asia to support our current US customers. Pharmaceutical, biotech and medical device companies have global manufacturing locations and they want to use the same manufacturing and sterilisation processes around the world. CEO Spotlight: Lawrence Bruder President and CEO, brings over 25 years of leadership and operational experience in large and small life science companies, including Becton Dickinson, Applied Biosystems, Leica, Olympus, and Guava Technologies. Most recently he was President and CEO of venture-backed Guava Technologies, which was sold to Millipore Biosciences in 2009. Most of his experience prior to Guava was at Becton Dickinson, where he held a number of significant positions over a 10-year period. His responsibilities in both companies included the clinical and regulatory aspects of 510(k) submittals to the FDA for medical devices, significant commercial interaction with pharmaceutical companies, and high-level business development transactional activity; all of these being a critical part of Noxilizer’s needs. Mr Bruder holds a BS from Rochester Institute of Technology and Master of Management in Marketing & Economics from the Kellogg Graduate School at Northwestern University. Product Information: Noxilizer provides medical device manufacturers with contract sterilisation services based on nitrogen dioxide (NO2) technology. The company also sells the RTS 360 Industrial NO2 Sterilizer (pictured) to customers interested in bringing sterilisation in house. Its proprietary, room-temperature NO2-based sterilisation solution compares favorably with traditional sterilisation methods using EO, gamma irradiation and hydrogen peroxide in terms of safety and processing cycle length. The standard cycle lasts 60-90 minutes and features immediate release. NO2 sterilisation maintains material properties, requires no additional aeration, leaves no cytotoxic residuals, and is highlycompatible with a wide range of products including bioresorbable implants, prefilled syringes, vials and drugdevice combination products. NO2 sterilisation is a safer, simpler, more economical alternative. 32/ MPN /SEPTEMBER-OCTOBER 2013

Considerations for Parametric Release Sterilisation by Bill Young, Vice President Global SteriPro Services, Sterigenics, and Peter Strain, Vice President Technology EMEAA, Sterigenics. Over the past two decades, the growth in popularity of single-use, pre-packaged medical devices has been followed by the increased industrial use of traditional terminal sterilisation methods such as ethylene oxide (EO), electron beam, and gamma irradiation. The growth in specific procedural and surgical needs has created a number of sterilisation challenges for these methods. This is due predominantly to the inclusion of drugs and greater diversity in product designs, material types and packaging applications. The relative suitability of EO to a broad range of materials, coupled with the flexibility of sterilisation process, has meant that EO has often emerged as the sterilisation method of choice. The effort to reduce overall EO sterilisation process time has provided a strong incentive to develop and optimise large-scale EO sterilisation technology while also continuing to deliver the required product sterility assurance levels. On the surface it is not uncommon for medical manufacturers to focus on the total process time which includes the processing time, aeration or degassing time and the product quarantine time which may coincide with the microbiological incubation period. Historically, a typical timeline for an industrial EO sterilisation process includes the following phases and times: l Preconditioning—18 to 24 hours (1 day); l Chamber Processes—8 to 14 hours (0.5 day); l Product Aeration—24 to 168 hours (1 to 7 days); and l Microbiological Testing—72 to 168 hours (3 to 7 days). Industrial and contract sterilisers have responded to the demand for improved processing time in a number of ways. Those clients who have been able to optimise their EO sterilisation process may be able to reduce the amount of EO necessary to provide the required 10-6 sterility assurance level and as a consequence end up with a shorter product aeration period (ie 24 -72 hours). Routine sterilised loads which are under quarantine pending successful microbiological results may be excellent candidates for using parametric release in place of biological indicators. The standard ISO11135-1:2007, Ethylene Oxide—Requirements for Development, Validation and Routine Control of a Sterilisation Process for Medical Devices, in conjunction with ISO11135-2:2008, which provides guidelines on the application of the former, identifies either one of two acceptable methods for routine release of EO sterilised loads. 1.Microbiological based (biological indicators). This method requires that the sterilisation process is audited to show compliance with the validated specification and is supplemented with biological indicator test results. The biological indicators are

commonly placed in a ‘worst-case’ process challenge device, placed on the sterilisation load before process, removed after processing and endpoint sterility-tested for 3-7 days. 2.Parametric release of a load is based on a documented confirmation that the process parameters delivered during the process within the validated specification only—this routine release method does not include the use of biological indicators, but does require the measurement of additional process parameters, that is to say humidity and ethylene oxide concentration within the steriliser. Benefits for manufacturers arising from these initiatives include a faster response to market and a reduction in work-in-progress materials. For those clients with relatively short aeration or degassing hold times, the implementation of parametric release (ie product is sterile) has been extremely advantageous given that the load is not held pending the microbiological incubation time. Speed to market for the product is then dependent on aeration time and conditions that are validated to ensure compliance with ISO10993, Part 7. ISO11135-1:2007 requires direct measurement of humidity and EO concentration from the chamber throughout the applicable phases during routine cycles. To meet this requirement, Sterigenics uses relative humidity (RH) data loggers and installed humidity/EO infra red (IR) spectrometer units for measuring concentration directly from the chamber. Sterigenics recommends a two-step process to establish the parametric release parameters once the validation has been completed. The initial step is to perform a run and record study to confirm the process capability in which the loads are released via the standard or conventional (biological indicator) approach while recording the key parameters necessary for parametric release. Once a suitable sample size of runs has been completed—as determined by the variation of the product types and load materials—the humidity and EO concentration data are analysed to identify a suitable set of parametric tolerances. Generally, Sterigenics suggests that the EO parameter is calculated by evaluating the average concentration throughout the EO gas dwell in order to meet the ISO11135 requirements. Prior to implementation of these tolerances, Sterigenics recommends that manufacturers perform a fractional cycle in which the EO concentration is set at or below the tentative parameters and demonstrate the ability of the minimal EO concentration as capable of delivering adequate lethality to products. In conclusion, rapid response to market has driven the implementation of parametric release for ethylene oxide sterilisation, and has resulted in its acceptance by regulators and application in all geographies across the world.

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STERILISATION

Technical Update on Supercritical CARBON DIOXIDE (scCO2) TECHNOLOGY by Janet L Huie, PhD, director of research and development, NovaSterilis

<< Figure 1: Nova2200 Sterilizer. (A) The vessel lift arm aids removal of the vessel lid, secured with locking stainless steel hemi-rings. The computer screen digitally controls the system and stores all run information for printout. (B) The 20-litre vessel houses removable additive and sample baskets. The propeller and motor below the vessel provide agitation during the run. >>

on ati riz

Ambient pressure and temperature

Dwell

Pressurization 5-10 minutes

ssu re -p

>1400 psi 95°F Supercritical 1100 psi 88°F

USA-based sterilisation technology company NovaSterilis markets supercritical carbon dioxide (scCO2) terminal sterilisation to sterility assurance level log 6 reduction in bacterial spores (SAL6). Sterility is achieved through a synergistic effect of scCO2 and a fully biodegradable co-sterilant additive. The final sterilised products are nontoxic and have excellent retention of biological and physical properties. A wide variety of materials are compatible with the scCO2 technology, including allograft materials, electronics, vaccines, compatible polymers and plastics, and surgical metals. In the supercritical state, CO2 has physical properties of both a liquid (density, solvency of a wide range of solutes) and a gas (diffusivity, viscosity and zero surface tension), which promote a high level of permeability of CO2 and dissolved solutes into even minimally porous materials. Carbon dioxide (CO2) gas enters the supercritical physical state above the critical point of pressure 1,000 psi/74 atm and temperature 31.1°C. These are gentle conditions relative to the 55°C temperature required to maintain ethylene oxide (EO) in the gas state and the high pressure used with steam sterilisation. NovaSterilis markets its Nova2200 device, shown in Figure 1, for sterilisation and lipid extraction. The device contains a 20-litre cylindrical pressure vessel with propeller agitation and custom wire sample baskets. The maximum pressure for the vessel is 2,000 psi. Sterilisation is performed at 1,450 psi CO2, pressurised by a compressed air liquid CO2 pump connected to a CO2 tank and heated to a temperature of 3235°C by a vessel heat jacket. A computer system allows the user to control the system and provides digital and remote readout and data storage. Within acceptable ranges, the user can adjust pressure, temperature, scCO2 exposure (run) time and other parameters. An 80-litre vessel is also available on the Nova8800 for scale up research and commercial sales. A schematic of the operating cycle is shown in figure 2. The typical pressurisation time is 5 to 10 minutes and depressurisation is 20 minutes. A run will fail if pressurisation is over 15 minutes or depressurisation over 30 minutes, unless the system is specifically programmed for a slower or more rapid pressurisation and/or depressurisation. The actual scCO2 exposure time is tunable. Typically, medical devices require between one and 60 minutes to achieve a sterility assurance level of 106 for bacterial spores (SAL6), while porous and/or thin biological items such as extracellular matrices (ECM) require 1-2 hours, and dense or thicker pieces, such as tendon and cortical bone, require 3 to 8 hours to achieve SAL6.

1 minute - 8 hours Time for SAL 10-6

15-20 minutes

<< Figure 2: Operating cycle for NovaSterilis Nova2200. Passive pressurisation occurs up to 700 psi, followed by active pumping to a target pressure of 1,436 psi. Note that the graph is not to scale, as pressurisation is typically 5 to 10 minutes, while depressurisation is 20 to 30 minutes, unless these stages are intentionally lengthened. Dwell time is variable time exposure to scCO2, depending on sample material characteristics. >>

Recently, NovaSterilis achieved a milestone for the company’s allograft tissue sterilisation technology. During 2012, almost 24,000 units of allograft tissue, including tendon and bone, were terminally sterilised using the Nova2200 device, sterilisation cycle and co-sterilant. The first supercritical CO2 sterilised tissue was introduced

to the US market in 2009, the same year that Australian Biotechnologies received regulatory approval to market a scCO2 sterilised cortical and cancellous bone product. In 2010, two additional US–based tissue banks adopted the technology and expanded its use to multiple products including sterilisation of bone and tendon. NovaSterilis recently licensed its scCO2 process to Europe–based tissue processor and contract manufacturer EMCM for product distribution in Europe, India, China and Malaysia. The chief advantages of scCO2 are low pressure, low temperature sterilisation, high permeability and biocompatibility, and the ability to sterilise both wet and dry materials in under eight hours. The co-sterilant is fully biodegradable and less cytotoxic than ethylene oxide and other chemical sterilant treatments. scCO2-sterilisation better retains the mechanical properties and biocompatibility of bone, tendon and extracellular matrices (ECM) compared to gamma-irradiation. scCO2-sterilisation is compatible with a wide range of polymers, plastics and electronics. The small footprint, easy accessibility and safety of the scCO2 system are also significant advantages over other large-scale sterilisation systems. scCO2 is also highly useful for lipid and chemical extraction, infusion of matrices, and coating of materials. While scCO2 is fully compatible with biopolymers such as collagen and polysaccharides, it is not compatible with all synthetic polymers. The foaming effect of scCO2 has been exploited for novel material syntheses. Nonetheless, foaming and distortion of most polymers affected by scCO2 can be eliminated or alleviated by adjusting the depressurisation rate. scCO2 has excellent compatibility with cellulose, Mylar polyester film, Tyvek nonwoven packaging material, nylon, polyethylene, polysulfone, polythetherimide, polyurethane, polyvinylidene and glass. These materials are frequently used in packaging for terminal sterilisation or in medical devices. NovaSterilis works closely with industrial and academic institutions as a research partner to test new materials, investigating scCO2 sterilisation or extraction conditions that best achieve the required level of sterilisation and retain the physical and/or biological requirements of each material. NovaSterilis also serves as a regulatory partner, assisting in preparation for FDA 510(k) submission of scCO2-sterilised materials. Current projects include novel applications of scCO2 sterilisation to sutures, complex tissue matrices such as whole organs, new biomaterials, vaccines, electronic sensors, and novel synthetic and biological polymers. SEPTEMBER-OCTOBER 2013 / MPN /35

Interface, a vertically integrated provider of outsourced services for balloon and catheter manufacturing based in the USA, has announced that it now offers an online tri-layer co-extrusion catalogue for ordering tubing with what the company describes as a quick turnaround and competitive pricing. The tri-layer catalogue offers extrusion for 0.014â&#x20AC;? (0.035 mm) guide wire for peripheral dilatation catheters along with minimally invasive catheters.

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THE FUTURE OF Medical-Device Miniaturisation Stephen B Wilcox, PhD, FIDSA, Design Science << Steve Wilcox predicts that diagnostic assays and tissue repairs, including repairs at the molecular level, will eventually be done via nano “drones” which will be “driven” by medical professionals through the body—through ducts and blood vessels, as catheters are placed today. >>

<< Steve Wilcox is principal at Design Science, a medical design agency based in Philadelphia, USA. >>

Medical Plastics News asked me to write something about miniaturisation, which grew out of a presentation I made recently at the MD&M East Conference in Philadelphia, USA. The UBM folks, who put on MD&M, asked me to give a presentation on what we should expect in the next 30 years from medical technology—in honour of the 30th anniversary of the event. It was an interesting exercise to try to think through what we might expect in the future, given how unlikely we were 30 years ago to accurately predict where we would be today. At any rate, I made two predictions regarding miniaturisation. One of my predictions was that miniaturisation will continue over the next several years, leading to the development of artificial organs. Making medical devices smaller provides a lot of advantages. It enables: l Devices to be moved from the hospital to the home (for example home dialysis systems); l Devices to be moved from the home to wherever the patient is (for example portable oxygen for COPD)*; l Devices to be moved from the hospital to wherever the medical professional is (for example smart-phone-based alerting systems); and l Devices to be moved from outside the body to inside the body (for example implanted defibrillators). The end point, or the Holy Grail, for many medical technologies, it seems to me, is the “artificial organ”. It would be great to have technology that, like our own organs, keeps us healthy without having to think about it or “do anything”. In my MD&M talk, I predicted that artificial organs will be developed, first, as wearable devices (for example smart insulin pumps with closed feedback loops; truly portable ventricle-assist devices), then as implanted devices. What will be needed for such

artificial organs are sensors that obtain sophisticated data, algorithms that, so to speak, know what to do with the data, and effectors (for example drug-delivery devices, electrical stimulators and mechanical devices) that act inside the body to respond to the relevant data. And all this will require power, data storage and data transmission. It follows that achieving the goal of creating artificial organs will require tiny, robust: l Sensors; l Processors; l Drug-delivery devices, including reservoirs and infusion pumps; l Mechanical devices to create physical movements; l Electrical stimulators; l Power supplies; and l Transmission systems. One key question is whether or not the necessary technology will grow naturally from new technology that is developed for other purposes or whether the medical device industry will have to develop its own. I don’t have the answer, but I think there are some very specific requirements that will limit direct application of technology developed for, say, the next generations of phones, watches, or computers. A list of such requirements and current technical constraints is as follows. For one thing, such devices are not generally developed to be imbedded permanently in fluids, let alone in body fluids. Issues over the years with pacemaker/defibrillator leads, artificial joints, and stents indicate that creating devices that can handle the rigours of years within the body is far from trivial. *

COPD stands for chronic obstructive pulmonary disease

Continued on page 41

SEPTEMBER-OCTOBER 2013 / MPN /39

40/ MPN /SEPTEMBER-OCTOBER 2013

PLASTIC ELECTRONICS Continued from page 39 Another issue is that of sterilisability. Will next-generation circuit boards (or their replacements) stand up to autoclaves, ETO or radiation? There’s also reliability. If your phone quits working for a few hours, it’s one thing; if your pacemaker quits working for a few hours, it something else altogether. And, of course, all materials must be biocompatible. There are also limits on the generation of heat and its dissipation. Also, sound and vibration have to be controlled. This is by no means a complete list, but even this short list indicates that a lot of enabling technologies will have to be developed. I suspect that one of the key technologies will be wireless power transmission so that power can be transmitted from outside the body to implanted devices. More power will be needed than we have today in implanted devices, and I sincerely hope that we can avoid having to replace devices simply because the battery runs out, as we do now. Miniature drones The other thing I predicted vis a vis miniaturisation is even more radical. I believe that diagnostic assays and tissue repairs, including repairs at the molecular level, will eventually be done via nano “drones” which will be “driven” by medical professionals (coming from as-yet nonexistent specialties, or better yet, control themselves) through the body—through ducts and blood vessels, as catheters are placed today. For this to be possible, devices will have to be built that can move through vessels and perhaps even move in and out of cells. These devices will require control of their movements and of their actions. They will have to be able to be brought to the right location and be made to perform desired actions (killing tissue? transecting tissue? closing transections?) possibly at the molecular level and transmit information. These devices will need nano propulsion systems, nano control systems, nano sensors, nano transmitters, and nano effectors to perform operations on tissue. Summary In sum, I predict that we will see two waves of miniaturisation— one for the creation of artificial organs and one for the creation of nano drones that perform diagnosis operations within the body, perhaps at the cell level, or at least on a micro scale. Creating these new devices will be extremely challenging, I know, because each wave of miniaturisation makes one set of skills obsolete, so requires a new set of skill, because scale matters. The engineer who develops a “bag of tricks” for solving a set of problems may not be able to use these methods when the scale changes. Auto-movement of a device, for example, means something very different when we are talking about movement within a blood vessel. Likewise, what will be the role of industrial design as the scale changes? Industrial design, which was developed, to a large extent, initially to address the form of large products, like cars and locomotives, or at least like radios and early-generation telephones, has had to cope with smaller and smaller objects. The profession has handled the challenge well by, among other things, becoming the owner of the “user experience”. Will they still be able to contribute when medical devices are being designed to move freely through blood vessels? It may be that designers end up focusing primarily on separate devices outside the body that are used for obtaining information from and controlling devices inside the body. Or, perhaps, their ability to understand and manipulate form will apply in different ways to nano devices. One way or another, I believe that we’ll soon find out how today’s skills apply to the development of tomorrow’s increasingly small medical devices.

Organic and Printed Circuits Revolutionising Microelectronics

<< Figure 1: Flexible electrophoretic colour display for e-readers and tablets with a backplane of organic transistors (OTFT). Source: Plastic Logic >> Plastics are an indispensable part of our everyday lives. They have highly modifiable material properties and are generally dimensionally stable in a wide range of forms—as thermoplastics, thermosets or elastomers, films or coatings, granular or expanded. As far as applications are concerned, they are used in everything from simple items of daily life to intricately designed structural elements in vehicles and buildings. With their functionally optimised physical and chemical qualities and their attractive appearance, they are constantly redefining the design paradigm for form and function which, in terms of the cost of mass production, is beyond the reach of traditional materials like wood or metal. New functionalities With suitable doping and molecular configuration, plastics are being used as electrical conductors and semiconductors. They serve as components in a new kind of microelectronics, that of organic and printed electronics. These components are called organic because their minute circuitry structures, with myriad transistors, sensors and LEDs, are based on carbon derivatives—rather than silicon or gallium arsenide—as is the case with traditional electronic components. They are termed printed because two-dimensional layouts of circuit patterns can be printed “from the reel” with structural fineness of currently just a few tens of micrometres onto light, flexible and also transparent substrates by using conventional mass printing processes (flexo, screen-printing and inkjet). Another currently favoured production method, for example for organic photoelectric cells, involves the sequential vacuum deposition of the functional layers in a vacuum. Integration in objects Printing and vapour deposition yield versatile, and electronically or photonically functionalised surfaces in the form of films or coatings that can be applied in any desired curvatures to all conceivable objects and even textiles. They form capacitive touch sensors and large-area luminous fields in the form of OLEDs (organic light-emitting diodes) as well as complete sensors and detectors for environmentally or medically important data, such as temperature and humidity. Or they operate as lightweight, flexible organic solar

Continued on page 42 SEPTEMBER-OCTOBER 2013 / MPN /41

PLASTIC ELECTRONICS << Figure 2: Flat batteries (Ni metal hydride) printed on film from the reel. Source: Varta >>

<< Figure 3: Printed array with an addressable non-volatile memory and transistor logic as an example of the system integration of organic electronics. Source: Thinfilm and PARC >>

Continued from page 41 cells. Or as flat, printed batteries that power miniaturised devices. This means that electronics and data technology are no longer confined to specifically designed devices like PCs, tablets, mobile phones and game consoles. In fact, they can be seamlessly integrated into all suitable objects. This facilitates previously unknown and even exotic applications in “smart” objects and yields an appreciable expansion of their connectivity with the networking of even controlled or independently operating data systems in the “Internet of Things”. Research-intensive field All over the world, research consortiums and companies of the chemical, pharmaceutical, medical technology, electronics, automotive, consumer goods and packaging industries are working on the development of suitable materials and products and the associated production processes. Organic and printed electronics constitute an extremely research-intensive sector with long development time-scales. The latest (fifth) edition of the Roadmap of the Organic Electronics Association (OEA), a work group of the VDMA (Verband Deutscher Maschinen- und Anlagenbau—the German Engineering Federation) on the applications and technologies of organic electronics, illustrates the state of progress and trends for the coming ten-year period. With over 220 members worldwide, the OEA coordinates research and development projects and standardisation under the supervision of the IEC (International Electrotechnical Commission) TC119 and other organisations. New plastics-based microelectronics have not yet fully arrived in all mass markets. But the first products, often not immediately visible to the user, are already available. The technology is regarded as a platform for a future industry that unites the fields of printing technology, electronics and materials research. Innovations in the organic and printed electronics sector will be on show at the Printed Electronics Products and Solutions Pavilion at K 2013—the world’s largest trade fair for the plastics and rubber industry in Düsseldorf from October 16-23, 2013. This is where not only printing technologies but also functionalised surfaces such as RFID (radio frequency identification) solutions, flexible displays and OLEDs will be given a platform for presentation to trade visitors from processing and user industries. OLED screens and displays, the first mass market Small OLED displays in mobile phones and smartphones have already developed into a first, highly successful mass market for organic electronics. As a result, sales of organic electronics came to US$9 bn last year, says British market researcher Smithers Pira, which is forecasting growth of the sector as a whole into a global annual market of US$200 bn by 2025. This matches the order of magnitude achieved today by conventional silicon chips. Larger, colour-intensive and extremely high-contrast OLED 55-inch television screens have been announced or are already available (for example from Samsung and LG).

<< Figure 4: Demo of a capacitive multi-touch sensor field with a transparent, conductive cover film. Source: PolyIC >> E-readers from Amazon and Sony that convincingly present ebooks on “electronic paper” enjoy widespread popularity because of the energy-efficient, bistable principle of their electrophoretic displays. They are essentially ideal for presenting static content such as book pages on the basis of pioneer E-Ink’s e-paper. However, their continued distribution is now facing strong commercial pressure from the high-resolution and video-compatible Retina displays in the tablet PCs from Apple with less bright LCDs—a technology that they should have superseded long ago in the innovative logic of technological evolution. Flexible displays The next step that ought to move the e-paper display a big step forward is the development of lighter, more flexible and maybe even roll-up e-readers and tablets—without the heavy, breakable cover glass. The most progress here has been made by the British company Plastic Logic (with a fully automated production base in Dresden, Germany), which already masters the art of the backplane loaded with organic thin film transistors (OTFTs), that is to say the active matrix for the individual brightness control of the various display pixels. The latest milestone along the way is a thin, easily flexible 10-inch e-paper display that, with a resolution of 150 dpi (dots per inch), comprises a matrix of 1280 x 960 TFTs, ie a total of 1.2 million pixels. In the organic sensor field, Plastic Logic in its cooperation with ISORG in France, an enterprise hived off from the large CEA-LITEN research complex in Grenoble, also clearly leads the field. The two of them recently unveiled a 4 x 4 cm image sensor with 89,30 pixels on a thin plastics substrate. Sealed against water vapour What is still hampering the development of flexible organic photovoltaics and display technology is the necessary hermetic encapsulation to provide protection from atmospheric water vapour that corrodes their electrode films and shortens their effective service life. So far, such encapsulation has only been possible with rigid cover glass. The appropriate solution for freely contourable solar cells and flexible displays is laminated films as barriers, for which transparent layers of amorphous silicon dioxide appear to be very well suited. These are being collaboratively researched and developed at various locations, for example at the Fraunhofer Polymer Surface Alliance (Polo) and at the Japanese National Institute of Advanced Sciences (AIST).

Continued on page 43 42/ MPN /SEPTEMBER-OCTOBER 2013

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<< Figure 5: Smart package for medicine with a smartphone-readable data memory. Source: Holst Centre >>

Continued from page 43 Application driving forces The driving forces in the development of applications can be found, says the OE-A Roadmap, in four major industries— automotive, pharmaceutical, consumer electronics and manufacturers of “smart” packages for foods, medicines and other consumer items. With printed RFID tags, smart packages are capable of making merchandise management and its large-scale logistics more efficient. Moreover, with printed, dynamically updated display fields, they can communicate the best-before date to the consumer, draw attention to gaps in the cooling chain for sensitive goods or guarantee the authenticity of high-grade articles with their data links to traceable supply chains. The German company PolyIC is playing a leading role in this field with its development of RFID tags and their printed antennas and with conductive transparent organic films. The OE-A Roadmap also mentions another current development. Some premium class cars are already fitted with printed antennas as well as printed sensors for seat occupancy integrated in the seat covers to trigger the airbags as necessary. They also detect the weight in order to distinguish children from adults. OLED displays for reversing cameras instead of the traditional mirrors are included in the cars’ equipment, as are the illumination of the instrument clusters on the dashboard and barely visible printed window de-icers. Next in line for the car are organic displays and touch sensors as replacements for mechanical indicators and switches. The first strategies for reversing lights with OLEDs are already in the pipeline, among other things at Audi, so that today’s LED lights can be replaced to save energy and money. Also in discussion are largearea OLED fields as dimmable and colour-adaptable headliners or for the accentuation of door sills. OLED lighting Of the four large fields of application identified by the OE-A Roadmap—OLED lighting, organic photovoltaics, electrophoretic (epaper) and OLED displays, and electronic components as a complement to classical silicon-based microelectronics—the OLED light sources are probably the most vigorously discussed and challenging elements, as they compete strongly with established LEDs and halogen lamps in the drive to save energy. Unlike LED and halogen spotlights, OLEDs promise dynamically colour-controllable light emitted over a large area. OLEDs can be attached in architecturally attractive ways to the surfaces even of familiar objects in the home, thus turning them into active light sources. OLED lights are already available in design studies and premium products, such as those from Osram and Philips. 44/ MPN /SEPTEMBER-OCTOBER 2013

Organic photovoltaics and batteries Organic photovoltaics (OPVs) are developing in parallel with hybrid alternatives made of titanium oxide and dye-sensitised solar cells and with purely organic polymer-based cells. They are already commercially available. However, because of their relatively low efficiency, they are not intended for feeding power into the public grids, but as local supply << Figure 6: Example sources (energy harvesting) and charging the of a smart package batteries of mobile data and consumer devices and for consumer goods measuring stations. The long-term outlook of the OEand foods with an A Roadmap also envisages applications in the integrated “HiLight” envelopes of vehicles and buildings (BIPV, buildingeffect. Source: Karl integrated photovoltaics) as of 2021. Knauer GmbH >> System components of organic electronics, whose favourable properties also make them suitable for hybrid integration in conventional circuitry, are available in printed data memories—for example, in the form of the ferroelectric, non-volatile memory films of the leading Norwegian manufacturer Thinfilm. This development as driven by Thinfilm is also an example of the system integration of organic components from different manufacturers into larger functional units on shared printed substrates. Thinfilm thus combines its memories with an also printed, first transistor logic produced at contract researcher PARC in California to yield a software-addressable memory module. The latter can also be extended with a printed thermistor as a temperature sensor and a display field (from the Swedish ICT Acre research institute) together with a printed battery to create a compact measuring system. Slim and flexible batteries produced through printing are also a focus of development in the system integration of organic electronics. At present, the market is dominated by single-use zinc-carbon batteries, while rechargeable, lithium-based equivalents are still undergoing development. As an alternative, energy-rich supercapacitors are available for the temporary supply of power to devices. Their discharge behaviour comes close to that of batteries. Such power supplies can be integrated with display and luminous fields, touch sensors and solar cells in packages, textiles and other consumer items, elevating them to new levels of value and functionality.

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DOCTOR’S NOTE Mapping a Polymer Product’s Lifecycle | SOME SIMPLE STEPS

Creating Vision Across the Polymer Lifecycle From plastics and composites, to foams, elastomers and adhesives, polymers are one of the most widely used materials in the life science industry. Despite widespread application, the importance of polymer properties and product lifecycle are often understated. As polymers flourish because of their diverse application potential, workers in R&D, product development, engineering, or laboratory environments must take responsibility for ensuring the quality of materials across the product lifecycle. Team members must identify critical questions needed to develop product requirements, map steps in the product lifecycle, and understand how individual contributions affect performance of the final product. There are numerous strategies used by industry to improve efficiency, design, and lifecycle management, but such strategies can become unwieldy when team members want to ask questions and understand the “big picture” or the product lifecycle. As such, gaps become apparent when individuals ask common questions like, “If I modify the manufacturing process or surface features, will my device still perform as intended?” or “If I change to a different polymer, will my product behave in the same way?”. These gaps in understanding can create frustration and inefficiency at the team level, but may have even greater consequences for the manufacturer and final product. Due to United States regulations, like the Biomaterials Access Assurance Act of 1998 (BAAA), gaps in material understanding can pose significant liability issues for product manufacturers. According to the BAAA, manufacturers are required to ensure the quality of materials purchased from their suppliers and used across the product lifecycle. By taking a simple, proactive approach to mapping the material lifecycle, identifying key questions, and knowing regulatory requirements, all parties can work together to form vision across the life of the product. Steps involved in creating a lifecycle vision Creating vision across the lifecycle should be a straightforward, information-building exercise and not an overwhelming, acronymfilled burden. The first step in creating a vision for polymeric materials is to define and map each step in the product lifecycle. Typical steps begin with the raw material supply chain followed by materials acceptance, and then formulation, manufacturing, packaging and performance of the final component. Steps will vary for different products and materials and should be defined by the team or contributors.

After defining these steps, establish a comprehensive list of all requirements for the final component by engaging relevant stakeholders and identifying critical factors such as regulations, specifications, modeling, and testing. The comprehensive list for the component should include regulatory requirements, operational requirements, expectations, form, fit, and function. Building the list can be a simple or complex exercise depending on how well these requirements are understood. In all cases, creating a list helps to cultivate the team’s understanding of the component and how it must perform. The list should also include key questions about specifications, modeling, and testing for the final component; for example: l Specifications: “What specifications exist, or are needed, to demonstrate the requirements?” l Modeling: “Is modeling being used to predict material properties, and what data is being used in the models?” l Testing: “Is more testing now required to demonstrate safety and achieve or maintain approval?” Once this exercise is completed for the component, it should be repeated for each step of the lifecycle (for example materials acceptance, mixing, moulding, sterilisation, and so on). This process results in a comprehensive list of requirements for the final component as well as each step within the lifecycle. Creating a list early on will have a profound effect on establishing project schedules, addressing materials selection, identifying testing needs, meeting regulatory requirements, and minimising potential liability. Not only can this simple strategy aid in product design, but it also helps with engineering evaluations, troubleshooting, process improvement, failure analysis, and product liability risk assessment. Case study: polystyrene cell culture containers Without proper context, “mapping the material lifecycle” and identifying critical factors and questions may seem abstract. The following case study provides an example of how to create vision across the product lifecycle to address a failure analysis investigation. This case study deals with polystyrene cell culture containers. Scientists use these products to grow cell lines for biological research. The containers come in various forms and undergo sterilisation and surface modification. The surface characteristics such as chemistry, roughness, hydrophilicity, and so on, are critical for culturing success. Chemical and biological contaminants can also impact culture success. Continued on page 48

<< Figure 1: Map of the lifecycle for a cell culture container. We used a “vision across lifecycle” approach to map the material lifecycle, identify material and process requirements, and then analyse the material at each stage of the lifecycle. We were able to identify the point of failure (moulding and surface treatment). This process gave us a comprehensive understanding of the material lifecycle and allowed us to proactively implement testing to mitigate future failures. >> 46/ MPN /SEPTEMBER-OCTOBER 2013

SEPTEMBER-OCTOBER 2013 / MPN /47

DOCTORâ&#x20AC;&#x2122;S NOTE Continued from page 47 In this study, the cell culture containers were part of a failure analysis or manufacturing anomaly analysis investigation. Although failure analysis was not intended to be part of the product lifecycle, understanding the lifecycle was critical to conducting the investigation, identifying potential failure points, and proposing a comprehensive, proactive testing plan to prevent future issues. The investigation started by mapping and defining the steps in the process. Additional information about the materials, research studies, product information, and requirements of the component from the manufacturer were compiled. << Table 1: Defining Requirements and Expectations. >> Function:

Containers used to culture and transfer cells.

Form:

Transparent polystyrene bottles, flasks, dishes. Surface area. Can have septa, ports, etc.

Fit:

Design must accommodate additional surface modification and sterilisation procedures. May integrate with stacking or automated system.

Regulatory Requirements:

Manufacturer-specific.

Operational Requirements:

Normal temperatures, atmosphere. Must be capable of sterilisation and surface modification. Optimal level surface characteristics for cell adhesion. Consistency and reproducibility are critical.

The requirements of the containers were largely based on surface oxygen content determined from x-ray photoelectron spectroscopy (XPS) spot scans. Based on our understanding of the issue and requirements for the component, our team embarked on an extensive analysis of the surface characteristics of the container samples. Extensive XPS studies on container surfaces included survey scans, variance assessment, spot-to-spot variability and scan-to-scan variability. XPS surface mapping studies were also conducted. Using surface mapping, significant oxygen content heterogeneity was observed on the surface. This heterogeneity was more difficult to observe with simple spot scans. The surface oxygen content has a direct impact on the performance of cell culture containers because of the cell adhesion interaction on the surface. Because our team established a map of the lifecycle and a requirements list, we could identify trouble spots within the manufacturing process, define better material and process requirements, and incorporate comprehensive testing to eliminate this failure in the future. Conclusion The simple strategy of creating vision across lifecycle can have a significant impact on product success and materials understanding. The simple strategy allows team members to: l Address tough questions and ask the right questions; l Map steps within the product lifecycle from raw material to final component; l Create a list of regulatory, operational, and other requirements that will affect the final product; l Define critical factors such as modeling and testing during each lifecycle step; l Ensure testing plan aligns with requirements and performance; and l Ensure products are compliant, avoid potential liability issues, and minimise product failure.

48/ MPN /SEPTEMBER-OCTOBER 2013

<< Figure 2: XPS O1s surface map on 40 mm x 40 mm section of polystyrene cell culture container. Extensive XPS studies on the cell culture container surface enabled us to determine the point in the material lifecycle where the failure occured. With this information we were able to implement comprehensive testing into the manufacturing process to eliminate this failure in the future. >>

About the author Crystal G Morrison Densmore, PhD, Macromolecular Science and Engineering, is currently a principal investigator and senior material scientist at RJ Lee Group, where she provides project management and technical direction for analysis supporting multiple industrial sectors. These areas include failure analysis, materials characterisation, product development, performance optimisation, and manufacturing quality assurance. Dr Densmore specialises in the areas of polymers, foams, elastomers, adhesives and composites. She has conducted studies on carbon nanotube separation methods and spectroscopy and has done extensive work developing synthetic optimisations of materials for industrial scale-up. Dr Densmore has also served as a peer reviewer for the Journal of Applied Polymer Science and the American Chemical Society journal Organic Process Research and Development. Dr Densmore presented "Polymeric Materials in Life Sciences: Creating Vision Across Lifecycle,â&#x20AC;? at the Biomanufacturing Education and Training Center (BTEC) in North Carolina in September 2013. The presentation identified critical factors at each step in the product lifecycle and discussed proactive techniques to ensure products meet requirements, perform correctly, and satisfy stakeholder needs. Case studies involving medical elastomers and plastics were used to illustrate the role of critical factors. SEPTEMBER-OCTOBER 2013 / MPN /49

REGULATION REVIEW

About the author: Rhonda Thompson Alexander is senior regulatory specialist for the drug and medical device divisions at US regulatory consultancy Registrar Corp. She has worked in a number of capacities in the drug research sector. She has trained regulatory and clinical professionals regarding patient safety and privacy, as well as compliance with Good Clinical Practices (GCP) and ICH guidelines. In addition to her work as a clinical research coordinator, she has acted as liaison between study sponsors, research centres, and institutional review boards on more than 70 clinical research trials. As a senior regulatory specialist, she assists Registrar Corp’s clients with 510(k) premarket notification, radiation safety reporting, and 513(g) requests.

The FDA’s 510(k) Modifications Policy By Rhonda Thompson Alexander, MS, MPA

The US government's regulatory framework for medical devices was enacted almost forty years ago—before medical software and many innovative medical devices were in use or even conceived. In 2012, the US Congress enacted new legislation intended to update the regulatory framework for the 21st century: the Food and Drug Administration Safety and Innovation Act (FDASIA). As part of FDASIA, the FDA is required to report key issues to Congress in January 2014 regarding the agency’s policy for modifications of previously cleared 510k devices. This report outlines the FDA’s plan to preserve the safety and effectiveness of medical devices that are legally marketed in the United States. It will ultimately determine whether the current guidance, “Deciding When to Submit a 510(k) for a Change to an Existing Device (K97-1)”, should be amended or replaced. The guidance, which went into effect in 1997, was put in place to provide industry with the FDA’s thinking about how the FDA views the threshold at which a change to an existing device warrants a new 510(k) submission. In 1976, the FDA proposed a rule that was broad in scope and noted that any change in a cleared device that “could affect” the safety and effectiveness of the device triggered the need for a new 510(k) clearancei. The next year in its final rule, the FDA limited the scope of its thinking and indicated that it did not want device manufacturers to submit new 510(k) submissions for all types of changes. The agency maintained in this final rule that the manufacturer is responsible for determining whether or not the changes meet the threshold of significance, requiring the submission of a new 510(k)ii. The K97-1 guidance document was drafted after two rounds of public review and input. Of key issue in the document is the clarification of the phrase “could significantly affect the safety or effectiveness of the device”, as mentioned in the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act of 1976iii. This statement, along with the phrases “major change or modification” and “significant change or modification” could be interpreted subjectively, and the guidance document was issued in an attempt to standardise the decision-making process for determining when a new 510(k) was requirediv. Though the guidance represents a cooperative effort between industry and the FDA, it has not been modified since its original publication. The FDA must now determine whether the current guidance continues to be relevant given the changes in technology that have emerged since 1997 and ensure that device 50/ MPN /SEPTEMBER-OCTOBER 2013

manufacturers are able to be consistent across the industry in their decision making when determining whether a new 510(k) is required. As it stands now, manufacturers have the responsibility of reviewing K97-1 and the decision-making flowcharts that are contained in that guidance document. The FDA does not review that decision-making process or the resulting paper trail, which can lead to erroneous or poorly documented decisions. On June 13, 2013, during a recent FDA meeting to discuss the FDA’s “past present and future policy on 510(k) modifications with external stakeholders”, the FDA heard comments from The Advanced Medical Technology Association (AdvaMed), Health Canada, the National Research Center for Women and Families and other stakeholders, who made recommendations for the modification or a complete replacement of K97-1. While some stakeholders maintained that the current guidance only needs to be supplemented to recommend that manufacturers evaluate changes and the need for a new 510(k) submission based on quality system procedures and results of validation and verification testingv, others believe that the FDA itself should determine when a new 510(k) is needed based on design control activities and critical specifications outlined by the FDA. In an effort to be comprehensive, the FDA is considering five possible approaches to a new 510(k) modifications policy—risk management, design controls, critical specifications, risk-based stratification, and periodic reporting. Risk management, an objective assessment using the standard ISO 14971 Medical Devices— Application of Risk Management to Medical Devices, allows manufacturers to identify hazards and possibly determine if proposed changes to the cleared device introduce new issues regarding safety and effectiveness. By implementing design controls, such as verification and validation testing, manufacturers are able to evaluate changes to the cleared device. The resulting documentation would provide a paper trail of the changes made to the device, which can be reviewed and evaluated by the FDA. Critical specifications would allow changes to medical devices within approved, specified ranges. New 510(k) submissions would not be required for changes that fall within those specifications. Risk-based stratification would require manufacturers to submit new 510(k)s based on risk. Only modifications to higher-risk devices would trigger the requirement for a new 510(k) submission. Through periodic reporting, the FDA would receive ongoing information

about legally marketed devices, allowing the agency to “catch” changes that would affect safety and effectivenessvi. Stakeholders suggested that in order for the FDA to determine the best course of action, it must first identify the public health issue that needs to be addressed. By finding a “data-driven rationale for change”, the agency can determine whether the K97-1 document should be modified or if it should be discarded and rewritten. It was agreed by many stakeholders that a “one size fits all” approach would not be suitablevii. Manufacturers must be able to implement controls and risk management activities that are based on the type of the device that is being produced. The FDA will continue to work with industry and other stakeholders to gather input that will allow the agency to devise a policy that preserves public safety, but which does not stifle medical device improvement and innovation. References: i Federal Register 37458 (1976). 42 Federal Register 42519 (1977). iii 21 CFR 807.81(a)(3). iv The US Food and Drug Administration. v 510(k) Memorandum #K97-1: Deciding When to Submit a 510(k) for a Change to an Existing Device (K97-1). January 10, 1997. pp 1-2. The US Food and Drug Administration. Workshop: 510(k) Device Modifications: Deciding When To Submit a 510(k) for a Change to an Existing Device, June 13, 2013. Available from http://www.fda.gov/MedicalDevices/NewsEvents/ WorkshopsConferences/ucm347888.htm. Accessed September 6, 2013. vi Ibid. vii AdvaMed. “Modifications to Cleared Devices In Commercial Distribution: Determination of the Need for Additional 510(k) Premarket Notification,” White Paper ( June 11, 2013). Available from: http://advamed.org/res.download/ 317. Accessed September 6, 2013. ii

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Polymer–Collagen Hybrid Materials IN BIOMEDICAL APPLICATIONS XIANG ZHANG, PRINCIPAL CONSULTANT FOR MEDICAL MATERIALS AND DEVICES AT UK-BASED MATERIALS DEVELOPMENT, CONSULTANCY AND TESTING COMPANY CERAM, RECOUNTS HOW POLYMER HYBRID TECHNOLOGY HAS EVOLVED AND WHAT BIOMEDICAL APPLICATIONS MAY BE POSSIBLE OVER THE COMING YEARS. A polymer hybrid can be described as a combination of a synthetic polymer with a natural polymer, such as collagen. Research into polymer hybrid materials for biomedical applications dates back 20 years or so. A search for polymercollagen hybrids on Google returns top hits comprising peer reviewed articles dated between 2004 and 2013—including a degradable hybrid scaffold and hydrogels for drug delivery. From peer-reviewed articles of the last ten years, we can get a general picture of polymer hybrid development over the last 20 years or so. Research on polymer hybrids first started around this time, mainly in the area of healthcare applications. What was the driver behind research into these materials? Many “artificial materials”—such as metals and their alloys, polymers, for example PMMA, PVC and bioresorbable polyesters, and ceramics, like alumina and zirconia toughened alumina—have been and are currently used for healthcare applications, particularly for implants. Use of these has not been without problems though, with many medical failures and accidents being attributed to such materials. Consequently, there has been a need to develop more “natural” materials. Hybrids are being developed by using metals, polymers and ceramics as a base material with an additional material—like collagen— combined in to add biological, physiological and mechanical perforamce properties. This fact, coupled with the upturn in synthetic polymer science and technology in combination with natural materials, has led to much research into this area. Biocompatibility is an issue that rears its head time and again. Combining a synthetic polymer or polymers with a natural polymer, such as collagen, polymer hybrids can go some way to solving this issue as natural polymers are naturally biocompatible. Further research in this direction has led to the development of more advanced polymer hybrid systems that can enhance bioactivity. For example,

cells can grow better and faster in association with natural polymers like collagen than they can with synthetic polymers. It is not difficult to understand why the majority of research work around developing this kind of polymer hybrid is in the area of tissue engineering, one of the biggest markets for medical implants. Another application area that is being explored by many researchers is the slow release of drugs, taking advantage, yet again, of the fact that new polymer hybrids are biocompatible. Thanks to the progression of polymer science and technology, overall development of new polymer hybrid systems containing natural polymers such as collagen has gone well. This is particularly the case in the area of polymer blends—which moved from theory to industrial practice well before the research into new polymer hybrids. As has been discussed, collagen is an ideal choice as a natural ingredient for new polymer hybrid material development. It is a natural material and is also the most abundant protein in animals, forming molecular strands that work either alone in the body in various forms or in hybrids, such as with hydroxyapatite. Hydroxyapatite is a naturally occuring mineral form of calcium apatite and is used extensively in orthopaedic medicine. Many orthopaedic implants are coated with hyroxyapatite to ecourage bone and tissue growth around the device. The mineral is also injected by surgeons into broken bones to act as a filler and help healing. [Editor’s note: In September UK-based Invibio announced the launch of a new grade of implantable PEEK containing hydroxyapatite—see overleaf.] Blends of collagen with other hydrophilic polymers can be used as biodegradable polymeric scaffolds, which avoids the removal of the polymer from the body when the implanted device is no longer needed. Complex polymer hybrids In addition to polymer-collagen systems, many scientists have already started studying more complicated polymer hybrids that contain inorganic biomaterials. Most of the research is using hydroxyapatite. There are no shortages of peerreviewed papers in this area. The logic behind this is that our bone is an advanced polymer hybrid. Bone consists largely of natural collagen and hydroxyapatite both at a nano-scale. Our understanding is still poor regarding the relationship between nano and micro-structures and properties of both natural and synthetic biomaterials, with particular reference to nano and micro-polymer hybrid containing inorganic and/or organic constituents, and the extent to which each constituent affects biocompatibility, bioactivity and biomechanical properties in medical applications. Soft tissues, such as skin and vasculature, have fundamentally similar properties when it comes to developing new synthetic and natural hybrids that are biologically active.

Outlook There is, in principle, the potential for polymercollagen hybrid systems to be used in other applications, for example degradable load bearing orthopaedic applications. The hybrid has a characteristic structure that mimics the structure of natural tissue and promotes new tissue generation while degrading itself at the same speed as that of new tissue regeneration; all of which occurs at molecular and/or nano levels. However, at present this is the weakest area of our knowledge with little progress to date, in terms of concept, development and market introduction. The goal of developing polymer hybrid materials with precisely the same mechanical properties as bone is a key area for the future. Using a very soft material like a polymer in combination with a very hard material like hydroxyapatite is an area being looked into. If you look at bone, one material is hydroxyapatite—the rigid phase—the other is collagen, the ‘soft’ phase (relevant to hydroxyapatite). I think that hybrid materials like this will become more and more popular in implantable orthopaedic applications. As it stands we have always used very pure materials in long term implantable products to achieve the mechanical properties we need. But the polymer hybrid technology opens a much wider field of complexity and application, especially if the materials can be safely degraded and metabolised in the body. The fact that the base material is a polymer allows a hybrid material to be moulded into shapes. The hydroxyapatite can make the material extremely hard with the required mechanical properties such as those needed for loading bearing implants.

About the author: Principal consultant for medical materials and devices at Ceram Dr Xiang Zhang is a leading polymer expert. He has worked with polymers in academia and in industry for over 30 years and has recently been appointed as a Royal Society Industry Fellow at the University of Cambridge, UK. A materials scientist, Dr Zhang undertook his PhD and postdoctoral research at Cranfield University where he studied micromechanics and micro-fracture mechanics of toughening plastics. After spending a further four years on polymer research for industrial applications, he was awarded an industrial fellowship at the University of Cambridge in 1995. SEPTEMBER-OCTOBER 2013 / MPN /53

NEW MATERIALS INVIBIO BIOMATERIAL SOLUTIONS LAUNCHES Hydroxyapatite Enhanced PEEK-OPTIMA Polymer INVIBIO BIOMATERIAL SOLUTIONS HAVE LAUNCHED A NEW PEEK-BASED IMPLANTABLE BIOMATERIAL CONTAINING HYDROXYAPATITE, DESIGNED FOR SUPERIOR BONE APPOSITION.

UKheadquartered Invibio Biomaterial Solutions, a leading solutions provider of PEEKbased biomaterials, manufacturing and application knowledge to medical device manufacturers worldwide, has today announced its launch of PEEK-OPTIMA HA Enhanced Polymer. The implantable biomaterial grade uniquely combines two clinically proven advanced biomaterials for enhanced bone apposition1: PEEK-OPTIMA, the principal PEEKbased biomaterial with over ten years of proven history in clinical use, and hydroxyapatite (HA), a well-known osteoconductive material. HA is fully integrated into the PEEK-OPTIMA Natural grade to provide a complete homogeneous compound which ensures that HA will be present at all surfaces of a device. John Devine, emerging business director explained: “Although PEEK is the most popular chosen material for interbody fusion applications, surgeon feedback has indicated that a version of PEEK that enhances bone on-growth on all sides of the device could be more effective. Invibio has invested in this new grade that offers the same advantages of PEEK-OPTIMA and additionally a superior solution for bone apposition. With HA available across the whole device the opportunity for bone on-growth is virtually unmatched with alternative bone apposition technologies.” Devine concludes: “We believe the launch of PEEK-OPTIMA HA Enhanced provides surgeons with improved technologies and enables device companies to differentiate their product offerings.”

<< High degree of bone contact with PEEK-OPTIMA HA Enhanced is shown on the histology image taken at 12 weeks in the study.>> Early Bone Apposition Within four weeks of implantation Invibio PEEKOPTIMA HA Enhanced polymer demonstrated enhanced bone apposition compared to PEEKOPTIMA Natural, in a pre-clinical in vivo study using a sheep model. Within 12 weeks of implantation the bone apposition levels are maintained with the new grade. PEEK-OPTIMA HA Enhanced Biomaterial provides excellent mechanical properties and performance, proven biocompatibility, a modulus similar to cortical bone, reducing stress shielding and a high degree of radiolucency that allows for clear fusion assessment. Developed by a world leader in implantable PEEK-based biomaterials this innovation not only offers the same processing simplicity as PEEK-OPTIMA, but also omits the extra processing time and expense of alternative bone on-growth technologies, such as coatings. Professor Bill Walsh, director of surgical and orthopaedic research laboratories, University of New South Wales, Australia, will present the latest data on PEEK-OPTIMA HA Enhanced, the new material for bone apposition, at the upcoming spinal meetings Eurospine on October 1-4, 2013, in Liverpool, UK, and NASS on October 9-11, 2013, in New Orleans USA. For more information visit: http://turbochargefusion.com/.

PEEK-OPTIMA is a registered trade mark of Invibio Biomaterial Solutions. 1

Study evaluated the bone in-growth and ongrowth of PEEK-OPTIMA Natural and PEEKOPTIMA HA Enhanced in a bone defect model in a sheep. Data on file at Invibio. This has not been correlated with human clinical experience.

<< PEEK-OPTIMA HA Enhanced from Invibio Biomaterial Solutions.>>

54/ MPN /SEPTEMBER-OCTOBER 2013

New Poly-Med Inc Patents Protect Two Polymer Based Bioactive Delivery Systems US contract developer of polymer-based medical devices and materials Poly-Med Inc (PMI) has announced the issuance of two patents the week of August 16, 2013. The first, US patent 8,506,988, deals with an intravaginal ring delivery system. A recent increase in focus on women’s health issues has motivated studies on intravaginal drug delivery for reproductive, disease-related, and oncological applications. Poly-Med research and development was issued a patent on a fibrereinforced composite ring for the controlled release of at least one bioactive agent. The ring system includes a biocompatible matrix reinforced with absorbable (biodegradable) fibres capable of providing the mechanical properties needed for insertion and positional stability within a body cavity for a desired period of time. The patent also includes combinations of absorbable and non-absorbable fibres to provide a wide range of ring constructions suitable for a variety of degradation and drug release profiles. Such a ring system can be used for the intravaginal, intraperitoneal, and subcutaneous delivery of at least one bioactive agent, including those used as contraceptives, antimicrobial agents, and/or antiviral agents, as well as those for the treatment of cancer. This technology is available to customers interested in delivering their bioactive agent for any of these indications. The second patent (US Patent 8,507,614) relates to the preparation of a lactide-based copolymer and continues the growth of Poly-Med’s Lactoprene family of materials. Lactoprene is a trademark of Poly-Med Inc. Especially useful for delivery directly to the tissue lining of body cavities, this polymer solution features the ability to transform in the presence of water into a tissueadhering film which can then degrade shortly after releasing a bioactive agent, such an antimicrobial, antiviral, ant-inflammatory, antibacterial, or antibiotic agent. The mechanical resilience and film-forming ability are distinct from other polyester solution/precipitant or hydrogel formulations that generally do not form coatings suitable for luminal linings. Poly-Med’s patented bioactive, hydroforming luminal liner compositions are formed of high molecular weight crystalline, absorbable co-polyesters dissolved in a liquid derivative of a polyether glycol. The composition undergoes transformation into a tissue-adhering, resilient interior cover or liner for the controlled release of its bioactive payload within clinically compromised conduits in humans. Potential applications include bacteria- and yeast-infected vaginal canals, esophagi, and arteries following angioplasty. This platform technology can incorporate almost any bioactive agent that a PMI client may care to deliver, and can provide a method of localised delivery without obstructing fluid passageways.

For more information on Poly-Med’s recent patents, see the patents section of the company’s website: www.poly-med.com/patents.

SEPTEMBER-OCTOBER 2013 / MPN /55

RHEOLOGY: An Essential Tool For Successful Extrusion By Roy Carter, Managing Director, Aptifirst, www.aptifirst.com PRODUCTION PROCESSES FOR THERMOPLASTICS OFTEN INVOLVE EXTRUSION IN ONE FORM OR ANOTHER, WHETHER IT BE PROFILE EXTRUSION, INJECTION MOULDING, OR PELLET PRODUCTION FOR SPHERONISATION. IN ORDER TO SELECT THE BEST PRODUCTION CONDITIONS FOR THE MATERIAL, AND TO OPTIMISE THE MATERIAL TO SUIT THE AVAILABLE PRODUCTION EQUIPMENT, IT IS VERY USEFUL TO EXAMINE THE RHEOLOGY, OR FLOW PROPERTIES, OF THE MATERIAL. All materials flow; rivers flow to the sea, blood courses through our veins, and land flows across the Earth. What is of concern in polymer processing is, in the main, shear flow, though extensional or elongational flow should not be disregarded. What interests us for the purpose of this article is converging flow of molten polymers and multi-phase materials, ie those with components such as a polymer binder, a filler and liquid plasticisers, and also perhaps pastes and doughs. A dough is similar to a paste but with elastic as well as viscous properties. Firstly, let us consider shear deformations. When a force or stress (force per unit area) is applied to a fluid, the fluid will usually flow at a rate (shear rate) which is dependant upon the rheological properties of that fluid. An ideal material will exhibit a linear relationship between the applied force, or shear stress, and the shear rate, and the slope of this line will be equal to the shear viscosity of the material. Such materials are known as Newtonian fluids, named after Sir Isaac Newton who first defined viscosity in his Principia; there are not many materials that behave this way, examples being water and liquid oxygen. There are many types of rheological behaviour, as demonstrated in Figure 1, and several of these may be encountered in the medical plastics field. << Figure 1: Flow behaviour types. >>

56/ MPN /SEPTEMBER-OCTOBER 2013

Most thermoplastic resin melts and other materials behave as pseudoplastic or shear thinning fluids. In this class of fluids the shear rate increases disproportionately to the applied shear stress. This can be beneficial from the processing point of view, as a greater volume throughput can be achieved for a marginal increase in expended energy. However, it does indicate that the rate should be controlled to avoid surges. The viscosity of such materials is not constant, but is dependent upon the shear rate. In contrast to shear thinning is shear thickening or dilatant flow: here, the shear stress, for example the pressure in an extruder, can increase exponentially as shear rate is increased beyond a critical point. Such behaviour has been observed for highly filled pharmaceutical pastes for extrusion spheronisation, especially with irregular particle shapes, as well as for polypropylene and polycarbonate melts, particularly at temperatures towards the lower end of their processing ranges. In such cases, increasing shear stress can induce stress crystallisation which, in effect, virtually crosslinks the melt, forming “bridges”. Such sudden increases in loading can be very dangerous, and can indicate the need for rapid-acting over-load cut-out devices. Other types of flow behaviour show the need to exceed a critical “yield stress” (within the timescale of the observation) before the material will start to flow. Those which flow in a linear or Newtonian manner after the yield stress has been overcome are termed Bingham Fluids, for instance fresh (wet) cement and concrete pastes. Other materials exhibit yield stresses; cellulosic materials, filled materials, and some rubber compositions have been shown to have significant magnitudes of yield stress and then flow in a shear-thinning manner, and these are termed Herschel-Bulkley Fluids. The existence of such a parameter as a yield stress may have drastic effects on processing. For example, a small tubular profile extrusion in a filled cellulosic material kept breaking the die pin (mandrel), and calculations of the forces exerted on the pin by the material before yield showed that the tensile force exceeded the tensile strength of the pin material. Shortening the die pin solved the problem. There are other time-dependent parameters, thixotropy and rheopexy, which are outside the scope of this article. There are several instruments that are useful for studying rheology. Rotational rheometers

SPONSORED BY such as cone and plate, parallel plate, cup and bob and rotating cylinder machines are widely used, but are limited to a maximum shear rate of about 100 s-1, after which they tend to give errors. Torque rheometers are basically small, instrumented mixers that are extremely useful for studying mixing and for preparing small samples. For a true process mimic of the extrusion process, though, the capillary extrusion rheometer is an ideal machine. Basically, a highly controlled and instrumented syringe, capillary rheometers, depending on the model, can deliver pressures up to 30,000 psi (2,100 bars), temperatures to 450°F (232°C) or more, and, depending upon the die geometry, shear rates in excess of 1,000,000 s-1. Using modern servo-drive technology, a speed ratio of better than 60,000:1 can be achieved continuously, without the need for a gearbox, so that a wide range of shear rates may be determined in one experiment, useful as the data is usually plotted logarithmically. Figure 2 shows a typical such capillary extrusion rheometer, the ACR2100, though there are smaller, bench-top versions too. As well as the shear viscosity rheogram, a capillary rheometer may be used to investigate a number of other parameters. For example, a viscoelastic material may well not fully relax as it passes through the die and may swell on exit, a phenomenon known commonly as “die swell”, but more correctly “extrudate swell” or the Barus Effect. This can, of course, cause problems if not fully characterised.

Another effect is viscous or shear heating, caused by the material heating due to friction at the die wall. The increase in temperature can be significant, perhaps causing thermal degradation and anisotropy through the section of the profile or volatilisation of core components. This can also trigger wall slip, where the material does not adhere to the wall of the die, although wall slip can be caused also by high filler loadings and by low molecular weight components forming a lubricating layer at the die wall. Wall slip can be detected from the rheogram as a deviation from the predicted behaviour, and it can lead to inferior mechanical properties of the extrudate. Additionally, it is essential to know if a material is likely to exhibit wall slip when considering what processing

EXTRUSION <<Figure 2: ACR2100 capillary extrusion rheometer. >>

equipment to use; for example single screw extruders will not work properly, and twinscrew machines should be used. Another parameter which is not considered very often but which really ought to be, especially in this age where computational fluid dynamics packages are used to design injection moulding tools and extrusion dies, is the pressure coefficient of viscosity. The viscosity of some materials, for example polypropylene, polycarbonate and some filled rubbers, can change drastically when subjected to hydrostatic pressures such as those encountered in injection moulding machines. Finally, we have, thus far, mostly considered shear flow. In some high shear-rate processes especially, extensional or elongational flow may become significant; this is a mode of flow in which tensile rather than shear forces predominate. Typical processes where extensional flow is likely to be important include fibre extrusion, injection moulding, wire coating and differential rolling. It is not unknown for two batches of material having similar shear flow behaviours to have different processing characteristics due to markedly different extensional flow properties.

SEPTEMBER-OCTOBER 2013 / MPN /57

EXTRUSION

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Composite Tubing in the Medical Industry Continuous fibre composite materials provide multiple benefits to the laparoscopic medical device manufacturer. The materials were originally designed to replace stainless steel in trocar ports primarily because the composite tubing provided thin walls, stiffness and strength—which at the time were not possible with injection mouldable materials. The composite tube also provided the benefit of being radiolucent, making it possible to leave the trocar ports inside the patient while imaging was performed. Since its beginnings, applications of composite tubing have grown in number in the medical industry, providing customers with unique solutions that cannot be achieved using common stainless steel or thermoplastics. What is a Continuous Fibre Thermoset << CFTCs: solutions for al nim Composite? mi al gic sur A continuous fibre invasive devices. >> thermoset composite (CFTC) utilises nonchopped fibres impregnated with a low viscosity resin. The resin is cured creating a solid macro-material. The process to do this is similar in respect to thermoplastic extrusion in that a material of continuous cross section is formed into long stock lengths. However, CFTCs have many benefits over thermoplastics. In addition to the processing technique, which is a pultrusion process, they are electrically insulating and multi-lumen capable while having physical properties similar to stainless steel—that is to say stiffness, strength and thermal stability. How is a CFTC made? The first decision when processing a CFTC is what input materials will be used. All CTFCs utilise a fibre roving and resin. Like compounded thermoplastics, properties of resins can be modified using additives. These additives can increase a part’s toughness, change its colour and improve processability. Fibres give the part its strength and stiffness. Common fibres are e-glass (glass fibre commonly found in fibre glass), s-glass (high strength glass fibres) and carbon. The combination of these materials determines the physical properties of the finished product. The process of using raw fibre and resin to create a final part is straightforward. First, the fibre roving is pulled through a series of guides to prevent overlapping. The fibres are then pulled through a resin bath. While in the bath, the resin is drawn into the fibre filaments by both physical pressure and chemical wetting agents added to the surface of the fibre. The “wet out” fibres are then pulled through forming tooling which shape the impregnated fibres into the desired cross section. The fibres are pulled further into a heated die. The heat from the die creates a chemical reaction resulting in a cross-linked network within the resin. The resin also reacts with the surface chemistry of the fibres creating a single macromolecule. What Properties do CTFCs have? CTFCs provide parts that have: 1. Around 10-12 times the stiffness of neat PEEK; 2. Four times the flexural yield strength of 304 stainless steel; 58/ MPN /SEPTEMBER-OCTOBER 2013

3. A strength to weight ratio higher than steel; 4. Excellent thermal stability—parts do not melt and will not warp above Tg; 5. Dielectric strength equivalent to most thermoplastics; 6. Low water absorption—less than 1% after a 24-hour soak; 7. Range in size from 1 mm to 15 mm inner diameters, with wall thicknesses as low as 0.25 mm and tolerances of 0.05 mm; 8. ISO 10993 and USP Class VI certifications; 9. Capable of multi-cannulae tubing; and 10. Surface accepts common adhesives and pad print inks. CFTC Medical Applications Mono-polar surgical instruments: CTFCs are excellent for replacing stainless tubing in mono-polar endoscopic instruments. The high dielectric strength of the material protects the patient from burns caused by hazardous electrical discharges. Like all plastics, the dielectric strength is constant through the wall of the part protecting the patient from handling defects that can occur without knowledge to the surgeon. The high thermal stability of CFTCs allows overmoulding of high temperature plastics such as Ultem and Radel. The CFTC will not extrude under the high pressures and temperatures required to mould high temperature thermoplastics. Also, the thermal stability and low water absorption allows parts to be autoclaved with no risk of warping or swelling. Finally, the stiffness of a CFTC tube allows for small diameter tubing providing low deflection under loading. This allows CTFCs to perform as both graspers and scissors in endoscopic surgeries. The high yield strength prevents kinking of the tube from mishandling. Irrigation tubing: CTFCs are used in irrigation, reducing the opportunity for sharp edges. When a CFTC is machined it does not create a sharp edge that requires buffing or polishing. Therefore, the material reduces the risk of trauma to tissue during surgery. The smooth surface finish, which is less than 20 Ra, eliminates the need for coatings to be applied to the tube. This lowers the cost of devices by eliminating secondary operations. Ablation devices: CTFCs excel in directed wave energy devices. The insulating properties of the CFTC prevent capacitance that can occur with a stainless tube. In some cases this causes electrical discharge into non-targeted tissues or, in some cases, it short circuits sensitive electronics that are critical to function. Furthermore, with the increased usage of technology in the operating room the insulating properties reduce or eliminate signal noise from the energy discharge. This is important when non-optical vision systems are being used to find and target tissues for ablation. CFTC’s stiffness allows surgeons to apply force to the distal end of the ablation device. Typical ablations require probe penetration into fibrous tissues that require significant force to penetrate. Multi Lumen and Irregular Cannula: Much like thermoplastic extrusion, CFTC is capable of making multiple and irregular lumen parts to very tight tolerances. It is possible to produce multiple cannulas from 1 mm to 2 mm plus, in diameter in the same profile. The process allows for irregular profiles and cannula to be produced. It is possible to maintain tolerances of ±0.05 mm for each wall of the part and also maintain perpendicularity of ±2°. Unlike thermoplastic materials, CFTC is capable of maintaining high stiffness at small diameters. This enables device designers to create multi-cannula tubing which can move organs and tissues without multiple secondary operations. It also allows device manufacturers to create stiff irregular profile tubing without the need for extensive secondary machining. Credit: Medical Plastics News would like to thank Larry Horine and Rob Paulin at Polygon Composites for providing this article.

SEPTEMBER-OCTOBER 2013 / MPN /59

DESIGN FOR LIFE

Successful Design for Manufacture OF MEDICAL DEVICES By Bill Welch, Chief Technology Officer, Phillips-Medisize. DFx refers to “Design for X”, in which “X” may be any desirable attribute. Design for manufacture (DFM), or the more specific design for mouldability, refers to ensuring the product design conforms to the guidelines for the manufacturing process to be used, such as injection moulding. Successful DFM requires the right DFM philosophy, an understanding of the DFM guidelines for the intended manufacturing processes, and the ability to look beyond component-level DFM to find system-level solutions that enhance device performance while meeting human factors, quality, cost, and risk requirements.

<< Bill Welch is Chief Technology Officer at PhillipsMedisize. >>

Core Component-Level DFM Guidelines Whether designing electronic components such as circuit boards or designing mechanical items such as plastic parts, there are core DFM guidelines that must be understood by the design team members. Even within plastics, every production technology—from extrusion to thermoforming to injection moulding—has its own specific design guidelines that need to be evaluated throughout the product development process. In the case of injection moulding, the five most common design guidelines to prevent downstream manufacturing issues are: l Match nominal wall thickness with material selection and processing; l Ensure suitable draft to enable part ejection and maintain a crisp texture; l Maintain 65% or lower rib-to-wall ratio, depending on material selection, to prevent sink defects; l Configure radii to maintain nominal wall and prevent areas of stress concentration; and l Establish adequate shut-off angles for steps in the parting line.

DFM as a Guiding Philosophy Successful DFM requires a culture that unites product development and manufacturing, and appreciates early manufacturing involvement starting at the concept phase. Since most of the product cost (as well as quality and risk) are driven by decisions early in the product development processes, the product development team must include expertise in DFM for the intended manufacturing processes. In the spirit of innovation and creating improved patient outcomes at a lower cost, it is recognised that the DFM guidelines must sometimes be challenged. In these cases, the product development team must be committed to risk mitigation by applying computer aided engineering (CAE) tools such as mouldflow, finite element analysis (FEA), and tolerance analysis to an unfinished design, and subsequent prototyping to verify the CAE output. In the case of injection moulded plastic components, the design team understands that part design dictates mould design, and can envision how steel is wrapped around part geometry to create tooling capable of meeting the required volumes and quality requirements when in production. From a development standpoint, both the mould geometry and injection moulding process must align with the part requirements, mould construction, and moulding process. Finally, the culture must support the belief that DFM must be applied across the product development process by a fully engaged multidisciplinary team including manufacturing representatives. DFM cannot be viewed simply as a checklist to be completed or a task in the development cycle. Early manufacturing involvement not only brings DFM expertise to the << Digital printing enables a two-shot part product development team, it also promotes such as this to have hardcoat applied only to concurrent early learning and buy-in by the the clear PC material where it is needed, manufacturing team, thereby reducing lead time saving on lead time, scrap, and cost while and risk downstream. providing improved sealing compared with a two-part assembly. >> 60/ MPN /SEPTEMBER-OCTOBER 2013

While prototyping always has a role in product development, it becomes even more critical when challenging proven manufacturing process principles. The purpose of prototyping goes beyond simply obtaining components for development builds. It is imperative that a manufacturing strategy is developed to “build early and build often” to reduce risk in downstream development phases. The intent of injection moulding prototypes is to: l Prove out-of-mould concept and injection moulding process in a prototype mould prior to investing in more expensive, higher cavitation production moulds; and l Learn as much as possible about the mould and process to prepare the manufacturing team for higher volume scale-up. Seek Elegant Solutions for Medical Device Systems Other desirable attributes under DFx may be assembly, test, disassembly, maintainability, and safety, among many others. While DFM tends to be focused on discrete component design, design for assembly (DFA) is by extension focused on how the components are brought together and assembled to form the finished medical device system.

Case Study of DFx Applied in Parallel to a Body-Worn Drug Delivery System Previous Process: Injection mould lens. Hardcoat lens (subcontract operation). Injection mould case. Sonic weld lens into case. Result: More manufacturing steps and higher piece part costs. Long supply chain. High scrap rates at lens coating and sonic welding operations. Inconsistent weld results in moisture intrusion. New Process: Two-shot case, with integrated lens. Digital printing of the lens (inline operations). Result: Higher tooling investment, but lower piece part cost. Shorter supply chain. Lower scrap rate at inline digital printer; eliminate sonic welding. Moisture intrusion issue resolved.

COMPAMED MEDICA

LEADING UK LARYNGOSCOPE MANUFACTURER

Overcomes Challenges Of Replacing Metals With Plastics

<< Shah Fayyaz is CEO of Timesco Healthcare, the leading UK laryngoscope manufacturer. >>

On November 20-23, 2013, one of the world’s largest trade shows dedicated to the healthcare supply chain, Medica, will open its doors in Düsseldorf, Germany. Colocated with Medica is Compamed, an exhibition for providers of technologies and manufacturing services for finished device manufacturers. In this preview, Medical Plastics News—Medica’s official UK media partner and exhibitor on stand 8b, M33—focuses on the wide range of UK exhibitors at both events, beginning with an exclusive interview with Shah Fayyaz, the CEO of leading laryngoscope manufacturer Timesco Healthcare.

Q: Tell me about your company and the products you make, including a little bit of history as to how Timesco was formed? A: We are the UK’'s leading laryngoscope manufacturer, with over 65% of the UK market and presence in over 60 countries around the world. We are also prominent in the manufacture and supply of medical devices for surgery, podiatry, diagnostics and primary care. The company was established almost 50 years ago as a trade manufacturer and we have evolved into a direct supplier under our own brands. Q: Tell me about how you use plastics in your products. A: Plastics are predominately used in our laryngoscopy portfolio for airway management devices. Key considerations have been to deliver lower cost devices to the NHS [National Health Service—the UK’s national healthcare provider] and international markets, whilst improving clinical performance and patient outcomes. The plastics have been required to replace existing metal devices so there has been a significant shift from current user perception—ie “metal is stronger, more reliable and more durable than plastic.” Plastic can sometimes appear to be a “cheap” alternative. We believe we are being successful in challenging this misconception. We have also been keen to keep environmental impacts high on our agenda during our development and design processes.

Q: What challenges have you overcome to integrate plastics into your product range? A: We have had to develop totally new ways of delivering power and illumination to these devices due to the plastic construction. This has, however, allowed us to enhance performance and the overall benefits of the systems. A key challenge has been to ensure strength and durability of a plastic version of a previous metal device. Using not only the right plastics, but the right design and moulding processes has been critical. Some products have been required to be repeatedly reprocessed through steam autoclaving and gas plasma systems—up to 1,000 times, a feat in itself. Others have been required to be low cost, single use, but still being able to be ETO or gamma sterilisable, so we have had our work cut out. Q: What technical areas are you focusing on in terms of research and development and what role do plastics play in this? A: We are focusing on how we can incorporate plastics into the wider portfolio we produce, both in laryngoscopy and other product portfolios. The key question is “why can’t a plastic device do a better job than its current metal counterpart and at a lower cost”, it is a simple but hugely challenging strategy.

<< Timesco's innovative Single Use Skin Laryngoscope handle, reduces cross infections and cost in airway management. >>

Q: Why is this important for your customers and their patients? A: The cost of metal and the manufacture of the same is likely to continue to rise. Most metal airway devices are hand-made and assembled, particularly for the single use devices. This can bring challenges in both quality control and a regular, reliable supply chain. We have also been able to drive production costs down which we can pass on to our customers and so reduce the cost of each procedure. Improved technology in these devices has also allowed us to reduce maintenance, reprocessing and battery costs, a significant saving in both asset costs and ongoing costs.

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COMPAMED MEDICA

Continued from page 63

Q: How many times have you been to Medica and when was the first time you visited and/or took part? A: Medica has been the core international show for Timesco for almost 20 years. It's almost like an annual pilgrimage now! Q: How does it compare with other healthcare trade shows around the world? A: I have to say that Medica is unlike any other trade event. The Germans just do it better than anyone else. We exhibit throughout the UK and worldwide, nothing really matches Medica’s coverage, organisation and presence. We, in the UK, could learn a lot from how this show is managed and coordinated. I do believe it is a real shame that the UK has a hugely influential medical devices sector and yet we have no domestic trade event that does us justice. Q: What are your experiences of doing business in Europe and the USA? A: We find the USA a relatively easy place to do business, they want to do business. Sometimes the EU seems to be less understanding of the real challenges faced by the medical devices sector. I tend to live "in the real world" but I am not sure the EU directives we are hearing about always reflect this. Let's see. Q: What is your outlook for the medical device market over the next 10-15 years? A: One thing is for certain, customers worldwide are expecting more for less. How does the medical device sector deliver this without compromising patient welfare and outcomes? Ideally, there needs to be a better co-ordination of the patient pathway to help drive costs down and so, possibly, collaboration in device development is the way to go. For us, keeping it simple and a common sense approach is the direction. Afterall, we make low technology, hand “tools”, no one wants to read a ten-page manual to use a screw driver. This may sound like I am underselling our products, I am not. Most elected surgeries will begin with the kind of products we make, so we play a hugely important role and the product has to be 100% fit for purpose and perform every time, without fail. We can add innovation in a variety of ways throughout the various hospital departments that are involved with our devices. We almost need to make them so good, that you hardly know they are there. Timesco are exhibiting at Medica in hall 16, G047. A list of the other UK exhibitors, as well as those from Ireland, at Medica and Compamed are overleaf.

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List of Exhibitors from the UK and Ireland at Medica and Compamed Exhibitors and Brands Hall / Stand A.C. Cossor & Son (Surgical) Ltd 16 G20-8 A1 Pharmaceuticals Plc. 06 A40 Accutronics Limited 08B F30 Adam Equipment Co. Ltd. 01 A27 Adam,Rouilly Ltd. 16 G18-2 Advanced Healthcare Technology Ltd. 16 F04-1 Advanced Medical Solutions Ltd 03 E92 ALG 16 G04-3 Alpha Laboratories Ltd. 01 F32 Amcor Flexibles Winterbourne Ltd. 08A K19 Amity Limited 12 F55 Ampac Security Products Ltd. 08B A25 Amplivox Ltd. 11 D71 Andor Technology PLC 16 G10-1 Anetic Aid Ltd. 14 B25 Apacor Ltd. 01 B02 Arc Devices Ltd 16 G25 Armstrong Medical Ltd. 16 G10-1 Asalus Medical Instruments Ltd. 16 F30 Aspen Medical Europe Ltd. 05 B21 Association of British Healthcare Industries Ltd. 16 F02-1/ G25 Association of British Healthcare Industries Ltd. 16 G19-1 Astell Scientific Ltd. 01 F15 Atlas Medical 02 A37 Atom Scientific Ltd 01 E05 Avental Ltd. 16 F20-7 Baltimore Innovations Ltd 16 F24-2 BBI Solutions 01 F24 BDF Guardian 06 D30 Bedfont Scientific Ltd. 11 B29 Bee Robotics Ltd. 03 F65 BeneCare Medical 06 C51 BioDot Limited 02 C47 Biofortuna Ltd. 01 D10 Biopanda Reagents Ltd Biopanda Reagents 16 G10-1 BIOtAK Ltd 12 A03 BMM Weston Ltd. 12 E24 Bodystat Limited 11 A53 Brandon Medical Co. Ltd. 13 C36 British In Vitro Diagnostics Association (BIVDA) 01 F06 Bytec Medical Ltd. 13 D31 C&G Medicare Ltd Williams House 16 F30 C-LA Europe Ltd. 16 F20-3 Cambridge Consultants Ltd. 01 E08 Capatex Medical 16 F04-1 Capillary Film Technology Ltd. 01 D08 Carville Ltd. 08A N15 CellPath Ltd. 03 C70 Charles Austen Pumps Ltd. 08A K13 Chart BioMedical Ltd. 11 C67 Chongqing Tianha Medical Co., Ltd. 16 G25 Clear Surgical Ltd. 06 D29 Clement Clarke International Ltd. 11 J71 Colorite Europe Ltd. 06 H30 Colson Castors Ltd. 14 D28 Crux Product Design Ltd. 08B K16 Daily Care Ltd. 16 F04-1 DCA Design International Ltd. 08A K26 Detecto Scale USA European Warehouse 12 B33 Dexela Limited (a PerkinElmer Company) 09 E65 DirectMed Ltd. Lake Forest House Forest Road 08A N11 DongBang Acupuncture (EU) Ltd. 05 B37 DTR Medical Ltd. 16 F30 DySIS Medical Ltd. 06 D26 E&O Laboratories Ltd. 01 B41 eg technology Ltd. 16 G20-2 EKF Diagnostics Holdings plc 03 C70 Elite Electronic Systems Ltd. 16 G10-1 Emblation Microwave 06 D26 EMS Physio Ltd. 04 C36 EUROHOB (UK) Co., Ltd. 01 F18 Evexar Medical Ltd 16 F18-4 Excellentcare Medical Ltd 16 G24-3 Exmoor Innovations Ltd. 16 F18-2 Exmoor Plastics Ltd. 16 F18-1 Exopack Advanced Coatings (North Wales) Ltd. 16 F30 Eyeline Organisation Ltd. 16 G25 Farla Medical Ltd. 16 F24-3 Fertility Focus Ltd. 16 G25 FI Marketing Group Ltd. 07 E40 Fino Healthcare 16 F04-1 Flexicare Medical Ltd. 06 G27 Forsite Diagnostics Ltd. 01 F16 Fortress Diagnostics Ltd. 01 D12 FRIO UK Ltd. 16 F30

Exhibitors and Brands G-Care Electronics Ltd. Gael Ltd. GAMA Healthcare Ltd. Gowllands Medical Devices Ltd. Grena Ltd. Guy-Raymond Engineering Company Ltd. Gwent Electronic Materials Ltd. GX Systems Ltd. Haigh Engineering Company Ltd Harlan Laboratories Contract Research Services Hart Biologicals Ltd HeartSine Technologies Ltd. Henleys Medical Supplies Ltd. Herga Electric Ltd. HMD Healthcare Ltd. Huntleigh Healthcare Ltd. Diagnostic Products Division Hydro Physio Immunodiagnostic Systems (IDS) plc Imutest Limited Inditherm plc Industrial Design Consultancy Ltd. (IDC) Innova Biosciences Ltd Innova Partnerships Ltd Inspiration Healthcare Ltd. Integrated Technologies Ltd. Interplex Medical (UK) Ltd. Intersurgical Ltd. Invest Northern Ireland Jackson ImmunoResearch Europe Ltd. Johnson Matthey PLC Noble Metals JPM Products Ltd. K-MED Ltd. KARE Orthopaedics Ltd. Kenex (Electro-Medical) Ltd KING'S HEALTH PARTNERS Kinneir Dufort Design Ltd. Lab M Ltd. Lab21 Ltd. Labtek Science & Development Co. Ltd. LaproSurge Ltd. Lec Medical (T/AGlen Dimplex Professional Appliance) LEEC Ltd. Limbs & Things Ltd. Lion Laboratories Ltd. Locamed Ltd. Lorne Laboratories Ltd. LTE Scientific Ltd. Luto Research Limited Luxfer Gas Cylinders Ltd. Mackworth Healthcare Ltd Mailbox: Stamford Products Ltd. Malem Medical Ltd. Maltron International Ltd. Mast Group Ltd. MasterControl Global Ltd. Max Medical Products Ltd. MC Diagnostics Ltd. MD Diagnostics Ltd. MedChip Solutions Ltd. Medical Developments UK Ltd. Medical Device Management Ltd. Medical Plastics News Medical Wire & Equipment Co, Ltd. Medicen Devise limited Medilink Yorkshire & Humber Ltd. Medisafe International Meditec International England Ltd. Micro Systems (UK) Ltd. Midmark EMEA Ltd MJS Healthcare Ltd. Mode Health Ltd. Molecular Products Ltd Monmouth Scientific Limited Morgan Advanced Materials MSE (UK) Ltd. Neoligaments Novarix Limited OGM Ltd OJ-Bio Ltd Omega Diagnostics Group PLC OptiGene Ltd Optimum Medical Solutions Owen Mumford Ltd.

Hall / Stand 16 G10-1 15 D58 06 B07 16 F20-5 06 H14 14 E18 03 C70 16 F30 16 F02-3 08A C33 01 F12 09 C35 16 G04-4 08A M31 06 G41 09 A32 05 H37 01 F23 01 F20 16 G20-6 08A P25 01 E04 06 D29 16 G20-5 03 H20 06 D30 11 A59 16 G10-1 01 E16 08B N08 04 C06 16 F02-4 06 D26 10 C51 16 G10-2 08B K10 01 F22 01 C16 16 F24-6 13 C29 13 A40 01 F17 16 G20-4 03 C70 16 F18-6 01 F13 12 B07 08A R21 11 C48 16 F30 13 C04 16 G20-1 16 G18-4 01 D04 08A R11 16 F04-4 03 C70 16 G24-1 09 C52 16 F24-4 09 B11 08B M33 01 F10 06 D29 16 F04-1 16 F20-4 16 F02-6 08A F19 12 F03 04 B47 06 D30 16 G20-3 01 E06 08B N16 01 F04 16 F18-8 16 G25 08B A37 01 F09 01 E20 01 F14 06 D43 16 G18

Exhibitors and Brands Oxford Immunotec Ltd Oxylitre Ltd. P3 Medical Limited Paradox Omega Oils Ltd. Park House Healthcare Ltd Patterson Medical Ltd. PDI Europe Pelican Feminine Healthcare Ltd. Penlon Medical Gas Solutions Pennine Healthcare PeproTech EC Ltd. Physio Supplies Ltd. Physiolab Technologies Ltd. Plinth 2000 Ltd. Poditech UK Ltd. Porvair Filtration Group Ltd. POWERbreathe International Ltd. Precision UK Ltd. Primasil Silicones Ltd. Priorclave Ltd. PRO - LAB Diagnostics Purple Surgical International Ltd. Randox Laboratories Ltd. Randox Life Sciences Reliance Medical Ltd. Remote Diagnostic Technologies Ltd. (RDT) Rigel Medical Rocialle Rocket Medical Rodwell Engineering Group Ltd. Sansible Ltd. Savience Ltd. Scapa - Healthcare Division Scottish Enterprise Scottish Enterprise SDIX Europe Ltd. Seaborne Plastics Ltd. Seers Medical Ltd. Sekisui Diagnostics (UK) Ltd. Serrations Ltd. Sheffield Hallam University Sherwood Scientific Ltd. Sidhil Ltd. SLE Ltd. Smallfry Smart Eye Co., Ltd. Sony Europe Ltd. SOZO Woundcare Ltd. SP Services (UK) Ltd. Spacelabs Healthcare Ltd. Spirit Medical Systems Springdew Limited Star Syringe Limited Starna Scientific Ltd. SunTech Medical Limited Supply Point Systems Ltd. SureScreen Diagnostics Ltd. Sutures Limited Swann-Morton Ltd. Synergy Health plc Synoptics Health A Division of Synoptics Ltd. Talley Group Ltd. Teal Patents Ltd. TensCare Ltd. The Gambica Association Ltd. The Gambica Association Ltd. The Magstim Company Ltd. The West Group Ltd. TIMESCO Healthcare Ltd. Tonus Europe Ltd. TPP TT Electronic Integrated Manufacturing Services Ltd. UK Trade and Investment Ultralife Healthcare Ltd. Ultrasound Technologies Ltd. University of St Andrews Uno International Ltd. VacSax Ltd. Variohm Eurosensor Ltd. Verity Medical Ltd. Viamed Ltd. Vigor Innovations Ltd. Wallace Cameron International Ltd.

Hall / Stand 01 E10 16 F20-1 05 D11 16 G10-1 14 C27 04 D16 05 E12 16 F30 16 F10-3 06 C41 01 F40 16 G25 16 F18-7 04 H50 16 F18-5 08A F08 04 J58 16 G10-3 08A R19 01 E02 01 F02 06 E06 03 A08 01 F30 06 C45 11 D74 11 H11 16 F30 16 F02-1 01 D06 06 D29 16 F20-2 06 E41 06 D26 06 D30 01 F08 08B M09 05 G37 01 A26 08A L07 16 F04-1 01 E07-1 14 E42 10 E05 16 G25 16 G24-4 10 G57 16 F04-1 16 F02-5 11 E39 16 F24-1 16 F30 16 F24-7 01 E12 09 A37 16 G24-2 01 F03 16 G04-1 13 F65 06 D21 01 F11 14 B30 16 G25 11 H41 01 D04/...F32 01 E09 16 F30 08A E03 16 G04-7 16 F30 16 F20-6 08A L11 16 G19-2 16 F04-1 09 D51 08A E33 03 B84 16 G25 08A M31 16 G10-4 11 E52 14 D47 06 D30

Exhibitors and Brands Wardray Premise Ltd. Warwick Sasco Ltd. Water-Jel Europe LLP Welsh Government Westfield Medical Ltd. Woodley Equipment Company Ltd. Zilico Ltd. Aalto Bio Reagents Ltd. Adhesives Research Ireland Ltd. Alere International Ltd. ArcRoyal Audit Diagnostics

Hall / Stand 10 A62 16 G25 06 D15 16 F30 06 K37 01 E14 16 F04-1 03 C64 08A M32 FG.3 03-1 05 P25 02 A05

Exhibitors and Brands Cambus Medical Enable Supplies Ltd. Filtertek - an ITW Medical Company Finesse Medical Ltd. Pharmed S3 Group Serosep Ltd. SteriPack Ltd. Trinity Biotech plc. Trulife Ltd. Vistamed Ltd.

Hall / Stand 08B E02 14 B62 08A K08 06 J33 13 B18 15 E04 02 B18 08A M01 02 B25 05 K21 08B E02

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COMPAMED MEDICA

Extrusion for Medical Components Plastics can be adapted like no other material and are therefore of increasing significance for medical technology. Especially where disposable medical items are involved that are subject to maximum quality requirements on account of their use in or on patients, for example medical tubes, whereby this involves both the art of attributing the base material the right properties and sound knowledge of the entire production chain which is obliged to meet the manifold statutory requirements (Good Manufacturing Practice). Apart from injection-moulding and multi-component injectionmoulding, extrusion is one of the most frequently used manufacturing processes in the technical medical environment. The extrusion process involves pressing plastics or other viscous temperable materials through a nozzle in a continuous process. To this aim, the plastic—or extrudate—is melted and homogenised by an extruder using heat and internal friction. The requisite pressure for flowing through the nozzle is developed in the extruder. Once it is expressed through the nozzle, the plastic usually hardens in a water-cooled calibration process. Vacuuming presses the profile against the caliber wall which then completes the forming process. This is often followed by a cooling zone in the form of a cooled water bath. The cross-sections of geometric bodies thus produced comply with the nozzle or calibration used. The possible manufacturing tolerances range between ±0.05 mm. Extrusion technology products can be found in a variety of areas of application, for example construction, automobiles, aviation, furniture, cosmetics, foodstuffs and especially in medical technology. Extrusion and co-extrusion processes are also used to manufacture single- or multi-lumen tubes for medical applications. Co-extrusion involves combining two or more materials in the extrusion head which cannot otherwise be blended or interfused. For example, it is possible to manufacture a tube whose internal material displays outstanding chemical resistance and whose outer material displays outstanding thermal properties. In principle, the range of possible polymers for use in co-extrusion is unlimited. But thermoplastic polyurethanes, polyamides, polyolefins and especially thermoplastic elastomers have proved ideal and can also be processed in micro-extrusion—an area of increasing significance in medical technology. The use of thermoplastic elastomers (TPEs) also ensures that the manifold requirements on medical tubes and tube systems are complied with. The ProvaMed portfolio of TPEs offered by Actega DS accommodates this requirement profile, enabling the manufacture of multi-lumen tubes which are often used for transporting air, material or liquids. In medical applications, a multilumen tube can assume several functions at the same time within the same restricted space (for example suction and rinsing). ProvaMed materials are also suitable for integrating stripes which are impervious to x-rays, thereby enabling surgeons to localise implanted drainage or surgical components using x-ray technology, for example. And even the particular challenge of co-extrusion of several polymer layers in the manufacture of micro-tubes can be met by these TPE formulae. Using special micro-extrusion plants, multi-layer tubes can be manufactured featuring up to four different materials, whereby internal tube diameters of a mere 0.1 mm and wall thicknesses of 0.05 mm are possible. At Compamed, November 20-22, in Düsseldorf, Germany, Actega DS will present more applications of these compounds developed for medical technology, pharmacy and cosmetics.

Precision Shape-Shifting Silicone Tubing

IS A REALITY Geo-Trans, a registered trademark, is a patented process that enables the cross sectional profile of a silicone tube to change “on the fly” during extrusion. The process was invented and patented by Specialty Silicone Fabricators (SSF) in 1996. The technology was originally developed to improve closed wound drainage products. Today, the far-reaching medical, mechanical and manufacturing advantages of transitional extrusion are well known. The process eliminates any secondary bonding operations to mate different tube profiles, thus significantly reducing costs. Also, because the process produces a single continuous tube, there is no need for leak testing, further reducing cost. Product quality and performance is vastly improved by eliminating any seams where CFUs (colony forming units) can gain a foothold and create potential infections. To produce parts with changing geometries requires tooling that can change “on the fly”. For example, a die might need to slide open so a circular outer diameter (OD) can transform to an oval, or it might need to close down from a circle to a square. Specialty Silicone Fabricators’s in-house tooling department is a world leader in the development of these complex variable dies. There have been many advances in the use of the Geo-Trans Process since its first introduction. Some of these include: The ability to extrude balloons of any length: This is done by a moving mandrel that maintains a constant OD while thinning the wall by varying the inner diameter (ID). This eliminates typical secondary bonding requirements and attendant costs while increasing production speed. The result is reduced labour and no potential worker injury from removing balloons from cores. Variable stiffness-flexibility ratio in a continuous tube: This is achieved with double extruder configurations that allow a very wide range of stiffness-flexibility ratios on the fly. For example, a flexible catheter that is easy to insert into the body speeds up the surgical procedure. The amount of flexibility can be controlled by thinning out the extrusion wall or by switching to a softer or stiffer material anywhere along the extruded profile. Multi-lumen continuous extrusions: << Top: A moving The Geo-Trans process can easily split two or mandrel enables more lumens off a centre lumen or merge balloons of any length two lumens into a single lumen—all in a to be extruded. single continuous extruded tube. For Middle: The peelable Y example the “peelable Y” configuration, configuration allows shown in the image, allows users to split the users to split the multimulti-lumen section as needed. The multilumen section as lumen process is achieved by employing needed. both moving dies and moving mandrels in Bottom: The Geo-Trans concert. Once again, product cost is Process can merge two improved by eliminating secondary lumens into a single moulding opera¬tions. Quality is improved lumen in an single by eliminating any possibility of cross continuous tube. >> contamination of fluids in the separate lumens. SSF will be exhibiting with its contact partner company MER-Europe at Compamed at the latter’s booth in hall 8B, stand K09. SEPTEMBER-OCTOBER 2013 / MPN /67

E&L CONFERENCE LONDON 2013

Extractables and Leachables: Words of Wisdom From a Polyolefin Supplier DR JAMES STERN, THE APPLICATION MARKETING MANAGER FOR HEALTHCARE AT POLYOLEFIN MANUFACTURER BOREALIS, SPEAKS EXCLUSIVELY TO SMITHERS RAPRA’S EXTRACTABLES AND LEACHABLES (E&L) TEAM ABOUT ISSUES RELATED TO E&LS IN POLYOLEFIN-BASED PHARMACEUTICAL PACKAGING. DR STERN WILL BE SPEAKING AT SMITHERS RAPRA’S UPCOMING EUROPEAN E&L CONFERENCE, DUE TO TAKE PLACE IN LONDON ON DECEMBER 10-11, 2013. SMITHERS RAPRA IS A LEADING UK POLYMER CONSULTANCY WITH A SPECIALISM IN TESTING. Q. With your long history working as a supplier for packaging and device materials for pharmaceutical applications what is your experience in general about the knowledge about extractables and leachables today compared with a decade ago? A. “Quite simply, there was no real supplier experience in extractables or leachables because the requests for such information were few and far between. However, in order to serve the healthcare industry in the best way, we at Borealis have understood that changes in our resins may have effects on a microscopic level to the packaging material and this needs to be quantified. As such, we have developed knowledge specifically around extractable studies and actively participated in conferences in order to help our customers make the most appropriate material choice.”

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Q. How does a major polyolefin supplier control the changes that inevitablely are made at the sub supplier and raw materials supplier level? A. “Borealis has an internal operating procedure which works in addition to our normal ISO9001 procedures with which we manage the changes. As you have said in your question, they are inevitable. The question is therefore how this is managed in the best way. We do this in a number of ways, but essentially we provide unchanged material to our customers. If a change must be made, for example for regulatory or operational reasons, we give a suitable period of time to allow them to qualify a new material. When a change needs to be made, our aim is to carry it out in such a way as to have a sustainable portfolio of resins as a result minimising the need for further changes in the future.” Q. Are these changes brought forward to the pharmaceutical company for evaluation of potential changes in the quality of the final drug product or device? A. “The question is actually ‘what is a change?’ This is the first point of discussion with our customers. Only our customers can determine, based on their experience and knowledge, whether the change is significant to their product. In the end, this boils down to good communications. We provide as much information as possible to allow the significance and risks of the change to be evaluated by our customers.” Q. What actions do you think pharmaceutical packaging suppliers can incorporate into their practice in order to minimise the variance in the material they supply to pharmaceutical companies? A. “Foremost, I would say having open discussions and working in good partnerships. Today, the total volume requirements of the healthcare industry are only a very small fraction of the total polymer production—that is to say change happens as it is driven by the world around us. To assist in keeping these changes to a minimum, Borealis, as raw material supplier, has ring fenced materials for use in healthcare, but we are continually faced with drivers for change coming from businesses with significantly higher volumes. Converters and pharmaceutical companies can therefore help to minimise the risk of change by selecting these grades for their applications. Additionally by communicating with raw material suppliers about where materials are

being used, current market trends and requirements all help the material suppliers develop sustainable portfolios thus allowing the packaging manufacturer to keep his product consistent. In short, open and clear communication.” Q. Today some pharmaceutical packaging suppliers support their materials with regular extractable testing. What is your thought on this and how far do you think a packaging and device material supplier can go in general? A. “Extractable testing is only worthwhile if the materials used in the packaging or devices are controlled. Further to this, the extractable profile of the final item can change at each step—that is to say conversion, sterilisation, colouring, application of labels or printing, and so on. Thus, extractable testing can assist with informed choices at the development stage. Due to changes in the material extractable profile through the production process, they can never fully replace testing of the final item as well. However, another dimension to be considered is the use of extractable testing during a change, so in addition to stating what the change is, a comparative study could provide additional supporting information to allow more informed risk assessment. As a raw material supplier, Borealis needs to serve a broad spectrum of customers, as specific extractable testing cannot be universally valuable. Our challenge is therefore to provide both general and specific extractable information in such a way as to support our customers’ needs.” Q. Why do you see it as important for the industry to come together at events such as Extractables and Leachables Europe, at which you are a speaker, to discuss these supply chain challenges? A. “As I said previously: communication is key. The industry needs to understand what is possible and what is not possible and that can only be done if we have this type of forum to discuss the challenges and opportunities. We are all experts in our areas and by sharing that information realistic expectation levels can be achieved. Together we need to match the requirements of the healthcare industry and the chemical industry, where the material suppliers sit.”

For information on the upcoming conference please visit www.eandl-conference.com.

EVENTS SPE MiniTec and MD&M Chicago Conferences Review, by Len Czuba << From MiniTec, Susan Montgomery (left) is the president of Priamus System Technologies and Dave Schwaba is senior manager at Design Integrity, representing the MedSource Coalition. Susan has been in the plastic processing field for 19 years, most of this time spent in plastics process instrumentation and injection moulding process controls. Ms Montgomery served as Chair, SPE Injection Molding Division from 2011-2012 and 2012-2013. She was Injection Molding Division Technical Program Chair for ANTEC 2011. She is frequently a featured technical speaker and also a published singer and songwriter. >> The week of September and mHealth (mobile health) introduced products that showed how 9, 2013, featured an technology is being used in products now and in the near future. interesting combination Wireless communicating patient monitoring systems no longer need of technical to be tethered to the wearable sensors. Critical conditions can now be programmingâ&#x20AC;&#x201D;one, measured continously rather than intermittently when healthcare sponsored by SPE (the Medical Plastics Division) and the other, a UBM workers are available. Better monitoring usually means better Canon conference programme at their MD&M Chicago event. On outcomes; but this comes with new complications such as how do Monday, more than 100 participants at the SPE MiniTec (a one-day healthcare workers manage and meaningfully interpret all the data no-frills technical conference) heard 14 presentations on both the pouring in from these 24/7 monitoring systems. latest in materials technology as well as advances in polymer Another intriguing presentation, this one by Shiv Gaglani, a processing for the medical device industry. medical student from Baltimore, discussed the explosive rise in Several speakers discussed the progress being companies and products that take advantage of made by suppliers to meet the needs of an ever smart phones as foundation for new medical changing industry with high performance polymers. devices. Two products were demonstrated. These high performance polymers are suitable for One was a portable, heart monitor (a one-lead both implantable devices but also for durable ECG) that uses a sensor that looks like a smart applications such as pump housings, instruments and phone case that is wirelessly linked to the iPhone diagnostics. The battle to reduce or eliminate which displays the patientâ&#x20AC;&#x2122;s heartbeat. It is Hospital Acquired Infections or HAIs, requires new simple, convenient and inexpensive. Another cleaning and disinfecting procedures with frequently product now available for physicians is an more aggressive chemical solutions. These products opthalmascope that couples with a smart phone challenge the materials of construction especially for camera for imaging the blood vessels on the back long-term use products such as those used in the OR of a patientâ&#x20AC;&#x2122;s eyeball. This easy to use instrument (operating room). The growth of home healthcare features a simple adaptor and scope to further challenges device companies and all the convert the smart phone into a << From MD&M Chicago, Shiv Gaglani sophisticated medical diagnostic tool for associated support industries to come up with (left) is a med student who is active in detecting glaucoma or other diseases of products that can be safely and effectively used in using electronic technology in the home setting often by non-technical family the eye. medicine. He gave a fantastic talk on members of the patients. The surge in adopting mobile devices mHealth and how hand held devices In meeting the needs of device manufacturers, for use in healthcare called mHealth, is can be adapted to improve patient tubing extrusion companies are coming up with clearly the future of healthcare. mHealth monitoring, diagnosis and treatment. value added options such as coextrusion, multihas resulted in over 90 start-up He is holding an instrument that with layer structures and unique material offerings for companies raising over US$2 mn in an iPhone can allow an optometrist or funding in the last 12 months. This the device industry. We heard how surface GP to look at the blood vessels on the treatment with ionised plasma can improve surface enabling technology helps by reducing back of the eye. The other person is a adhesion, printing and bonding or improved cost, increasing availability and stimulated retired orthopaedic surgeon, Dr Denis novel product innovations. overmoulding and materials compatibility. Drennan, who attended the SPE session Two presentations on advance processing No session on medical device at the event. He is holding an accessory materials would be complete these days offered interesting methods or techniques to used with the iPhone that takes a improve the injection moulding operation. And the without mentioning the concerns about portable EKC reading of the heartbeat. HAIs and the various actions that are closing speaker of the MiniTec gave a most It shows on the iPhone even though it is being taken to mitigate this widespread interesting presentation on how CT (computed only wirelessly attached. >> tomography) scanning can be used in product problem. New additive technology and development, manufacturing and process improvements to the polymers used monitoring. The system uses an instrument and procedure originally have improved the surfaces resistance to frequent cleaning and intended for use in hospital diagnostics for human patients. The repeated sterilisation. Next generation materials for use as flexible system is modified and can now be used in the moulding company to solution container materials were presented as were alternative image plastic parts. The system uses CT to convert a moulded part materials for clear, moulded components. into a computer dataset that can be assembled into a CG (computer The conference programming was followed by a surprisingly large generated) model. This model can then be viewed and manipulated and well-attended exposition that took place in the Lakeside centre at in the electronic environment of the screen. It makes analysing McCormick Place in Chicago. It was a good week for everyone able to complex forms possible and the degree of accuracy unparalleled by participate. OGP (optical gauging product) or CMM (contact measuring machine). For info on mHealth and examples of products available, check out: At the MD&M conference, the focus of the leadoff session was on http://www.medgadget.com. breakthrough technology. Two presentations on wireless technology 70/ MPN /SEPTEMBER-OCTOBER 2013