MPN EU Issue 13 by MPN Magazine

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MEDICAL PLASTICS NEWS INVIBIO CELEBRATE 500TH IMPLANTABLE PEEK-OPTIMA DEVICE APPROVED IN THE USA, 80TH IN CHINA

ALSO IN THIS ISSUE: PEEK and Other High Performance Polymers Drug Delivery Update A Guide to the 510k Additive Manufacturing for Plastics Engineers

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Contents 5. Editor’s Letter: Reader poll Medical Plastics News polls readers to compare biocompatible polymer brands with one another. European regulations—Page 6

Cover story—page 10

6. On the Pulse: Industry news Device regulations update—Don’t lose the 3—can medical PVC recycling catch up, ABHI partners with Mediplas and comparison of melt processing polycarbonate and copolyester. 10. Cover: 500 PEEK implantables Invibio celebrate regulatory milestone as FDA approves 500th implantable PEEK device, 80 in China. 13. Material Diagnosis: PEEK An update on PEEK and other high performance polymers, including laser micromachining, PEEK SLS additive manufacturing, carbon fibre reinforced PEEK, shape memory PEEK and a device roundup.

PEEK laser micromachining—page 13

Optical inspection of tubes—page 30

22. Clean Machines: Additive manufacturing A guide to additive manufacturing for plastics engineers, trends in 3D printing of customised medical devices and a table of biocompatible additive manufacturing materials. 26. Country Focus: USA The state of the US device manufacturing sector in 2011-12, device tax senator speaks at industry conference and a guide to the 510k. 30. Folio: Precision tubing inspection Pixargus’s optical inspection system.

33. Regulation Review: USP Chapter 1 December 2013 will see the introduction of a new USP standard for labelling drug vials. Markus vor dem Esche of West Pharma explains what’s required. 34. Product Focus: Drug delivery Round up of news including anti-static compounds, engineering polymer selection, parenteral nutrition, cyclic olefin copolymers and Makrolon connectors. 40. Product Focus: Opthalmics An article about silicone intra ocular lenses (IOLs) by NuSil and an snapshot of a new contact lens material from Bausch & Lomb. 45. Design 4 Life: SLA at 150 μm IDC Models uses stereolithography to produce a microfluidic protein sampler. 46. Doctor’s Note: Clinical input Renfrew explain how by engaging with NHS patients, carers and clinicians it has excelled in clinical design. 48. MD&M East: Celebrating 30 years Stephen B Wilcox looks back to MD&M’s beginnings, American Kuhne describe automatic die centring technology, what makes a good notification period for changes to material formulations, polymer marker bands for catheters and news from exhibitors. 58. Events: Diary June-July 2013 diary and Innoplast’s second US medical plastics conference.

Online and in digital MD&M East exhibitor news—page 48 Disclosure: Medical Plastics News may charge 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. MAY-JUNE 2013 / MPN /3

EDITOR’S LETTER

CREDITS

Medical Plastics News polls readers to compare biocompatible polymer brands with one another

Sam Anson

editor | sam anson n an unprecedented piece of research, I have embarked on a poll of Medical Plastics News readers to compare biocompatible polymer brands against one another. The brands selected for the poll are those described by their manufacturers as medical grade, most of which are tested according to a number of sections of ISO10993, the international standard for biocompatibility, and USP Class VI, a set of standards for plastics used in healthcare applications produced by independent association United States Pharmacopoeia (USP). The number of tests performed under these standards varies from one brand to another. The polling process involves a survey of readers, asking them to comment on a list of brands of Source: Julian Brown press and public relations biocompatible polymers by saying photogtrapher, courtesy of UK-based charity Shelter. how well they have heard of them and, in turn, how favourably they feel towards them. The survey will also collect high level The categories of polymers are as follows: information from readers about their - Polyolefins; outlook on the medical plastics industry. - Engineering polymers (including PC, ABS, PS and PA, among others); Working directly with leading resin - Resorbable polymers; manufacturers and a top UK independent - Polyketones (PEEK, PEKK, PAEK); polling company—DJS Researh, which is - High performance polymers (eg PEI, PPS, registered with the UK government’s PVDF, LCP, PARA, PAI, PPSU); Information Commissioner as adhering to - Thermoplastic polyurethanes; that country’s data protection laws—I have - Silicone rubbers; designed the survey to ensure that it is fair - Thermoplastic elastomers; and representative of the biocompatible - PVC compounds; resin purchasing community. - Fluoropolymers; and One of the key challenges when - Ionomers. performing market research on polymer resins is ensuring that we group like products together. It is pointless comparing At the time of going to press, the survey brands of commodity polyolefins like was due to go live before the end of May. Bormed from Borealis with Invibio PEEK, for Respondents will be entered into a draw example, because they are completely for an iPad. different products sold at different price points for very different application areas. For more information or to request to take I have grouped polymers together so part in the survey please contact me at that meaningful comparisons can be drawn sam.a@rapidnews.com. between the many products branded as medical polymers. We are also qualifying respondents to ensure that they are upstanding members of the polymer purchasing community.

advertising | gareth pickering art | sam hamlyn production | peter bartley production | tracey roberts publisher | duncan wood Medical Plastics News is available on free subscription to readers qualifying under the publisher’s terms of control. Those outside the criteria may subscribe at the following annual rates: UK: £80 Europe and rest of the world: £115 subscription enquiries to subscriptions@rapidnews.com Medical Plastics News is published by: Rapid Life Sciences Ltd, Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE T: +44(0)1244 680222 F: +44(0)1244 671074

© 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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INDUSTRY NEWS | Roundup

European Medical Device Regulations Update Following the publication of a proposed replacement to Europe’s medical device regulations in late 2012, a number of industry groups have sharply criticised the proposal’s way of handling new high risk devices—the Scrutiny Procedure. The most vocal group opposing this is Europe’s association of medical device industries, Eucomed. Since the proposal was published Eucomed have released several campaigns in an attempt to drum up support for opposition to the Scrutiny Procedure. Eucomed’s criticism is that the procedure is over the top, and will stifle innovation. They say that with the scrutiny procedure in place, the quality of care in Europe is at risk and that Europe’s currently dynamic and responsive healthcare industry, admired by many in the world, will slow down where the release of new innovative life-saving devices are concerned. Having asked various observers in the medical device manufacturing industry, Medical Plastics News understands that Eucomed’s views are widely supported. Eucomed’s most recent campaign is called Don’t Lose the 3. The 3 refers to what Eucomed describe as a three-year

April 12, 2013 US and EU Trade Agreement Brings Medical Device Industries Together

advantage regarding when devices become available—saying they’re available in Europe three years before markets elsewhere in the world. An example which demonstrates this, a landmark invention, is Abbott’s landmark fully resorbable Absorb stent, which was launched in Europe in 2012 but has only just begun clinical trials in the USA. It is Medical Plastics News’s understanding that much of the work in developing and manufacturing the Absorb stent was done in Europe, notably Ireland.

“As the single largest free trade agreement in history, the TTIP [Transatlantic Trade and Investment Partnership] will promote EU and US international competitiveness, create jobs and grow our respective economies,” said Stephen Ubl, president of AdvaMed.”

April 26, 2013 Eastman Launch Sensitive Grade of Eastman 168 Phthalate free Plasticiser

“We are excited to bring to market the next evolution in non-phthalate plasticisers,” said Jon Woods, plasticisers business director, Eastman Chemical Company. “For the most sensitive applications, formulators need assurance of the high purity that Eastman 168 SG offers.”

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Eucomed’s statement on the thinking behind the campaign is as follows. “Today in Europe, people have access to life-saving medical devices three to five years sooner than other parts of the world. The reason for this is Europe’s unique decentralised device-specific approval system, which has proven to be as safe as other systems in the world and is saving and enhancing many lives every day.”

<< Eucomed hopes that its Don’t Lose the 3 Campaign will persuade Europeans to register opposition with their MEPs over the proposed Scrutiny Procedure for approval of high risk devices under the proposed European medical device regulations. >>

April 29, 2013 Senator Amy Klobuchar Talks Device Tax Senate Vote at Minneapolis Conference Ms Klobuchar said: “The senator from Indiana and I were some of the only ones standing up on the Democratic side saying “you don’t tax manufacturering like this—putting it on a revenue as opposed to profit will especially hurt the small start-up companies.”

May 3, 2013 First International PEEK Meeting Takes Place in Philadelphia, USA John Devine, marketing and technology director at Invibio commented, “Sponsoring gives our customers a better understanding about how new PEEK-based compounds and processing techniques can be exploited to improve upon today’s medical implants..”

ON THE PULSE

Sponsored By:

Antec Correspondent: Comparison of Polycarbonate and Copolyester Resins Reveals How Physical Properties Affect Mouldability

Energy/Part (kWh)

ABHI’s support of Mediplas—it is an important milestone for the medical plastics sector in the UK. Mediplas is the only major international meeting dedicated to medical plastics in Europe. This is in contrast with the USA, where there are a handful of wellestablished medical plastics conferences held throughout the country each year.” He added: “Medical plastics is a fast growing niche. In October 2012, despite a gloomy economic outlook, US business consultants Frost & Sullivan forecast that sales of medical plastics in the USA will grow by 5.2% a year to 2018.”

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and a medical copolyester resin—moulded into a part with precise features 160 typical in medical part designs. Through this process, the authors 120 considered the physical properties of the materials and how they influenced 80 their cycle times. They also compared the variability of moulded parts and the 40 energy consumed during production. These factors serve as bases for insights into the relative total costs to 0 co-PET manufacture medical devices PC HT-PC using each of the three resins. Tmold Tmelt Menego explained that in their efforts to determine the optimal cycle time for each << Figure 1: Comparison of melt and resin, they discovered that the cycle time mould temperatures to a material’s depends more on the modulus of a glass-transition temperature. >> material—particularly at the cooling temperature—than on the material’s heat << Figure 2: Energy consumption per resistance or viscosity. Due to their high stiffness properties, both the polycarbonate part measured during moulding of 20 parts of each resin. >> and high-heat polycarbonate resins achieved very rapid cycle times. On the 0.3 other hand, a copolyester with a lower modulus required a much longer cycle time. “We observed greater weight variability in the medical copolyester that we tested,” said Menego. “We feel that it’s at least 0.2 partially because of the greater viscosity fluctuations that copolymers undergo as well as the greater viscosity fluctuations with temperature change.” The study’s final experiment investigated the energy consumption of each of the 0.1 three resins as they were processed for use in a medical device. Energy consumption for the copolyester resin was found to be greater than the two polycarbonate resins, potentially due to the copolyester’s relatively longer cycle time. “Going against 0 conventional wisdom,” explained Menego, HT-PC PC co-PET “increasing the polycarbonate resins’ melt temperatures actually reduces the energy Mold T Temp e emp em Controllers ollers consumed per part.” Hot Runner DTg (°C)

t the largest technical conference in the plastics industry—Antec 2013, held on April 21-25, 2013 in Cincinnati, USA—a presentation was made which provided results of a comparison of the mouldability of polycarbonate and copolyester. The presentation was made by Ian Menego, an engineer at the US subsidiary of German polycarbonate manufacturer Bayer MaterialScience. The paper was entitled Material Properties and Their Influence on Moulding Productivity and Efficiency of Medical Resins and was held as part of the Injection Moulding session of the conference. The press release announcing the paper is as follows. Both physical properties and processability play key roles when injectionmoulded parts are mass produced. When producing medical parts, a consistent, high degree of accuracy is also vital. It is relatively simple to adjust a process to account for differences in molecular weight once that process is optimised for a specific polymer. It is much more complex to adjust the process for changes in polymers. Bayer MaterialScience engineers Ian Menego and Mark Yeager along with Bayer scientist Dr Pierre Moulinie performed a study to determine the processability of three resins and the effect their physical properties have on their mouldability. The study looks at three transparent resins—a standard medical grade polycarbonate, a high-heat polycarbonate

Machine

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500 DEVICES MADE FROM PEEK-OPTIMA APPROVED TO DATE IN THE USA | 80 in China

Invibio Celebrate

REGULATORY MILESTONE

THERE IS A GENERAL TREND IN ALL AREAS OF MANUFACTURING WHEREBY METALS ARE BEING REPLACED BY HIGH PERFORMANCE ENGINEERING POLYMERS. THE LATTER OFFER COMPARABLE TOUGHNESS AND RESISTANCE TO DEGRADATION BY CHEMICALS AND HIGH TEMPERATURES. BUT THEY ALSO OFFER DESIGNERS MUCH MORE FREEDOM IN TERMS OF GEOMETRIES AND PROCESSING WHILE BEING SIGNIFICANTLY LIGHTER IN WEIGHT.

n long-term implantable devices—for example spinal cages and rods, supports used to repair broken bones, and anchors for arthroscopy procedures—this trend is especially evident. An important material for applications like these is biocompatible PEEK. UK-based Invibio Biomaterial Solutions is the oldest and first manufacturer of this material, having begun production of its PEEK-OPTIMA implantable brand in 1999. In March 2013, the company’s director of regulatory affairs, Craig Valentine, announced that Invibio had achieved considerable regional regulatory milestones, particularly significant in the current regulatory climate. As of February 2013, the number of implantable medical devices manufactured from PEEK-OPTIMA and cleared for market in the USA reached 500, with more than 80 approved for market in China. Commenting on the announcement, Craig Valentine said: “The environment globally is more challenging than ever. Support of data and knowledge through the process can help device companies

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overcome regulatory barriers. We are committed to continuing our investments in resources to support medical device companies’ regulatory submissions across global markets.” He added: “Invibio maintains a Drug & Device Master file data at the FDA and has specific test data required for both China and Japan available to customers on file. This data is utilised by the regulatory authorities and provides the verification of PEEK-OPTIMA’s biocompatibility and biostability, which is supported by a dedicated global regulatory team.” The steady rise in the medical device industry’s use of PEEK-OPTIMA in spine as well as other applications is mirrored elsewhere around the globe as well with PEEK-OPTIMA based implantable medical devices approved in all the BRIC emerging markets. Valentine noted: “As medical device companies look for growth in these emerging geographies, as evidenced by recent market acquisitions, knowledge and experience of the regulatory pathway is an advantage to speeding access to market”. In 1999 PEEK-OPTIMA became the firstever biomaterial to replace the use of metal in spinal applications, when it was incorporated into an interbody fusion cage. Today, PEEK-OPTIMA interbody fusion devices are the standard of care in both lumbar (see image) and cervical fusion, and device manufacturers have selected it for use in other spinal applications including TDR (total disc replacement), spinal rods and interspinous devices. “As demonstrated by these global regulatory milestones, PEEK-OPTIMA continues to set an industry standard for biomaterials biocompatibility and quality. Invibio’s commitment to advancing medical device design innovation does not stop at our biomaterial capabilities. Our strong strategic alliances within the research and surgical community and across the global medical device industry, combined with our depth and breadth of biomaterials, and manufacturing capabilities enable Invibio to

<< Examples of devices made from PEEKOPTIMA implanted in a finger joint and in the lumbar spine. >> partner with our customers to access and accelerate their time to market in a challenging environment,” said Valentine. Since 1999, the versatile family of PEEKOPTIMA polymers have steadily gained market acceptance. Today these marketleading biomaterials are extensively used in over four million medical devices worldwide. The applications span trauma (plates, nails and screws for example); arthroscopy (for anchors and interference screws); orthopaedic (for structural components and finger (pictured), hip and knee components); cranial plates; dental; cardio, neurological and bariatrics. Dedication to the Medical Industry: The First International PEEK Meeting The First International PEEK Meeting convened on April 25-26, 2013, at The Union League hotel in Philadelphia, USA. The conference provided a global forum to share leading edge research on advancements in medical grade PEEK technology and clinical applications. A mix of medical device designers,

COVER STORY

Q&A with Dr John Devine, marketing and technology director at Invibio material scientists and clinicians specialising in biomaterials attended the meeting. Podium and poster presentations covered a wide range of PEEK topics including: properties, test methods and processing; biocompatibility; wear properties; modifications that alter cellular reactions; biomechanical performance of devices; and clinical performance and retrieval studies of PEEK based implants. The conference is a testament to the rate at which PEEK is becoming the preferred implant material across a growing number of medical applications. More than 35 abstracts that cover applications as diverse as posterior spinal rods, self-tapping suture anchors, joint replacement bearing surfaces and patient specific craniomaxilofacial implants were accepted for inclusion in the conference programme. This inaugural meeting was organised by the Implant Research Centre at Drexel University in Philadelphia and the engineering and scientific consulting firm Exponent and was supported by Invibio Biomaterial Solutions. Invibio reportedly strives to advance medical device innovation through support of robust PEEK research and development programmes. The company has been involved in many of the research projects presented at the PEEK International Meeting, through collaborations with industry and academia. John Devine commented: “Since its inception in 1999, Invibio has invested heavily in basic science and applied research related to high performance implantable polymers used in medical devices. Sponsoring the International PEEK Meeting not only gives researchers and industry a forum for sharing and discussing their research, but also gives our customers a better understanding about how new PEEKbased compounds and processing techniques can be exploited to improve upon today’s medical implants and practical advice for getting those new devices to market faster.”

Medical Plastics News caught up with John Devine at Invibio’s UK headquarters.

Q: How do you support material selection for customers? A: Invibio approaches this by asking three questions: i) will this material achieve the device performance criteria, ii) does it offer maximum design and manufacturing flexibility, and iii) will it present or negate any barriers to market. Our team invests substantial time with customers to understand their requirements and the objectives of the project. We’re in a unique position, as the company that introduced PEEKbased materials to the market almost 15 years ago. Invibio offers unparalleled depth of knowledge and breadth of experience in design for manufacture, production processes and the regulatory pathway. An applied example of this is the data maintained by Invibio, mentioned in the article [left]. The Drug & Device Master file data held at the FDA and specific test data required for both China and Japan is utilised by the regulatory authorities and provides the verification of PEEK-OPTIMA’s biocompatibility and biostability, which is supported by a dedicated global regulatory team. Involving Invibio at the outset of the project can optimise the project outcome in a shorter period of time. Q: What do OEMs expect from you as a supplier? A: OEMs expect Invibio to work together with their teams as solution partners, not only consulting on the

materials properties and processing options, but to work with them to validate processing steps in our laboratories and consultant on best practice approach for collecting data to support a regulatory submission. The partnership between Invibio and its customers is strengthening as OEMs expect Invibio to assist throughout the product development process. Q: How critical is device design when using PEEK in a device that previously used a different material? A: It is critical to consider the device design during the material selection process, as design features need to be compatible with the material of choice and the manufacturing route compatible to the material. It’s important to consider that some features are only possible through a particular manufacturing process, or additional manufacturing steps may be needed. An example: Cycle time to machine the part is one hour per part. To injection mould the same size part would be less than one minute. The faster the production will reduce costs per part, however production of design via the injection moulding route can be limited, and it may be necessary to include a design modification or secondary step to achieve the same design features. Typically within the medical device industry, every step requires validation, therefore the fewer steps the simpler the validation process.

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MATERIAL DIAGNOSIS PEEK | Update

Laser Micromachining of PEEK and Polyimides: Advanced Tube Geometries words | David Moore and David Gillen, Blueacre Technology

oday, engineering plastics are widely used in the medical device industry. Polyether-ether-ketone (PEEK) and polyimides (also known as Kapton) are among the more commonly used plastics for these purposes. The medical device industry is focused now more than ever on creating less invasive surgical tools, and this trend has caused a shift towards the miniaturisation of devices. Traditionally many medical implants have been manufactured from biocompatible metals such as stainless steels, titanium, and nitinol, mainly due to their physical characteristics. However engineering plastics are now leading a new frontier in implant design as the industry comes to grips with the advantages they can offer and gains experience in the complexities of machining these materials. As the transition to smaller devices takes place the advantages of polymers such as PEEK and polyimideÂ from a manufacturing perspective become clearer. Not only do these devices offer excellent biocompatibility, it is also possible to

extrude smaller tubes with plastic than with metal. This fact opens up a wide range of possibilities in terms of arterial implants, for example, as it becomes possible to offer products smaller in diameter than those which were previously possible using metals. Blueacre Technology based in Dundalk, Ireland, designs laser micromachining systems and provides contract laser micromachining services, mainly for the medical device industry. Blueacre Technology has performed extensive development in-house to optimise the laser machining of polymer tubing. The findings of these developments have revealed the advantages and manufacturing challenges that must be overcome for the efficient and effective laser machining of polymer tubing. For example, traditionally, laser machining is used in the manufacture of metallic arterial stents, and when optimised this process can offer both great flexibility and repeatability. However, current metal cutting processes almost always require post-processing to remove the laser machining dross.

When it comes to polymer machining the considerations are quite different. The developments that Blueacre Technology has performed mean that very little postprocessing of laser machined polymer tubes is required. For instance, it can be the case that the only post-processing required for laser machined plastics is cleaning in an ultrasonic bath, as opposed to metals for which it is normally necessary to utilise a high cost post-process such as electrochemical etching. This means that production costs can be significantly lowered for devices that can perform a similar function. In the medical device industry, metals have been used widely for many years, hence their material and machining characteristics are well known within the industry. For instance, the process of laser cutting of metallic stents has been very well developed, while on the other hand the laser micromachining of polymer stents requires the consideration of factors not normally encountered during metal machining. As polymers inherently have less Continued on page 15

<< Figure 1: PEEK stent which has been laser cut using Blueacre Technologyâ&#x20AC;&#x2122;s proprietary dynamic alignment system. Strut widths are as small as 20 Îźm. >>

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MATERIAL DIAGNOSIS Continued from page 13

Solid Concepts Adds High Temperature PEEK to Laser Sintering Materials Portfolio

stiffness than metals, polymers tend to move around significantly more than metals during laser machining. This problem becomes more significant when machining small features (less than 50 μm) on thin-walled tubes. Blueacre Technology has become an expert in the field of the machining of polymer tubing having developed proprietary advanced auto-alignment systems. These systems offer the ability to track the tube position in real-time, allowing for high cutting speeds while holding tight tolerances over long parts and offering accuracies better than 5 μm. While the mechanical alignment and stability of the laser cutting process is crucial, the quality and choice of the laser source is equally important. Considerations in choosing an appropriate laser source for any application include the colour of the emitted light, how the laser is operated (continuous wave or pulsed) and, if pulsed, the length of the pulse duration.

<< Figure 2: Polyimide stent laser cut using a pulsed UV laser source. The only post-processing required is cleaning in an ultra-sonic bath (Photo by Tomasz Staszak, 2013). >> The colour or the emitted light strongly relates to how the light is absorbed and how the material is machined. UV lasers are very effective at machining polymers as the light is both well absorbed and has sufficient energy to break the inter-atomic bonds of the material, allowing for very clean cuts. Pulsed laser sources that operate with short pulse durations (less than 50 nanoseconds) also offer improved machining characteristics as it is possible to finely control the amount of heat generated in the work piece during machining, thus reducing any heat affected zones (HAZ) and reducing any effects on material integrity. David Moore is R&D manager and David Gillen is managing director at Blueacre Technology, a supplier of laser machining equipment and services in Ireland.

ccording to a report published in April 2013 on IndustrialLasers.com, USA-based selective laser sintering (SLS) service provider Solid Concepts is now successfully working with PEEK HP3, a grade of PEEK from German additive manufacturing machinery and materials manufacturer EOS. EOS offer the only available laser sintering machine in the world, the EOSINT P 800, for processing high temperature materials, including its own PEEK brand PEEK HP3. According to the report, PEEK is the first true high performance polymer to be offered by Solid Concepts with additive manufacturing technologies. Parts created with PEEK are compliant with flammability requirements for aircraft cushions FAR 25.853 as well as the US Underwriters Laboratory (UL) plastics flammability standard UL 94 V0, and have very good chemical and hydrolysis resistance. The addition of PEEK to Solid Concepts’s SLS technology offerings adds the full benefits of complex geometries with high strength and heat deflection. Additive manufacturing of PEEK maintains the same high performance properties as moulding, extrusion and machining applications such as high stiffness and temperature resistance up to 240°C (464°F). Prototypes and production parts built with PEEK are said to not only withstand chemical deterioration and damage, but also maintain good flexural and compressive strength at temperatures well beyond the operational range of standard nylonbased SLS parts. Solid Concepts provides rapid prototyping and custom manufacturing services, with capabilities in PolyJet, stereolithography (SLA), Z-Corp, SLS, direct metal laser sintering (DMLS), fused deposition modelling (FDM), CNC models and patterns, QuantumCast advanced cast urethanes, and composites.

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MATERIAL DIAGNOSIS PEEK AND OTHER HIGH PERFORMANCE POLYMERS IN MEDICAL DEVICES | Update

News from Manufacturers of Long Term Implantable Polymers PEEK-OPTIMA Ultra Reinforced Promotes Optimal Clinical Outcomes by Addressing Persistent Challenges to Maximal Implantation Success UK-based Invibio have written about how its carbon fibre reinforced brand of PEEK, PEEK-OPTIMA Ultra-Reinforced, an alternative to metal in implantable devices, is promoting optimal clinical outcomes by addressing “persistent challenges to maximal implantation success”. Invibio’s article is as follows. References are available on request. The use of metal-based medical devices in trauma applications is the current gold standard in patient treatment for internal fracture fixation (fracture plates and intramedullary nails). Although quite effective the use of metal presents an ongoing challenge to long-term implantation success1, 2, 3, 4. Optimal clinical outcomes could benefit from improvement in persistent shortfalls associated with use of metals. Challenges with metals: Chief among these shortfalls is implant failure, due to fatigue performance challenges and the high stiffness of metal. Cold welding and galvanic corrosion also present difficulties during the removal or revision of devices due to the inherent properties of metal. Another challenge is the poor imaging characteristics (radiopacity) of previous plate materials (which could contribute to improper placements that preclude appropriate fracture site coverage, obscured screw placements hampering optimal construct strength and stability, and masked imaging hindering healing assessment accuracy). There is a clear clinical need for non-metallic biomaterials that speed and enhance healing, enable dynamic loading, promote bone conservation, and improve fatigue performance and healing assessment.

<< Invibio’s carbon fibre reinforced brand of PEEK is helping surgeons reduce metal implant failure due to fatigue performance challenges and the high stiffness of metal. >> A novel alternative to metal: Designed to the highly specific demands of trauma applications, Invibio’s PEEK-OPTIMA Ultra-Reinforced material combines the high performance material properties of PEEK-OPTIMA natural polymer with carbon-fibre reinforced strength (similar to that of metal, but with a bone-like modulus). Dynamic testing of trauma fixation devices demonstrates that PEEKOPTIMA Ultra-Reinforced has a higher fatigue strength compared to titanium, while providing radiolucent properties that enable proper plate placement to assure appropriate fracture site coverage, precision screw placements to enable optimal construct strength and stability, and artifact free imaging for appropriate healing assessment during follow-up.

Compared to radiopaque implants made of metal, PEEK-OPTIMA UltraReinforced implants allow for better bone fragment visualisation during image guided intraoperative fracture reduction procedures. Implant radiolucency also aids in post-operative visualisation of callus formation for improved healing assessment. Invibio’s revolutionary, non-corrosive polymer also provides benefits that address the cold welding and galvanic corrosion issues that have plagued previous generations of trauma plates. No corrosion enables easier screw removal and promotes smoother device retrieval uneventful to the benefit of surgeon and patient. Biologically inert and with low tissue adhesion, PEEK-OPTIMA Ultra-Reinforced reduces tissue adhesion to the implant, simplifies implant removal, and allows for greater conservation of the bone during surgical revision procedures. The inert nature of PEEK-OPTIMA Ultra-Reinforced additionally allows for sterilisation through all standard technologies, and is backed with almost 15 years of proven biocompatibility. Manufacturing pathway: PEEK-OPTIMA Ultra-Reinforced brings the material characteristics and performance capabilities to address the issues and shortfalls associated with metal, while advancing surgical techniques and approaches, and optimising patient outcomes. Invibio is a true biomaterials solution provider and device partner offering the expert capabilities to deliver commercial PEEK-based trauma devices. PEEK-OPTIMA Ultra-Reinforced meets the requirements of ISO10993 standards for long-term implantable medical devices and are included in the FDA master file. Testing demonstrated no evidence of cytotoxicity, systemic toxicity, irritation or macroscopic reaction response. Continued on page 18

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P n Partner artner er With With i TThe he e Leader Leader ea IIn 3D Bioprin Bioprinting ting EEquipment quipment TTo o lear learn n more more about our capabilities in 3D Biopr inting, please visit our website website at: at: Bioprinting, w ww.envisiontec.com www.envisiontec.com Or call us at at +49 2043 9875 0

MATERIAL DIAGNOSIS Continued from page 16

Solvay and Evonik Announce FDA Approvals of PEEK Spinal Cages Polymer manufacturers Solvay Specialty Polymers, part of Belgian chemical company Solvay, and Evonik, based in Germany, have provided details of PEEK spinal implants approved for sale in the USA by the FDA. The details from Solvay Specialty Polymers regard a device made from that company’s Zeniva brand of PEEK by Maxim Surgical, described by Solvay as a new designer and manufacturer of spinal implants based in Texas, USA. Maxim Surgical has received 510(k) clearance for its new MaxFuse-C cervical interbody fusion system (see image) machined from Zeniva PEEK rods. Zeniva PEEK—part of Solvay’s line of Solviva biomaterials—is said to have a modulus very close to that of bone plus excellent toughness and fatigue resistance. The press release providing the information reported that the FDA clearance was based, in part, on Solvay’s master access file for Zeniva PEEK. The MaxFuse-C cervical interbody fusion system is hollow so that bone can grow through the device, fusing the adjacent bony surfaces of the vertebrae. The cervical spacer for the spinal fusion market is Maxim Surgical’s first orthopaedic implant. Evonik’s announcement, made at Medtec Europe in February 2013, is that the FDA has approved an implantable spinal cage made from its Vestakeep brand of PEEK. This is the first spinal cage to be made from Vestakeep to have been approved by the FDA. The associated premarket notification 510(k) has been successfully issued and, according to Evonik, this will make it far easier in the future for medical device manufacturers looking to use Vestakeep to get approval. Evonik describes Vestakeep PEEK as having good processability properties, lending itself well to injection moulding

and cutting processes in production and supports freedom of design in the development of new implant technologies. In general, PEEK offers numerous advantages over metals such as titanium for spinal implants. The material offers many important benefits including biocompatibility, chemical inertness, and a modulus of elasticity that is close to that of bone. Solvay points out that, based on biocompatibility testing, Zeniva PEEK demonstrates no evidence of cytotoxicity, sensitisation, irritation, or acute systemic toxicity, and meets ASTM F2026, the standard specification for PEEK polymers for surgical implant applications. It also boasts high strength and stiffness and has radiolucent properties which enable x-ray procedures without interference. The MaxFuse-C cervical interbody fusion system is machined from 16-mm and 20-mm diameter Zeniva PEEK rods. It is available in two footprints—15 mm x 13 mm and 17 mm x 14 mm in both neutral and six degree lordotic options—offering surgeons flexibility in meeting different patient anatomies. The system also provides a large graft window which facilitates a bigger graft volume for fusion. Maxim offers an easy-to-use single tray system which includes simplified instrumentation for all of their available implant options. Maxim plans to explore the future use of Zeniva PEEK in a range of other spinal fusion products. “We’re excited about the commercial success of Zeniva PEEK in the orthopaedic implantable market,” said Shawn Shorrock, global healthcare market manager for Solvay Specialty Polymers. “The ongoing acceptance of Zeniva PEEK has validated our approach to the orthopaedic implant market and we’re encouraged by the momentum we’ve generated.” << These cages are machined from Zeniva PEEK by Texas-based Maxim Surgical, a privately held medical device company focused on the development of innovative solutions for the spinal fusion device market. >>

18/ MPN / MAY-JUNE 2013

<< This injection moulded Morphix suture anchor is made from a proprietary shape memory PEEK material called Altera. >>

MedShape Develops Shape Memory PEEK for Suture Anchors and Soft Tissue Fasteners A US orthopaedic implantable device manufacturer, MedShape, has developed a proprietary shape memory PEEK material called Altera. The material is based on Solvay’s Zeniva PEEK. The company has used Zeniva PEEK for two new products. The first, an anchor for sutures for tendon and ligament repair, is the Morphix anchor. The second is the ExoShape soft tissue fastener for reconstruction of the anterior cruciate ligament (ACL), one of the four major ligaments of the human knee. MedShape is the first to develop and commercialise FDA-cleared devices manufactured from shape memory polymers. Using Zeniva PEEK as the base material, Altera reportedly allows devices to enter the target surgical site in a compact geometry and then be triggered to deploy with minimal mechanical force into the optimal geometry for fixation.

RADIOLUCENT R ADIOLUCENT

CF CFRP R P IINSTRUMENTS N ST R U M E NT S

<< The ExoShape soft tissue fastener is made from PEEK and is designed for tissue fixation involved in ACL reconstructions. >> The Morphix suture anchor is injection-moulded. It is said to offer improved cyclic loading stability, which means less chance of the surgical repair failing during the healing process. The Morphix suture anchor deploys dynamic wings with a high bearing area into the cancellous bone beneath the cortical shelf for improved device fixation. According to MedShape, active rehabilitation can cause anchor migration and loosening which may lead to clinical failure of the repair. Furthermore, laboratory testing has reportedly shown that traditional anchor pullout can occur below 1,000 cycles at a load less than 50% of initial pullout strength. The Morphix suture anchor is said to respond positively to cyclic loading due to its dynamic geometry and stored shape memory strain. After implantation, cyclic loading stimulates the Morphix suture anchor to attain its permanent, fully open “zero-strain” state. This results in continued wing expansion and retention of initial pullout strength, according to the company. The shape memory Morphix suture anchor is delivered pre-compressed in a low-profile geometry that inserts easily into the surgical site, utilising a simple and reproducible tap-in technique. It is available in diameters of 2.5 mm, 3.5 mm, 4.5 mm, and 5.5 mm and a range of suture and needle configurations. The ExoShape soft tissue fastener is designed for fixation of the soft tissue graft on the tibial side of the knee joint in ACL reconstructions. It is said to offer unparalleled accuracy to ensure the most anatomic and stable reconstruction, strong fixation, complete graft protection, simplified insertion, and total biocompatibility. The ExoShape sheath is machined from 6 mm, 9 mm, and 13 mm Zeniva PEEK rod.

The ExoShape soft tissue fastener reportedly provides a straightforward, non-rotational insertion and expansion which eliminates “graft wrap” and preserves the preferred graft orientation. The graft bundles stay exactly where they’re placed, promoting a more anatomic reconstruction, according to Kathryn Smith, MedShape marketing manager. Other fixation devices can drive the graft back up the tibial tunnel, introducing unwanted graft laxity. The ExoShape soft tissue fastener’s “closed force loop” design eliminates this problem by preventing retrograde force being applied to the graft, according to the company. “We’ve been very pleased to work with MedShape as they develop improved approaches for orthopedic fixation devices,” said Shawn Shorrock, global healthcare market manager for Solvay Specialty Polymers. “The ongoing acceptance of Zeniva PEEK has validated our approach to the orthopaedic implant market and we’re encouraged by the momentum we’ve generated.” The manufacturing site for Zeniva PEEK and other Solviva Biomaterials in Alpharetta, Georgia, USA, is ISO13485 registered and the relevant aspects of current Good Manufacturing Practices are also applied. Solvay says its biomaterial manufacturing processes are carefully validated and enhanced controls provide product traceability. In addition, all materials are tested in a lab accredited to ISO17025—the general requirements for the competence of testing and calibration laboratories. Solvay Announces TranS1 VEO Interbody Fusion System Uses Spinal Implants Made of Solvay’s Zeniva PEEK Another example of Solvay’s biomaterials being used in medical devices is in US minimally invasive spinal implant manufacturer TranS1’s VEO direct lateral access and interbody fusion system. The system incorporates a lumbar fusion cage implant made from Zeniva PEEK and a tubular retractor made of Solvay’s Radel polyphenylsulfone (PPSU) resin for radiolucency and the ability to withstand repeated steam sterilisation. TranS1’s VEO is a direct lateral fusion Continued on page 20

C A R B ON F I B R E R E I N F O R C E D C OM P ON E N T S M A DE FROM PEEK , PE I A ND EPOX Y

ISO 9 0 01 ISO 134 85

· Biocompatibility Biocompatibilit y ISO ISO 10993-1 10993-1 · Hot Hot steam steam sterilisable sterilisable · Highest Highest precision precision and and dimensional dimensional stability stabilit y · Best Best price-performance price -per formance ratio ratio We support you with the realization of your design ideas and manufacture final products from carbon laminates for applications in the following areas: · Orthopaedics and trauma instruments · External fixators · Wound retraction systems Benefit from our many years of experience: Gsell, your partner with the Plus.

CH -5630 MURI AG + 41 56 675 40 40 www.gsell.ch w w w.gsell.ch · info @ gsell.ch

MATERIAL DIAGNOSIS Continued from page 19

manager for Solvay Specialty Polymers. “In addition, the ongoing acceptance of Zeniva PEEK has validated our approach to the spinal market and we’re encouraged by the momentum we’ve generated.” Meanwhile, TranS1 was able to draw again on Solvay’s extensive product offering by using Radel PPSU for the tubular retractor that was designed to prevent soft tissue intrusion. The highperformance material reportedly provides superior strength, high thermal performance, chemical resistance, and the ability to withstand repeated steam sterilisation. The retractor is made from 50 mm diameter Radel PPSU rod stock in lengths of 100 mm, 120 mm, and 140 mm.

<< TranS1’s VEO is a direct lateral fusion system for the lumbar spine. It incorporates a PEEK cage and a tubular retractor made from PPSU. >> system for the lumbar spine. VEO’s interbody cage is made from rod stock offered in various sizes, including widths of 17 mm and 22 mm and lengths from 40 mm to 60 mm. The implant has a large centre channel to allow bone growth through the device, fusing the adjacent bony surfaces of the vertebrae. The VEO direct lateral system is said to bring clear and direct visualisation to lateral fusion surgery. Through a combination of direct psoas visualisation and clear lateral fluoroscopic views, the system offers complete visualisation of the operative site. This approach was designed to help minimise iatrogenic trauma to the psoas muscle and the nerve plexus to help reduce the risk of postoperative complications. The system offers a comprehensive portfolio of interbody implants in both parallel and lordotic angles to match various anatomical dimensions. The interbody implants contain five tantalum markers for precise fluoroscopic visualisation. The large centre channel is readily visualised and can be easily evaluated for progression of fusion. “This is a perfect example of the value Solvay brings with its breadth of products, expanding the options for designers in terms of design flexibility and performance optimisation,” said Shawn Shorrock, global healthcare market 20/ MPN / MAY-JUNE 2013

Call for Abstracts Involving Technical and Clinical Advances in Medical Grade UHMWPE for Orthopaedic Implants The organisers of the sixth International UHMWPE Meeting—the University of Torino, the Implant Research Center of Drexel University and Exponent—are inviting authors to submit presentation proposals on advancements in medical grade ultra high molecular weight polyethylene (UHMWPE) technology and clinical joint replacement applications. Engineers, scientists and clinicians from academia and industry are invited to present leading edge research during the said meeting on October 10-11, 2013, at the congress centre Unione Industriale in central Torino, Italy. Sponsored by Ticona, the manufacturer of GUR implantable UHMWPE, the meeting will focus on clinical and retrieval studies of standard, crosslinked and stabilised UHMWPE. There will be a special emphasis on performance of thin acetabular liners and knee arthroplasty, advances in vitamin E and new antioxidant technologies for UHMWPE, structural composites and woven fibre applications of medical grade UHMWPE, and advances in biologic aspects of UHMWPE wear debris incorporating vitamin E. Quadrant Provide Machining PPSU Guidelines Jack Sharp, tooling manager at the US subsidiary of Quadrant EPP, a company which specialises in machined plastics, has written a guide on how to achieve the best

machined finish for PPSU parts. The guide is as follows. PPSU has virtually unlimited resistance to steam sterilisation making it ideal for medical devices which come in contact with the body or bodily fluids. This FDA and USP Class VI compliant material also withstands the rigours of repeated use and demonstrates high mechanical strength and stiffness. Today, various colours of PPSU are being used for orthopaedic trial implants and other surgical tools where size identification is required. Improper machining of criticalsized coloured PPSU components can result in poor surface finish, improper tolerances or parts that do not meet customer specifications—and ultimately affect your bottom line. To achieve the best machined finish and ensure proper dimensional control for critical tolerance parts, the incoming material should be allowed to stabilise in the environment in which it will be machined for 24 hours. Correct tooling, feeds and speeds are critical and using a water-based coolant is highly recommended. For very tight tolerance work, roughly machine components to within 0.05-0.075 mm (0.020-0.030 inches) on all surfaces and leave the parts to rest for up to 48 hours to allow machined-in stress relief. Best results can be achieved with solid carbide, uncoated (polycrystalline diamond turning inserts work extremely well) cutting tools (two flute end mills and turning tools with 0.031-inch radius) because of their rigidity and long cutting life—although high speed cutters can be used. Coated tooling is not recommended for use with PPSU as the cut will not be as sharp and may “pull” at the material rather than cutting. This may impart excess heat and material movement causing a loss of stability. Whether turning, milling or drilling, process at the highest reasonable RPM and use a feed rate for roughing of 0.010 to 0.020 inches per revolution. For finishing, feed rates should be 0.003 to 0.007 inches per revolution. This high speed approach moves the cutting tool quickly across the material and keeps heat generation to a minimum. Remember these are just guidelines or starting points and may not be the optimum conditions for all types of equipment and setups.

Think Big. Think Solvay. Leading Supplier of High-Performance Healthcare Plastics for Over 20 Years When it comes to material selection, why limit your choices? With Solvay, you get the industry’s biggest selection of the highest performing plastics offered for medical devices. High-Performance Medical Grade Plastics

Solviva Biomaterials* for Implantable Devices

• Radel® PPSU

• Zeniva® PEEK • Veriva® PPSU • Eviva® PSU • Proniva® SRP

• Udel® PSU • Ixef ® PARA • AvaSpire® PAEK

www.solvay.com

• KetaSpire® PEEK

* Only products designated as part of the Solviva® family of biomaterials may be considered for use as implantable medical devices.

ADDITIVE MANUFACTURING IN PLASTICS | A Beginner’s Guide

A Guide to Additive Manufacturing FOR PLASTICS ENGINEERS words | Phil Kilburn, medical markets manager at 3T RPD

here are a number of terms used to describe the process of building a solid object, layer by layer, but the principles are the same. The object to be created is first modelled in a 3D data format (known as a CAD design), then the data is sliced into thin layers and transferred to a machine which then gradually builds the object, one layer at a time, slice on top of slice, using a range of materials from nylon through to steel and titanium. Known most widely in the consumer press as 3D printing, amongst the industry it is more frequently known as additive manufacturing or rapid prototyping. Such printers range in sophistication from a home version that can be bought for US$1,000 to a full industrial 3D printer which can cost anything up to US$1 mn. Additive manufacturing was originally conceived as a prototyping technology which produced models to demonstrate fit, form and function. But things have developed to such an extent that in 2013 the range of sectors and uses that parts produced by additive manufacturing is wide and continuing to expand. For example, end-use parts manufactured using the technology are on cars racing in Formula 1, are in space on experimental vehicles and are implanted into humans. In addition to these bespoke utilisations, the technology is being used to build production parts for engines, manufacturing lines and consumer products, all of which would be either impossible or prohibitively expensive to produce by traditional, subtractive technologies. Types of additive manufacturing technologies There are a range of types of additive manufacturing systems, including stereo lithography (SLA), fused deposition modelling (FDM), 3D printing, and plastic laser sintering (also known as selective laser 22/ MPN / MAY-JUNE 2013

sintering—SLS). The systems build parts in a range of materials including epoxy-based materials, ABS, wax, polystyrene, ceramic and nylon. All the systems conform to the principles of building layer by layer, but vary in how the materials are applied (for example, as a fine powder, liquid polymer or molten plastic) and how they are cured (for example, by melting with a laser or activating UV resin with a laser). The material most commonly used in non-implantable medical applications is nylon 12. Parts made with nylon 12 have good long-term stability, offer resistance to most chemicals and are easily sterilised. High levels of complexity are achievable in the finished part and the material delivers good impact strength and durability. Tensile and flexural strength combine to make tough plastic parts, with the flex associated with many production thermoplastics. Nylon 12 is non-hygroscopic, thereby negating the requirement to seal the surface on components being used with liquids. The process by which a part is created is that a fine layer of nylon powder (between 0.1 mm and 0.15 mm thick) is laid on to a base platform. One or more powerful lasers melt the fine powder in accordance with the outline described by the sliced data which creates solid nylon where the laser has acted leaving the remaining nylon as powder. A further layer of nylon powder is then applied and the laser melting process is repeated. As each layer is completed, the platform upon which the process is taking place drops by the depth of one layer. At the end of the build cycle, the platform has a cake of nylon sitting on top of it—of which some is still fine powder sitting around a series of solid parts. The platform is removed, cooled, and the parts removed and airblasted to clean off the loose powder. A limiting factor to the current technology is the boundary box of the build chamber of

the machine—700 mm x 380 mm x 580 mm, but this is an area that continues to develop. At the point the part is removed from the powder cake and cleaned, it can be used as a finished piece or have a number of post-process finishes applied to it. These include colouring, plating in metal, surface finish refinement and having inserts applied. However, the finished piece can have hinges and threads designed in to the part from the outset, meaning that designers have a wide range of options available to them. Tips in designing for additive manufacturing When designing parts for additive manufacturing, in addition to designing in specific features that are required, there are a number of pointers to help produce accurate and appropriate designs. For example, a minimum wall thickness of 1 mm is advised and a minimum layer thickness of two layers. Many file types can be accepted, but whether the source is a CT scan or Google Sketchup, the data will be translated into an STL file—a standard triangulation language file—which represents all points on the part via triangles. Scaling of a part is crucial and the team at 3T RPD works with all customer data to ensure that accuracy is maintained as the heat generated by the build process will result in parts shrinking during cooling. Some examples of additive manufacturing in the medical market Over the last ten years the use of additive manufactured models for the treatment of craniomaxillofacial trauma and reconstruction has become the gold standard. The use of additive manufacturing models has resulted in a reduction in the time the patient spends in theatre, a shorter recovery and an improved clinical outcome for the patient.

CLEAN MACHINES << The Facemaker project, worked on by UK-based rapid prototyping bureau 3T RPD uses additive manufacturing techniques, giving a new way to produce facial prosthetics. Credit 3T RPT. >>

These models are used in a variety of ways: Implants: The patient is scanned using a computerised tomography (CT) scanner. This generates thin slices though the body. The slices from the scans are virtually reconstructed using computer software to recreate the scanned area as a 3D model. This model is then built with an additive manufacturing machine which re-assembles the slices to give an accurate 3D representation of the patient. The models are then used by the maxillofacial technologists to sculpt the implant, initially using wax. The wax is either cast to manufacture the final implant directly or used to manufacture a press tool to produce a shaped titanium plate. Alternatively, using metal additive manufacturing, a cranial plate can be built directly from the CT data—a technique that has already been successfully undertaken for a patient in a collaboration with Nottingham’s QMC and 3T RPD. Guides: Surgeons are also using 3D CAD models to design drill and saw guides. The guides are custom designed using the CT data from the patient. They are then manufactured using additive manufacturing. This has improved the placement of implants and allowed the surgeons to accurately cut and place bone grafts. The models and guides also help surgeons plan surgery before entering theatre, debate the approach with colleagues and also discuss the surgery with the patient. A model produced by 3T RPD for a UK hospital recently resulted in a change of approach to surgery and a much improved outcome for the patient.

Prosthetics: With the development of photogammetry, the capture of a 3D surface is as quick and simple as taking a picture. Images taken by this process are automatically generated into 3D models. 3T RPD worked on a project to develop this application to create a new way to produce facial prosthetics—The Facemaker Project— with a number of UK partners including Nottingham University, Queens Medical Centre in Nottingham, and UK design software specialist Delcam. The outcome allows the data generated to be used in many applications that have revolutionised the manufacture of prosthetics. For example, the surface data can be offset and used to manufacture a formtool that can be used to manufacture burns masks. A further example is to take the data of a healthy ear, then mirror it to produce a representation of a replacement ear that can be used to produce a mould tool for a prosthetic replacement ear. In a more extreme example, the process was used to capture data from the face of a father and son. The father had lost his nose and part of his face due to complications with a tumour. The son’s face was morphed to that of the father and the resulting model used to produce a successful prosthetic.

Selected Biocompatible Additive Manufacturing Material Brands Tested According to ISO10993 or USP Class VI 3D Systems VisiJet EX200

Crystal—clear

3D Systems VisiJet MP200

Stoneplast—clear

3D Systems Accura ClearVue for SLA

clear and selective colouring, amber

3D Systems VisiJet Clear for SLA

clear and selective colouring, amber

3D Systems Accura Y-C 9300R

selective colouring, pink

3D Systems Dreve Fototec SLA and SLE

hearing aid material, clear, skin tone, red, blue

3D Systems DuraForm PA SLS nylon

white

3D Systems DuraForm PRO SLS nylon

white

DSM SOMOS Watershed XC11122

epoxy-based photopolymers

DSM SOMOS Protogen 18420

liquid ABS-like photopolymer

DSM BIOCLEAR

EnvisionTec E-shell 600

clear tough polymer ABS-like low viscocity photopolymer, colours include pink, tan, beige, cocoa and mocca clear, sterilsable, tough. Colours include water, rose, red and blue Clear guide—Clear rigid

EOS PA2200

nylon

Fortus PC-ISO

clear sterilisable polycarbonate

Fortus ABS-M30i

ABS

Objet MED610

PMMA

OPM OXPEKK (implantable)

similar to PEEK

EnvisionTec E-shell 200 EnvisionTec E-shell 300

MAY-JUNE 2013 / MPN /23

CLEAN MACHINES ADDITIVE MANUFACTURING | Customised Dental Drills, Dental “Temporaries”, Hearing

Aids and Tissue Engineering Scaffolds

Trends in 3D Printing of Customised Medical Devices words | Jenna Franklin, marketing and event coordinator, EnvisionTec

<< A 3D printed skeleton of the foot. Photo credit: Stratasys. >>

printing technologies have opened up the capabilities for customisation in a wide variety of applications in the medical field. Using biocompatible and drug-contact materials, medical devices can be produced that are perfectly suited for a particular individual. Another trend enabled by 3D printing is mass customisation, in that multiple individualised items can be produced simultaneously, saving time and energy while improving manufacturing efficiency. Early adopters of 3D printing technology for the mass production of customised medical devices include dental laboratories and hearing aid manufacturers. In addition, preclinical research in materials science, neuroimaging, toxicology, and a diversity of other disciplines is rapidly increasing, with 3D printing enabling the development of revolutionary ideas and methods. Dental laboratories have adopted 3D printing to increase production efficiency and precision in the manufacture of medical

24/ MPN / MAY-JUNE 2013

devices. The introduction of 3D printing to a digital workflow decreases lead time by speeding up the flow of patient diagnostic information between the dentist and the dental lab. To begin the process, a dentist scans the patient’s mouth to quickly and comfortably obtain precision data for the dental laboratory. The data is analysed using dental software such as 3Shape CAMbridge or DWOS-RPM from Canadian dental CAD/CAM software supplier Dental Wings, based in Montreal, and a solution is developed for the patient. The laboratory can immediately and seamlessly use the data to begin production of the necessary components for the case. Multiple cases can be produced simultaneously, allowing laboratories to fulfill their customer requirements quickly and with consistent quality. Advances in materials research have led to the availability of 3D printing options that are biocompatible and certified for use directly within the mouth, for both short and

long-term use. One such material is E-Shell 600 (trade named Clear Guide) for use on the EnvisionTEC Perfactory series of 3D printers. Clear Guide is certified by United States Pharmacopoeia (USP) Class VI testing for the production of drill guides on EnvisionTEC’s Perfactory mini desktop 3D printer. The surgical drill guides are medical devices which allow for precise drilling into a patient’s mouth for the placement of dental implants. Each drill guide must be carefully planned for the individual case and biocompatibility is essential, as it will remain in the patient’s mouth in contact with exposed tissue and nerves during the implant process. The spectral and light energy output of the Perfactory 3D printer is a critical component for ensuring biocompatibility, thus linking both the machine and the material to the USP Class VI certification. Dental temporaries represent another application area for biocompatible 3D

printed materials. The dental implant process requires significant healing time between the original surgical preparation and the final implant procedure. This healing process may take from several months to a year depending on the need for bone grafting to ensure the viability of the implant. During this period of time, a temporary crown may be placed to preserve the gum architecture surrounding the implant location as well as to serve an aesthetic function. Due to the length of time the temporary crown will reside in the mouth, biocompatibility as well as material stability is required. EnvisionTEC’s E-Dent material for use on the Perfactory line of 3D printers was the first CE (Conformité Européenne) Certified and 510(k) FDA-approved 3D printed material for the purpose of creating temporaries. E-Dent comes in three commonly used dental shades (A1, A2, and A3). The structures can be cut back and then layered using any light-curable shade composite in order to match the existing surrounding teeth. 3D printing allows for the production of highly accurate temporaries in a matter of hours, saving both time and labour. The hearing aid industry boasts perhaps the highest “installed base” of customised final consumer devices that were produced using 3D printers. The E-Shell line of liquid photo-reactive acrylates is both CE-certified and classified as Class IIa biocompatible according to ISO 10993/Medical Product Law for Hearing Aids when used according to the published guidelines on an EnvisionTEC Perfactory 3D printer. Available in over fifteen colours, including transparent and opaque options, the E-Shell line of materials are water and perspiration-resistant. This range of materials enables the hearing aid manufacturer to offer a custom patient solution in terms of both fit and skin colouration. EnvisionTEC Perfactory and 3DBioplotter systems have been used since 2002 for a variety of medical applications. Most research done to date using our machines has been in the pre-clinical setting, yielding many publications (abstracts provided upon request) by pre-eminent scientists from the materials science, neuroimaging, and toxicology disciplines. In the clinical setting, patient CT or MRI scans are used to create STL files to print solid 3D models which can then be used as templates for implants. Tissue engineering and controlled drug release applications require 3D scaffolds

with well-defined external and internal structures. The 3D-Bioplotter from EnvisionTEC can fabricate scaffolds from a wide array of materials, from soft hydrogels over polymer melts to hard ceramics and metals. The technique may be described as the deposition of material in three dimensions using pressure. Materials range from a viscous paste to a liquid, and are inserted using syringes moving in three dimensions. Air or mechanical pressure is applied to the syringe, which then deposits a strand of material for the length of movement and time the pressure is applied. Parallel strands are plotted in one layer. For the following layer, the direction of the strand is turned over the centre of the object, creating a fine mesh with good mechanical properties and mathematically well-defined porosity. By permitting the use of pastes, hydrogels, melts, and any other liquid which may be quickly solidified, this technology enables a wide range of 3D printing applications. The building platform may be a glass plate, a cooled metal surface or even a liquid, which not only allows for solidification through ionic transfer and other cross-linking methods, but also provides buoyancy support for plotted strands during the solidification process. By controlling the strand thickness, precise drug releasing properties are achieved. The strand thickness is also relevant when adding cells to the process itself, as the distance between the surface of the strand and the cell position is crucial to its proliferation. Finally, the design of the interior of the object will strongly affect its mechanical properties, which may be changed to mimic the type of tissue it is replacing or supporting. In summary, there are a number of existing application areas for 3D printing that require specialised materials that meet rigid and stringent biocompatibility standards. A range of materials for the hearing aid and dental industry already meet those requirements and are in the marketplace today under the brand name EnvisionTEC. Scientists from multiple disciplines conducting pre-clinical research are experimenting with their own proprietary or third party materials, including resorbable and non-resorbable biomaterials, using EnvisionTEC machines. Future 3D printing applications for the medical field will certainly emerge with the development of suitable additional materials for diagnostic and therapeutic use that meet CE and FDA guidelines.

3D Printing Regenerated SPINAL DISCS

ccording to a report on dvice.com, scientists at Cornell University, led by Dr Lawrence J Bonasser, are utilising 3D printing techniques loaded with stem cell-infused “bio-ink” to make pioneering inroads into repairing and replacing degenerative spinal discs. The report describes the research as follows. “Imagine an operating room that looks something like a printing bay. The operating table is equipped with a printer head and scanning devices. Soon after the patient is prepped for surgery, the printer begins printing strings of stem cells onto highly specific portions of a patient’s spinal disc. Once the surgery is over, the stem cells begin to enact their pre-designated “biological programming” and populate themselves as brand new spinal disc tissues. After a couple of weeks, this process completes itself and the patient is the proud owner of a newly-repaired spine.” Apparently this vision, while still very early in its research phase (the process has been performed successfully on a rat), is a reality for the future. EOS Advise on “Keeping the Quality Triangle” in Balance Stephanie Kochbech, medical business development manager at German additive manufacturing systems and materials supplier EOS, has provided readers who looking to invest in additive manufacturing equipment with some useful advice, as follows. In additive manufacturing for industry applications, part quality is determined by seamless yet complex interaction between three key aspects: the additive manufacturing systems, the powder materials that can be processed on a system—plastics or metals, taking into account their chemical and physical composition—and the additive or “building” process itself, including the build strategy, supports, heat treatment and post processing. If any of the three factors is subject to change, this will result in a different part quality. As such this three-factor-interplay needs to be adjusted accordingly in order to continuously ensure a consistent quality of the end part.

MAY-JUNE 2013 / MPN /25

USA SENATOR SPEAKS DEVICE TAX TO INDUSTRY | US Industry Stats

The State of the US Medical Device MANUFACTURING SECTOR words | Sam Anson

ccording to a recent report published in 2012 by USheadquartered business consultancy Ernst & Young, (E&Y) Pulse of the Industry: Medical Technology 2012, revenues generated by publicly listed US medical technology firms grew by 4% in 2011 to US$204.3 bn from US$196.4 bn in 2010. Of this total, conglomerates—with a share of 37% of 2011 revenues—increased by 7% to US$76.3 bn. Pure-play companies, with the remaining 63% share, rose by 2% to US$128 bn. Net income generated by these companies expanded by a significant 19% from US$11.5 bn to US$13.7 bn while spending on R&D rose by 2% to US$9.9 bn. However, the report points out that this increase was “boosted by the fact that Boston Scientific, Alere and Hologic incurred significant merger-, impairment-, and litigation-related charges in 2010”. Normalising these charges puts net income growth at 2%, bringing it back in line with revenue growth. In 2011 the public companies involved in medical technology employed a total of 439,800, up by 2% from 431,000 in 2010. The total number of public companies fell by 4% to 254. The report assesses the impact of the economic downturn which began in 2008. It states that before 2008, the US medtech industry would typically generate doubledigit increases in revenue but since 2008 single-digit growth has become the norm. The reasons given for this are: the industry “grappling mounting financial pressures of payers” and “considerable regulatory uncertainties”. The report also states that 2011 revenues were helped by a weak US dollar. Indeed, E&Y estimate that nearly 40% of revenue growth by the top ten US pure play companies was the result of favourable foreign exchange rates. Without these exchange rates, total revenue growth by all public companies would have been 3%, not 4% while the rise in revenues of pure play companies would have halved to below 1%.

26/ MPN / MAY-JUNE 2013

Table 1: The US Medical Technology Sector at a Glance Public company data

2011

2010

% change

Revenues (US$ bn)

204.3

196.4

- congolmerates

76.3

71.5

- pure play companies

128

124.9

R&D Expense (US$ bn)

9.9

9.6

Net income (US$ bn)

13.7

11.5

Market capitalisation (US$ bn)

303.8

326.6

-7

No of employees

439,800

431,100

Number of public companies

254

264

-4

of which:

Source: Ernst & Young. Market capitalisation data shown as at June 30, 2012 and June 30, 2011.

Democratic Senator and Republican Congressman Speak Out in Minneapolis Following “Symbolic” Senate Vote to Repeal Device Tax On April 29, 2013, two leading US politicians—Senator Amy Klobuchar of the Democrats, who represents the state of Minnesota, and Congressman Erik Paulsen of the USA’s Republican party (both pictured), who represents Minnesota’s 3rd district— spoke to the US device manufacturing community about their success in March in persuading 79 senators to vote to repeal the 2.3% device tax. John Eckberg, director of media relations at the Cook Group and Stephan Ogilvie, vice president of corporate development, at NuVasive also spoke. The four formed an open panel answering questions from the floor of conference delegates. A recording of the session is available at: http://bit.ly/1974gQ3. The conference organiser, Joe Hage of

the Medical Devices LinkedIn Group (http://linkd.in/MDGroup), asked the politicians: “After your success with the 79 to 20 Senate vote, the The Wall Street Journal characterised the vote as largely symbolic. What do you say to that?” Amy Klobuchar responded with: “When we first started our debate a number of years ago about repealing the device tax people would look at us with blank stares because they thought they didn’t have any medical device companies in their state or district.” She added: “The senator from Indiana and I were some of the only ones standing up on the Democratic side saying “you don’t tax manufacturing like this—putting it on a revenue as opposed to profit will especially hurt the small start-up companies”.”

<< Senator Amy Klobuchar (below), who represents the state of Minnesota in the Senate, and Congressman Erik Paulsen (right) spoke to delegates at the 10x Medical Devices Conference in Minneapolis at the end of April. >>

She went on to say: “We were able to get the tax halved, from US$40 bn to US$20 bn. And with help from Erik Paulsen, who has been a staunch supporter of the device tax repeal, we managed to get 18 democratic senators on a letter saying it should be delayed for a year. That was a major step forward and a surprise to the [Obama] administration.” The vote in the Senate took place in March when 79 senators voted in support of repealing the tax. In April, a writer in US business magazine Forbes described the vote as a “feel good vote”, acknowledging the tax as “stupid” but boldy saying the road to repeal was “more potholed and twisted than many medical device manufacturers think”. In March The Wall Street Journal posted along a similar vein. It stated that while the vote was a “boost” for repeal supporters, “the search to replace the nearly US$30 bn the levy provided to fund other parts of the law will impede efforts to unwind it”. Apparently the Democrats who voted for the repeal said they would only pass it into law if the cash could be found elsewhere. The WSJ also noted that “Strikingly, 34 lawmakers who caucus with the Democrats signed onto the repeal, including many who created the tax by voting for the 2010 Affordable Care Act.” This is noteworthy because the tax is part of President Obama’s healthcare act, who is himself a Democrat. Obama’s healthcare act, also known as “Obama Care”, is intended to make the USA’s healthcare services more accessible to America’s poor.

<< Joe Hage (above), founder of the Medical Devices LinkedIn group, chairs the 10x Conference in Minneapolis. >>

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USA GETTING FDA APPROVAL OF YOUR MEDICAL DEVICE | A Guide

An Overview of FDA Regulatory Requirements for Medical Devices words | Mark Prinz, regulatory specialist at US regulatory compliance specialists Registrar Corp

he United States government utilises a complex array of laws and regulations to oversee the marketing of medical devices in the USA. Beginning in 1938, then President Franklin D Roosevelt signed into law the Federal Food, Drug, and Cosmetic Act (FD&C Act), which remains the principal law regulating all medical devices today. This Act, detailed in the United States Code (USC), directs the US Food and Drug Administration (FDA) to promulgate regulations to enforce the law. As these regulations are written, they are added into Title 21 of the Code of Federal Regulations (CFR). Medical device regulations in particular occupy 21 CFR Sections 800-898. There are four major steps that a device manufacturer must take in order to comply with the regulations set forth by the FDA. Step 1 The first step is to determine if the product actually meets the definition of a medical device found in the FD&C Act. Medical devices are defined as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory, which is intended for use in the diagnosis, treatment, mitigation, cure, or prevention of disease, or intended to affect the structure or any function of the body of man or other animals. Examples of medical devices include a wide range of products, from cotton swabs to MRI machines. Crucially, a medical device must not achieve any of its primary intended purposes through chemical action within or on the body, and cannot be dependent upon being metabolised for the achievement of any of its primary intended uses. Inclusion of any chemical or metabolic action may cause the device to be classified as a combination product, consisting of both a medical device and a drug.

28/ MPN / MAY-JUNE 2013

Step 2 Once a product has been verified to fit the statutory definition of a medical device, the next step is to determine the class of device under which the product will be regulated. The FDA separates devices into three classification levels based on the potential risk to human health, and imposes stricter requirements on higher risk devices. There is also a separate group of devices known as “preamendment devices,” which were legally marketed in the US prior to the 1976 Medical Devices Amendment Act and have remained substantially unchanged. Class I devices, such as elastic bandages and examination gloves, are subject to “general controls,” consisting of establishment registration, device listing, good manufacturing practices (GMPs), labeling, and submission of a Premarket Notification [510(k)] prior to marketing the product in the US. Over 800 generic types of Class I devices, however, have been exempted from the 510(k) requirement. The 510(k) relates to the reference number of the form which needs to be filled in and submitted to the FDA. General controls alone are insufficient to assure safety and effectiveness of Class II devices, such as powered wheelchairs and infusion pumps. Accordingly, such devices are also subject to “special controls,” which may include special labeling requirements, mandatory performance standards, and postmarket surveillance. Some Class II devices, however, have also been exempted from the 510(k) requirement. For Class III devices, there is insufficient information to assure safety and effectiveness solely through general and special controls. Such devices are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. To market a Class III device, a firm must obtain Premarket Approval (PMA)

from the FDA through the submission of scientific, regulatory, and clinical data affirming the safety and effectiveness of the product. When a manufacturer is unsure as to how the FDA would classify a device, section 513(g) of the FD&C Act allows any person to submit a written request for classification to the FDA. Within 60 days of the receipt of the request, the FDA will respond with whether or not the product can be classified as a medical device, what the classification is, and what requirements apply to the product, including whether or not the product is exempt from premarket notification requirements. Step 3 If it is determined that a product is subject to premarket requirements, then the next major step to marketing the device is the development of data or information necessary to submit a marketing application to the FDA to obtain clearance or approval of the product. Depending on the classification of the device, this may require a 510(k) or PMA application. The 510(k) notification is intended to demonstrate that the device is substantially equivalent to a legally marketed device, or predicate device, and is therefore as safe and effective as the predicate device. If the FDA accepts that the product is substantially equivalent to a legal predicate device, it will grant marketing clearance for the product. The 510(k) process does not, however, lead to product â&#x20AC;&#x153;approval.â&#x20AC;? In order to obtain approval of a device, one must complete a PMA application, which as stated previously, requires the submission of scientific, regulatory, and clinical documentation to assure the device is safe and effective for its intended use(s) or indication(s) for use. Devices that are required to submit PMA applications may not legally market the device until obtaining FDA approval.

Step 4 The owners or operators of establishments or facilities that are involved in the production and distribution of the device are required to register annually with the FDA, and most are also required to list the devices that are produced or processed there and the activities that are performed on those devices. When an establishment registers with the FDA for the first time, it must do so within 30 days of beginning its device operations. The registration must then be renewed every year between October 1 and December 31. With the initial registration, the FDA will assign an Owner/Operator Number prior to issuing an Establishment Registration Number. An owner or operator is assigned only one Owner/Operator Number, but may have multiple establishments, each with its own Establishment Registration Number. For the purpose of registration, an establishment is any place of business under one management at one physical location at which a device is manufactured, assembled, or otherwise processed for commercial distribution. Foreign establishments must also declare a US agent in its registration. The agent must reside or maintain a place of business in the US and assists the FDA in communicating with the foreign establishment. Summary In addition to the steps above, certain devices may be subject to additional FDA requirements. Many devices, for example, have specific labeling requirements. The design and manufacture of medical devices must comply with GMPs set forth in the Quality System Regulations (QSR), a quality assurance system similar to ISO13485. In addition, once a device enters the US market, any significant adverse events, such as deaths, serious injuries, or malfunctions of the device, must be reported to the FDA. Finally, any medical device that incorporates electronic components may also subject to Radiation Emitting Device (RED) regulations, which may have separate labeling and reporting requirements.

Registrar Corp has the expertise to assist companies in complying with FDA medical device regulations, including US Agent services, establishment registrations, labeling, and 510(k) administrative reviews, as well as RED requirements for electronic devices. With 19 global offices, Registrar Corpâ&#x20AC;&#x2122;s team of multilingual regulatory specialists is available to assist you. For immediate assistance with, phone Registrar Corp at +1-757-224-0177, or receive Live Help at www.registrarcorp.com.

MAY-JUNE 2013 / MPN /29

FOLIO << At Medtec Europe in February 2013, Pixargus presented for the first time its new ProfilControl 6FFI system for optical inspection of cut pieces of hypo and precision tubes for medical applications. These tubes need to comply with extremely exacting surface and edge quality demands. The system is used for 100 percent inspection of hypo and precision tubes used in medical instruments and apparatuses as well as for cannulas made of metal and plastics. The system detects and classifies surface defects, such as inclusions, grooves, scratches or dents, over the complete product length. Furthermore, by means of a newly developed algorithm it checks whether the edges have been properly cut and/or feature no burrs. This ensures that only products completely checked and free of flaws are shipped. The view here is into the measuring head, which has been opened for taking this picture. Cut pieces of tubing are inspected while “flying” through the gap of the feeding system. >>

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REGULATION REVIEW USP CHAPTER ONE | Labeling Revisions

Preparing for Printing Changes: What Pharmaceutical Manufacturers Need to Know about USP Ch <1> Labeling Revisions e, Interview with Markus vor dem Esch t men elop Dev uct director Metals Prod Europe and Technical Customer Service, West Pharmaceuticals.

On December 1, 2013, a revised labelling standard will become effective— the United States Pharmacopeia (USP) General Chapter <1> Injections, Labeling on Ferrules and Cap Overseals (USP 34-NF 29 November 1, 2010) for injectable drug vials. The revised chapter affects all injectable drug products, human and veterinary, intended for sale in the USA. Markus vor dem Esche of USheadquartered contract manufacturer of drug delivery systems West Pharmaceutical Services offers guidance to pharmaceutical manufacturers seeking to comply with the new standards. Q: How does the new standard impact pharmaceutical packaging? A: The revision places limits on what drug manufacturers can print or otherwise display on the top surface of cap overseals and ferrules (aluminum shells) used to secure injectable drug vials. This revised standard is specific to injectable human and veterinary drug products that are intended to be sold in the USA, so even manufacturers based in Europe or Asia Pacific must comply if the product is intended for sale in the USA. Q: How will the revised chapter affect what can be printed on caps and/or seals? A: Many pharmaceutical manufacturers currently print or display information on the surface of the plastic cap or seal. Printed information often includes the trade name of the product, company logos or the company name. West also embosses and prints our registered “Flip-Off” name on seals. The revised standard prohibits this type of information, and the USP has specifically cited these examples as messages that can no longer appear on the cap or seal.

In addition, the revised chapter restricts printing to cautionary statements, which are statements intended to prevent an imminent life-threatening situation and may include instructional statements that provide potency or other safety-related instructions if warranted. Cautionary labeling statements must be simple, concise and devoid of nonessential information. Only cautionary statements may appear on the top (circle) surface of the ferrule and/or cap overseal of a vial containing an injectable product. The statement should be printed in a contrasting colour and be clearly visible under ordinary conditions of use. Other statements or features, including but not limited to, identifying numbers or letters, such as code numbers, lot numbers, company names, logos or product names, may appear on the side (skirt) surface of the ferrule but not on the top (circle) surface of the ferrule or cap overseal. Q: Will any current statements be grandfathered under the revision? A: It is our understanding that no printing or information displayed on caps or seals is grandfathered by the revised standard. So although their printing or labeling may have been approved in the past, pharmaceutical manufacturers must make sure that it is in compliance with the revised standard. Q: What should pharmaceutical manufacturers do now to prepare for implementation? A: It is critical for pharmaceutical manufacturers to understand their inventory depletion plan to ensure that their supply chain is not interrupted. Many manufacturers have large amounts of unused seals in inventory and it takes time for those raw materials to be depleted. It also takes time for packaging component manufacturers like

West to produce new seals according to customers’ specifications to be in compliance with the revised standard. Q: What can pharmaceutical manufacturers do if they wish to retain current printing on the cap or seal? A: The USP explains that if manufacturers believe there is a need to include a cautionary statement on the ferrule or cap overseal, then the manufacturers must provide a rationale to the FDA for why the situation addressed in the statement is considered to be life threatening. They will need to present the FDA with data and rationale to support that the statement meets the intent of the standard, and is the best message to minimise a potential lifethreatening situation. At West, our regulatory department can provide a customised regulatory technical package to help present additional information and rationale to assist in aligning the ferrule and cap overseal printing with the USP standard. These customised packages were created to provide the rationale denoted in USP Frequently Asked Questions General Chapter <1> Injections, Section on Labeling on Ferrules and Cap Overseals, dated August 4, 2010. USP recommended giving data and information to the FDA for their evaluation and determination for retention of the current printing consistent with the revised USP <1> standard. More information is available at West’s online resource centre, including the compendial notice from the USP.

Medical Plastics News would like to thank Martin Gleissner of Swedish public relations company MSL Stockholm for arranging this contribution. MAY-JUNE 2013 / MPN /33

DRUG DELIVERY PRODUCT FOCUS | Antistatic, Engineering Polymers, Parenteral Nutrition, COCs and Makrolon Connectors

Plastics in Drug Delivery Devices White Paper Explains Effects of Static Electricity on Plastics Used in Drug Delivery Devices Dr Joe Bell, product development engineer at US-headquartered compounder RTP Company, has written a white paper which details the effects of static on plastics used in drug delivery devices. The paper is coauthored by Josh Blackmore, RTP’s global market manager for healthcare. The abstract of the paper is: “Drug delivery in dry powder and aerosol inhalers can be hindered by static attraction of the drug substance to plastics used in the drug flow path. RTP Company has initiated a series of projects [experiments] to characterise this interaction, measure the effect of static build up, and create conductive plastic solutions which reduce the static charge in plastics used in the drug flow path of drug delivery devices.” The paper is divided into the following sections: objectives, introduction, static electricity, conductive standards, specifications, tests and technologies, experimental setup, results, conclusions, selection criteria for plastics suppliers, and references. In essence, the experiment described in the white paper tested the effect of static on two plastic tubes—one with and one without an antistatic polymer compound— while controlled static charges were placed on the tubes. The static effect was measured by adding a predetermined weight of lactose powder to the tubes and weighing the tubes before and after the powder was added to see how much powder sticks to the plastic. The conclusions of the experiment are as follows. Static charges that build up on the plastics used in the drug flow path and housing materials in pressurised metered dose inhalers (PMDIs) and dry powder inhalers (DPIs) have demonstrated the ability to attract the drug formulation and therefore reduce the amount of drug delivered. Antistatic plastics help to eliminate this variable in both PMDI and DPI devices. The paper cites RTP’s PermaStat brand of antistatic compounds as an example. The PermaStat compounds reduced the drug 34/ MPN / MAY-JUNE 2013

from sticking to the plastic compounds in this test from 20% down to 2.5%. This is an 87.5% improvement in drug delivery. In addition, the PermaStat compounds reduced the variability in the amount of drug delivered.

<< Without “charge-neutral” conductive materials, inhalers can attract and hold residual amounts of medication due to static build-up, especially inhalers that have replaced chlorofluorocarbon (CFC) propellants with hydrofluoroalkane (HFA). >> RPC Develops “Twist n’Hale” Dosing Wheel and Dosage Count Indicator for Powder Inhalers The group responsible for drug delivery devices at German packaging manufacturer RPC Bramlage-Wiko has announced it has developed two features available for inhalers—Twist n’hale [read twist and inhale] and a dose count indicator for

<< Twist’n’hale is suitable for adhesive types of powder blends and a variety of drugs, and can be tailored to different dosing amounts. A choice of decoration options is available to personalise the dispenser for individual medicines. >>

pressurised metered dose inhalers (PMDIs). RPC Formatec’s Twist n’hale is a new contraption which allows users to twist a wheel on their inhaler to prepare it prior to breathing in the dose. The system, created for blister-based powders, is said to offer a simple-to-use operation across a wide range of different flow rates. The Twist’n’hale features a turning wheel on the side of the container. When the cap is opened, the wheel is rotated clockwise in a single movement up to the stop point, which releases the dose. Users then inhale and close the cap. Usage is monitored via a dose counter and reloading the dispenser is easy. RPC Formatec’s new Dose Indicator has a counter that indicates the number of times an inhaler has been used. The company says it enables users of all types of pressurised metered dose inhalers (PMDIs) to accurately and reliably monitor the number of doses taken from their inhalers. The new patented device is FDA approved and has been designed to fit all common types of valves including 3M, Bespak, VARI and Valios. As well as being available for new inhalers, the Dose Indicator can be easily integrated into existing dosing aerosols with only slight modification of the mouthpiece.

<< This injection moulded design provides a counter that indicates the amount of times the inhaler has been activated. The system can be tailored to specific customer requirements for the number of actuations—between 40 and 225 individual doses. >>

Drug Delivery Device Functionality is Driving Demand for Engineering Polymers, says DuPont UK Ian Wands, market development representative at DuPont’s UK subsidiary in Hertfordshire, England, has written an article in European medical device manufacturing magazine EMDT about engineering polymers for drug delivery devices. The article describes how a growing trend for design functionality in drug delivery devices is stimulating demand for specialist engineering polymers. The article will help designers consider DuPont’s materials during their material selection process. It is split into the following sections—introduction, including the pyramid of thermoplastic materials sorted by melt temperature; semi-crystalline polymers; functional plastic components for devices, which talks about POM, unreinforced nylons, PBT polyesters and TPEs (including DuPont’s Hytel TPE-ET); specially tailored grades for the medical device market; low friction materials; and trends and future needs. Two case studies are presented: a reusable insulin pen designed by Industrial Design Consultancy (IDC), based in the UK, and a disposable injector pen featuring a

low friction grade of Delrin acetal homopolymer. For a copy of the report please contact the editor at sam.a@rapidnews.com. Technoflex Focus on Parenteral Nutrition In the April 2013 edition of Flexmag, the customer magazine of French manufacturer of IV bags Technoflex, Sylvie Ponlot, editor in chief, has focused on the subject of parenteral nutrition, feeding patients intravenously in the event of a deficiency of their gastrointestinal tract. The magazine features two articles on the subject. In addition, an interview with a Technoflex line operator about switching manufacturing operations from PVC to PP— among other things—follows a piece on biopharma. The first article about parenteral nutrition looks at the complete picture when manufacturing IV systems for parenteral nutrition, including dealing with ingredients like glucose, lipids and amino acids and preventing oxidation to maintain freshness. The article asks whether it is best to use compounded or ready-to-use preparations. The second parenteral nutrition article looks at PP multi-chamber bags, made from

PP-based film with a high oxygen barrier. The different chambers allow ingredients to remain separate. Peelable welds are included to maintain the separation. For the clinician to mix the ingredients, the welds can be squeezed and broken. The report about biotech describes a perceived race to develop biotech products in new emerging markets, especially Brazil, Russia, India, China and South Africa.

<< Sylvie Ponlot of Technoflex has written extensively about IV systems for parenteral nutrition in the April edition of her company’s magazine Flexmag. >> Continued on page 37

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<< TopPac syringes from German glass specialist Schott are made from cyclic olefin copolymer, a highly insert polymer with “excellent” barrier properties. >>

Continued from page 35

Schott Doubles Production Capacity for Cyclic Olefin Copolymer Syringes To address the increasing global demand for prefillable polymer syringes, German glass specialist Schott has expanded its manufacturing capacity for small size Schott TopPac syringes. Small size syringes comprise volumes from 1 to 10 ml. A new production line installed at Schott’s site in St Gallen, Switzerland, has expanded the existing production capacity by 100% from April onwards. This enables the company to offer customers a greater degree of flexibility and ensure supply security. Schott describes itself as a pioneer in ready-to-fill syringes made of cyclic olefin copolymer (COC). Over the past 15 years, Schott made significant investments to develop and industrialise COC material for pharmaceutical containers for injectable drugs. Schott’s brand of COC syringes is TopPac. COC is an inert material and the Schott TopPac syringe system is designed to be compatible with a broad range of drugs. COC has excellent barrier properties and, as a result, Schott’s TopPac syringe system allows long term storage of drugs even in small syringe sizes. In addition, Schott TopPac syringes have a glass-like transparency, and are break resistant and lightweight. Schott TopPac syringes are available in capacities ranging from 1 ml to 50 ml, with cross-linked silicone for optimal functionality. Schott says that pharmaceutical companies benefit from the fact that TopPac syringes are manufactured in cleanrooms with a fully automated process starting from injection-moulding to the final packaging in nest and tub. The syringes are sterilised and are ready for aseptic filling operations. Schott says “it intends to achieve further growth in the field of polymer and glass syringes and also underscores its

DRUG DELIVERY commitment to offer ideal product solutions to pharmaceutical companies—today and tomorrow”. Makrolon Polycarbonate Selected for Valve Connectors to Prevent Exposure of Cytotoxic Drugs to Medical Workers The US subsidiary of German polycarbonate manufacturer Bayer MaterialScience has announced that its Makrolon brand of polycarbonate has been used to make valve connectors in Infusion Innovations’s (I3) Q-FLO cytotoxic drug delivery device. Bayer says Makrolon has been selected for its strength, clarity, lipid and chemical resistance, biocompatibility and gamma stability. Q-FLO is cleared by the FDA for use in reconstituting, dispensing or transferring, administering, and disposing of potentially hazardous fluids. These fluids include those used in chemotherapy, radioactive isotopes, blood products and nuclear medicine, as well as non-hazardous fluids. The connector can be embedded into the barrel of a 3 ml (3 cc) syringe. The medical grade polycarbonate meets IS0 10993-1 and USP Class VI tests for up to 30-day contact with human tissue. The use of Makrolon is important as it represents a significant advance in the manufacturing of closed system devices, offering improved safety and convenience for healthcare workers administering cytotoxic drugs to patients. “When engineering the Q-FLO we wanted an approved and established material that had FDA clearance along with a proven safety and functional profile,” said Dr Babak Nemati, president and CEO of I3. “Bayer’s plastic not only met these stringent requirements, it also offered the level of chemical resistance required for use with cytotoxic and nuclear medicine.” According to I3, the Q-FLO closed, no drip, valved male luer connectors offer complete swabability at the top of the connector, with a flat, smooth surface allowing for true friction disinfection during pre-access swabbing; and a sequential locking mechanism, which prohibits accidental discharge. Additionally, it has a unique visual indicator confirming connection status. “The Q-FLO represents an innovative product that meets a real need in the healthcare market,” said Bruce Fine, market segment leader for the medical and consumer products, polycarbonates group

at Bayer MaterialScience’s US subsidiary. “We worked closely with I3 to provide a high-quality, proven material that meets rigorous requirements and reduces the risks for medical professionals administering lifesaving medications.”

<< The Q-FLO, which utilises Makrolon Rx1805 medical grade polycarbonate, is a closed, no drip, valved male luer connector featuring a unique visual indicator confirming the connection status. >> Gerresheimer Builds New Czech Production Hall to Fulfil Sanofi Injector Pen Commitment German drug delivery device and components contract manufacturer Gerresheimer has built a new production hall in the Czech Republic to produce components for a new order of insulin pens from healthcare company Sanofi. The preparations for the production lines and all required qualifications and validations were completed within eighteen months. The structural components for the disposable insulin pen manufactured in the new hall consist of several plastic parts manufactured by Gerresheimer Medical Plastic Systems. The final pen assembly is carried out at Sanofi’s facility in Frankfurt in Germany. The production and assembly of the structural components involves injection moulding machines, removal robots, different measuring and testing systems as well as pad printing lines. The complex and highly automated assembly line with several assembly and testing stations was planned and installed entirely by Gerresheimer Medical Plastic Systems. The specialist also developed several of the required moulds. These were manufactured by their in-house mould engineering department. Especially for this project, the manufacturer built a new hall with 3,500 sqm cleanroom areas to ISO class 8 for production and assembly as well as a fully automatic high-rack storage facility. Carsten Dormeier, project manager at Gerresheimer’s technical competence centre in Wackersdorf, Germany, pointed out that adherence to the extremely tight schedule is the most impressive achievement of the Continued on page 38

MAY-JUNE 2013 / MPN /37

DRUG DELIVERY Continued from page 37

project: “We were able to adhere to the ambitious schedule of this extensive project from the start of the planning phase in Wackersdorf through to production startup in Horšovský Týn [location in the Czech Republic] thanks to the high commitment of our staff at both facilities.” The high speed of development will be maintained. The new project is the second Sanofi order for the production of insulin pens from Gerresheimer. Reusable pens are already manufactured at the company’s Pfreimd facility.

<< The new purpose built plant in the Czech Republic moulds and finishes components for this Sanofi injector pen. The fact it was built in 18 months is testament to “high commitment” of Gerresheimer staff. >> Becoming a Full Service Solution Provider: IGS GeboJagema Observe Changing Nature of Traditional Toolmaker Dutch medical mouldmaker IGS GeboJagema has written about how working with manufacturers of drug delivery devices requires far more than simply making a tool for one or two parts. IGS cite the example of a modern drug delivery device comprising as many as 20 moulded parts with drug formulation timeframes being 1015 years in development and costing more than €1 mn. The message that the report portrays is that tooling for drug delivery is a major project and requires a toolmaker that has a strong “financial backbone”. The full report is as follows. Global modern pharmaceutical companies audit with their own sourcing teams high tech toolmakers and value their capabilities on project management— design for manufacturing and mould validation. The development costs of a new drug can increase to more than €1 mn and can 38/ MPN / MAY-JUNE 2013

take 10 to 15 years development time. In most cases, new respiratory drug delivery devices need to be developed to achieve the optimum drug delivery to the human lung. In the last decade IGS GeboJagema experienced that the required part-formanufacturing knowhow is not always available at the pharmaceutical companies and often external medical device development companies are involved in the engineering of this new drug delivery platform. A new COPD respiratory inhaler device normally consists of more than 20 injection moulded thermoplastic parts. This is where the need for a professional tooling partner for pilot-, pre production- and multi-cavity moulds is born. Toolmakers that supply the healthcare industry and are involved in large scale tooling programmes such as the delivery of multiple 32-cavity hot-runner moulds need to have more skills than just innovative mould engineering and accurate mould manufacturing capabilities. They have to add value with senior project management, design of experiments (DOE) and design failure mode and effects analysis (DFMEAs), captive validation capabilities for factory acceptance tests, skilled process engineers and appropriate metrology equipment. Besides these technical skills, toolmakers supplying the healthcare industry need to have a solid financial backbone to be able to support the moulds during the full lifetime of the medical device. In the 1990s IGS GeboJagema recognised the need to change from an ordinary mouldmaker to a full service solution provider and invested in tool manufacturing efficiency programmes, such as robotised automated equipment for high speed milling and spark eroding, and enhanced the engineering team to almost 25 professionals, including five project managers. Each project manager is dedicated to a medical device project. Some projects even have a back-up project manager, to safeguard the continuity of the project. So from start to finish the project manager is the contact person during the entire project for the customer, whether it is about mould design, Gantt charts, DFMEA studies or metal steel safe re-cuts. IGS GeboJagema also installed a new validation centre with more than 10 injection moulding machines in separate validation cells to guarantee the full secrecy of the customer’s developments. The factory

acceptance test (FAT) of the moulds at IGS GeboJagema can be done either on IGS’s own machine or on a customer’s injection moulding machine which can be temporarily installed in one of the available validation cells. IGS GeboJagema is equipped with hotrunner controllers, chillers, coolers, resin drying and masterbatch colouring equipment. The well-trained process engineers are more than operators, but are always striving to develop the most efficient and optimum processes. They exactly know how to run a factory acceptance test, including dry cycle tests, process development, first out of tool (FOT) programmes, balance of fill analyses, DOE analysis and 4-hour FAT runs and prepare a number of shots for a full first article inspection report. They will make sure that moulds are production-ready, within the demanded process performance index (Ppk) values and dimensional tolerance. This is why IGS GeboJagema is involved in medical devices programmes and is able to support large scale tooling projects. IGS GeboJagema has transformed from a normal average toolmaker to a full service solution provider and says it is the professional partner the modern pharmaceutical companies are looking for today.

<< Medical multi-cavity two-shot mould and high speed milling Makino at IGS GeboJagema. >> Maillefer Adds Features to PML Model for PVC IV Tubing Extrusion Swiss manufacturer of extrusion machinery Maillefer has announced new

features for its PML extrusion line model for the production of PVC intravenous (IV) tubing. Thanks to cooperation with the world’s leading medical device manufacturers, innovations on tube surface finish and conditioning have been brought about. Advantages are said to be an increased speed and optimised processing carried over to the manufacturing processes located downstream. The press release announcing the new features includes the following. A smooth and glossy IV tube surface may be appealing but it has the undesirable effect of surface tackiness, which is accentuated when conditioned on coils. The winding and later unwinding operations are slowed as a result. Maillefer has added features to its extrusion technology that result in a tube surface with lower adherence. The positive gain is felt on the extrusion line speeds and on the following operation being sourced with coiled tube. Three conditioning possibilities are available from the line: a full length coil, a multiple length coil, and individual cut lengths. The classic method calls for tubes of long length wound into coils through use of a fully automatic dual coiler at the end of the extrusion line. The delivered coil then needs to be unwound and cut into individual lengths during the assembly step. Another solution is to deliver short lengths produced directly on the extrusion line with an integrated cutting machine. The third solution innovates by combining both methods. Here, short tubes are prepared online, while maintaining a tractable tube for coiling. The advantage is having easy-tohandle coils while delivering tube that is easily separable. Maillefer’s PML 032 line is geared for a speed of 300 m/min. Manufacturers’ typical tube constructions are produced at 200 to 240 m/min. The line operates at constant speeds, even during coil transfers. Available control features include process monitoring, data logging, event alarms, recipe storage, scheduler, report generator and video monitoring. The entire line is designed and built to the strict requirements of the medical device industry. In 2007 Maillefer announced that IV drug manufacturer B Braun’s US subsidiary ordered and installed a customised Maillefer PML extrusion line. The order for the machine was placed in 2005.

<< Maillefer has added features to its extrusion technology that result in a tube surface with lower adherence. The positive gain is felt on the extrusion line speeds and on the following operation being sourced with coiled tube. >>

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OPTHALMICS INTRAOCULAR LENSES | IOLs

Silicones

in Ophthalmic Application words | Brian Reilly, marketing and sales director, medical implants, and Danielle Peak, technical writer, both at NuSil Technology Medical devices accomplish big feats on a small scale. This is especially the case with ophthalmic applications like contact or intraocular lenses (IOLs), in which whole devices are no larger than the eye and virtually unnoticeable. Intraocular lenses, or IOLs, are similar to contact lenses, except that they are implanted into the eye while contact lenses are not1. Both are virtually unnoticeable not only for their size but perhaps even more so for their transparency and optical clarity. As their function is to improve sight, these devices must be highly optically clear. Contact and intraocular lenses are often made with silicone, which has been used in medical device applications since the 1950s. This is because silicone provides chemical stability, dynamic mechanical properties, and biocompatibility. Additionally, silicone chemistry lends itself to optimisation. So, for instance, attaining a specific viscosity and varying the degree of optical clarity and permeability are readily achievable goals. << Figure 1: Intraocular Lens >> One reason for silicone’s versatility is due to the relatively large bond angles2 of the repeating helical silicon-oxygen (Si-O) bonds on the polymer backbone and the variability of the substituent, or R’, groups attached to the open valences of the silicon atoms. The bond angles yield large amounts of free volume, leaving space for design or, more specifically, for managing the amount and type of substituent group and filler, such as resin, that are often assimilated into a silicone system. Phenyl groups incorporated into the siloxane (Si-O) polymer backbone of a silicone can influence the silicone’s permeability as well as its refractive index. Refractive index, or RI, is defined as the ratio of the velocity of light in a vacuum to the velocity of light in a material3. When light passes through a lens or thin film, it is refracted, meaning it passes through, twice—once when it enters and once when it exits. However, not all light striking a surface or interface will refract; some light is reflected instead of transmitted through the material. The more light a material refracts and the less it reflects, the more transparent it will appear. The more slowly light passes through the silicone, the larger its RI. Optically 40/ MPN / MAY-JUNE 2013

clear silicones are highly responsive to light, meaning that far more light waves are transmitted through the material than reflected back out. << Figure 2: Basic structure of polysiloxane chain. >>

Clarity of vision is governed by the eye’s reception of light. Blurred vision is the result of what is known as refractive error. Variations of this occur as complications with light refraction by the cornea and the crystalline lens or with light transmittance to the retina— or both—in which the optical power of the eye is diminished. One of the reasons silicone is used in ophthalmic applications is because of the opportunity it affords for RI adjustment according to different requirements for repairing or enhancing sight. In this way, silicone is accommodating to the function of intraocular and contact lenses. Low consistency silicone elastomers (LCEs) lend themselves for attainment in lens applications of the mechanical and physical properties needed to make the device not only effectively undetectable but also comfortable so that the user experiences no discomfort— only clearer vision. These are resin-reinforced and flowable, often at 1 mn cp (centipoise—a measure of dynamic viscocity) when used in lenses, and they are easily tailored to achieve desired levels of permeability to accommodate and even imitate rather than change the eye’s environment. Assuming a natural rather than intrusive feel is a task of medical devices, and silicone rises to the challenge to help achieve this. In ophthalmic applications, silicone allows the benefits and not the burden of a device to meet the eye.

References: 1. “Ocular Implants”, College of Optometrists, Charity no: 1060431, http://www.college-optometrists.org/. 2. Mark, James E, “Some Interesting Things about Polysiloxanes”, Accounts of Chemical Research, Volume 37 No. 12, 946-953, 2004. 3. “Guide to Selecting Refractive Index” TN118, Horiba Instruments, Inc., 2004.

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OPTHALMICS CONTACT LENSES | Product Focus

All about Contact Lenses words | Sean Lyons, Bausch & Lomb, Ireland Development of Contact Lenses Development of contact lens materials has accelerated in the last century since the advent of the original glass shell lenses. Starting with the use of PMMA in 1937, followed by the development of the corneal lens in 1947, the pace of contact lens development has increased as the biocompatible materials and manufacturing sectors matured. Otto Wichterle, a Czech chemist, developed the modern soft lens in 1961, Bausch & Lomb brought the first contact lenses made of poly-HEMA (Poly(2-hydroxyethyl methacrylate)—a polymer that forms a hydrogel in water—to the market in 1971, mass-produced, disposable lens were popularised by Johnson & Johnson Vision Care in 1988 and Ciba Vision were the first company to develop and commercialise silicone hydrogel (SiHy) contact lenses. The Market Data from Robert W Baird ( Jeff Johnson, OD, CFA, director, senior research analyst) indicates that the value of the worldwide contact lens market is approximately US$7.1 bn, with the US market valued at approximately US$2.4 bn at the manufacturer level in 2012. Premium lenses such as torics (20%) and multifocals (5%) making up significant portions of the market and spherical lenses accounting for the majority of the remainder. Daily disposable lenses continued to grow in popularity, accounting for around 39.5% of 2012 worldwide sales. Daily disposables are the ideal lenses for patients who want an irregular wearing schedule for sports, work or social events. They eliminate altogether the need for cleaning and solutions—ideal for the atopic and indolent patient alike. Engineering Considerations During the development of such a lens there are several key parameters to optimise, including lens design, water content, Dk—oxygen permeability, which allows the cornea to breathe, modulus, mechanical property, resistance to 42/ MPN / MAY-JUNE 2013

deformation, tear strength—if low, lens is fragile and breaks easily—surface properties, coefficient of friction, wettability (contact angle) and surface chemistry/charge. During lens development, each property must be optimised for performance based on the required modality of the lens. As shown in Figure 1, modulus of the material is important for numerous reasons and a balance must be struck in order to attain the best performance from a material formulation. Oxygen transmissibility to the open eye for some of the leading brands are shown in Figure 2. 30

150 Modulus

Floppy Good Comfort Poor Handling

Stiff Poor Comfort Good Handling

eye. The true breakthrough of the HyperGel material is that it has an outer surface that is designed to mimic the lipid layer to prevent the lens from dehydrating and therefore maintain consistent optics. This is important because current contact lenses can dehydrate throughout the day, leading to discomfort and blurred vision. The lipid layer of the tear film contains naturally occurring surfactants that provide a natural barrier against dehydration. The HyperGel formulation contains a specially developed surfactant (Figure 3) that is permanently enriched at the surface of the contact lens during the manufacturing process.

RGP 1000+

<< Figure 1: Effect of material modulus on contact lens properties >> << Figure 3: Introduction of novel surfactant during Biotrue ONEday manufacturing >>

<< Figure 2: Oxygen transmissability data for some leading contact lens brands >> HyperGel: An evolution in silicones and hydrogels One of the most exciting recent developments in daily disposable contact lenses came in May 2012 with the release of the HyperGel material (nesofilcon A) by Bausch & Lomb. The material is used in the Biotrue ONEday contact lens family and is the first daily disposable lens inspired by the biology of the human eye. The bio-inspired lenses contain 78% water, the same water content as the cornea, while delivering virtually the same oxygen level as the open

Recent studies of the new daily disposable contact lens have shown that, even after 16 hours of wear, the lens was losing, on average, only 1.5% water, compared with other lenses, which lose 6% to 8% water under normal conditions. To assess dehydration in the lens, clinicians also conducted studies in humidity-controlled rooms, with a relative humidity of around 5%, comparable to desert conditions. Even under such arid conditions, water loss with the new daily disposable contact lens was only 1.5%. HyperGel is an exciting new class of material not a silicone hydrogel and not a conventional hydrogel but an evolution of contact lens material.

Medical Plastics News would like to thank Austin Coffey, chair of the European Medical Polymers Division of the Society of Plastics Engineers, for providing this article.

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DESIGN 4 LIFE MICROFLUIDIC DEVICE | Produced in Plastic Using Stereolithography

IDC Models Uses Additive Manufacturing Technique to Produce Intricate Microchip for Biological Cell Research UK-based IDC Models, the rapid prototyping and model making division of UK design consultancy IDC, has contributed to the development of a new approach to building flow cells for maintaining biological sample integrity during x-ray diffraction. These new cells, designed by Dr Peter Docker of Diamond Light Source, the UK’s national synchrotron facility, take advantage of stereolithography (SLA), a form of additive manufacturing where liquid resin is hardened selectively to form a three dimensional shape. IDC Models refers to this process as the more general term of rapid prototyping (RPT). Synchrotron is a particular type of particle accelerator used to analyse particles of matter at a molecular level. Using RPT IDC Models have enabled the flow cell and all its internal channels and chambers to be included in a single build operation. RPT takes advantage of a turnaround time of days from concept through to testing, with at least an order of magnitude in cost saving. The particular flow cell (shown in figure 1) is to be used in tests where small angle diffraction is measured to give information about proteins. The protein sample is placed in the small 1 mm hole inside the chip. As the sample is exposed to x-rays, a buffer solution (used to stop the sample degrading) is released from reservoir one and flows over the protein sample to reservoir two. Due to scale, the flow of the buffer is primarily affected by surface area and not (as it would be in the macro world), by volume. This allows devices to be designed to give appropriate flow rates just by altering channel geometry. A more advanced flow cell is currently being designed which will incorporate a pump (only 7 mm x 7 mm x 1 mm in size) that will allow the buffer solution to be pumped over the sample. Using RPT, this integration requires a small alteration to the CAD of the part being reprinted.

<< Figure 1 (LEFT): The flow cell produced using stereolithography by IDC Models in the UK is to be used in tests where small angle diffraction is measured to give information about proteins. >>

About the SLA process Working with Diamond Light Source, IDC Models used their Viper stereolithography (SLA) machine, a 3D printer that constructs models by selectively hardening liquid resin, to produce the prototype. The SLA process involves “slicing” a CAD model into cross-sections which are traced by high-power lasers onto the surface of the resin. The resin cures and hardens where it is exposed to the laser, allowing objects to be built up layer by layer. The SLA machine can produce minute components with feature sizes of 150 μm, in build steps of just 17 μm. The external dimensions of the microchip in figure 1 are just 20 mm x 12 mm x 1.5 mm. Typical traditional methods of prototyping, including photolithography etching and bonding two halves together, were considered to be time consuming and a costly process given this microchip is still in its development stage. Having the flexibility of RPT allows for many more iterations and a more organic approach to design. IDC Model’s SLA machine was chosen to produce the prototype as its high degree of accuracy enables Diamond Light Source to understand the chip architecture, where the channels are best positioned and the exact sizing of the chip reservoirs required. The microchip model was showcased in the USA at Nanotech 2013 on May 12-16,

<< The dimensions of the chip are 20 mm x 12 mm x 1.5 mm. >>

2013—described as being the world’s largest nanotechnology event. Nanotech is said to deliver application-focused research from the top international academic, government and private industry labs. At the time of going to press, IDC Models expected the intricate design of the microchip to be of interest to fellow exhibitors and visitors.

MAY-JUNE 2013 / MPN /45

SETTING STANDARDS IN CLINICAL DESIGN | with Patients, Carers and Clinicians

Renfrew Listens, Understands THE UK’S NATIONAL HEALTH SERVICE words | Sam Anson

n April 11, 2013, I visited a new medical technology trade show and conference, Med-Tech Innovation Expo, in Coventry, UK. One of the attractions at the show was a new design for a wheelchair for children and young adults, the Chair 4 Life (CFL). Visiting the stand of the company who designed the chair, UK-based product design consultancy Renfrew Group, I was pleased to find much more than a wheelchair. It was immediately obvious that Renfrew are a group who, when approaching the design of a revolutionary product like the C4L, see it as a minimum requirement to engage with everyone involved in the wheelchair, including patients (the users), clinicians, carers and manufacturers. “Traditionally, design of wheelchairs and the provision service has meant limited adaptability and flexibility to individuals’ growing needs and often led to a very lengthy waiting time for new products,” explains Renfrew design development director, Mike Phillips. “But a child in a wheelchair is far more than just that. The patient has a wide range of needs, including social ones, and the needs of the patient’s carer is another consideration,” he added. In developing the chair design, Renfrew documented problems from everyone

46/ MPN / MAY-JUNE 2013

involved in looking after a child or young adult in a wheel chair, including the child themselves. “We listened to patients who said they didn’t like the fact that when they entered a room all people saw was the chair,” said Mike. “Our engagement with all people involved, including carers, gave us the information we needed to develop a chair which met the needs of the patient, the carers and the clinicians.” Experienced in Working with the NHS The C4L project was carried out in partnership with the UK’s state-funded National Health Service (NHS). The NHS has recently undergone some of its biggest structural changes in decades, stimulating innovation in healthcare technology. Decisions regarding expenditure have been given to local and smaller groups of clinicians, mainly general practicitioners (GPs), allowing more decisions to be made at a local level and giving these clinicians more choice in procuring supplies, including medical devices. Medical Plastics News supports this move because it opens up working relationships between industry—who know how to design and make things—and

clinically-based experts and patients, who know what their unmet needs are. Medical Plastics News works with a number of clinicians who are based in the NHS and one of their most common complaints is that access to procurement is difficult, never mind providing valuable feedback to medical technology suppliers. Renfrew’s work with the NHS is farreaching. Mike Phillips explains. “The need for efficiencies, driven by austerity, is currently driving a £20 bn reduction in spend. People are talking about a demographic tsunami—by 2040, aging baby boomers will demand a 300% increase in expenditure in real terms on long term care and treatment of conditions most common in the elderly, like dementia, cancer, cardiac disease, stroke and diabetes. Innovation for constant improvement is seen as the only means of meeting these challenges. On top of this, there are the regular and seasonal challenges of healthcare—healthcare associated injections (HCAIs) and emerging infection threats, for example.” “Organisations, including the NHS and the UK government’s Department of Health, looking for revolutionary change, or practical delivery of innovations, come to us for help in facilitating change. Jointly with the organisations’ leadership and front line staff, we create, prototype and test new thinking. We use group creative problem solving, leadership in lateral thinking, visualisation, linked with prototyping and manufacturing capability to challenge thinking and test ideas with the users.

<< Feedback from users and staff allowed Renfrew to understand their needs and added a number of practical features like an adjustable reclining position, and ease of transport and handling for the mobile service. >>

DOCTOR’S NOTE Solving problems with the end user at the heart of the process doesn’t only ensure the result is user centred, but helps acceptance, buy-in or ‘adoption’.” Two noteworthy UK government initiatives in which Renfrew has involvement are Innovation Health and Wealth (IHW) and the new Academic Health Science Networks (AHSNs). Both have the potential to harness technology and innovation with the benefits of working with the NHS for the good of the UK life science industry. Medical Plastics News wants to point out that access to NHS clinicians, carers and patients is major benefit for the UK’s medical technology industry in giving manufacturers a steer in helping to meet unmet clinical leads. Innovation Health and Wealth (IHW) Innovation Health and Wealth, a report published by the UK government in December 2011, gives an integrated set of urgent and immediate measures and actions to turn the NHS into a healthcare organisation defined by a commitment to innovation, research, and the rapid adoption of new ideas, products, services and clinical practice. The report also proposed the designation of a number of Academic Health Science Networks (AHSNs), formed to help the NHS and academia work collaboratively with industry. Local visions for AHSNs are being developed by the NHS and academia with advice from industry and these seek to use the process of creating an AHSN to establish a set of relationships, including public health and social care that can “transform the quality of care locally by bringing together work on innovation with other levers, including research, service improvement, education and training and wealth creation”. Closing, Mike Phillips’s remarked: “What is clear is that UK life science industry and the NHS are balanced in a unique and perhaps precarious moment. There still exists an opportunity to form truly constructive collaboration. It would seem that to overcome some of the internal machinations, silo thinking, and procurement issues that present barriers to innovation, that perhaps this is a role over which an external or overarching body should preside.” He added: “The long term care revolution is a plan being backed by the Technology Strategy Board (TSB)—a UK government body that is responsible for delivery of public funds to stimulate

technological innovation—seeking really revolutionary thinking to give a half a chance of addressing the oncoming tsunami. Perhaps we need a 50-year plan. Something outside the Department of Health, where a clear view of the whole health benefits of innovation, to the nation might be afforded. A role for a cross party treasury perhaps?” At the Med-Tech Innovation Expo event in Coventry, Renfrew showed me other design projects worked on with direct involvement from NHS clinicians and patients. Renfrew listened to feedback from blood donors when developing a blood donor chair with easily adjustable and supportive positioning to make donors more comfortable and secure while giving blood, and to allow staff to reposition the donor if they require attention for example

for the rare occasions when they feel faint and when getting on and off the chair. (see image). A temporary side room, designed to give hospitals extra single side room capacity for infection control and during peak times, was developed in tandem with clinicians.

<< BELOW: A key goal when designing the Chair 4 Life was that it would allow patients to interact socially with able bodied people, shown by the adjustable heights of the chair in the image. Without engagement from the NHS, patients and clinicians, valuable feedback like this would not have been obtainable. >>

<< ABOVE: A doctor makes use of this temporary side room, designed by Renfrew, for infection control during peak hospital times. >>

MAY-JUNE 2013 / MPN /47

MD&M EAST CELEBRATING 30 YEARS | Medical Design and Manufacturing on the USA’s East Coast

n What do MD&M East, Lotus 1-2-3, the First Versio First of Microsoft Word, the First Music CD and the Mobile Phone Have in Common? Stephen B Wilcox, founder of Design Science Consulting, Reflects on 30 Years of MD&M East

That same year, the military spun off a civilian version of their Advanced Research Projects Agency Network, or ARPANET, which was the very beginning of the internet. 1983 was also the year that Lotus Software launched its spreadsheet software Lotus 1-2-3. Lotus Software is now part of IBM. Lotus 1-2-3 is widely regarded as playing a pivotal role of the success of the IBM PC in the corporate environment.

n June 17, 2013, medical device manufacturers located on and near to the USA’s East Coast will meet in Philadelphia for the 30th Medical Design and Manufacturing (MD&M) East trade show and conference. Some readers were involved in the medical device industry back then, when the first few shows took place in the early to mid 1980s. How well they remember it will vary from one reader to the next. But an industry player who was around at that time has written exclusively for Medical Plastics News — Stephen B Wilcox, founder of Design Science Consulting based in Philadelphia. Reflecting on 30 years of MD&M East and the next 30 years of medical technology Regulation: In ‘83, the Medical Device Amendments, which had been passed in 1976, were beginning to be felt. The key changes which they authorised were creating the device class system and requiring premarket approval for the first time. The FDA’s Centre for Devices and Radiological Health (CDRH) formed in 1982 and was beginning to create requirements. Thus, the 30-year period in question goes from the beginnings of premarket regulation to the 1990 Safe Medical Devices Act, which added validation requirements, post market surveillance and the authority to require recalls, up to the 2011 Draft Human Factors Guidance. There’s also a history of usabilityrelated standards for devices. The first was HE 48 (93), then HE 74 (01), then IEC 60601-1-6 (04), then IEC 62366 (07), then HE 75 (10). So the whole landscape has dramatically changed. Canon: Canon began in 1979, just 4 years before, with the publication of MD&DI. The founder, Van Shears, had the vision of creating a bridge between device 48/ MPN / MAY-JUNE 2013

Medical devices: In 1983, there was virtually no minimally invasive (MIS) surgery except for a few things that were going on in gynaecology. Implanted pacemakers were physically huge, and there weren’t yet implanted defribrillators. The controls and displays on devices were really primitive by today’s standards. They rarely had even dotmatrix displays—LEDs were the norm. There were all sorts of large workstations for devices that are simple handheld devices today. There were few disposable diagnostic tests, and many fewer disposables.

manufacturers and the FDA, in light of all the changes that were taking place at the time. Technology: It’s interesting to note the technology of the era and remember just how different it is now. The first mobile phone was introduced in 1983, the Motorola DnyaTAC 8000x, at a cost of $9,000 in today’s dollars. It weighed 2.5 lb ( just over 1 kg) and was only slightly larger than an actual brick. The year 1983 also saw the introduction of Apple’s Lisa computer, the first to offer a graphical user interface, and Atari had a whole work station for computer use with several large units. Microsoft Word was introduced in 1983, along with camcorders, and the music CD.

The next 30 years?: It is always a problem to make predictions. A simple approach is to project out our current trends—for example miniaturisation, more computing power and more interconnectivity. But it’s much harder to anticipate what the new trends will be when we don’t have any precedents to refer to — as the appearance of the internet exemplifies. What are these new disruptive technologies that will appear? Here are some possibilities: small remotely-controlled moving devices (ie drone technology), automated diagnosis and treatment, voice control, remote diagnosis and treatment, laboratory-grown organs, personalised medicine, and gene therapy.

MD&M EAST EXHIBITOR NEWS | Extrusion Machinery

American Kuhne Develops Automatic Concentricity Adjustment Steve Maxson, vice president of extrusion systems, American Kuhne

roducers of precision medical tubing used in medical device applications are confronted with very stringent product quality and process capability requirements. The requirements cover physical properties of final tubing such as burst strength, elongation and lubricity. Medical tubing must also be free from surface quality imperfections such as gels, knit lines and melt fracture (rough surface finish). While most of these requirements can be controlled with proper process parameters, tooling design and clean product contact surface finishes, they cannot necessarily be controlled in a closed-loop fashion. The final tubing dimensions such as outside diameter, wall thickness and concentricity must also comply with the specification of the tube. Fortunately with the use of diameter and wall thickness measurement control systems, the diameter and average wall thickness are often automatically controlled. For instance, the diameter of the tube can be controlled by automatically adjusting air pressure in the die and the average wall thickness can be controlled by automatically adjusting the puller (haul-off ) speed. This leaves concentricity as the dimension that is not controlled automatically. Typical adjustable centre crosshead die heads that are used for small medical applications incorporate four die adjustment bolts that are manually “fine-tuned” to adjust concentricity of the tubing to avoid thin and thick sides of the tubing cross section. In many cases an on-line ultrasonic gauge is used for displaying real-time tubing wall thickness and concentricity. The majority of the manual concentricity adjustments occur during “set-up” operations. This procedure can be very time consuming and is difficult to repeat. Over time, as tubing is being produced, it is often the case that the die centre needs to be manually adjusted to compensate for uncontrolled variables such as die buildup. American Kuhne has leveraged the die centring technology previously developed by their partner US blow moulding engineering firm Graham Engineering under patent number 5,674,440 for parisan side wall adjustment on blow moulding machines. It has successfully implemented automatic die centring technology for small medical tubing applications. In fact, American Kuhne will develop the Graham Engineering technology a step further and incorporate closed-loop control of tubing wall thickness concentricity. This technology will be showcased in a live demonstration at the upcoming MD&M East Exposition in Philadelphia on June 18-20, 2013. American Kuhne’s new die centring technology allows for automatic die centring for uniform wall thickness distribution

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for both inline die heads and crossheads. The new development includes a fixed centre die head, trademarked by the company as AK-u-Tube Fixed Center (Figure 1). AK-uTube is used to eliminate manual die centring and instead the die pin centre location relative to the die bushing is precisely adjusted by touchscreen control of four die pin heaters. These heaters are located in the mandrel of the die head where they can be heated in an uneven pattern to “flex” the die pin to control its position. The pattern will then expand the mandrel on one side and move the die pin stem and pin accordingly. An adjustment system, trademarked by American Kuhne as the AK-U-Center Adjustment system, is integrated with an on-line ultrasonic gauge for full closed-loop control of concentricity. This involves capturing the data from the gauge controller and executing an algorithm in the PLC to perform the process control. The operator has the ability to view graphically the current centring positions, make manual adjustments and control automatic operation. Once the line is running the operator merely has to flip a switch to bring the die to centre. (Figure 2).

<< Figure 1: Fixed centre die head (left) compared to an adjustable centre die head (right). >> This system has been successfully tested in American Kuhne’s laboratory both in manual and automatic closedloop control modes running medical tubing from a Pebax resin. In one experiment with 50% die pin heater power on one side, a medical tube with a 0.13 mm (0.005 inch) concentric wall thickness changed to 0.05 mm (0.002 inch) wall thickness on one side and 0.23 mm (0.009 inch) wall

<< Figure 2: Screen shot from Touchscreen Control of Concentricity >> Significant benefits can be realised with this technology such as reduced product changeover times by eliminating operator manual adjustment of die centring during set-up that can be time consuming and difficult to accurately reproduce. Improved product quality and process capability (Cpk) is also achieved during production by maintaining concentricity with automatic closed-loop control. These benefits will result in reduced start-up times, lower defect rates and improved overall process repeatability.

thickness on the other side.Â Concentricity changed from 100% to 25% in approximately one minute. Tip flexing has a very quick reaction to power inputs, but the control system is designed for stability and to react to longer term changes in concentricity so as not to over-react to short term gauge reading fluctuations which can be caused by air bubbles or tube location within the gauge head. << The tube with a reasonably centred wall on the left and with partial power on one side of the tip on the right. >>

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MD&M EAST EVENT PREVIEW | Celebrating 30 Years of Medical Design and Manufacturing

What is a Good Notification Period FOR CHANGES TO MATERIAL FORMULATIONS? words | Sam Anson On the fourth day of MD&M East, Thursday June 20, 2013, Vipul Davé, director of R&D for Johnson & Johnson’s global over the counter (OTC) technology division, will chair a conference called Medtech Polymers. The day will feature a number of interesting papers relevant to readers, including the following selected subjects: the future of biomaterials (Vascular Sciences), suture and fibre materials for cardiovascular device components (Teleflex), polymeric bioresorbable vascular scaffolds (Abbott), catheter development (Daikin), antimicrobial parylene coatings (Specialty Coating Systems), laser micromachining (Resonetics), MEMS intraocular drug delivery devices (Exponent). Change control: fair notification for device manufacturers of formulation changes An important issue for medical device quality control professionals is change control, also known as formula lockdown—the phenomenon whereby a supplier of a material agrees to provide a minimum period of notice before changing ingredients in a material formulation or making a material obsolete. When an ingredient changes, a medical device manufacturer must inform regulators of those changes in order for the device to maintain its clearance in the market. A supplier who doesn’t tell its customers that it has changed one of its ingredients is at risk of making the manufacturer liable for any issues caused as a result of the change. By contrast, a supplier who agrees to give notice when changing ingredients gives its customers plenty of time to notify the regulators of the change and line up alternative formulations to maintain its compliance in the marketplace. There are variations from one supplier to the next when it comes to change control policy. Some suppliers are helpful when it comes to notification of change control. These provide notice that they plan

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to change one or more ingredient in a customer’s device. The minimum requirement is that a supplier tells a manufacturer when they have changed an ingredient. But smaller suppliers, perhaps new entrants in the medical device sector, may not fully understand the device manufacturer’s position with respect to what happens when an ingredient changes. When these companies don’t inform their customers that they have changed one of their ingredients, no matter how small, this can cause a problem for a device manufacturer. Suppliers change formulations more often than one might expect, not realising the consequences further downstream. Even if the change does not have a noticeable effect on the properties of the end material, a change means a device manufacturer must requalify the material. Medical device manufacturers will maintain very close relationships with suppliers to try and be aware of changes. Change control agreements place an obligation on suppliers to notify customers prior to making any changes to formulations and ingredients. Medical Plastics News is in the process of canvassing opinion on what the best practice is in terms of how long materials suppliers should agree to give in terms of notifying customers before changing an ingredient, no matter how small. So far responses have ranged from 5 to 10 years in long term implantables and 18 months for products in contact with tissue for up to 30 days. The situation is complicated by the fact that an OEM may have up to three tiers of suppliers, all of which need to be on board with change control notification. The issue of change control also affects manufacturers in other industries, including automotive, aircraft and consumer electronics manufacturing.

EXHIBITOR NEWS | End of Line and Assembly

Putnam Plastics Polymer Marker Bands Reduce Catheter Manufacturing Costs

USA

-based advanced medical extrusion company, Putnam Plastics, based in Connecticut, north west of New York, has developed a line of polymer marker bands for fluoroscopic illumination of catheter tips used in minimally invasive medical procedures. These bands reduce costs by eliminating traditional gold or platinum marker bands and offer greater adhesion to catheter shaft tips. A traditional marker band is a short, thinwall tube made from radiopaque gold or platinum that is placed on the tip of a catheter shaft to provide high levels of visibility under fluoroscopy. Fluoroscopy is an imaging technique that uses x-rays to obtain real time moving images of the internal structures of a patient through the use of a fluoroscope. Making a catheter

radiopaque allows surgeons to precisely locate the catheter features deep within the body for deployment of balloons, stents, and other devices in blood vessels. These metal marker bands require a multi-step forming process to create seamless small diameter tubes. Specialised manufacturing equipment is used to crimp or swage metal bands to the polymer shaft tip such that they do not fall off during the medical procedure. This process is costly and time consuming, and quality controls to ensure sufficient mechanical bonding between these dissimilar materials can be significant. Putnam’s marker bands are made from tungsten filled polymers, such as nylons, urethanes and thermoplastic elastomers. Bands are customised using the same polymer specified for the catheter shaft to

allow heat bonding of the band for a more secure assembly. Tungsten loadings range from 65% to 80% by weight to meet radiopacity requirements. Using proprietary co-extrusion technology, Putnam applies an unfilled polymeric outer surface to these bands similar to the surface of the catheter shaft to ensure minimal trauma to blood vessel walls. Putnam Plastics offers polymer marker bands with inside diameters ranging from 0.014 inches (0.356 mm) to 0.200 inches (5.080 mm) and wall thicknesses ranging from 0.002 inches (0.051 mm) to 0.030 inches (0.762 mm). “Our thermoplastic composite bands are cut from tubes extruded in a single process, which can provide cost savings and shorten lead times,” said Ray Rilling, general manager at Putnam.

+ We combine high-performance materials and top-performing engineers to create your ideal implant. Our core competences – Micromechanical production of medical implants with complex geometries made from precious metal or titanium alloys. – Injection molding and machining of PEKK, the newest generation in highperformance polymers. – Surface treatments and ﬁnishes of implants. – Complementing offerings incl. laser marking, washing, simple and complex assembly, testing, packaging and inventory management.

Cendres+Métaux SA P.O. Box CH-2501 Biel/Bienne

Phone +41 32 344 22 11 Fax +41 32 344 22 13 www.cmsa.ch/medical

Medical

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PlasticsOne ®

Medical Design and Manufacture You dream it. We build it.

M MD& East, Booth 2401

We work with OEM’s worldwide to create custom solutions for your medical device needs. Plastics One is a progressive USA Contract Manufacturer with over 64 years of proven success and one of the most trusted names in the industry. t Medical cables, connectors and components t Injection molding t High-end audio cables t Medical pouch sealing t ISO 7 & 8 Cleanrooms t In-house R&D/design/engineering/prototyping

CUSTOM-ENGINEERED CUSTOM-ENGINEERED ND EXTRUSIONS A EXTRUSIONS AND C ATH T ETERS CATHETERS Deep expertise. Decades of experience. Extensive, in-house product development and production services. You should partner with TELEFLEX MEDICAL OEM to get your project off the drawing board and into the market. n PTFE, FEP P, EFEP P, • Global leader in and PEEK extrusions • Custom interventional and diagnostic catheters • Single- and multi-lumen tubing • Composite and catheter tubing • Braid and coil reinforcement • Comprehensive add-on and ﬁnishing operations TELEFLEX MEDICAL OEM Ireland: +353.61.331906 USA: 1.606.532.7706

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MD&M EAST EXHIBITOR NEWS | From the show floor

Product Recalls, Balloon Prototyping, Heart Valves and Microfluidic Welding Talking to Your Materials Supplier About Product Recalls In a recent report entitled The Safety Net, Josh Blackmore, global healthcare manager at US polymer compounder RTP Company, has written about the recent uptick in medical device product recalls due to patient safety issues. He provides advice for medical device manufacturers on how to increase overall patient and product safety through materials selection and enhanced product performance. The report also looks at additives specific to drug delivery devices, as well as high-temperature and other performance properties. Josh begins the report with an interesting reference. According to the FDA, there were 49 Class I medical device recalls in 2012. The FDA defines a Class I recall as “a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death.” In addition, there were hundreds of Class II and Class III recalls in 2012. Josh’s report will be published in full in a future edition of Medical Plastics News.

<< Mexico’s Plásticos y Materias Primas (PyMPSA), a leading manufacturer of medical devices and components for the healthcare industry worldwide, was able to develop an epidural catheter using a custom RTP 2900 Series polyether-block-amide (PEBA) thermoplastic elastomer compound that is radiopaque, so it can be easily observed during x-ray imaging to ensure proper placement. >> RTP Company: Stand 3129 www.rtpcompany.com

<< Vention’s new online design tool, specially developed for balloon catheters, will reduce customer waiting times for prototype work. >> Vention Medical Offers Quick-Turn Modular Balloon Catheter Prototypes US medical device design and manufacturing consultancy Vention Medical has introduced an online design tool that allows customers to design their own balloon catheter prototypes built to their specifications, for delivery in as little as two weeks. The new ModCath Online Design Tool allows users to select from a full range of modular options for complete balloon catheters, delivered at a fraction of the time and cost of traditional methods. Customisable options include shaft size and length, balloon diameter, material, and much more. Many standard sizes are available for delivery in as little as two weeks. Vention’s customers will be able to use ModCath to accelerate the R&D process and speed up early-stage evaluation of prototypes for proof of concept, streamlining project timelines and ultimately, time to market. As an online tool, ModCath is available 24/7 from Vention Medical’s online store, so there’s no need to wait for a quote. To develop this product line, Vention Medical leveraged its advanced polymer balloon technologies in conjunction with other in-house expertise in extrusion, bonding, and catheter assembly. Vention has more than 30 years of experience in the medical device field. The company specialises in components and

services used in interventional and minimally invasive surgical products, including medical balloons, advanced extrusions, heat shrink and multi-layer tubing, cleanroom injection moulding, complete device assembly, and packaging services. Samples will be on display at MD&M East, booth 2513. Vention Medical: Stand 2513 www.ventionmedical.com

The Future: Intelligent Materials Design for Heart Valves Peter D Gabriele and Ryan Heniford The future of biomaterials is an investment in understanding the physiological, economic and bioengineering constraints of materials. When assessing the development of heart valve devices, most of those that have synthetic components at the device or native tissue interface use polyester or PTFE because, along with a proven history, these materials have been deemed biocompatible by the FDA. However, current materials are limited by low durability and long-term degradation (leading to premature device failure), calcification, and cusp stiffening (Seifalian, A M, et al, “Current Developments and Future Prospects for Heart Valve Replacement Therapy,” Journal of Biomedical Materials Research Part B: Applied Materials (pp. 290300). doi: 10.1002/jbm.b.31151). These limitations can impact the longterm performance of heart valve replacements and may require that patients take anticoagulants daily due to the risk of clotting. When exploring the future of cardiovascular materials engineering, it is important to develop materials that promote long-term indigenous physiological activity. On average, the heart pumps an estimated 2,000 gallons (7,570 litres) of blood each day. As a result, materials that are used in heart valve replacements undergo a tremendous amount of haemodynamic stress. Heart valves of the future need to be Continued on page 56

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Continued from page 55

biologically smart, meaning that they must Achieving the right loading conditions while incorporate polymers that are biomimetic. the valve is working, along with the optimal The new material must be able to perform degradation times and proper cell growth, its service function while surviving in the could lead to the creation of an all-fabric body without causing a shift in homeostasis. << Analytical tools such as Fourier Through intelligent materials design, such a transform infrared spectroscopy, which polymer will be engineered to provide examines the chemical composition of a early-stage mechanical and performance material, can help researchers assess a properties while gradually allowing the materialâ&#x20AC;&#x2122;s ability to degrade over time. >> body to regenerate the anatomical part. Other properties that must be considered for a next-generation polymer include: l Mechanical strength: elastogenicity, burst strength, haemodynamic adaptation, fatigue strength and durability, and suturability, l Compliance/compressibility, l Vasoactivity, l Low thrombogenicity, l Degrees of freedom in fatigue, l Resistance to infection, inflammation and hyperplasia, l Promotion of healing, l Minimisation of capsule formation l Flexibility. Fabrics or textile components could be made out of next-generation polymers for use in the heart valve leaflet and the stent.

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valve that degrades over time in the body and thus creates a new valve, enabling the valve to heal itself. Regenerative medicine technologies will provide materials with the ability to degrade over time and be replaced by functional tissue. To meet this promise, however, a serious mechanical challenge with resorbable materials must be addressed: Can a valve construct be designed to manage the mechanical stress of life support while at the same time promote the remodeling as a regenerative process? This truly is the barrier to the development of future heart valve polymers. Peter D Gabriele is vice president, emerging technology, at US medical textile manufacturer Secant Medical, and Ryan Heniford is that companyâ&#x20AC;&#x2122;s director, business development. Secant Medical: Stand 3629 www.secantmedical.com

Precision Welding of Microfluidic Seams, Repeatability of 10 Îźm Microfluidics are gaining in significance because they offer an increasing number of biological analysis opportunities, especially

MD&M EAST

<< Lab-on-a-chip cartridges can be welded using the LPKF PrecisionWeld. >>

in areas like lab-on-a-chip. German laser welding equipment manufacturer LPKF will be on hand to answer questions about a laser system that enables the creation of completely new product layouts for this component. The functional zone in a microfluidics unit generally consists of planar surfaces. The lower component has channels created by hot stamping. The upper cover is placed on top to seal the channel structure. The channels are so fine that the capillary forces dominate and gravitational forces can be ignored. Laser welding has established itself as the technology of choice for creating the highly precise join between the upper and the

lower components. It can combine the two parts without damaging the sensitive channels with interfering particles, melt blow-out or additives. The LPKF PrecisionWeld is reportedly able to create weld seams with a thickness of only 100 μm. Positioning repeatability is 10 μm. It has been said that this level of precision has never been achieved before by any technology in this field. This is achieved constructively by mechanically decoupling the housing from the processing compartment. The system has a scanner system to guide the laser beam, as well as a positioning table. This expands the effective working area to 320 mm x 320 mm. An integrated camera system allows the detection of specially applied fiducial marks or uses the geometrical elements of the component. This allows compensation for tolerances in the component and in the component holder. With the LPKF PrecisionWeld, parts can be joined using the classic transmission laser welding technology as well as the new LPKF ClearJoining technology. In transmission laser welding, the two parts to be joined have different absorption properties, for example

a laser-absorbing basal unit has a clear cover plate. The laser beam passes through the laser-transparent upper component but is absorbed when it hits the lower part, so that the energy in the light is converted to heat and melts the plastic. A moderate joining pressure is applied which promotes thermal conduction into the upper part to produce a reliable and precise weld seam. This technology has established itself as transmission laser welding. Because it has a laser wavelength of 1,940 nm, the LPKF PrecisionWeld is also capable of joining two transparent components. This takes advantage of the new LPKF ClearJoining technology: at this wavelength, most technical polymers absorb enough of the light to melt at high energy densities. The laser beam is focused very precisely on the welding horizon to apply the energy where it is required to create a weld—without additives. The system also has an automatic focus setting which identifies the surface of the component and automatically adjusts the focus to the optimal position. LPKF: Stand 2013 www.lpkf-laserwelding.com

YOUR SPECIALIST FOR RESORBABLE IMPLANTS

I N S PI R E D BY E L E G A N C E A N D P E R F E CT I O N

D e g r a d a b l e S o l u ti o n s AG · Wa g i s tr a s s e 23 · C H - 8 9 52 S c h l i e r e n · Te l. : + 41 4 3 4 3 3 62 0 0 · w w w.d e g r a d a b l e s o l u ti o n s.c o m

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EVENTS medical plastics diary | JUNE-JULY 2013

Silicone conference June 10-12, 2013 Munich, Sweden

Polyolefins conference June 18-19, 2013 Istanbul, Turkey

Medilink networking event June 26, 2013 Birmingham, UK

Medical device conference June 14, 2013 Sheffield, UK

Medical design and manufacturing trade show June 18-20, 2013 Philadelphia, USA

Medical plastics conference June 26-28, 2013 San Francisco, USA

Plastics trade show June 18-19, 2013 Telford, UK

Medtech conference and trade show June 25-26, 2013 Athlone, Ireland

Eurotec plastics conference July 4-5, 2013 Lyon, France

InnoPlast Solutions Announces Second Conference

on Emerging Trends in Polymers and Plastics in Medical Devices

he theme for this year’s two-day conference on Polymers & Plastics in Medical Devices, taking place in San Francisco on June 26-28, is to bring the participants up to speed on the newest trends and technical advances in the field of medical devices as it relates to polymeric materials. The target audience is medical device producers, moulders of sub-assemblies, plastic and additive suppliers, equipment and prototype designers, regulatory professionals, sales, marketing, and business development leaders throughout the entire supply chain of the healthcare industry. The conference has been structured to provide ample opportunity for networking to encourage the sharing of new ideas and concepts throughout the value chain. Conference chairs are Dr JaiPal Singh, CEO Prana BioTech, USA, Larry Johnson, director healthcare marketing, PolyOne, USA and Dr Linda Braddon, CEO, Secure BioMed, USA. The conference advisor is Dr Nicolas Chronos, interventional cardiologist, CEO/President, Cardiology Care Clinics, USA. The conference is split into the following sections: selecting polymeric materials for medical devices: engineering and regulatory challenges; polymeric materials in cardiovascular devices; polymeric materials in orthopaedic devices; polymeric hydrogels in medical devices; and advances in polymeric materials and coatings. Speakers include representatives from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, DePuySynthes-Johnson & Johnson, Ethicon EndoSurgery-Johnson & Johnson and Becton

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Dickenson (BD). The organiser is Dr Yash P Khanna, recipient of two international awards in the areas of plastics and analytical sciences, has 36 years of highly diversified industrial experience. His career is credited with over 120 research publications, 22 US patents, Society of Plastics Engineer’s International Engineering/Technology Award (2001) and North American Thermal Analysis Society’s Fellowship (1988) and its highest honour, the International Mettler Award (1997). A highpoint of Dr Khanna’s career has been to identify several new phenomena in common polymers, already in existence for 40-60 years. Most recently, Dr Khanna was Senior Technology Fellow and Director of Technology at Imerys, a US$5 bn minerals company. The majority of his career, 1975-2001, was at AlliedSignal’s (now Honeywell) Corporate Research & Technology Center as a Research Group Leader and Senior Principal Scientist. During 1990-2001, he also held positions as Business Unit Liaison to Specialty Films and key technologist for Packaging Resins, where scientific fundamentals formed the basis of new product / process development as well as technology marketing in North America and Europe. These significant business contributions were recognised through five Special Recognition awards and three business awards (“Growth,” “Sale of the Year,” and “Save of the Year”). Now at InnoPlast Solutions, Dr Khanna’s technology driven business experience is playing a key role in offering “Value-Driven” conferences and courses as well as consultation services.

COME AND SEE US ON STAND 3501