MPN EU Issue 7

MPN

MEDICAL PLASTICS NEWS

ALSO IN THIS ISSUE: 3D MIDS LASER SINTERED PEEK CRANIAL IMPLANTS ACCELERATED POLYMER AGEING CUSTOM POLYMERISATION FOUR- AND EIGHT-AXIS COMPOUNDING

PEEK IMPLANTABLE FABRICS: SOLVAY RECOMMENDS A FRIEND TURN TO PAGE 10...

ISSUE 6 May | June 2012 WWW.MPNMAGAZINE.COM

MPN

All Medical, All Plastics

Contents

Page 10

5. Editor’s Letter: Toxic DEHP Proof that DEHP is causing an inflammatory response after migrating from extracorporeal PVC components to tissue via the blood.

7. On the Pulse: Industry news Phthalates and bisphenol A and a £180 million grant fund for UK SMEs.

Page 17

10. Cover Story: Innovations in PEEK Solvay recommends a friend in fabrics, carbon reinforced implants, stents, colouration and laser sintered cranial implants.

18. Doctor’s Note: Blu Ray to hips Glasgow University pioneers nanopatterns for stem cell growth.

20. Product Focus: Single use devices Gamma stabilised polyarylamide for disposables and estimating the shelf life of plastics through accelerated ageing.

Page 24

34. Product Focus: Respiratory devices Respiratory tubing, antimicrobial porous plastics for airborne microorganisms and world first in respiratory rate counting.

38. Folio: High resolution images Topas copolymers for syringes and LPKF’s patented laser direct sintering (LDS) process.

40. Regulation Review: ISO 13485 update Harmonised MDD will encompass cosmetic surgery.

42. End of Line: Plasma treatment Metal-plastic overmoulding perfected with in-mould plasma surface activation.

45. Design 4 Life: Rapid prototype moulds Endoscope project benefits from moulds delivered in 15 days.

24. In the Zone: 3D MIDs and thermoforming Injection moulded and laser sintered circuit boards and twin sheet thermoforming.

46. Clean machines: Compounding Four- and eight-screw high rpm small diameter extruders ideal for delicate additives like APIs.

28. Country Focus: USA AdvaMed and Eucomed join forces, high end catheters, customised polymerisation and “no 2.3% device tax”.

49. Machined plastics: No mould, no metal PPSU for brachytherapy cancer treatments.

Page 37

50. Events: Diary September 2012 perfect timing for Mediplas as UK reforms healthcare commissioning procedures.

Online and in digital Page 46

Medical Plastics News is available online, at www.mpnmagazine.com, and in digital (on the iPad, mobile phones and computers) via MPN Xtra.

MAY | JUNE 2012 / MPN /3

MPN | EDITOR’S LETTER

MPN | CREDITS

editor | sam anson advertising | gareth pickering art | sam hamlyn

It’s Wrong to Ignore the Toxicity of DEHP Dialysis patients are suffering as leached phthalate molecules from extracorporeal systems slip through the regulation net The sixth result from a Google search for DEHP returns the result “One of the Top 6 Chemical Threats to Humans”.

Following this link brings you to a page

by Dr Mercola, a certified physician and surgeon, a New York Times Best Selling author, and interviewee in half a dozen leading international media, including TIME magazine, the LA Times, CNN and Fox News. The page, written by Dr Mercola, is a clear account of the toxic risks of DEHP plasticisers, or phthalates, in the human body.

At the bottom of the page, there are 133 comments about the topic.

The first comment, from Sayer Ji, founder of evidence-based medical research website GreenMedInfo.com, provides access to 22 studies which “confirm the profound endocrine disruptive properties of this chemical category, particularly on the male hormone health”. Scanning through these studies, it’s easy to see why there’s so much concern. But one theme seems to recurr, that DEHP has a damaging effect on the male testis.

So what brought me to this query?

Following a recent trip to the University of Strathclyde’s Bioengineering Unit in Glasgow, UK, I was shocked to hear from Professor Terry Gourlay that his research team has identified that toxic DEHP molecules migrate from the PVC used in extracorporeal systems and into the tissues of patients via the blood, where they cause an inflamatory response and lead to both short and long term complications.

For the first time, the researchers have identified that patients who have multiple extracorporeal exposures, for example those undergoing kidney dialysis, are particularly at risk. The work is being done in close partnership with a local, national and international clinical community.

Professor Gourlay told me that the key objective for them is to find technological solutions to very complex conditions.

On hearing this, I was understandably concerned. The obvious thing to ask was what was being done about it. Apparently, manufacturers of extracorporeal systems such as extracorporeal membrane oxygenation (ECMO) and dialysis systems say their hands are tied. For many applications they claim there are no alternatives and nothing can beat the durability of PVC. However, back in 2005 it was reported that a California hospital became one of the first to stop using PVC IV bags and tubing, having stated that the risk of DEHP migrating into the body is generally accepted.

So it seems that this is an issue for the regulators. While drug delivery systems are subject to strict and detailed rules about acceptable levels of extractable and leachable molecules allowed, it seems that PVC tubing and bags used in extracorporeal systems, defined as Class IIa and IIb products in the Medical Devices Directive, are slipping through the net.

art | tracey roberts production | peter bartley subscriptions | tracey nicholls publisher | duncan wood

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© 2012 Plastics Multimedia Communications 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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MAY | JUNE 2012 / MPN /5

ON THE PULSE ON THE PULSE | News from the industry

The Urgent Need to Change Materials –

Real Issues or Marketing Hype?

BY LEN CZUBA, PAST CHAIRMAN MEDICAL PLASTICS DIVISION AND PAST SPE PRESIDENT 2005/06, DISTINGUISHED HONOURED MEMBER PVC in Medical Devices After decades of negative publicity related to the use of flexible PVC in single use medical devices, one of the largest US hospital buying groups has announced their intention to stop purchasing products that use PVC. It has not been made clear whether the decision was related to alleged safety issues associated with phthalate plasticisers or to cost issues.

Alternative materials have long been available but in the past, as now, no compelling reason was found to justify a switch. One report indicates that the company will save money by switching. But how such savings can be realised is unknown, since the currently available alternative materials are all more expensive than PVC and the manufacturing costs will certainly exceed those of PVC. The most popular alternative to PVC — TPE — does offer material savings due in part to the significant difference in specific gravity (0.9 vs 1.3). Furthermore, its flexibility and clarity approach the superior physical properties of flexible PVC. Several suppliers are also developing versions of modified olefins that approach the properties found in PVC. But every alternative brings added costs related to more complicated manufacturing requirements — such as heat sealing and adhesive bonding.

I believe that PVC should be avoided only where a proven risk has been found — such as in chemotherapy infusion or infusion of lipid emulsions — and in other very limited situations.

It may be surprising for many to learn that non-PVC alternatives for IV containers and infusion tubing have

been available for more than 20 years. Some companies have used these products where PVC is the wrong choice of material for the application. But to date, no major effort has been successful in moving the industry from its successful reliance on PVC. It remains to be seen if the latest announcement will lead to a wider adoption of non-PVC alternatives.

Polycarbonate and Bisphenol A The latest “concern” raised by a relatively small number of researchers claims that there is a problem with bisphenol A (BPA) found in polycarbonate (PC). It has been suggested that minute levels of BPA are released from the plastic and these levels are hazardous to health. The US Food and Drug Administration (FDA) is in the process of doing a multi year assessment of the possible hazards related to exposure to BPA and although their assessment is not complete, they recently denied a request to ban BPA in food packaging saying that the science does not show an immediate concern.

In medical devices, the amount of potential BPA exposure from PC is extremely low because the surface area and time of solution contact in most cases is minimal to the point of making BPA levels almost unmeasurable.

So why is there so much hype over the potential for BPAfree alternatives to PC? There is a glut of information available related to BPA, some of it describing the hazard potential and other studies attempting to prove its safety. Much of the reported data is based on weak science and unfounded allegations and these reports get much media and public attention. Hospital administrators and healthcare workers are hearing rumours of concern about BPA from these reports, leading many to make knee jerk reaction decisions while motivating device designers to seek and develop BPA-free devices.

The views expressed above are those of Len Czuba. It must be stressed that they are personal and are not in any way the position of SPE.

MAY | JUNE 2012 / MPN /7

ON THE PULSE | News from the industry

Potential of UK Medical Identified in £180 At the end of April, a new government scheme opened for applications. The scheme will provide £180 million worth of funding for innovative small and medium sized enterprises (SMEs) and academics to develop solutions to healthcare challenges.

The scheme, the Biomedical Catalyst, is a key element of the Strategy for Life Sciences launched by the UK’s prime minister, David Cameron, in December last year. It will see the country’s Medical Research Council (MRC) and Technology Strategy Board working together to take the best British medical breakthroughs through to commercial success.

The Biomedical Catalyst will accept promising ideas from SMEs and academics in sectors or disciplines that demonstrate the potential to provide significant positive healthcare and economic impact. It will support the development of innovative technologies emerging from partnerships between clinicians, academics and industry.

When commenting on the development, David Cameron said: “The UK boasts a world leading life sciences sector which is changing at an incredible pace. And I’m absolutely committed to helping it widen its significant foothold in the global market. Benefiting both patients and the British

HEALTHTECH AND MEDICINES KTN ARRANGE WORKSHOPS TO HELP SMES GET CASH

APRIL 4, 2012 Medical Plastics Guru Wins Lifetime Education Award at SPE ANTEC Gala

8/ MPN / MAY | JUNE 2012

Gerry McNally, senior lecturer in Polymer Engineering at Queen’s University, Belfast, was recognised for his contribution to teaching as well as his applied research programmes with industry. This prestigious SPE Education Award was established in 1976 and Gerry is the first European academic to be given it. Left to right: Jim Griffing, incoming SPE president, Gerry McNally and Willem De Vos, the new SPE chief executive.

April 12, 2012 Global Demand for Prefilled Syringes to Soar

economy, this £180 million programme will support both SMEs and academics and help to ensure that they can turn their promising ideas into innovative technologies.”

Announcing the opening of the fund at a life sciences roundtable event in Japan, minister for universities and science David Willetts reiterated the prime minister’s comments: “We have a world leading life sciences industry in the UK that is changing fast. The government is absolutely committed to ensuring its future success and one of the key challenges is tackling the so-called ‘valley of death’. This exists between the moment that a bright new idea is developed in the laboratory and the point when a new drug or technology can be invested in by the market. The £180 million Biomedical Catalyst programme will bridge this funding gap and support innovative businesses and our research base, bringing benefits for patients and the economy.”

Sir John Savill, chief executive of the Medical Research Council said: “The Biomedical Catalyst will give SMEs greater access to leading academic researchers and patient groups.

The MRC is particularly keen to help SMEs engage with clinical proof of concept studies, where partnerships with academic research groups and patient participation are vital.

Professor Mehdi Tavakholi, technical director of the HealthTech and Medicines KTN said: “We very much welcome the support of the prime minister and the

According to Christoph Lhota, head of medical at Engel, “Process integration is becoming increasingly important in medical technology. Prefilled syringes are a growth market for two reasons. First, they reliably prevent errors in the medication dosage, and secondly they reduce the packaging overhead because the applicator is also the packaging.”

April 16, 2012 MedPlast Acquires United Plastics Group (UPG)

According to Harold Faig, CEO of MedPlast: “The combination of MedPlast and UPG represents tremendous opportunities for both firms and for our customers. MedPlast’s enhanced global footprint and added technical capabilities will bring powerful synergies to customers looking for creative solutions to their design, development and manufacturing challenges.”

ON THE PULSE

Device SMEs mn Government Grants availability of the new Biocatalyst Fund. This is excellent news for UK companies, academics and other organisations involved in the life sciences sector. Continued support for life science SMEs is particularly critical to ensure that innovation in life sciences continues to lead to commercialisation — benefiting the UK industry and, ultimately, patients all over world.”

Three categories of grant awards will be available through the Biomedical Catalyst scheme — feasibility, early stage and late stage. Any SME or academic undertaking research and development, either individually or working in collaboration, may apply and applications will be accepted at any time. Individual grants to businesses will range from a maximum of £150,000 for feasibility awards to £3 million for early and late stage awards.

Prime Minister David Cameron has

<< Readers wishing to apply for a grant should contact the Healthcare and Medicines KTN at http://bit.ly/IEEcBa. >>

recognised the potential of the UK’s life sciences sector with a £180 million grant for small and medium sized enterprises (SMEs).

23:05:2012

PREVIOUSLY ON MPN MAGAZINE.COM April 16, 2012 Stratasys and Objet Merger Creates $1.4 bn 3D Printer Giant

“Today [April 16, 2012] marks a significant milestone for Stratasys and an important development for the 3D printing and direct digital manufacturing industry,” said Scott Crump (pictured), chief executive officer and chairman of Stratasys.

April 16, 2012 UK Medical Device SMEs Potential Identified in £180 mn Government Grants

The UK’s prime minister, David Cameron, said: “The UK boasts a world leading life sciences sector which is changing at an incredible pace. And I’m absolutely committed to helping it widen its significant foothold in the global market.”

May 23, 2012 MEDTEC UK Opens Doors to Public

Notable suppliers include machining expert Carville, distributors Albis and Distrupol, prototyping provider Protolabs and contract manufacturers Raumedic, Amcor, Carclo, ProTek Medical and The West Group.

24 MAY | JUNE 2012 / MPN /9

Can Your PEEK Supplier Recommend a Friend?

Solvay’s standing at epicentre of technical network accelerates implantable PEEK fabric development Solvay has used its close ties and market expertise to foster the development of high performance implantable PEEK fabrics.

As innovation creates The initiative is opportunities in medical device an example of how Solvay can development, it brings with it intelligently unique challenges, particularly in “recommend” terms of new supply chains. To technologies to be successful, designers must its customers, charter new territory. Any having misstep can derail an otherwise capitalised on perfectly orchestrated project. its epicentral position in the Given that PEEK is enjoying more PEEK supply novel applications than many, chain by MPN caught up with Shawn connecting Shorrock, global healthcare manufacturing market manager for Belgium- partners whose based Solvay. We wanted to find paths, without out how the company has helped Solvay, would not have some of its customers overcome otherwise this dilemma, especially in the crossed. development of implantable The project PEEK fabrics. began when, 18 months ago, Solvay customers began making inquiries about the possibilities of procuring PEEK fibres and fabrics. Given that this was new territory for all companies concerned, the team at Solvay knew that the main challenge was to coordinate a group of suppliers who could collaborate to provide the required technical solutions.

Shawn explains: “Procuring the right technology was only one aspect of the puzzle. PEEK is a high temperature polymer, which automatically limited the number of suppliers that had the ability to extrude the plastic into fibre form. When you combine this with the requirement that the supplier needs to be operating under the auspices of ISO 13485, the list of potential candidates shrinks even further.”

Solvay joined forces with USA-based biomedical fabrics manufacturer Secant Medical and an unnamed fibre manufacturer. Thanks to Solvay’s help, the supply chain became simple and streamlined. Because of the synergy between the three parties, previously anticipated

by Solvay, the project was able to benefit from proven processes, including Solvay's extensive biocompatibility testing. The overall result that Secant could offer its end users was a fully validated supply chain from PEEK in its raw state to a finished implantable biomedical textile.

Solvay was crucial in prospecting and locating the right extruder, something it was only capable of doing thanks to its central position in the PEEK market, combined with its own technical expertise and creativity.

“We collaborate with channel and technology partners to simplify the supply chain process,” says Shawn. “Now, if a customer needs a specific PEEK technology and there is sufficient market demand, we can secure the right converter and put the various pieces of the supply chain together so they get the finished material they need. This type of direct response offers benefits to customers that might not be available otherwise.”

Shawn goes on to explain that supply chain management is all about relationships. “Rather than relying solely on the historical performance of our product, we establish strategic relationships with reliable supply and technology partners. These partners have the knowledge and experience sought by customers who want to advance beyond current technologies.”

Implantable PEEK fabric production — for variable tissue growth in situ Right from the beginning, Solvay and Secant’s close relationship was beneficial in the development of PEEK fabrics. Strong collaboration between the two gave birth to refinements in the extrusion process for converting PEEK resin into a fibre which can be converted, either by weaving, knitting or braiding, using certified medical textile manufacturing techniques.

COVER STORY << Solvay was instrumental in connecting complementary suppliers, leading to the development of implantable PEEK medical fabrics for tissue engineering. >>

Collaboration Cubed: Solvay’s Top Tips For a Complete and Transparent Supply Chain Shawn Shorrock believes that a tailored business relationship based on mutual trust, openness and shared financial risk and reward accelerates business performance and provides a greater likelihood that outcomes meet expectations. Such a partnership arrangement goes far in helping OEMs be more competitive and profitable than could be achieved by two firms working independently.

Medical device development, in particular, faces some significant supply chain issues that can negatively impact progress and which can be best approached with collaborative teams. In Solvay’s experience, the issues and some suggested solutions are:

By varying the orientations, geometries, and combinations with other materials, PEEK-based biomedical fabrics can be designed to control tissue growth in some areas while serving as a tissue barrier in others in order to achieve a desired biological response.

“Our partnership with Solvay alleviates the burden of managing raw materials and component manufacturing for device developers interested in exploring new engineering opportunities,” said Jeffrey Koslosky, VP of Advanced Technologies, Secant Medical.

PEEK and Device Certification Regulators generally prefer to work with materials they are already familiar with, and Zeniva PEEK has the advantage of having been used successfully in dozens of devices that have obtained CE marks and 510K clearances over the past decade. This track record helps smooth the approval process, especially for new innovations that often struggle with the pressures of healthcare policies that conflict with rising physician and patient expectations while meeting the unaddressed medical needs of aging patient populations and developing countries which are experiencing growth.

• Long design to production cycles: These require quickly developed prototypes which will work in the desired design state.

• Inherent pitfalls of new technologies: These require innovative processes and special tooling and packaging.

Almost always these areas are best addressed by suppliers with specialist expertise.

• Frequent design changes: These necessitate quick change management and cost traceablity. This can be best achieved if the integrated development team stays in constant and close communication.

• Cost containment pressures: These can be proactively addressed with items such as design for manufacturability (DFM), mistake-proof assembly and alternative component sources.

• The need for enhanced risk management: This is attained by involving the supplier in conversation at the early stages of development. Key areas to consider are component lead times, safety stock or critical component plans and functional testing.

MAY | JUNE 2012 / MPN /11

MATERIALS PEEK | MATERIALS DIAGNOSIS

<<Investigations into superior materials for hip implants are fuelling design experiments>>

Mounting Safety Concerns Over Metal on Metal Joints Spotlights Value of Advanced Biomaterials

Todayâ&#x20AC;&#x2122;s orthopaedic device manufacturers are challenged to remain competitive while operating in a business environment marked by highly publicised international recalls of metal on metal hip implants, growing safety concerns and heightened regulatory scrutiny.

Debates surrounding patient and public concern over the safety of metal on metal hip implants continue. Recent studies indicate that hip replacements using these implants are more likely to fail than with devices made from other materials (Lancet, 2012). According to the analysis, more than 500,000 patients in the USA and 40,000 in the UK have metal on metal hips and are at a higher risk of device failure. Overall 6.2% of patients need a second operation in five years due to aseptic loosening; this is about a third higher than devices made from ceramic or polythene on metal materials.

It is no wonder that with statistics such as these that researchers are calling for further investigations into superior substitute materials.

6.2% OF PATIENTS WITH METAL HIP IMPLANTS REQUIRE SECOND OPERATION WITHIN FIVE YEARS

Carbon Fibre Reinforced PEEK for Joint Arthroplasty Rising numbers of orthopaedic device designers and manufacturers are experimenting with alternative biomaterials for use in hip replacement devices.

Steadily rising performance expectations for joint replacement have for years outstripped the limitations of traditional biomaterials. More and more, designers and manufacturers are relying on advanced materials like Invibio Biomaterial Solutionsâ&#x20AC;&#x2122; implantable grade PEEK to meet the performance and safety demands of their customersâ&#x20AC;&#x2122; device requirements.

MOTIS (carbon fibre reinforced PEEK) from Invibio has been extensively assessed in terms of mechanical strength, wear 12/ MPN / MAY | JUNE 2012

<< UK-based PEEK manufacturer Invibio Custom Solutions helps device companies optimise each stage of product development from concept to commercialisation. >>

performance (measured against metal and ceramic counterfaces), bony fixation, and immunological/biological response to wear debris generated by the material. Specifically developed to meet the critical requirements of joint arthroplasty, MOTIS provides device designers redefined performance possibilities and advanced approaches in replacing metal components.

Design Challenges For designers, turning raw materials into joint replacement implants that are safe, innovative, and effective is essential.

MOTIS provides alternative processing and design options to device designers; those unfamiliar with the biomaterial may require expert assistance with advancing their concepts through to commercialisation. The key challenge therefore is concerned with adapting their innovative ideas into realistic and achievable commercial devices. Choosing the right partner to assist with these design challenges can be instrumental to the success of bringing a device to market quickly and efficiently.

Manufacturing partners who are experts in processing the specific material can offer advice and guidance based on their specialised processing knowledge. For companies considering PEEK-based biomaterials, UK-based Invibio Custom Solutions offers designers support in designing, processing and manufacturing PEEK-based biomaterials in applications such as joint arthroplasty.

With over 10 years of experience and critical market insight within the medical field and over 3 million implanted devices globally, Invibio Custom Solutions claims to have an understanding of realistic material tolerances and subsequent design capabilities. According to the company, their expert processing knowledge can assist with the production of prototype components, which in turn can help to alleviate design difficulties prior to the undertaking of full scale manufacturing.

Invibio is a registered trademark of Invibio Limited.

PEEK | MATERIALS DIAGNOSIS

Research into

PEEK Stents Underway Plastic stents are traditionally made from polyamide or polyester. However, Medical Plastics News can confirm that research is underway to manufacture stents from PEEK filaments. The research team, who wish to remain anonymous, are working with Evonik’s polyetheretherketone (PEEK) Vestakeep.

According to Evonik, Vestakeep boasts not only excellent biocompatibility, which the company claims to have verified in tests by external testing institutes, but also high biostability. The latter is a direct result of the aromatic, partially crystalline properties of the PEEK polymer, which not only imparts outstanding resistance to corrosion, hydrolysis and chemicals but also renders it inert to bodily liquids — so the material retains its stability, even under aggressive conditions. The stents mark a new and significant medical application for Vestakeep PEEK. According to Marc Knebel, director of business management at Vestakeep Medical: “This high performance plastic is easy to work into versatile shapes — an argument not only for the complex construction of stents but also for use as an extremely thin walled battery housing in cardiac pacemakers, in dental technology, or as an implant pump for patients who, for instance, suffer from excess fluid in the abdomen as a result of liver disease.”

Evonik’s cast polymer subsidiary, Evonik Polymer Technology (EPT) manufactures PEEK rods and plates for machining purposes. The PEEK versions are certified to ISO 13485:2003.

In addition to biostability and biocompatibility, Evonik claims that the advantages of Vestakeep include outstanding mechanical properties, such as high dimensional stability based on low water intake, high stiffness at low weight, high resistance to heat distortion, and a long term service temperature of 260°C.

14/ MPN / MAY | JUNE 2012

MATERIALS

Clariant Expands PEEK Colour Palette and Gains New Biocompatibility Approvals As part of a continuing effort to expand the colour and appearance options available for PEEK medical polymers, Clariant Masterbatches has EXPANDED developed a new palette of TESTING GIVES colours specifically for PEEK. At the same time, the company has DEVICE announced completion of testing MANUFACTURERS for compliance with additional MORE CONFIDENCE parts of the ISO 10993 and USP parts 87 and 88 (Class VI) standards. The PEEK masterbatches and custom compounds are marketed under Clariant’s trademarked MEVOPUR brand.

According to Garrett Allen, regional technical manager Clariant North America, Global Segment Medical and Pharmaceutical: “In their natural form, many PEEK grades inherently have a light brown tone, which makes colour matching challenging. In addition, they are normally processed at over 371°C (700F) so any pigments, fillers or stabilisers need to be very heat stable.”

Clariant began offering colours for PEEK resins in 2009, but the palette was limited largely to primary colours and greens.

More recently, however, the company has uncovered previously unavailable new pigment chemistries that promise to open up new options, including a range of purples, brighter reds and oranges.

The new PEEK colours are being developed and marketed under the MEVOPUR brand name. This family of products was created to assure developers of medical devices and pharmaceutical packaging that all raw materials have been biologically evaluated, and that information to support the regulatory approval process can be provided.

The masterbatches are produced at Lewiston, Maine, USA, one of Clariant’s three ISO13485 sites dedicated to production of medical materials. All compounding is carried out under carefully controlled conditions to minimise risk of contamination, while segregated storage and change control processes ensure consistency.

“

PEEK polymers offer many properties that are attractive to developers of medical devices.

They provide high mechanical strength combined with excellent stress crack resistance. They can withstand the high temperature conditions and chemical exposure encountered during sterilisation, and they are dimensionally stable and electrically resistant.

”

Expanded Testing The pigments and additives used in the PEEK materials have also been subjected to an expanded battery of tests. Not only are they evaluated under the USP 87 and 88 standards for Class VI devices, but also ISO10993, parts 5, 10 and 11. Additional test data has been generated using ISO 10993 Part 4 — which looks at hemolysis or interactions with blood — and Part 18, that looks for extractables.

This higher level of ingredient pretesting, which is standard procedure for MEVOPUR masterbatches and compounds, gives the makers a clear picture of the materials they select, helping to minimise the risks and costs associated with non-compliance during a product’s development and lifecycle.

MAY | JUNE 2012 / MPN /15

<< PEEK cranial implants can now be individually designed to fit the contours of a patient’s skull.

Notice the roughened surface and lattice structure which encourages bone growth. >>

PEEK

cranial implants now possible from MRI Scan

PEEK | MATERIALS DIAGNOSIS Following FDA approval of a line of custom milled PEEK skull implants in 2011, the first ever laser sintered PEEK cranial implant prototype has The reconstruction of the skull been created by a following a serious head injury has team of doctors, relied on titanium plates for many design engineers years. Because every injury is and materials unique, it’s difficult for surgeons specialists working to use standardised implant sizes. together in an EU funded research So the replacement of any bone project called must be done on a case by case Custom IMD. basis. But the manufacturing After deciding process for titanium plates is on PEEK for the expensive and slow, and the heat cranial portion of conducting properties of titanium the project, make it uncomfortable for the Custom IMD asked laser sintering patient. Thanks to advances in machine maker additive manufacturing (AM) EOS to join them. technology, however, it is possible The key issue here to laser sinter complex lattice was PEEK’s melt shaped PEEK plates one at a time temperature of while matching the exact curvature 385°C. EOS’s high of a patient’s skull. temperature EOSINT P 800 laser sintering system is the first to operate at this temperature range.

When used in conjunction with additive manufacturing, PEEK can be laser sintered into highly complex geometries that promote osseointegration—the infiltration of a patient’s own bone cells (osteoblasts) into the structure of an implant over time. Conventionally titanium and PEEK machined or moulded implants can include holes to accommodate this tendency for bone ingrowth. But because laser sintering is an additive 3D

manufacturing process, it can produce much more intricate structures, free of the constraints of traditional methods, that are impossible via any other technology.

To further promote bone growth, the finished PEEK structures were infiltrated with a bioabsorbable polymer filled with 50% hydroxylapatite (HA). HA is a naturally occurring calcium phosphate. It is the primary component of bones and teeth and gives them their rigidity.

FEA Software Facilitates Projects Underpinning the entire project is a new type of software from UK-based design software specialists Within Technologies.

The software generates CAD files for scaffolded lattices that can be customised to follow the contours of a particular skull injury (the surgeon requires a plate which fits a hole in the skull which is never a perfect shape). An element of Within’s software — an enhance tool — controls not only the design of the internal lattice (resolution, strut thickness and topology), but also the width of the part’s walls or skin in a fluid and continuous fashion.

Once an object is defined, in order to predict its behaviour when in situ, the Within Technologies model is integrated with finite element analysis (FEA) in a feedback loop that allows rapid iteration between optimising the design and seeing how it will perform under stress.

Strength and Biocompatibility Testing According to tests, the implant prototype can withstand greater than 100 megapascals (MPa) of pressure with minimal deflection, and any stress at impact dissipates quickly without being transferring to the brain — a key safety requirement. The implants have also been tested for biocompatibility standards according to the relevant ISO 10993 requirements. Tests have also shown that there is no degradation after e-beam sterilisation.

MAY | JUNE 2012 / MPN /17

DOCTOR’S NOTE

Nanotechnology Enables Stem Cell Growth around PEEK Hip Implants << The nanopatterned surface will encourage bone growth on PEEK implants.

The technology in the first image, which shows a sample just 2.5 cm wide and 2 mm thick, will significantly improve an implant’s useful life in situ. >>

In-mould e-beam lithographic technique covers implant in 120 nm-wide pits

Scientists at the University of Glasgow in Scotland, UK, are working to harness the regenerative power of stem cells to improve orthopaedic The technology will implant surgery. They are eventually eliminate collaborating with expensive follow up surgeons at Glasgow’s surgeries which conventional Southern General Hospital implants currently require to develop a new type of orthopaedic hip implant.

In hip replacement surgery, the head of the thigh bone is removed and replaced with an implant which is held in place by a rod fixed inside the marrow along the length of the bone.

Marrow is a rich source of mesenchymal stem cells, which have the potential to divide, or ‘differentiate’, into other types of cells such as skin, muscle or bone which can improve the process of healing. However, stem cells can also differentiate into cells which have no use in therapy. Artificially controlling the final outcome to ensure the desired type of cells are created is very difficult, even under laboratory conditions.

When conventional implants are fixed into bone marrow, stem cells usually differentiate into a buildup of soft tissue which, combined with the natural loss of bone density that occurs as people age, can weaken the bond between the implant and the body. Treatment requires expensive and painful surgery.

The team at the University of Glasgow have found a reliable method to encourage bone cell growth around a PEEK implant.

The method uses electron beam lithography to impart the required structure onto a nickel film. This film is then inserted into the mould where the part is produced in one step. The technology is similar to that used for the manufacture of Blu Ray discs and DVDs. Dr Matthew Dalby of the university’s Institute of Molecular, Cell and Systems Biology, explained: “Last year, we developed a 18/ MPN / MAY | JUNE 2012

plastic surface which allowed a level of control over stem cell differentiation which was previously impossible. The surface, created at the university’s James Watt Nanofabrication Centre, is covered in tiny pits 120 nanometres across.”

He added: “By covering an implant in this surface, we can ensure that the mesenchymal stem cells differentiate into bone cells. This will help the implant site repair itself much more effectively than has ever been possible before and could well mean that implants will last for the rest of a patient’s life.”

Dr Nikolaj Gadegaard, senior lecturer in biomedical engineering, explained: “The inertness of PEEK has made it difficult to use in implants outside of spinal surgery before.

However, our nanopatterned surface may allow the plastic to interact with stem cells in the hip and enable an effective integration between the implant and the body for the first time.”

He added: “Although our nanopatterned surface is complex, the process of production is similar to that which makes Blu Ray discs, which means that future mass production of the implant is a very real possibility.”

Dominic Meek, consultant in orthopaedics and trauma surgery at Glasgow’s Southern General Hospital, has been participating in the development of the new implant. He said: “It’s an extremely exciting project to be working on, with implications for improving a wide range of joint replacements and other orthopaedic surgeries. We’re keen to see a prototype ready for use in orthopaedic surgery within 3 to 8 years.”

The research to date has been funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC), the Engineering and Physical Sciences Research Council (EPSRC (including the University’s Knowledge Transfer Account (KTA) in nanotechnology)), the Scottish Government’s Chief Scientist Office and the European FP7 project NaPANIL.

PRODUCT FOCUS

Surgical Savings with Single Use Plastic Devices High performance gamma stabilised polyarylamide (PARA) composite beats reuasable materials on price and performance For medical device engineers, Ixef PARA is a relatively new material. But it is actually a legacy high performance plastic which has Disposable single use medical been used as a metal replacement in the products like gloves and automotive and syringes have been telecommunications commonplace in the healthcare industries for many industry for many years. High years.

Ixef is a 50% glass performance plastics, however, fibre reinforced are making inroads in new polyarylamide applications — particularly in compound which the replacement of metals — as can reportedly clinicians strive to deliver high match the levels of care under the pinch peformance of tightening budgets. One characteristics of showing particularly strong many metals. promise is Ixef polyarylamide Specifically, it has a (PARA), a 50% gamma high tensile strength, significant flexural radiation stabilised glass fibre strength and high reinforced compound from flowability and can Belgium-based Solvay. be used in injection moulding and finished with a smooth coloured surface that is comparable with any painted metal.

For single use devices, medical grade Ixef offers the significant advantage of being less expensive than other commonly used materials such as metal alloys and reusable plastics. It is also gamma radiation stabilised, which means it can be gamma sterilised post moulding — something which is not always possible with lower performance plastics such as polycarbonate/ABS blends.

Low PARA Prices Can Cut Customers’ Costs In general, the price of metals tends to be considerably higher and more volatile than that of plastics.

This is reflected in the ongoing trend of migration by device manufacturers from the use of metal to plastic in their products.

A direct cost comparison between plastic and metals in medical devices can be difficult given the wide range of processing steps for each step, but most manufacturers accept that plastics are more cost effective than metals, even if the savings can’t be easily quantified.

Kathleen Murtagh-Galea, healthcare sales development manager for Solvay, points out that at €14 to €16

20/ MPN / MAY | JUNE 2012

per kilo, the price of Ixef is more palatable than that of the plastics used in reusable devices — which ranges from €35 to €50 per kilo. In addition, device users must add the cost of in-hospital sterilisation after each use as well as other maintenance and storage costs.

Gamma Stabilised Materials Keep Their Colour…

Gamma ray radiation is a preferred method of sterilisation in single use device manufacturing because no moisture is involved and it can easily accommodate large quantities of prepackaged instruments at one time. But there are manufacturing challenges with this technique for lower performance plastics, such as polycarbonate/ acrylonitrile butadiene styrene (PC/ABS) blend. It results in shifts in colour and mechanical properties of the material, compromising the integrity of any finished product. Ixef overcomes these problems as it allows gamma radiation of single use plastic devices without negatively impacting its properties.

Because gamma stabilised Ixef PARA comes in an assortment of colours, hospitals and medical device OEMs have the opportunity to create unique branding schemes.

This comes in handy in situations where there are a large number of instruments that accompany a device such as an implant. In this case, a variety of tools are needed to address the potential sizes, anatomies and medical conditions of the subject patient population. Stable colour provides a quick visual reference for differentiating instruments and matching medical disciplines with hospital wards, for example, red for obstetrics and blue for pediatrics.

“The medical community wants instruments that are both aesthetically appealing and functional,” says Kathleen. “Towards this end, colour coding is beneficial in identification and for sizing, allowing the surgeon to quickly and safely select the required instrument during a procedure. This can be a significant benefit over metal instruments, which are typically very similar in appearance.” …and Reduce In-house Sterilisation Costs Prepackaged tools can eliminate costly in-house sterilisation.

According to Solvay, a study has estimated that each sterilisation load of reusable equipment costs between €6.20 for the pH neutral method and €78 for the steam method, not including the capital investment of sterilisation equipment.

For hospitals looking to reduce overhead and costs, having a more balanced mix of reusable and single use devices may be something to consider. An appropriate combination provides more flexibility in operating rooms and frees up equipment to be used on the instruments that absolutely need to be decontaminated.

Ixef Instruments Fight HAIs Patient safety is always a main priority for medical providers. But according to the US Center of Disease Control each year in the USA alone there are approximately 1.7 million hospital acquired infections (HAIs) — or 4.5 per 100 patient admissions — and nearly 100,000 related deaths. In addition to the obvious human cost, the financial cost of these infections is estimated at over $5 billion a year.

There is evidence that prion diseases such as Variant Creutzfeldt-Jakob Disease may be able to survive for up to 10 sterilisation cleaning cycles. This raises additional concerns for patients and hospital staff alike that reusable surgical instruments could be contaminated despite best efforts at decontamination.

Pre-sterilised disposable instruments are a way of addressing these problems. And according to Solvay, instruments made of Ixef PARA ensure high quality performance and safety standards of the equipment used in hospitals and for care continued at home.

<< Solvay’s high performance Ixef glass fibre reinforced polyarylamide composite is ideal for single use disposable surgical devices. It beats metal alloys on cost, is colour stable after gamma sterilsation post moulding and can help in the fight against HAIs. >>

JULY 2011/ MPN /21

PRODUCT FOCUS Single Use Devices | PRODUCT FOCUS

Estimating the Shelf Life of Medical Plastics by Accelerated Ageing While ageing occurs more rapidly when polymers are exposed to weathering, polymer ageing is also observed in medical plastic products stored in protective opaque packaging.

Several mechanisms are responsible for the typical ageing effects seen in unpigmented polymers of yellowing and a loss in flexibility. This degradation is All materials degrade over chiefly caused by UV exposure, time, but the effects of oxidative damage and changes ageing on polymers can be to the polymerâ&#x20AC;&#x2122;s crystalline particularly dramatic. Just structure, referred to as have a look at PVC physical ageing. Ageing can reduce molecular weight by guttering or black PP car chain scission, induce bumpers that have been crosslinking and modify exposed to the elements crystallinity, all of which alter for several years, leading mechanical performance giving to severe embrittlement rise to the risk of product and bleaching. failure.

Polymer ageing is monitored using a range of analytical methods including thermal analysis, spectroscopy, gel permeation chromatography, density measurements and mechanical tests.

Ageing is particularly important in critical medical applications, such as implants or devices which come in to contact with the nervous or circulatory systems. HDPE acetabular (a surface of the pelvis) cups and PEBAX angioplasty balloon catheters are examples of such critical components. Ageing

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effects in medical applications are often exacerbated by the fact that medical grade polymers frequently lack antioxidant, light stabiliser and pigmentation additives. In addition, gamma, ebeam and EtO sterilisation can cause additional polymer damage and accelerate subsequent ageing reactions.

Since oxidative damage depends on the diffusion of oxygen from the surface, the geometry of the part will affect the ageing process. In addition, the thermal history experienced by the component during production will influence the crystallinity, altering any subsequent physical ageing. It is therefore vital that ageing tests are conducted on representative production parts as opposed to test coupons.

The FDA and EU regulators require data supporting shelf life claims made for medical products by their manufacturers. Real time shelf life testing of polymer parts at ambient conditions over the required shelf life is generally impractical due to the time and costs involved. Therefore, a form of accelerated ageing is frequently used instead, with the financial benefits of early product introduction outweighing any potential risks.

Evaluated temperatures sometimes in conjunction with increased humidity are used to accelerate the ageing process.

The Arrhenius equation states that the rate of a particular chemical reaction increases exponentially with temperature.

Therefore, the reactions which cause ageing at room temperature can be accelerated by storing the product at evaluated temperatures. A log plot of the reaction rates or degradation times versus 1/Tempature (or 1000/Temparture) is

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<< Arrhenius Plot for PEBAX between 18°C (1000/k = 3.4) and 85°C (1000/k = 2.8). >>

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referred to as an Arrhenius plot and is used to demonstrate the validity of the model over a particular temperature range.

A straight line relationship confirms that the Arrhenius relationship holds over the temperature range studied, giving confidence in data obtained from accelerating ageing studies.

However, at high temperatures different ageing mechanisms can dominate, leading to curvature in the Arrhenius plot and inaccurate room temperature shelf life estimates. Several reports recommend a maximum ageing temperature of 60°C, with temperatures of 45-55°C typically being used. This appears prudent as many polymers (including PP, PE and PEBAX) show curvature in the Arrhenius plot above this temperature. It is also important that the polymer is in the same physical state (such as below the glass transition) at both the ageing and ambient temperatures. A simplified approach is known as the 10°C rule, which assumes that the ageing reaction increases by a fixed factor (Q10 often 1.8 or 2) for every 10°C above ambient. For example using a Q10 of 2, 6 months at 40°C would be equivalent to 2 years at 20°C. This is a more simplistic approach than the Arrhenius relationship which assumes a particular reaction constant and the two approaches are not directly equivelent.

Using accelerated ageing to produce data to demonstrate the shelf life of a critical medical product reduces the time to market. However, a detailed understanding of the materials used and their ageing behaviour is necessary to avoid potential pitfalls.

About the Author Dr Dorian Dixon is a lecturer in the School of Engineering at the University of Ulster in Northern Ireland. He has written over 30 papers in the areas of medical polymers, polymer ageing, dielectric barrier discharge treatment of polymers, nanocomposites, metallic nanoparticles for drug delivery and design of experiment methodologies.

He works closely with industry and is an investigator in the EPSRC funded MATCH project (match.ac.uk) investigating the value of new medical devices.

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MAY | JUNE 2012 / MPN /23

IN THE ZONE

3D MIDs: Plastic Metallisation for Injection Moulded Electronic Circuitry WORDS | SAM ANSON Thanks to a happy marriage between microelectronics and injection moulding, borne from integrated antennae in mobile phones, electronic medical devices can be improved through the use of 3D We are aware that the moulded healthcare sector is renowned interconnect for pushing technological devices, or 3D boundaries. Indeed, it is one of MIDs (pictured).

3D MIDs are the most welcoming adopters of injection moulded breakthrough processing parts with methods. But did you know that integrated highly functional and reliable electronic circuit electronic circuits can be traces. They offer a injection moulded from complementary thermoplastic materials to form technology to unusual but handy compact conventional printed circuit three dimensional shapes? And boards (PCBs) and did you know that the market are used for dental for this technology is growing at tools, insulin pens a stomping 20% a year? and hearing aids.

Generally, PCBs consist of conductive pathways etched from copper sheets laminated onto a flat non-conductive substrate. The way that PCBs are manufactured — ie using a flat 2 dimensional substrate — means that designers of electronic devices are faced with design limitations because PCBs can only be 2 dimensional, mainly squares and rectangles. This means that devices either have to be conventionally shaped, or the space inside intricately shaped devices is not optimised.

3D MIDs, by contrast, consist of a single moulded substrate into which the circuit of conductive pathways is integrated.

Because the electronic aspect is integrated, the substrate can be moulded into interesting and unique shapes, offering space saving advantages for manufacturers.

Thanks to the extremely tight tolerances which can be achieved, structures as small as 150 μm are possible for small quantities. For larger production runs, ie greater than 1 million, sizes of conductor tracks and the distances between them can be as small as 300 μm. Conveniently shaped parts with less components make assembly cheaper and quicker while rendering the devices lighter in weight.

Materials and Manufacturing Processes According to the German Research Association for Molded Interconnect Devices, based in Nuremburg, up to eleven polymers can be used for 3D MID substrates. These are, starting

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<< 3D MIDs are an essential technological enabler in the quest for ever more miniature electronic devices. >> with the cheapest, polypropylene (PP), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyamide (PA), polyphenylene sulfide (PPS), polysulphone (PSU), polyether sulphone (PES), polyetherimide (PEI), and liquid crystal polymer (LCD).

The manufacturing of 3D MIDs is essentially a two step process. First, the moulding of the circuit substrate is performed, and second, the conductive pathways are structured and metalised. The two most common approaches for producing 3D MIDs are laser direct structuring (LDS) and two shot moulding.

Laser Direct Structuring (LDS) The laser direct structuring method (LDS), patented by German laser equipment supplier LPKF (pictured), uses a thermoplastic polymer doped with a laser activatable metal polymer additive. It is most suitable for short production runs where a number of layouts are required.

When a laser beam hits the activatable polymer it activates the metal complex and creates a precise track with a rough surface. Exposed metal particles in this track form nuclei for a subsequent metalisation coating process, which occurs in a metalisation bath.

In terms of materials, the metal oxide containing additive must be evenly distributed and sufficiently concentrated in the thermoplastic resin. Examples of these materials include Lanxess’s Pocan polyester based on polybutylene terephthalate (PBT) and polyethylene terephthalate (PET), PA6/6T, a partially aromatic polyamide based on BASF’s Ultramid, a crosslinkable PBT (polybutylene terephthalate) based on Vestodur from Degussa, LCP (liquid crystal polymer) based on Vectra from Ticona and PC/ABS (polycarbonate and acrylonitrile butadiene styrene) from

DSM. Sabic and Mitsubishi have recently issued pigmented LDS materials.

Due to its low set up costs and high locus of control, LDS can also be used as a prototyping method before a product is fully developed.

Two Shot Moulding of 3D MIDs For larger production runs, the most efficient method of 3D MID production is two shot moulding. This process relies on plateable and nonplateable polymers. Plateable polymers can be plated, or covered, with a metal such as copper.

During the two shot moulding process, a plateable polymer is moulded in the first shot and then overmoulded with a nonplateable material, leaving some areas of the plateable << Laser direct structuring is material exposed. a patented process of laser Next, metal is adhered to the equipment supplier LPKF. >> exposed areas using an electroless plating process. Here, the surface of the plateable polymer is roughened, allowing the metal to be adhered in selected areas. Typical polymers used in this method are ABS for the plateable substrate and PC for the non-platable layer. The plating chemistry can be controlled to prevent the roughening of the PC portions of the component.

Company Profile: Cicor Claiming to be Europe’s leading contract manufacturer of 3D MIDs for medical device manufacturers is Switzerland-based Cicor. The company is an established expert in printed circuit boards (PCBs), microelectronics and customised electronic product assembly and moulding for the medical industry.

Given this vast and highly specialised experience in electronics markets, a strong knowledge base in injection moulding and the LPKF LDS method, and the strong overlap between electronics and plastics in 3D MIDs, it’s easy to see how Cicor has become a leading light.

Supporting this view, the company has a technology centre dedicated to R&D in 3D MID design and manufacturing in Boudry, Switzerland.

Cicor has recently opened a new sales hub in the USA, operated by newly established US subsidiary Cicor Americas.

According to CEO Roland Küpfer: “Launching our own sales company in the USA represents a key milestone for Cicor in our efforts to further penetrate the American market. It substantially improves our chances of acquiring new customers in the region.”

Cicor works with a variety of base materials and blends — PC/ABS, PBT, PBT/PET, PA and LCP.

MAY | JUNE 2012 / MPN /25

IN THE ZONE

Heavyweight Twin Sheet Thermoforming Enters the Ring …

In thermoforming, heavy gauge (or thick gauge) processes are essential for devices — particularly in housings. But the process can get lost among the hype of thin gauge thermoforming for packaging. Our editorial team was understandably intrigued, therefore, when they heard about twin sheet thermoforming. We spoke to Wynn Kintz, owner of Kintz Plastics — one of the few thermoformers which can handle parts up to 11 m2 in size.

<< These 1 metre-tall doors for the enclosure of Siemens’ Immulite diagnostic system are made by twin sheet thermoforming. Their attractive appearance is only possible by thermoforming. >>

Q. Please explain the twin sheet thermoforming process and how it differs from other thermoforming techniques.

A. Twin sheet thermoforming consists of two simultaneous vacuum forming operations which produce an integrally welded, hollow part, similar to one which has been blow moulded. The two halves of a twin sheet part can be of the same or dissimilar materials and thicknesses, with finished surfaces on the front and back.

The two plastic sheets are heated in a double framework setup and then transported to the forming station. The two moulds are brought together, air is evacuated, and both heated sheets are pressed and fused together at predetermined weld points.

Combining two sheets into a unified part is more difficult than forming a single sheet. Thermal bonding has to be precise, making proper alignment of tools critical. Control of conditions in the area between joined sheets is also important.

Q. What advantages do you gain with twin sheet thermoforming?

A. Twin sheet thermoforming can replace two processes with one, saving labour, reducing weight and yielding greater strength compared with separately formed parts that are mechanically fastened or bonded with adhesives. The twin sheet process gives us greater control in manufacturing and a more consistent shape and size of parts.

We can make lighter, better performing parts while using less expensive capital equipment, less expensive tooling, and more flexible production. Parts offer excellent stiffness, and more 26/ MPN / MAY | JUNE 2012

<< In twin sheet thermoforming, the upper and lower plastic sheets are heated and then simultaneously vacuum drawn into top and bottom female moulds. >> detailed geometry than labour intensive fibre reinforced versions.

Q. Please give an example of a medical application of twin sheet thermoforming.

A. We turned to twin sheet thermoforming with a proprietary thermoplastic alloy to produce redesigned heavy duty enclosures for an Immulite immunoassay medical

diagnostic testing instrument from Siemens Healthcare Diagnostics. The two side doors of the medical device were previously moulded of fibre reinforced plastics (FRP).

Q. What challenges did the application present?

A. The previous doors were heavy and required long lead times because of labour intensiveness in producing them. The finished parts could also vary slightly in size and shape.

Q. What advantages does the part gain?

A. Twin sheet thermoforming lowered the cost of the doors by 30-50%. An overall weight reduction of the immunoassay instrument decreases shipping costs to customers, and makes the unit easier to move around in the hospital. Unlike the previous design, virtually no variation occurs in the dimensions of the part.

The smooth and finely detailed surface finish, part of Siemenâ&#x20AC;&#x2122;s redesign on both sides of the doors, results in a highly attractive appearance.

Q. Discuss the thermoforming material, and why it was selected.

A. The original redesign of the side door enclosures called for flame retardant ABS/PVC sheet, but we opted for a rigid proprietary thermoplastics sheet from USA-based Boltaron for improved properties and cost/performance benefits. The material, Boltaron 4335, is a fire proof, extruded alloy sheet offering a UL 94 V-0 rating, impact resistance of 2.1-2.5 kg/m, and broad chemical resistance, allowing cleaning using concentrated cleansers. We use the sheet in thicknesses of 4 mm for the front and 3.2 mm for the back. It is extremely formable, and allows only minimal â&#x20AC;&#x153;thin-outâ&#x20AC;? in deep recesses and on outside corners.

Along with the front doors, we manufacture a large front bumper enclosure for the Siemens instrument, which is pressure formed from Boltaron 4335 sheet.

Q. What secondary operations do you perform on the immunoassay enclosure after twin sheet thermoforming?

A. Once moulding is complete, secondary operations include extensive machining and trimming with a three axis CNC router.

Backside mounting blocks for hinges are incorporated, a screw block is bonded to the sheet with an epoxy system, and brass inserts are ultrasonically pressed into the part. Both side doors are painted for a two tone colour, after which we apply a metal based EMI/RFI spray shielding component on the interior side for antistatic protection.

MAY | JUNE 2012 / MPN /27

USA FOCUS Crossing the Atlantic: AdvaMed Promotes Collaboration between Europe and the USA

by Stephen J Ubl, president and CEO of Advanced Medical Technology Association (AdvaMed)

The integrity of collaborations between the medical device industry and health care professionals is central to innovation and the advancement of technology in the medical device industry.

The goal at AdvaMed is to create and preserve a business environment that fosters medical innovation, no matter where that innovation occurs. To facilitate this, we work with medical associations, governments and companies worldwide to harmonise compliance and codes of conduct for ethical business practices.

In Europe, AdvaMed and the European Medical Technology Industry Association (Eucomed) signed their first joint statement on ethical interactions between medical technology companies and health care professionals in 2010. The agreement was later adopted by several other international medical technology trade groups. In January 2012 AdvaMed and Eucomed developed and adopted a joint guidance initiative which encourages companies to adopt compliance programmes that integrate risk analyses and local laws. It aims to ensure that there are ethical interactions with entities hired for assistance in medical device marketing, sales and/or distribution.

The interactions between medical technology companies and health care professionals ensure patients have access to advanced medical technologies. But because this spans many natural borders, they can be highly complex and involve laws from multiple countries. We strongly believe a proactive marketing approach helps companies, and teaming with Eucomed has allowed us to provide more thorough guidance.

With hopes of encouraging similar industry collaboration and reducing barriers to innovation, AdvaMed, Eucomed and 14 other medical technology associations for the past five years have jointly hosted an annual International Medical Device Industry Compliance Conference. The conference, this year held May 9-11 in Stockholm, Sweden, addresses an array of compliance issues and covers trends in anti-corruption, transparency and technology convergence. AdvaMed hosted a similar conference this year in Miami focused on Latin American industry executives and government officials.

28/ MPN / MAY | JUNE 2012

Europeans Flock to New England for High End Catheters Three layer lubricious and bondable guide wire catheters meet variable durometer single extrusions Putnam Plastics has been a leader in advanced catheter extrusions for nearly three decades. During this time they have partnered with medical Our USA Country Focus device companies in Europe starts with one of the best to develop designs that meet known US contract extruders challenging product among Europeans, specifications and novel Connecticut-based Putnam market requirements. The key Plastics. In this article we factor behind their success examine why European here is that they are very manufacturers flock to good at what they do, and Putnam for difficult and what they do is extremely advanced catheter challenging. manufacturing technologies, Their products, particularly in co-extrusion. lightweight extruded medical catheters, are particularly advanced. For European OEMs, any added costs of sourcing from the USA are easily outweighed by the fact many believe that Putnam are the undisputed experts in their field. Their ability to develop prototypes and put them into production, all from a basic concept, means that customers don’t need to do much apart from meet with their European field representative, present their idea, agree on technical requirements and provide prototype refinements before going into production.

The foundation of this is Putnam’s engineering ability. Lisa Vicker, director of Putnam’s sales operations agrees: “High end catheters require highly skilled extrusion engineers. And these guys are few and far between. But at Putnam we’re lucky, because we have some of the best in the world.”

Dan Lazas, president of the medical plastics marketing firm Lazas Marketing Group, concurs: “Putnam’s talented extrusion engineering team, inhouse tool manufacturing and wide range of capital equipment allow them to develop even the most complicated state of the art catheter extrusions”.

Tri Layer Extrusion for Lubricious and Bondable Guide Wire Catheters One of Putnam’s signature products is a tri layer extruded catheter. The tubing combines a lubricious inner surface with a bondable outer surface ideal for inner member shaft components used in coronary, neurovascular and other catheter applications. The low friction interior surface

<< Putnam’s Total Intermittent Extrusion (TIE) tubing enables surgeons to push the catheter around corners without it kinking.

Notice the gradual change in colours. This represents the gradual change in material along the extrusion, giving a variable durometer. >>

enhances movement of guide wires within the shaft, while the exterior allows for bonding of distal tips, balloons, or proximal connectors. A middle layer bonds the two distinctly different polymers used for the inner and outer layers. Tri layer extruded tubes are particularly useful in catheter systems that navigate deep into the vascular system by following a preplaced guide wire. Tri layer extrusions are also used as working channels within a catheter assembly to allow for insertion of a tool or implant through the lumen to the therapeutic site.

Variable Durometer Tubing — Total Intermittent Extrusion (TIE) Putnam’s trademarked TIE technology is a co-extrusion which imparts variable flexibility in a catheter. In simple terms, variable flexibility refers to the fact that the tip of the catheter is soft and the base is stiff. The stiff end allows practitioners to push the catheter shaft into a lumen, the soft end being flexible enough to bend around corners.

Putnam’s variable durometer tubing is produced by intermittent extrusion of variable durometer polymers along the length of the shaft (pictured). Hence the brand name Total Intermittent Extrusion, or TIE. A Bright Idea – Tri Layer Variable Durometer Catheters Recently, Putnam combined these technologies and introduced and trademarked Tri-Tie continuous extrusion technology. In this technology, a stainless steel braid is applied to the outer surface of the Tri layer extrusion, followed by a TIE variable durometer layer. Putnam Plastics’s Tri-Tie extrusion technology eliminates traditional manual assembly of multiple components.

MAY | JUNE 2012 / MPN /29

USA FOCUS

CUSTOMISE

Resorbable Polymers to Suit Your Design, Not The Other Way Round

by M Scott Taylor PhD, consulting manager, Poly-Med Engineer: “We are developing a new resorbable device and are having problems with poly-glycolide — the material fails under shear load. Could you help us develop a heat treatment to enhance flexibility?”

MST: “How do you need the material to perform, and do you know that poly-glycolide is not your only option?”

The conversation above provides an all too familiar framework for the initial call with a design Tailored engineer having polymerisation trouble with material yields resorbable selection. You could ureteral stent insert any “off the shelf” resorbables, like poly-l-lactide (PLLA) or 90/10 poly(lactic-co-glycolic acid) (PGLA) in place of poly-glycolide and many other failure modes in place of shear load, including processing difficulties.

While it is true that these polymers have histories of use in several applications, they often fail to meet performance requirements for advanced and specialised device designs. So instead of trying to design a device around available materials, we often see that it is more productive to include material selection as part of an integrated design approach. By this, I am describing an integrated design approach where the product is developed as a whole and in parallel, including mechanical design, material and process development including customised polymerisation, sterilisation, and packaging.

This integrated approach defines our methodology and represents a paradigm shift from traditional device design. By starting with the basic design needs and identifying the best polymers, engineers

Keys to design with resorbable materials

30/ MPN / MAY | JUNE 2012

can create devices with improved functionality, often providing a distinct advantage over competitive products.

Case Study 1: Degradable Ureteral Uriprene Stent Ureteral stents are currently based on non-degradable materials and require painful removal after treatment. Providing a fully degradable stent is an obvious advance but has not before been realised primarily due to degradation properties of the materials used. To meet the clinical need, Poly-Med developed a stent to (a) provide initial mechanical integrity, (b) degrade in a controlled and predictable manner, and (c) degrade into soft particles for easy excretion. This required development of several customised polymer materials, a unique construction, and selection of the proper sterilisation technique.

Case Study 2: Custom Polymerisation of PGLA Overcomes Moulding Warpage Issues 90/10 PGLA is a random copolymer that was originally developed for Vicryl, a brand of sutures manufactured by Johnson & Johnson’s Ethicon, based in New Jersey, USA. The material was originally developed for textile applications, but has more

1. Have a clear understanding of performance requirements — mechanical strength, expected length of mechanical functionality and ultimate limits for mass retention.

2. Know necessary versus optional attributes. Is it acceptable to see

<< Uriprene stent from PolyMed is entering clinical trials. >> recently been used for injection moulded articles. A client had originally specified 90/10 PGLA for a small moulded part, but was having difficulty with part warpage after moulding. Analysis related this warpage to relatively slow crystallisation kinetics, which is a benefit for multifilament textile extrusion but leads to difficulty with the injection moulding process. To correct, Poly-Med recommended a 95/5 PGLA which exhibits much faster crystallisation kinetics, resulting in faster cycle times and lower scrap rates.

There are typical hesitations to this type of approach, including fear of high polymer cost and potential regulatory hurdles. However, more often than not, these are unfounded. Customised polymers are cost competitive and follow a similar regulatory path when compared to “standard” resorbable polymers.

residual material after 12 months for a four-month device?

3. Use materials supplier as a resource to assist with material selection.

4. Know the material selection process can involve changes and adjustments.

MAY | JUNE 2012 / MPN /31

USA FOCUS Foster Corporation | USA FOCUS

Custom Blending of Implantable Polymers Custom blending of implantable polymers is a challenging skill in which tolerances are minute and precision is an absolute must. Tony Listro, managing director of USA-based Foster Corporation’s Delivery Science unit, provides insight into how these compounds are being enhanced and tells us why orders are coming for exciting new recipes from Europe, and the rest of the world.

Custom compounding such materials requires facilities, equipment and processes necessary for implantable applications. In order to achieve the biocompatibility required for implants and the precise release rates of bioresorbables, contamination must be kept to an absolute minimum. All batching and hot melt extrusion processes must be conducted in a clean environment — ISO Class 7 (10,000) class cGMP certified is a minimum.

Twin screw extruders are often required to provide optimal distributive and dispersive mixing when melt blending liquid and powdered additives into a implantable polymer matrix. Small scale twin screw extruders are required from an economic standpoint as ingredients for enhanced orthopedic implants are relatively expensive.

Pre- and post-extrusion equipment is also highly specialised for implantable polymers. Desiccant and vacuum driers are required to prepare active

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<< Foster’s compounding of implantable polymers is conducted in an ISO Class 7 (10,000) cleanroom. >>

ingredients in fine powder form and pellets of bioresorbable polymers with low melt temperatures. Polymers having dissimilar bulk densities are best fed into the extruder separately using multiple single screw loss in weight feeders. Fine power additives are also fed separately using twin screw or disk type loss in weight feeders. Liquid ingredients are injected into the melt blend with peristaltic, gear, piston, or syringe pumps.

Post-extrusion cooling of the polymer blend is essential for precise sizing and metering. Long term implantable polymers are cooled using water while bioresorbable polymers must be cooled with a dry air supply. In both cases the cooling medium must be clean and maintained at a specific temperature.

To learn more about compounding machinery for implantable and other medical grade polymers, including fourand eight-screw extruders, see Clean Machines on page 46.

LinkedIn Members Petition US Medical Device Tax A discussion group with 110,000 members on social networking site LinkedIn has launched a website to collect votes in its petition against a proposed 2.3% medical device tax in the USA, due to take effect in January 2013. The initiative is called No 2.3.

The new website, found at www.no2point3.com, is an online petition to US Congress featuring video, articles, and downloads about the medical device tax.

The discussion group which has set up the site is the Medical Devices Group. It claims to be a spam free curated forum for intelligent conversations with medical device thought leaders.

According to the group, the tax, to be paid by firms with or without net income, roughly doubles the industry’s total tax bill and raises the average effective corporate income tax rate to one of the highest faced by any industry in the world.

According to a September 2011 study entitled Employment Effects of the New Excise Tax on the Medical Device Industry, the tax could result in job losses in excess of 43,000 and wage losses of more than $3.5 billion.

Joe Hage, leader of the Medical Devices LinkedIn group, conceived the No 2.3 lobbying initiative. “I created the website so the group I represent could raise its collective voice in unison with 400 medical device companies, the Medical Device Manufacturers Association (MDMA), the Advanced Medical Technology Association (AdvaMed), the US Chamber of Commerce, the National Association of Manufacturers (NAM), the National Federation of Independent Business (NFIB), the National Venture Capital Association (NVCA), and others.”

The site was funded in part by Cook Medical, the multi-specialty global medical device OEM, and medical device marketing consultancy Medical Marcom.

MD&M East Relocates to

Philadelphia On May 22, 2012, the Pennsylvania Conference Center in Philadelphia, USA, housed the newly relocated MD&M East trade show for medical device designers and manufacturers. The event, which is the longest running medical manufacturing event on the USAâ&#x20AC;&#x2122;s east coast, has moved from its previous home at Jacob K Javits Convention Center in New York.

The decision to move to Philadelphia appears to have been driven by a density of medical technology firms in the Greater Philadelphia area. According to the MD&M East prospectus, Greater Philadelphia is home to more than 2,100 medical technology firms. And according to a recent Miliken report, in 2007 the life sciences sector in the area was responsible for generating 380,800 jobs, $20.2 bn in earnings and $39.7 bn in output.

Visitors were keen to hear that two new events were colocated at this yearâ&#x20AC;&#x2122;s show, both of which are US spin offs from successful European trade shows. The debuts were drug delivery and packaging event Pharmapack North America and pharmaceutical contract manufacturing event ICSE. On May 21, a day before the trade show started, the SPE Medical Plastics Division held its usual conference.

Topics covered included polyolefins for blow fill seal (BFS) applications, medical grade PUs, trends in materials, antimicrobials and HAIs, resorbable lactides and processing considerations, and silicones and active pharmaceutical ingredients (APIs).

On May 23, the second day of the trade show, at 4.30 pm, the Medical Device Excellence Awards (MDEA) Winners presentation ceremony was held during a special cocktail reception inside the downtown Marriott Hotel in Philadelphia. The ceremony consisted of a number of highlights including the announcement of the 2012 MDEA winning products, the awarding of the bronze, silver, or gold awards for each category, the Best in Show award, the 2012 MDEA Lifetime Achievement Award and the announcement of the winners of the US young graduate and undergraduate inventors competition BMEidea.

MAY | JUNE 2012 / MPN /33

RESPIRATORY DEVICES

Respiratory Tubing: The Facts words | SAM ANSON

All respiratory devices have one thing in common — they are given to a patient to deliver a gas to their lungs.

Typical applications Respiratory devices rely on are ventilators (to help extruded plastic tubing for patients breathe) and delivery of air and other gases delivery of an to the patient. Applications anesthetic.

range from ventilators on high dependency units and anesthetic delivery to mobile aids for people with breathing difficulties. In this article we look at some of the most innovative designs for respiratory tubing and profile one of the leading contract supplers, Canada-based GlobalMed.

Ventilators There are two main types of ventilators, those which deliver assisted ventilation and others which provide controlled ventilation. Assisted ventilation is typically for patients who have difficulty breathing as a result of lung diseases, such as chronic obstructive pulmonary disorder (COPD).

Controlled ventilation is for patients who cannot breathe on their own, which tends to be those in critical

care, whereby air delivery is given using a timed mechanical ventilator.

The key technology at work for these applications is positive airway pressure (PAP), which refers to a mechanical action whereby air is “blown” into the lungs.

Ventilators utilise a number of types of PAPs, the most common of these being continuous positive airway pressure (CPAP). CPAP was originally designed for sufferers of sleep apnea, a condition whereby the upper airway becomes narrow as muscles relax during sleep.

Sometimes the patient can stop breathing for minutes at a time. The CPAP machine is able to sense when this happens and blows air into the patient’s mouth to maintain a steady breathing rhythm. Nowadays, CPAP technology is used for most assisted ventilation devices.

In terms of the tubing carrying the air to the patient, it is almost always made from corrugated plastic. However, there are specific design aspects to the tubing which affect the performance of the device.

Poor quality tubes can get caught on sharp corners and uneven corrugations will mean that tubing does not bend properly.

Also, the surface on the inside wall of the tubing will determine the overall level of sterility for the patient. A

<< GlobalMed’s smooth corrugated tubing is used by patients all over the world in portable CPAP devices like this one. The smooth interior surface improves air flow and reduces the likelihood of infection. >>

34/ MPN / MAY | JUNE 2012

rough surface will encourage growth of bacteria, leading to increased likelihood of infections whereas a smooth interior will help to prevent this.

For some respiratory devices, plastic tubing is a single use item. However, thanks to improvements in medical grade polymers, sterilisable tubings are gaining important attention from device designers.

Supplier Profile — GlobalMed Claiming to be North America’s leading manufacturer of corrugated and collapsible tubing products for medical applications is Canada’s GlobalMed. The ISO 13485 certified company, which also supplies the fittings (or cuffs) by which tubing can be attached to devices, has been working with ventilation and anesthesia device OEMs for over 30 years.

Their most popular product is tubing for CPAP devices for the home and hospitals. The tubing has a smooth interior and is favoured above standard corrugated tubing because it provides unrestricted, optimal airflow to the patient.

GlobalMed also supplies reusable CPAP tubing made from DuPont’s Hytrel thermoplastic polyester elastomer (TPC-ET). The tubing, which is autoclavable, is used primarily in hospitals for long term ventilation systems in critical care. The tubing comes with integral cuffs in

<< GlobalMed’s collapsible corrugated tubing is used in anesthesia, respiratory and ventilation devices in hospitals throughout the world. >>

diameters of 10 mm, 15 mm and 22 mm as well as with over-moulded cuffs.

In addition to ventilation, GloblMed’s smooth corrugated tubing is used for delivery of anesthesia where an unrestricted smooth flow of gas is essential.

Smooth corrugated tubing can also be used for smoke evacuation. The tubing has been installed in smoke evacuation devices for surgeons to remove toxic smoke by way of suction.

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<< Scientists believe technology may have respiratory device applications >>

Antimicrobial Porous Plastics with Crystalline Chlorhexidine Kill Microbes Healthcare associated infections (HAI) are a major concern for the medical industry. Almost all practitioners feel that there is a growing need to prevent them.

A popular solution to the problem is to use antimicrobial materials. Following on from our previous story about respiratory tubing, here we look at a new porous material and how its use in respiratory devices may help prevent the spread of airborne HAIs.

Scientists at USA-based porous plastics manufacturer Porex Corporation believe their new microbicidal porous material, Porex Barrier Technology, may have applications in a range of respiratory devices, including ventilators, oxygen masks, CPAP masks, therapeutic devices and inhalers.

Following third party laboratory tests according to the official antimicrobial standard JIS 2801 (ISO equivalent is 22196), there is proof that the technology is effective against a broad spectrum of microbes, including gram positive and gram negative bacteria and fungi (table 1).

<< Figure 1: Pores (in red) in sintered porous plastic. >>

<< Figure 2: The effect of chlorhexidine on a microorganism.

The walls of the cell in the second image have been ruptured. >>

As a porous media component it can be seamlessly integrated into respiratory devices to function as a vent, filter, wick or diffuser.

What makes Porexâ&#x20AC;&#x2122;s new material different from others on the market is that it incorporates crystalline chlorhexidine base material. Chlorhexidine gluconate, a different soluble form of chlorhexidine, is a chemical antiseptic substance already used in solutions for preoperative preparation liquids and antiseptic hand scrubs as well as mouthwashes, albeit in very small concentrations. Porex Barrier Technology is a sintered porous media incorporated with chlorhexidine. The homogenous antimicrobial open cell porous structures (figure 1) can have a range of morphologies depending on the application.

Based on the independent tests the technology has been proven to have a strong antimicrobial effect against three of the most common strains of microorganisms known to cause HAIs â&#x20AC;&#x201D; the S. Areus bacterium, the E. coli bacterium and the C albican fungus (figure 2).

Table 1: The JIS 2801 results provide valuable back up for antimicrobial claims.

S. aureus (gram positive)

E. Coli (gram negative)

Candida albican

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Product

Initial CFU

24 hour CFU

% Log reduction reduction

Standard product (without CHX)

3.3 x 106

3.4 x 106

-2

-0.01

Barrier technology (with CHX)

3.3 x 106

<200

>99.994

>4.22

Standard product (without CHX)

2.4 x 106

2.8 x 107

-1075

-1.07

Barrier technology (with CHX)

2.4 x 106

<200

>99.9915

>4.07

Standard product (without CHX)

1.8 x 106

5.8 x 105

67

0.48

Barrier technology (with CHX)

1.8 x 106

5

-99.99973

-5.56

RESPIRATORY DEVICES

Respiratory Rate Counter Monitors Breathing During Surgery UK-based Anaxsys, a respiratory device manufacturer, recently launched respiR8 (pronounced respirate) — which it claims is the world’s first continuous electrochemical respiratory rate counter.

Targeted at perioperative environments, respiR8 is reportedly an accurate, simple to use and cost effective means for enabling early detection of patient deterioration and providing improved patient outcomes.

Anaxsys came to Cambridge, UKbased Team Consulting to get help with the design work. Team were apparently chosen for their ability to understand user needs and combine electronics and software engineering with strong industrial design capabilities, including medical plastic moulding.

Anaxsys had developed a sensor system that could be used to monitor a patient’s respiration rate. The system was novel as it measured the moisture in a patient’s breath and could provide a critical early warning sign when a patient deteriorates, especially after anaesthetic or opioid pain relief.

Team took the Anaxsys’ sensor concept, conducted in-depth user research, defined the product specification and then used their expertise to develop a prototype.

Anaxsys used this prototype as the basis for the design which was used in clinical trials to obtain their CE mark.

“Respiratory rate has been identified as a key predictor of potentially serious clinical events, yet it is the vital sign least often recorded and most frequently omitted from hospital documentation,” stated Deryk Williams, CEO of Anaxsys. “respiR8 has been developed to address this clinical need for more accurate monitoring of respiration rate in clinical environments such as perioperative, and is intended for use on patients requiring supplemental oxygen via a face mask.” respiR8 consists of an oxygen mask, fitted with Anaxsys’ patented sensor which measures each breath, and a small electronic monitor that captures, displays and records the patient’s continuous

respiratory rate. The patient’s respiratory rate can be viewed in either a real time numeric breaths per minute display or a trending display on the monitor’s screen. respiR8 also allows healthcare professionals to safely monitor a number of patients at the same time, thereby improving hospital productivity while

ensuring quality patient care.

The plastics used in the device are as follows: ABS for the casing; clear polycarbonate for the screen; and PP and flexible EPDM rubber for power lead bung. The mask is made from a combination of PVC, PP and TPE.

<< Team Consulting’s prototype respir8 was used

by Anaxsys in clinical trials to gain their CE mark. >>

MAY | JUNE 2012 / MPN /37

FOLIO THANKS TO HIGH CLARITY, LOW EXTRACTABLES AND GOOD INERTNESS, TOPAS MEDICAL GRADE CYCLIC OLEFIN COPOLYMERS (COCS) ARE AN IDEAL MATERIAL FOR THE REPLACEMENT OF GLASS IN SYRINGES.

FOLIO

LPKFâ&#x20AC;&#x2122;S PATENTED LASER DIRECT SINTERING (LDS) PROCESS IS A KEY STAGE IN THE MANUFACTURING OF 3D MOULDED INTERCONNECT DEVCES (3D MIDS).

REGULATION REVIEW

Towards Regulatory Harmony?

ISO 13485 and the Medical Devices Directives The harmonised single European MDD will encompass cosmetic surgical procedures Increasing numbers of medical device manufacturers and service providers are using ISO 13485 certification in the regulatory and supplier approval process as it provides the first step in The ISO 13485 management achieving system is generally accepted as compliance with being an essential certification for European regulatory compliance among regulations. It also medical device manufacturers and delivers a structure their service providers. In March to gain CE marking so that the medical 2012 the standard was revised, device can be sold harmonising it with the EU’s throughout the EU. Medical Devices Directive For service (93/42/EEC), the Active providers it gives an Implantable Medical Devices extra level of Directive (90/383/EEC) and the In assurance to Vitro Diagnostic Medical Devices medical device manufacturers that Directive (98/79/EC). Who better the company has to give us the lowdown on these robust systems in changes and more than Jean-Louis place.

Evans, managing director at TÜV ISO 13485 is SÜD, one of the leading product also accepted testing and certification outside the EU and organisations. in some countries it is a legal requirement. For example, it is legally required for the Canadian and Japanese markets.

Where there is no specific legal requirement to hold the certification, a notified body authorised by the European national Ministries of Health may wish to audit a manufacturer’s suppliers of key components. But the notified body may dispense with an audit if the supplier already has ISO 13485 certification. So, if a supplier holds a suitable ISO 13485 certificate then this is used as the basis not to require a visit from the notified body to the critical supplier. In effect for those that do not belong to the ISO 13485 “club”, market opportunities may well be shrinking.

Adherence to the standard also brings other benefits, including an improved likelihood of customer satisfaction, as the standard will result in products being of a high quality, reliable and safe. Adherence should also bring improved risk management and reduced costs, as the continual improvement of processes increases efficiency and reinforces good practice.

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<< Jean-Louis Evans, managing director at TÜV SÜD, gives us insight into what the harmonised MDD might look like. >> Gaining Registration In Europe, all activities associated with regulatory compliance of a product must be reviewed by a notified body. If a key supplier already has ISO 13485, it often negates the need for a site visit from the notified body – saving an organisation time and cost.

The process of ISO 13485 registration follows four simple steps. First, the application forms must be completed, second the production facility must be audited, third the company must be issued with a certificate — ideally by an accredited certification body — and, fourth, annual surveillance visits and a three-yearly re-certification audits must be scheduled and carried out. For the fourth step, some organisations insist on a twice-yearly surveillance audit, thereby adding unnecessary cost and regulatory burden.

Harmonised Regulation Within the next few years, the European Medical Device Directives will become one regulation. This has far reaching implications for all those products that must currently comply with one or more of the medical device directives. The main implications of the change to a regulation will be that each EU country will have to implement the regulation word for word and no transition period will be allowed.

The regulation, which is currently at the initial draft stage, includes new areas such as cosmetic surgery, cosmetic contact lenses and liposuction. While this implies far reaching consequences for the medical device supply chain, best practice advice would be to keep up to date on the planned changes to the Medical Device Directives and also ensure that ISO 13485 is followed in your organisation.

END OF LINE

Perfect Metal to PC Bonding?

Gira’s Impermeable Oxygenator Fitting Makes the Grade

By Graham Porcas, director, Plasmatreat UK For medical device manufacturers, plasma treatment offers significant benefits for the surface treatment of components to facilitate and improve adhesion and bonding potential.

The technology is ideal for cleanroom environments as it can be integrated into fully automated high speed production lines. It is also completely clean (it’s essentially a series of jets of ionised air) and the treated surfaces do not produce any dust. In the following case study we present how plasma treatment has enabled a German company to produce metal and plastic oxygenator fittings as a single part.

Plasma treatment is based on the principle that when energy is added to a gas, that gas becomes ionised — that is to say the electrons gain more kinetic energy and leave their atomic shells. This builds on the simple principle of state change in physics. When you add energy to a substance, the states of matter change. By adding energy to a solid it turns into a liquid and then into a gas.

Adding energy to a gas creates a plasma — also known as the “fourth state of matter” — which consists of free electrons, ions and molecular fragments.

When these are applied to a material, they create a change on its surface at a molecular level in order to improve its propensity for bonding and adhesion. In addition, any contaminant on the surface

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can be removed, providing a valuable cleaning effect.

At normal atmospheric pressure the ionised gas is relatively useless for industrial applications because it is highly instable. In order to utilise the benefits of plasma the gas needs to be kept at a lower pressure than that of the surrounding atmosphere.

When Plasmatreat’s Openair plasma technology was developed in 1995 it opened up new opportunities. By developing and using plasma jets, or nozzles, it became possible for the first time to integrate plasma into industrial production processes at atmospheric pressure. The nozzles shoot a sharp burst of free ions onto the surface of a material, allowing “activation” of the surface as well as removal of any microscopic contaminants. The technology can be integrated inline, meaning it can be used for large scale pretreatment of material surfaces at normal atmospheric pressure.

Perfect Metal to Polycarbonate Bonding Germany-based manufacturer of plastic electrical goods, Gira, uses Openair plasma technology in a class 10,000 injection moulding cleanroom to produce complex fittings for oxygenators.

An oxygenator is a medical device that is capable of exchanging oxygen and carbon dioxide in the blood of a human patient during surgical procedures.

The fittings are a critical component of the oxygenator. Inside each fitting is a metal insert (pictured) which, during an operation, measures the temperature of the blood. If the temperature changes it triggers the heat exchanger to adapt and maintain a constant temperature.

The metal insert is placed in the mould and then overmoulded with

<< Plasma treatment enables critical metal and plastic parts to be injection moulded as a single component.

Source Gira. >>

<< The finished components are checked in the cleanroom under extremely stringent reliability requirements.

If the fittings fail, someone’s life will be in danger. Source Gira. >> polycarbonate. The bonding between the metal and the polycarbonate must be absolutely impermearble to ensure that the fitting functions reliably. And this is where plasma treatment comes in.

Apparently, extensive tests have shown that pretreatment with plasma is the only process which can fulfill the requirements of the part. Also, due to the close contact with the blood, the use of adhesion

<< Plasma treatment activates and cleans the metal inserts to ensure perfect impermeability before they are placed into the mould. Source Gira. >>

modified compounds or an additional bonding agent layer is not permitted by guidelines regulating the device.

To produce the fitting, prior to moulding individual metal parts are picked up by a robot from a spiral conveyor and deposited in the plasma treatment station. The atmospheric plasma beam pulsates at approximately two second intervals to activate and clean the rotating work pieces over their entire surface area before the inserts are placed in the mould by the robot ready for moulding. As the inserts are placed in the mould, finished components are removed.

The plasma operates directly on the surface of the metal and ensures that the melt polymer wets the metal surface for perfect impermeable bonding. Any organic impurities which might inhibit this process are oxidised away. As a result of this “activation”, the metal’s surface energy increases to more than 72 mJ/m².

Plasmatreat’s integrated monitoring system ensures that this step proceeds correctly and without errors.

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<< Ovesco’s device, sold under the brandname OTSC (Over the Scope Clipping), reportedly offers a high success rate and all but eliminates the need for subsequent surgery. >>

DESIGN 4 LIFE SPONSORED BY

Endoscopic Clip Dispenser Closes the Gap for Bowel Surgeons Prototype parts delivered in record time, satisfying immediate demand

Ovesco’s new solution to bowel surgery makes use of an endoscope, an optical instrument Because bowel surgery involves used for looking inside the intestine. a highly muscular part of the When the clip is body which is impossible to closed, the tissue immobilise, surgical procedures around the lesion is are prone to complications. A sealed and a key issue is that rectal lesions comprehensive and are difficult to close, particularly reliable closure is given the only closures are maintained.

Gunnar Anhöck sutures or tacks. Post surgical is responsible for ruptures lead to localised research and bleeding or, at worst, fatal development at blood poisoning. However, a Ovesco: “You new device from German could say that we endoscopy equipment supplier apply a kind of Ovesco reduces these trap, which is successful because difficulties by using a heavy of its simplicity. It is duty clip inserted via an currently the best endoscope. alternative method to seal a lesion.”

“Treating rectal fistulas is very difficult,” says Mr Anhöck, “and can often cause either injury to the sphincter or obstruction of the intestinal mucosa, both with corresponding complications. We developed and tested the OTSC [Over The Scope Clipping] system for this new application and we had a great response. With immediate demand, it was necessary to quickly deliver our first products.”

Mr Anhöck chose US headquartered prototyping company Proto Labs for the prototyping and development of the parts and the initial production run.

Part of this service included Proto Labs’s FirstCut prototype machining service and its Protomold prototype mould making service. “Initially, we ordered milled prototypes using Proto Labs’s FirstCut service. But, once we’d finalised design of the parts we wanted them to be produced in greater numbers. So, we tested the free quotation service that Protomold offers on its website.

We loaded up our 3D SolidWorks models and within one day we received detailed cost quotations and manufacturability analyses. Once we placed an order, we were amazed by the speed of the service despite the low volumes involved. With Protomold, the parts were delivered very quickly indeed.”

For example, for all parts of the dispenser, Proto Labs supplied them in just 15 working days. “By comparison, our standard tool supplier could take 12 to 15 weeks,” says Mr Anhöck, “at huge cost. In addition, the Proto Labs service is fully flexible, so we were able to make changes throughout the ordering process without incurring additional cost. We looked at services from other prototype manufacturers, but they required far too much time and were at least twice as expensive as Proto Labs.”

Mr Anhöck also recalls how working with the Proto Labs engineers to optimise Ovesco’s 3D models was a very positive experience. “The placement of the holes for the mounting screws, different surface structures on the handle, a folding backup pad on the trigger, the respective injection points, ejector pin placements, and the connection of the clip holder with the metal guide are all things we have altered. As a result, we got perfect parts without the typical defects such as bubbles, flow lines, streaks or sink marks. Proto Labs has even been able to support us by supplying the specific medical material we requested.”

MAY | JUNE 2012 / MPN /45

SPONSORED BY

Precision Extrusion Bridges Gap Between Devices and Drugs Custom engineered four- and eight-screw compounders for pharmaceutical polymers, radiopaques, fluoropolymers, bioresorbables and antimicrobials As healthcare professionals realise the time and cost saving benefits of plastic devices with added functionality, demand is growing for high specification polymer compounds — including those with active pharmaceutical ingredients (APIs). But the compounding of these polymers is not to be sniffed at. Because of the sensitive nature of the chemicals involved and the fact that dispersion and mixing tolerances are extremely tight — especially with active pharmaceutical ingredients which cost €38,000 per kilo — extrusion and pelletising must be carefully controlled and executed to precise specifications.

One of the best suppliers of compounding equipment in this realm is Japan based Technovel. Kohei Sawa, founder and president of the company, explains exactly what the company’s capabilities are.

6 mm “Nano” Twin Screw Micro Compounder…

Technovel has introduced what it claims to be the world’s smallest compounder — the KZW06 Nano compounding machine. The extruder, which was shown at April’s NPE trade show in Florida, has a 6 mm screw diameter, a 15:1 length to diameter (L/D) ratio and is suitable for powders, liquids and gels. The screw is fully programmable with mixing and feeding segments, and the torsion strength needed to perform under load. Note that the nano reference in the title is a branding reference rather than a technical reference to something less than 1 x 10-9 meters. Small screw compounders have historically been limited to a 12 mm screw diameter, and larger. Innovation in metallurgy, design and fabrication technology have enabled Technovel to overcome this limit.

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…for Pharmaceutical and Polymer Compounds…

In particular, the KZW06 Nano fills an important void in pharmaceutical materials research. Here, precise compounding is essential. Material availability may be limited to grams, and a small batch of active pharmaceutical ingredients (APIs) can cost more than €38,000 for one kilogram, and the minimum quantity available may be 10 grams or fewer.

Another feature of the KZW06 Nano is its scalable design. Technovel has designed this micro compounder to be scalable to fit different production scale systems. As a result, volume scale up cycle times are reduced as the need to reengineer processes are eliminated. …and Implants To ensure medical device performance in implantable applications, precise control and engineered processes in heating, shear, venting and cooling is required. Technovel’s compounders are modular so they can facilitate flexible process design, and can be configured to be cooled with water or air, based on the materials to be processed. Dispersion, critical to dosing, can be well controlled, and dual drive pelletising systems allow customisation of pellet configuration.

<< Technovel’s four screw extruders are ideal for the highly demanding technical requirements of medical grade compounders, especially for handling additives like APIs and radiopaques. >>

CLEAN MACHINES

Four- and Eight-Screw Technology: Enabling Compounding Research in Massachusetts Technovel has developed four-screw and eight-screw compounders to extend compounding capability. These are important when low heat shear is important to material processing, where longer residence time is needed in a relatively small space, and where uniform filler dispersion is critical. A proprietary design offers improved feeding and venting as well as an opportunity for energy savings. A four-screw compounder is currently in production and will be delivered to the University of Massachusetts in Autumn 2012, where it will support research and education in the Technovel Compounding Laboratory of the University of Massachusetts Lowell Emerging Technologies Innovation Center.

The four-screw compounder will join Technovel’s high torque and high revolutions per minute (rpm) 15 mm compounder, delivered to the University in Autumn 2011. The high rpm compounder can deliver up to 4,400 rpm and 60:1 L/D, and offers flexible mixing in a powerful, small diameter system. The speed is significantly faster than generally accepted rpm limits in the range of 1,200 to 1,800 rpms. Nanocomposite dispersion, high filler loading and depolymerisation via chain scission are among the capabilities of the system.

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MACHINED PLASTICS Machined Plastics for Short Run Implants – No Mould, No Metal Machined PPSU parts used for brachytherapy cancer treatment applicators The new generation of sophisticated high temperature polymers are particularly suitable for implants thanks to the fact that The popularity of they have machined medical some key plastic parts is properties growing apace thanks which are to continuous similar to metals, their improvements in high impressive performance strength, high polymers — such as melt PEEK, PPSU, PMMA, temperature POM, PSU and PEI — and extreme enabling device durability. A designers to replace benefit over metals is that metals with plastics, plastics are especially in thermal implantable devices. insulators, so Two key suppliers of they do not biocompatible get cold like materials for metals, making machining are implants more comfortable Germany’s Ensinger for patients. and Switzerland’s Compared Quadrant. In this with moulded article we look at a parts, the case study from main benefit Quadrant. of machined plastic parts is that high quality components can be manufactured without the upfront cost of

developing a mould. This means that short run parts can be made quickly.

The materials required for machining are extruded into special shapes — rods or sheets. For medical applications, these are supplied as medical grade materials produced under ISO 13485 conditions.

Materials are also tested for biocompatibility under ISO 10993 and US Pharmacopeial Class VI standards.

A Case Study: Cancer Treatment Applicators – Brachytherapy Brachytherapy, a form of radiotherapy, is an advanced minimally invasive oncology procedure commonly used in the treatment of prostate, vaginal, cervical and head and neck cancers. A small radioactive source is placed in or near the tumour itself, giving a high radiation dose to the tumor while minimising the radiation exposure of the surrounding healthy tissues.

Brachytherapy applicators are used in the surgical procedure to insert the radioactive source and to position it in or near the tumour area to be treated.

Positioning often takes place with the aid of CT (computerised tomography) and MRI (magnetic resonance imaging) scans.

Crucially, these scans need to provide extremely clear images for accurate positioning of the probe. Following treatment procedures, the applicators

and accessories are autoclaved so materials need to be able to withstand high temperature and harsh chemical cleaning.

The material used for this application is a biocompatible PPSU from Quadrant EPP, under the brand name LSG PPSU. The material was selected as it outperforms metals and other polymer materials, particularly because it delivers no CT or MR image distortion, has excellent radiation resistance, and withstands high frequency autoclaving of more than 1,000 cycles with complete material property retention.

In terms of biocompatibility, Quadrant’s PPSU has been certified to ISO 10993 (chapter 10 and 11) and USP Class VI standards. Although OEMs are ultimately responsible for testing and certification for device compliancy, relying on pre-certified materials aids the certification and approval process and ensures security and consistency of material supply.

Quadrant provides manufactured finished parts directly to OEMs as well as semi-finished parts through its distributor channels. It works closely with OEMs by providing technical advice and support on key design aspects such as part dimensions and tolerances.

Quadrant is also equipped to provide specialised machining expertise. Two ISO 13485 certified machining centres, one in Tielt, Belgium, the other one in Sinsheim, Germany, machine high end medical instrument components made from predominantly PPSU, PC, pure PEEK and PEEK modified with carbon fibres. << Machined plastic implants are often colour coded to help surgeons easily identify sizes. >>

MAY | JUNE 2012 / MPN /49

EVENTS medical plastics | DIARY 2012

Orthopaedics conference and trade show May 28 - June 1, 2012 Amsterdam, Holland

Plastics in medical devices conference June 12 - 13, 2012 Ohio, USA

Medical plastics trade show September 25 - 26, 2012 Birmingham, UK

Orthopaedics conference and trade show May 31 - June 1, 2012 Lyon, France

There are important changes occurring in the UK healthcare industry.

The coalition government has recently announced new ways in which the National Health Service (NHS) will procure its supplies. The changes will transfer purchasing decisions from central public departments to small groups of general practitioners (GPs). This is expected to result in an opening up of the NHS to more competitive supply contracts. It should, in theory, provide device manufacturers with greater marketing opportunities to UK buyers.

On September 25-26, 2012, a brand new UK trade show for manufacturers of medical plastic devices and components will take place at the NEC in Birmingham.

The event, Mediplas, will showcase the leading technologies in medical plastics. It will be held alongside the product development and additive manufacturing event TCT Live and the high precision technology events MM, MEMS and Nano Live UK. According to the organisers, 50/ MPN / MAY | JUNE 2012

Medtech Innovation conference September 11, 2012 London, UK

Regenerative medicine knowledge transfer conference June 19, 2012 London, UK

Medical devices trade show September 26 - 27, 2012 Modena, Italy

Medical plastics conference September 25 - 26, 2012 Boston, Massachusetts, USA

Mediplas Perfect Timing for UK Healthcare Industry Changes Rapid News Communications Group, Mediplas fits perfectly with these shows, due to their strong following from the medical and plastics communities.

Launched following the return to form of leading UK plastics trade show Interplas, Mediplas has received stand confirmations from a number of exhibitors. Of these, one of the biggest names is Engel.

Graeme Herlihy, managing director of Engel UK told MPN: “For us, the decision to exhibit at Mediplas was a no brainer! It’s an ideal opportunity to mix with a wide range of people from the medical industry, and this sector is so important for us now.”

The show has attracted interest in exhibitors from

Global trade in plastics conference June 11 - 12, 2012 Istanbul, Turkey

“ << Anatol Sattel of BFA Solutions: We recognise the UK medical and pharmaceutical market (as well as the Irish) as very strong. >>

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overseas. One such company is the Swiss provider of manufacturing information software BFA Solutions, whose PI Inject product is dedicated to medical injection moulding.

Anatol Sattel, BFA sales manager, said: “We see the UK and Irish medical and pharmaceutical markets as being very strong. A dedicated focus on regulation and quality means that the products require global suppliers for a local manufacturing base.”

<< Graeme Herlihy, managing director of Engel UK, said that exhibiting at Mediplas is a no brainer. >>