MPN EU Issue 9

MPN

MEDICAL PLASTICS NEWS

NEWLY BRANDED RESILIA, A KEM ONE COMPANY, SHOWCASES BIOMEDICAL PVC COMPOUNDS AT COMPAMED

ALSO IN THIS ISSUE: Clinical Evidence of DEHP Accumulation in Tissue Innovations in Extrusion Advanced Copolymers for Medical Packaging

ISSUE 8 September/October 2012 WWW.MPNMAGAZINE.COM

MPN Page 14

All Medical, All Plastics

Contents 5. Editor’s Letter: September events Eleven events took place in two days on September 25-26, including Mediplas.

6. On the Pulse: DEHP accumulation Clinical evidence of DEHP accumulation in tissues stimulates regulatory debate over extracorporeal treatments.

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14. Clean Machines: Extrusion Innovations in extrusion including intermittent extrusion, vertically upwards PEEK extrusion and data loops.

21. Product Focus: Packaging Advanced copolymers for medical packaging—Sabic PP, Barex, COCs, fluoropolymer film, Health + and Bormed.

26. Folio: Micro fluidic injection moulding An image of the injection moulding of a micro fluidic diagnostic device substrate.

28. Country Focus: India On paper, India should be near the top of the list for FDI, but regulatory hurdles are severely hampering the development of a domestic device manufacturing industry.

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31. Materials: Nitrogen dioxide sterilisation of polymers Nitrogen dioxide is a new low cost alternative sterilisation option for device manufacturers. Three polymers are reviewed in this article by Dr Evan Goulet of technology developer Noxilizer. First FDA-approved devices using the method are expected in Q1 2013.

33. End of Line: Assembly Considerations for automated assembly of drug delivery devices, by Manfred Baumann, CTO of Gerresheimer.

37. Cover Story: Compamed preview Marco Toscano, general manager of biomedical PVC compounder Resilia, talks about his company’s future goals with chief communications officer Sophie Suc following the successful establishment of the new vinyls giant and owner of Resilia, Kem One. 40. Compamed: Exhibitor news Materials news from Eastman, Porvair, Wittenburg and Bayer. Injection moulding news from Wittmann, Spang & Brands, Axxicon, Apple, Sony and Philips-Medisize. Extrusion news from Saint-Gobain, Parker Hannifin, Vesta, Teleflex Medical OEM, Raumedic and Kelpac. Also news in packaging, end of line, testing and inspection, diagostics, connectors and plastics machining.

48. Doctor’s Note: Textured implants Orthopaedic consultant surgeon Prof Simon Donell advises readers about the realities of the operating theatre.

49. Design 4 Life: Using data wisely Bob Ketelhohn of USA-based product development firm Farm gives insight into efficient use of data.

50. Events: Diary and review Upcoming events in October to December 2012 plus a review of the new UBM Canon Medtech Polymers event in Chicago, USA.

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

SEPTEMBER/OCTOBER 2012 / MPN /3

MPN | EDITOR’S LETTER

MPN | CREDITS

editor | sam anson advertising | gareth pickering

Remember Remember, Events in September 22 Trade Shows and Conferences in One Month In Europe and the USA there were as many as 22 trade shows and conferences relevant to medical device manufacturers in September. Of this total, eleven events fell on just two days, September 25-26.

There was a hardcore of three events dedicated entirely to medical plastics—the new UK-based trade show Mediplas UK, the annual AMI-organised Medical Grade Polymers conference, a new conference organised by industry magazines Plastics Today and MD&DI—as well as the Fifth Plastics Technology in Medical Products conference in Shenzhen, China.

The Mediplas UK event was the first plastics trade show to be dedicated entirely to the medical industry. It hosted a wide variety of exhibitors, including suppliers of machinery, materials and semi finished products.

The show was organised by Rapid News Communications Group, which colocated the show with its other events—the rapid manufacturing TCT show, the micro manufacturing MM, Mems and Nano Live events, and sensing and monitoring Sensing show. A total of 4,593 people attended all four events over two days. Medical Plastics News reported from the event. I gained insight into the importance of ISO13485 from Medilink connectivity director Chris Dyke and learned from materials distributor Distrupol about why two year polyolefin supply contracts are the norm. At the same time, spokespersons for KraussMaffei and Kebo Moulds told me how they are helping to improve productivity in multicavity moulding. KraussMaffei is able to increase platen size to allow larger mould sizes while Kebo is increasing moulding efficiency thanks to its inhouse designed hot runner system.

Elsewhere, Peter Ing from Boy demonstrated the Boy XS 10-tonne micro moulding machine and explained

why it’s ideal for cleanroom environments and Nigel Flowers from Sumitomo (DHI) Demag told me about his new machine, which features a built in class 7 cleanroom moulding chamber, meaning that it can be operated in an non-cleanroom environment and still meet ISO regulations.

Mediplas took place on September 25-26, 2012—possibly the busiest two days of the medical device manufacturing 2012 calendar. Other key events on these days included the first World Medtech Forum in Lucerne, Switzerland, the medtech manufacturing shows Medtec Italy and Medtec China, the sustainable medical industry event CleanMed 2012 in Sweden and AMI’s Medical Grade Polymers conference in Boston, USA. Regular attendance at the industry’s leading events is a priority for Medical Plastics News. By talking to exhibitors and conference speakers at these events, I find I often get the best leads for content.

In reflection of this, you’ll see a exclusive report on DEHP in medical devices starting on page 6 overleaf. The issue concerning DEHP as a plasticiser in PVC has been around for a long time, but new evidence of accumulation in tissue from the University of Strathclyde, UK, suggests that we should be more concerned about certain treatments, particularly haemodialysis and other extra corporeal blood handling processes. The release of the evidence from the team at Strathclyde is timely. On September 24, 2012, the EC closed applications following a call for experts on DEHP from the clinical field. The EC said it was particularly interested in perinatal paediatricians and epidemiologists. The report on DEHP involved a lot of research in ascertaining what is new in this area. It also involved sifting through journal articles to differentiate fact from fiction. I hope you find it a useful read.

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SEPTEMBER/OCTOBER 2012 / MPN /5

INDUSTRY NEWS | Accumulation of DEHP in Tissue

Clinical Evidence of Accumulation of DEHP in Tissue Stimulates Regulatory Debate on Blood Contact Devices WORDS | SAM ANSON

On September 10, 2012, following a call for experts by the European Commission into DEHP in medical devices, Medical Plastics News hosted a conference call in which Prof Terry Gourlay of the University of Strathclyde, UK, presented evidence that DEHP accumulates in the tissues of rats— particularly the brain and the liver—and remains there for up to 28 days, increasing the risk of an inflammatory response.

Prof Gourlay also said that the results can be extrapolated to human cells. The presentation was made to a number of experts in medical plastics with an interest in plasticised PVC and alternative technologies.

The issue about DEHP in the medical device industry is complex.

When used with PVC, the chemical is a very good plasticiser in terms of mechanical performance and is generally inexpensive.

For many years it has been—and in many countries still is—used by compounders, making PVC flexible and durable while maintaining transparency.

On a number of occasions over the past few years, the safety of DEHP has been brought into question. Because there is no covalent bond between molecules of DEHP and molecules of PVC, DEHP is free to migrate from a PVC compound and onto or into whatever that compound is in contact with. And tests of DEHP on animals have given adverse results, particularly on the reproductive systems of adult males.

For medical devices which come into contact with blood, the issue is complicated further because DEHP is lipophillic, which means it is attracted to lipids. So when in contact with blood, DEHP is attracted to the lipids in red blood cells where it binds to and stabilises the cell membrane.

6/ MPN / SEPTEMBER/OCTOBER 2012

In blood bags, this is a beneficial characteristic because the stabilisation of the red blood cells actually preserves the cells. It keeps them fresh by stopping them from rupturing and the releasing their contents—a process known as haemolysis—which would otherwise render them useless.

However, Prof Gourlay’s evidence raises a crucial new concern about DEHP plasticised PVC in extracorporeal applications like haemodialysis, haemofiltration, cardio pulmonary bypasses, and extra corporeal membrane oxygenation (ECMO). Like in blood bags, DEHP migrates from the PVC used in these devices and into the blood where it binds to red blood cells. Prof Gourlay says that pump-based systems which compress DEHP plasticised PVC increase the rate of migration as DEHP is “squeezed” out of the PVC and into the blood.

<< Prof Gourlay’s evidence that DEHP accumulates in tissues for 28 days raises concerns about tubing in haemodialysis machines which are used to filter a patient’s blood for two to four hours once every two to four days. >>

ON THE PULSE

Prof Gourlay works closely with clinicians at a leading UK hospital who are investigating inflammatory responses in patients undergoing extracorporeal treatments. In addition to attempting to manage these responses with drugs, Prof Gourlay has looked at the materials used in the systems themselves, including DEHP-plasticised PVC. Prof Gourlay is concerned that DEHP may be creating an inflammatory response in neonates and repeat dialysis patients. He believes that neonates are more at risk than adults because there is an extremely high ratio of surface area of DEHP plasticised PVC to the baby’s body mass, significantly increasing the dosage in relative terms compared with adults.

And because he has evidence that DEHP stays in the tissue for up to 28 days, repeat dialysis patients, who are typically treated once every two days, are exposed to a multiplied dosage of DEHP. Prof Gourlay’s experiment involved radioactively tagging molecules of DEHP and using this DEHP to produce plasticised PVC and then exposing different surface areas of this material to rats via an extra corporeal circulatory system which is mimetic of clinical systems. The research follows existing work published by Prof Gourlay that shows that DEHP is proinflammatory in both humans and rodents.

When presented with Prof Gourlay’s evidence, medical PVC expert and former Baxter polymer engineer Len Czuba said: “Prof Gourlay’s evidence suggests that there may be regulatory gaps for certain devices which contain DEHP-plasticised PVC. However, it is crucial that any conclusions about DEHP are communicated clearly to manufacturers and consumers. In the past, people have carelessly lumped DEHP and PVC together and this has resulted in confusion about whether PVC is safe or not, especially in the USA. Regulators must make it clear that phthalate-free PVC is a suitable alternative for many applications at comparable prices. Phthalate-free PVC is particularly popular in Europe, where PVC in general has a good press.” << Table 1: Treatments whereby the FDA suggests precaution when using devices containing DEHP, published on August 28, 2012 >>

Current DEHP Regulations In Europe, along with a handful of other phthalates, DEHP has been classified as a substance of very high concern (SVHC). It is banned in children’s toys and usage in other sectors is strictly by prior authorisation from the European chemical industry’s regulating body Reach. The explanation given for this is that at certain high doses there is evidence which suggests the chemical is a reprotoxin that disrupts the endocrine system of young males.

At the time of going to press, all medical device manufacturers in Europe are exempt from Reach’s regulative restrictions on DEHP usage. But under the Medical Device Directive (MDD) any devices containing DEHP must demonstrate the effect that migratory DEHP molecules have on the device’s performance. They must also bear labels stating that the device contains DEHP. On September 6, 2012, the Danish government banned the use of phthalates in shower curtains and oil cloths. There is pressure on the government in that country to extend the ban to more products including medical devices.

In the USA, there are no regulatory restrictions on the use of DEHP. But in a report published on the FDA website on August 28, 2012, by biologist Laura A Alonge, there are precautions about its usage in certain treatments. The warnings concern similar treatments to those raised by Prof Gourlay (see table 1).

The FDA’s recommendations are to “play it safe”. The report states: “Don’t avoid performing high-risk procedures simply because DEHP could pose a health risk. Forgoing a necessary procedure is far riskier.

However, you can take some precautions.”

Its suggestion is: “For some procedures, you can use PVC devices that don’t contain DEHP or use devices made from other materials, such as ethylene vinyl acetate, silicone, polyethylene, or polyurethane. If you must use devices with DEHP, you can minimise exposure by using the freshest possible blood products stored at the lowest possible temperature or by using heparin coated ECMO circuits.”

Transfusion (especially multiple transfusions in neonates, trauma victims, and adults undergoing extracorporeal membrane oxygenation (ECMO) ECMO in neonates Multiple procedures in neonates Haemodialysis in peripubertal boys and pregnant or lactating women Enteral nutrition in neonates and adults, particularly total parenteral nutrition (with lipids in a PVC bag) Heart transplantation or coronary artery bypass graft surgery Continued on page 8

SEPTEMBER/OCTOBER 2012 / MPN /7

INDUSTRY NEWS | Accumulation of DEHP in Tissue Continued from page 7

The next stages of Prof Gourlay’s work will involve a specific investigation into inflammatory responses resulting from repeat DEHP exposure during two-day haemodialysis cycles on rats. There is also potential to take some human tissues from a tissue bank which have been exposed to DEHP through haemodialysis but this will require ethics approval.

A podcast of the conference call in which Prof Gourlay presented his evidence is available at www.bit.ly/QWxzwN. DEHP Supply According to Andrea Zanichelli, technical director at Italy-based medical PVC compounder Resilia KemOne, the European market for DEHP is shrinking fast. Already manufacturers of the chemical have exited the continent and just one producer of medical grade DEHP, Arkema, remains. Mr Zanichelli conceives that the use of the chemical will become more restricted going forward, which could push Arkema to exit or switch production to another chemical.

Should this happen, a European medical DEHP market would be wiped out completely forcing up the price of DEHP in Europe as importers face fees for registering the chemical with Reach. Mr Zanichelli argues that a higher price for DEHP removes one of its key advantages—it’s low price—encouraging the use of alternatives.

JULY 19, 2012 Teleflex Divests Metal Orthopaedic Surgical Tools Manufacturing “The decision to divest the OEM orthopaedics business is consistent with our strategy to focus on our branded products, invest in latestage innovative technologies to support our long-term growth, and expand both our gross and operating margins,” stated Benson F Smith, chairman, president and chief executive officer of Teleflex.

8/ MPN / SEPTEMBER/OCTOBER 2012

July 31, 2012 PolyOne Begins 3D Printing Materials Research Project

According to a statement from Eastman Chemical, one of the largest producers of DEHP, “the company does not produce or sell DEHP in Europe.” Eastman Chemical is a member of the PVC Medical Alliance, set up by the European Council of Vinyl Manufacturers (ECVM).

In the USA, the situation is far more fluid. As long as the FDA doesn’t regulate against DEHP, companies will be free to use it. Eastman Chemical supports the safe use of DEHP in FDA cleared medical devices. The company’s brand is Eastman DOP Plasticiser.

Eastman offers a wide range of DEHP alternatives including Eastman 168 non-phthalate plasticiser. The company is giving attention to this chemical’s potential use in a wide range of medical applications, including DEHP-free blood bags.

DEHP in Blood Bags For most DEHP-plasticised medical devices, there are many alternative materials available, including phthalate-free plasticisers and alternative flexible polymer compounds like TPUs, TPEs and silicones.

There is one product, however, that is almost completely dependent on PVC plasticised with DEHP—blood bags.

USA-based specialist polymer compounder and distributor PolyOne has begun a three-year collaboration project to develop advanced 3D printing materials. “We are honoured to be part of this collaborative project and provide our formulation expertise to develop these specialty applications,” said Dr Christopher Murphy, chief innovation officer at PolyOne Corporation.

AUGUST 9, 2012 West European Market for Medical Plastics will Grow by 9 Per Cent a Year to 2018 “A rapidly greying population with its attendant healthcare needs will have a positive impact on the medical devices market and, by extension, on polymers used in such equipment,” noted Frost & Sullivan research analyst Tridisha Goswami. “This will be reinforced by the uptake of increasingly sophisticated equipment by the healthcare industry and the growing importance of portable, impact resistant medical devices that can be used in homecare settings.”

ON THE PULSE

The reason for this is that, as mentioned earlier, DEHP appears to be a natural preservative of blood.

The chemical migrates from PVC and binds with membranes of the red blood cells, preventing haemolysis and keeping them fresh for up to 42 days.

A 42-day shelf life for blood bags is critical for blood banks to manage their supply chain and provide a continuous and reliable supply to clinicians. Because they rely on donations, supplies from donors can be uneven and feature peaks and troughs. Without the shelf life, these peaks and troughs would be unmanageable.

Medical Plastics News is only aware of one commercial blood bag system which does not contain DEHP—the Pearl BPU, a PVC blood bag plasticised with butyl trihexyl citrate (BTHC). The bag was developed in 1991 and is currently marketed by US infusion systems manufacturer Fenwal, formerly owned by Baxter Healthcare.

The hexanol in the BTHC is the chemical which preserves the blood and the level of leaching from the PVC is believed to be lower than with DEHPplasticised PVC. According to an investigation by the EC in 2008, BTHC does not accumulate in the tissues.

Strangely, dependence on DEHP was purely accidental. PVC blood bags were first used by the US army in the Korean war in the early 1950s. PVC was used to replace glass so that bags of blood could be thrown out of helicopters without them smashing to pieces. The fact that DEHP extended the shelf life of blood was an unexpected bonus.

Prof Gourlay’s new evidence about the accumulation of DEHP in tissues may open a debate as to whether there is a need in the industry for DEHPfree blood bags. However, Prof Gourlay says that because the majority of blood bags are used in serious trauma incidents involving adults where there has been a lot of blood loss, the risk of inflammation as a result of exposure to DEHP is minute compared to the reward of saving a person’s life. Furthermore, the percentage of DEHP which migrates into the blood is very small.

However, taking into account the treatment of neonates and small children, there is a much finer balance between risk and reward. The fact that the baby’s body mass is a fraction of the size of an adult’s means that any single dosage of DEHP is proportionately more significant.

Continued on page 11

PREVIOUSLY ON MPNMAGAZINE.COM

AUGUST 13, 2012 Electronic Medical Device Recovery and Recycling Targets Take Effect The revision of the Waste Electrical and Electronic Equipment (WEEE2) Directive (2012/19/EU) has come into force in Europe. EU member states have until February 14, 2014, to transpose the directive into national law. In addition to defining products which are subject to regulation, the directive sets out target rates of recovery and recycling of waste electrical and electronic devices, including those used for medical applications.

AUGUST 20, 2012 Potential for Biodegradable Drug Delivery with Nitrogen Sulphur Polymers “The ability to incorporate nitrogensulphur linkages into a polymer backbone brings a wealth of opportunities ranging from biomaterials to microelectronics,” commented polymer expert Craig J Hawker, a former IBM researcher now at the University of California, USA. “It’s not often that a new class of polymers is developed that bears little resemblance to current materials—these polymers are really something unique.” Image courtesy of Mitsui Chemicals Inc.

17:10:2012 AUGUST 24, 2012 EC Issues Call for Experts on Medical Devices Containing DEHP

The European Commission (EC) has requested the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) to deliver an opinion on the potential health impacts caused by DEHP-containing medical devices. The relevant SCENIHR working group has identified a need and has made a call for experts in this topic. Image courtesy of the Bureau of Investigative Journalism.

24 SEPTEMBER/OCTOBER 2012 / MPN /9

ON THE PULSE INDUSTRY NEWS | Accumulation of DEHP in Tissue Continued from page 9

Alternative Materials for Blood Bags The reliance of blood bags on DEHP makes them an interesting case study. Indeed, there are a number of scientists who are attempting to develop PVC free alternatives, primarily for neonates.

For these researchers, the main challenge is how to keep blood fresh for a shelf life of 42 days, as required by the blood bank sector.

The closest product is a prototype multilayered polyolefin solution, developed in the USA but not yet commercialised. The bag can preserve blood for the 42 days but is does not meet standards required for physical properties related to welding, flexibility, transparency, durability, centrifuging and handling.

Lubrizol, the USA-based speciality chemicals company, claims that its thermoplastic polyurethanes (TPUs) are theoretically suitable for the replacement of DEHPplasticised PVC, although there is still a fair way to go on their research and TPUs are generally more expensive than most polyolefins and PVC. Their approach is also a multi-layer approach. It aims to apply a similar technology to that used in its monolithic breathable films, currently in medical garments. They hope to incorporate a preservative into the inner TPU layer of the bag and allow the preservative to leach into the blood over time. The release rate of the preservative can be controlled in the TPU structure. The advantage of a TPU layer, according to Lubrizol, is that it exhibits similar physical properties to PVC, including being easily weldable.

Weaning Neonates off DEHP A broad consortium of healthcare suppliers and clinicians in Scandinavia, known as PVC Free Blood Bags, are targeting development towards serving a high risk group of transfusion therapies—neonatal babies. Their goal is to develop a blood bag which avoids PVC entirely.

The consortium has no commercial ties to the blood bag manufacturing industry and can therefore operate independently. It consists of a leading Swedish hospital— the Karolinska University Hospital—as well as Swedish green chemistry research institute Jegrelius, Finnish medical packaging films extruder Wipak, medical tubing maker Totax and polyolefin compounder Melitek, both based in Denmark, and Italian blood bag and tubing contract manufacturer Haemotronic.

According to project manager Lena Stigh, the consortium’s goal is to demonstrate to industry that it is possible to make a PVC free blood bag that meets the technical and regulatory requirements in an attempt to fuel demand from European healthcare companies.

They aim to remove PVC from blood bags altogether, arguing that even with newer plasticisers, no one can be sure they are safe until it is too late.

In terms of progress, the group has secured conditional orders via signed letters of intent from seven Swedish county councils. The councils say they will buy PVC Free blood bags if they can meet the specific requirements of the industry.

The group has stated that the mass production of competitively priced 100% PVC free blood bags is theoretically possible. Since its formation in September 2011, it has gathered information about what is required by the industry and has developed the technical specifications needed for their first prototype—based on the multilayer polyolefin system created in the USA and mentioned earlier, which is their starting point.

In parallel to this Melitek, the polymer compounder in the group, is working on a Eurostar-funded project called SafeBlood. In this research, Melitek is looking to impart an alternative stabiliser into a polymer material which could then be used to extend shelf life.

The consortium believes that there may be instances when a blood bag system does not need to remain fresh for the full 42 days. In these cases, there would be many more DEHP-free options to utilise for the blood bag system, but it would require a change of culture.

There is still a long way to go for the PVC Free Blood Bag consortium. They hope to demonstrate two key issues. First that there is a demand for a PVC free product in blood transfusions for neonates, chronically sick children and other high risk patients—including those with sickle cell disease, thrombotic thrombocytopenic purpura and haemolytic disease of the newborn. Second, it is theoretically possible to produce a PVC free product.

Article Credits: John Cahill, Eastman Chemical Company Len Czuba, SPE Medical Plastics Division and Czuba Enterprises Brigitte Dero, European Council of Vinyl Manufacturers (ECVM) Terry Gourlay, Bioengineering Unit, University of Strathclyde Ole Grondahl Hansen, PVC Information Council, Denmark Ralf Huther, Lubrizol Jesper Laursen, Melitek and PVC Free Blood Bag Sherry MacDonald, Practise Greenhealth Rainer Otter, BASF Craig Sandford, Fenwal Ted Schettler, Healthcare Without Harm Lena Stigh, PVC Free Blood Bag Andrea Zanichelli, Resilia KemOne

SEPTEMBER/OCTOBER 2012 / MPN /11

ON THE PULSE INDUSTRY NEWS | SPE

SPE Celebrates 70th Birthday In recognition of the 70th birthday of the Society of Plastics Engineers (SPE) professional networking organisation, the chair and councillor of the European Medical Polymers division of the association, Dr Austin Coffey, gives his view on the society’s achievements and future objectives.

The SPE is the only place where people from all parts of the plastics and related industries can come together around important technical and market related issues. The association’s vision is to spread knowledge, strengthen skills and promote plastics. SPE’s contribution to the plastics industry for the past 70 years has made a significant difference to the technologies and innovations which the industry enjoys today. In the process, a 20,000member network of leading engineers, scientists and other plastics professionals has been developed, including technicians, salespeople, marketers, retailers and representatives from tertiary industries.

Today, the industry is more interdependent than ever and professional networks have taken on global dimensions. Such networks are almost impossible to develop and maintain in our fast-paced industry.

Participation in SPE is a key success factor for those who want to thrive in today’s business environment. The medical plastics and European medical polymers divisions of the society are thriving. This is a reflection of the significant global growth in medical devices over the past five years, with an expected growth rate of 6.1% per year over the next five years.

There are plans afoot to extend Antec to China, following the hugely successful EuroTec conference. It is expected that India and China will be the driving countries for growth over the next five years. The opportunities in creating closer alliances in China will prove to be highly beneficial in this era of open innovation for the existing medical device companies of the US and Europe. This is the sharing of ideas and constructive collaboration. And, with the objective of many companies being to move higher up the value stream, convergent technologies encompassing many aspects of plastics engineering with other areas are necessary. The SPE offers a conduit for differing specialties to mix; from medical plastics to injection moulding, from composites to polymer analysis, from extrusion to thermoforming.

<< Austin Coffey is chair and councillor of the SPE’s European Medical Plastics division and a lecturer at Waterford Institute of Technology in Ireland. >>

A European CEO An SPE strategy of “embracing the world” is reflected in the recent appointment of the society’s new chief executive, Mr Willem De Vos, from Belgium. This is the first time in the 70 year history that the highest executive position has been offered outside of the USA. The SPE’s mission of strategic growth to encompass all corners of the world is being realised with Willem’s expertise in extending business activities into emerging markets. The SPE’s international plastics conference, Antec, which takes place each year in the USA has extended its borders.

EuroTec 2011 was held for the first time in Barcelona in November 2011. A follow-up EuroTec 2013 is scheduled for July 4-5, 2013, in Lyon, France. In addition, Antec Mumbai will take place on December 6-7, 2012, in Mumbai, India.

SEPTEMBER/OCTOBER 2012 / MPN /13

EXTRUSION

EXTRUSION PIONEERS:

Multilayer, Vertically Upward PEEK and Data Loops WORDS | SAM ANSON

THIS REPORT PROFILES A SELECTION OF INNOVATIONS IN EXTRUSION OF MEDICAL POLYMERS.

Intermittent Extrusion Machinery Italian microextrusion machinery supplier Gimac’s intermittent coextrusion equipment enables catheter extruders to make a single tube made with an unlimited combination of material proportions, especially soft and hard materials.

The process works on the principle of a loop of information being fed from the dimensional recipe to the conditioning parameters, such as the extruder’s feed rate and puller speed, and then being controlled by sensors along the process.

Sensors at the die head monitor material behaviour while measurement devices after the cooling tank measure the dimensional characteristics. Any changes due to variations in viscosity, like pressure and dimensions, are fed back to the controls and necessary adjustments are made automatically in order to stabilise the process.

So for tubing with a variable durometer, diameter or thickness, controlled adjustments to material flow rates can be made carefully and automatically. This allows manufacturers to produce seamless and smooth gradual changes—from hard to soft materials and bigger to smaller diameters and wall thicknesses—along a single piece of tubing.

Good examples of how this can be used in practice are catheters which are hard and stiff at one end—to give a surgeon good grip when inserting it into a lumen—and soft and flexible at the other, to allow the tube to be bent around tight corners in the body, making the device less invasive. In addition, welding-friendly materials or radiopaque additives can be introduced at regular intervals giving easier assembly or cost effective radiovisible properties, respectively.

<< Pressure tubing from Novaplast is made using complex multilayer extrusion techniques. >> 14/ MPN / SEPTEMBER/OCTOBER 2012

Multilayer Coextrusion of Wide Ranging Viscosities and Melt Temperatures Leading custom tubing manufacturer Novoplast, based at one of Europe’s leading medical coextrusion facilities in Germany, has mastered the art of coextruding materials whose melt viscosities, melt temperatures and re-crystallisation temperatures vary widely—traditionally a very challenging task. Novaplast’s tubing is used mainly in IV, angiography and urology devices.

This ability enables Novaplast to combine layers of hard and soft materials in one process and replace older, more traditional material combinations. The most used material is polyurethane but the company works with all thermoplastics.

In infusion tubing, Novoplast was approached to develop an economic replacement for braided and reinforced filling tubes using its skills in multilayer coextrusion. The key challenge was to produce a highly flexible, transparent tube which could resist a burst pressure of 1,500 psi (104 bar). It managed to combine a soft TPU with a hard nylon, despite these polymers having a wide deviation in melt temperatures.

The company is also working on a project to produce a drainage tube for the brain made from a TPU with an embedded radiopaque stripe. The tube is transparent yet it still shows up on X rays.

Another option here is to coextrude embedded stripes for colour matching. In these cases the kinking direction or elongation can be influenced easily.

Novaplast has six extrusion lines installed in class 8 cleanrooms at its plant. There are plans for a new cleanroom and two new extrusion lines to be added soon.

Continued on page 16

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CLEAN MACHINES | EXTRUSION Continued from page 14

Vertically Extruded PEEK Tubing and Aptiv Films Leading US-based extrusion machinery supplier American Kuhne (AK) has successfully extruded PEEK tubing using a vertically upward extrusion line. A patent covering the technology is pending. In a series of experiments, the company has found that by passing tubing through an oven placed above the die head, it can be annealed and the outer diameter and ovality can be controlled to ±0.0007” (0.18 mm) and ±0.001” (0.25 mm) respectively. The process of annealing gives PEEK the time to crystallise uniformly as it cools, giving optimum physical properties.

AK’s discovery of the vertically upward extrusion and in-line annealing process followed unsuccessful attempts at extruding PEEK horizontally and vertically downwards. The horizontal attempt, performed with a 24” (61 cm) gap between the die head and the quench bath, resulted in a semicrystalline tube but with inconsistency in outer diameter (OD) and ovality.

Horizontal extrusion resulted in a non-uniform level of crystallinity between the top and the bottom of the tube. The vertically downward attempt resulted in a “snake-like” product with bends and kinks in the tube, due to the PEEK not having enough melt strength to hold the weight of the extrudate.

PEEK films have been successfully extruded by UK-based PEEK resin manufacturer Victrex.

The films, sold under the brand name Activ, have been used recently to make permanent durable labels for sterilisation trays. The labels, designed to replace less resilient laser engraved labels that degrade over time, are resistant to sterilisation by steam, chemicals and radiation and are hard wearing but extremely lightweight.

The manufacturer of the labels, Germany-based S+P Sansom, is a specialist in durable identification labels for a wide range of industries.

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Fluoropolymer Extrusion for Lubricity, Inertness and Thermal Stability Being able to melt extrude fluoropolymers into catheter tubing marks an important development for manufacturers. The materials are extruded at temperatures as high as 260°C, requiring specialist machinery and expertise.

Inherently, fluoropolymers have low friction coefficients. As a result, when used in catheters, fluoropolymers provide these products with excellent lubricity on both the inner and outer layers.

A common example is a guiding catheter—a device which is inserted into a lumen to allow a surgeon to deliver another device via a wire, usually a stent, camera or laser. In these cases, a lubricious outer layer is important for the device to allow the catheter to travel up the lumen without sticking. A lubricious

<< AK have successfully extruded PEEK to close tolerances on ovality and outer diameter using a vertically upwards procedure. >> inner layer allows the guide wire to travel up the catheter to the target area without catching on the inside of the catheter. A lack of friction is essential to making a device of this nature minimally invasive.

Fluoropolymer-based catheters have been around for many years in the form of PTFE coated metal braids. These have been manufactured using paste

EXTRUSION extrusion—a process carried out at room temperature whereby PTFE powder is mixed with a number of chemicals in left to “age” before being compressed into a preform and then being formed around the braid using a combination of a compression and extrusion process.

The lubricity of fluoropolymers means device designers must alter their surface by etching, flaring or flanging or in order to attach other components.

Fluoropolymer-based catheters also offer excellent biocompatibility thanks to their chemical inertness, wear resistance, good thermal stability and high dielectric strength. A selection of melt extrudable materials includes fluoroethylene propylene (FEP) copolymer, perfluoronated ethylene-propylene (eFEP) copolymer, ethylene tetrafluoroethylene (ETFE) and perfluoroalkoxy (PFA).

A leading fluoropolymer extruder is USAheadquartered Teleflex Medical OEM, the custom product design and development arm of medical device manufacturer Teleflex, also based in the USA. A recent innovation from Teleflex Medical OEM is a multilayer co-extrusion process, using eFEP and a polyamide- or PEBA-type material, which eliminates the need for etching, allowing catheter manufacturers to save time and costs in assembly. According to the company, tubing stiffness can be tailored to specific applications by varying the durometer of the coextruded materials.

Real Time Data Loop Yields High Precision Silicone Peristaltic Pump Tubing The need for improved flow rate accuracy in healthcare based fluid delivery systems is driving innovation in healthcare fluidics. As pump systems continue to push the limits of performance, system manufacturers are challenged with decreasing the level of variation in their pump flow rates. This ultimately improves patient safety by ensuring more accurate volume deliveries of drugs and nutrition. A reduction in the variation of the tubing used in the pump system is part of the overall system improvement.

In recognition of this trend, the Healthcare Markets business unit of USA-based Saint-Gobain Performance Plastics, a subsidiary of the French materials manufacturer Saint-Gobain, has developed a new silicone extrusion process, which it calls Compass Technology.

The new process incorporates what the unit describes as state of the art manufacturing techniques, including closed loop process controls and real time data acquisition, to improve dimensional control and reduce lot-to-lot variability. The closed loop system continually monitors the finished tubing as it is being produced and will automatically adjust the settings at the extruder to ensure that the process is always within the targeted Continued on page 19

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EXTRUSION Continued from page 17

dimensional range. Additionally, the system allows for the real-time measurement of critical tubing dimensions as the product is being produced, including both inner and outer diameter, as well as concentricity. This data can then be provided to the customer as part of the certification data package for the production run. As a result, SaintGobain is able to offer highly precise and reliable silicone tubing for pump-based fluid delivery devices.

The other facet of Compass is the ability to custom compound unique silicone formulations based on the end user’s performance needs. Drawing upon decades of silicone formulation and process experience, Saint-Gobain translates the customer’s requirements into physical properties in the material, optimising properties like durometer, tensile strength, elongation and modulus.

Because it is chemically inert and extremely resilient, silicone tubing is often the material of choice for peristaltic pump applications that require high levels of flow rate accuracy.

Another silicone tubing extruder, Helix Medical, also based in the USA, offers custom black jacketed multilayer silicone extrusions for light sensitive drugs and other fluids. An inner silicone layer keeps fluids away from the black outer layer. << Precision silicone tubing produced from Saint-Gobain’s Compass extrusion technology >>

Piezoelectric Film Shows Promise for Ultrasonographic Transducers Chemical manufacturer Teijin, in partnership with Kansai University, both based in Japan, have developed a flexible, transparent multilayer film with what Teijin describes are unprecedented piezoelectric effects.

Piezoelectricity is a electric charge which is generated in a number of solid materials, such as crystals, ceramics and bone, in response to an applied mechanical stress.

Piezoelectricity is reversible—a material can also be made to generate a mechanical strain as a result of having an electrical field applied to it. Sound waves used in ultrasonic equipment are created with reverse piezoelecticity.

Teijin’s new film can be made by coextruding two layers of polylactic acid (PLA): poly-L-lactic acid (PLLA) and optical isomer poly-D-lactic acid (PDLA). Piezoelectric performance can be controlled by varying the number of layers, enabling customised designs to suit specific needs.

According to Teijin, the film is the world’s first binary blended PLA multilayer film with piezoelectric performance that surpasses that of lead zirconate titanate (PZT), a conventional and widely used piezoelectric material. The company also believes the new film will pave the way for larger and more lightweight products that in the past have been difficult to achieve.

High Definition Micro Fibre Extrusion USA-based custom fibre developer Adhesives Research has developed a highly tuned melt spin extrusion process called ARmicron high definition micro extrusion (HDME). The technique, which utilises nano- and micron-sized fibril components, can be used to form precise and unique structures within a fibre.

As many as four different materials can be incorporated into a single fibre, with a wide variety of material combinations, including a bioresorbable material mixed with a polymer like PET. Islands-in-the-Sea: An example of a fibre which has been made using the HDME process is what is known as an island in the sea—a combination of “channels” of resorbable and non-resorbable polymers within the same fibre allowing the fibre to be handled during weaving prior to the resorbables being washed away to give an extremely fine mesh used in the treatment of hernias and urological slings. Without the resorbable components, the ultra fine non resorbable fibres would break during weaving.

Fractal Fibres: The HDME method can also be used to make fractal fibres—fibres which can be extruded with nano scale grooves and raised areas to encourage cell growth. << Resorbable and non-resorbable polymers can be combined at the microscopic level in these islands-in-thesea fibres using HDME. >>

<< Nano scale grooves and raised areas can encourage cell growth in polymer fractal fibres. >>

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PACKAGING

ADVANCED COPOLYMERS FOR MEDICAL PACKAGING:

Innovation Roundup WORDS | SAM ANSON

A NUMBER OF ADVANCED << Thanks to good processing characteristics COPOLYMER PACKAGING and affordability, copolymers are finding use in many novel medical packaging applications. >> MATERIALS HAVE COME TO THE FORE WHICH ALLOW DESIGNERS TO EXPAND ASPECTS OF A DEVICE’S PERFORMANCE, LIKE LENGTHENING SHELF LIFE AND IMPROVING CLARITY WHILE OPTIMISING PROCESSING PROPERTIES TO ENSURE NEW INNOVATIONS ARE AFFORDABLE. THE FOLLOWING ARTICLE PROVIDES A ROUNDUP OF THE NEWEST INNOVATIONS. Polyolefins Thanks to their favourable chemical and mechanical properties, the most common materials used in medical packaging applications are polyolefinbased plastics—either polyethylene (PE) or polypropylene (PP). According to Saudi Arabian petrochemical manufacturer Sabic, the use of PE and PP in medical device applications has been increasing for 40 years, and growth remains strong to this day. The company estimates that global growth of polyolefins in healthcare applications remains in high single digits.

PP possesses a combination of properties that make it very useful for a wide variety of medical uses. It has extremely high chemical resistance, it can be sterilised by all commonly used methods, it can be formulated to have high impact resistance, and compared with alternatives, it is a relatively low cost material.

A wide range of specialist copolymers and advanced alternative polymers are available for packaging applications. Many of these are advanced forms of conventional polyolefins while others are designed to be combined with them.

Sabic: High Purity PP Random Copolymers Clarify Pre-Fillable Syringes In February 2011, Saudi Arabiaheadquartered petrochemical manufacturer Sabic launched two new grades of high purity PP random copolymers—one for BFS applications and the other for pre-fillable syringes. The latter featured not only high clarity but also good antistatic properties, necessary for injection moulded housings of disposable syringes.

Since then, Sabic has continued to extend its high purity PP random copolymer range for the healthcare sector. The new range features a high clarity random copolymer grade with enhanced fluidity and another high purity clarified grade containing a slip agent specifically designed to make the components in three-part syringes slide next to each other during usage.

Sabic has also developed a high flow HDPE injection moulding grade, intended amongst other things for syringe plungers in two-part syringes. The high fluidity of both the new HDPE grade and the enhanced fluidity PP random copolymer

helps reduce cycle time and so increases production efficiency and reduces production costs.

The PP materials have been enhanced with nucleating clarifiers. They work by creating multiple nuclei around which the polymer crystals can form. Because there is only a finite space in which to grow, the crystals end up being smaller than in a non-nucleated PP. In this case, Sabic says that small is beautiful, because the smaller crystals are less disruptive of the passage of light through the material than larger ones, giving an improved level of clarity.

In addition to beneficial physical properties, Sabic says there are processing advantages. The total crystallisation process takes less time, which means that the part can be ejected from the mould earlier, and the cycle time is reduced.

Moreover, the new PP random copolymers can be processed at lower temperatures than their predecessors, so syringe makers are rewarded with lower electricity bills.

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PACKAGING Continued from page 21

Barex Copolymer Helps UHMWPE Vitamin E Implants Stay Fresh Barex acrylonitrile-methyl acrylate copolymer (AMAB) from Swiss headquartered petrochemicals company Ineos is an advanced packaging material for injection and blow moulding, extrusion and calendering. The material, available from European distributor Velox, offers high barrier properties to gases such as oxygen and nitrogen, as well as chemical resistance and inertness.

At the same time, the material is sterilisable using gamma radiation as well as ethylene oxide. The material is used commonly for sealing large catheter trays as well as drug elution products including nicotine therapy patches.

The material has been shown to be especially effective in the

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packaging of orthopaedic implants made of cross-linked ultra high molecular weight (UHMWPE) polyethylene by providing a barrier layer between the implant and oxygen in the atmosphere.

According to Elena Maria Brach del Prever et al in the scientific journal J Orthop Traumatol, UHMWPE degrades when in contact with oxygen. Degradation results in an increased rate of wear of the implant’s surface while decreasing its mechanical strength. Wear-induced UHMWPE debris may cause a degeneration of the bone tissue all around the implant (osteolysis) when in vivo and lead to the implant’s removal.

Using Barex or another suitably powerful oxygen barrier reduces the implant’s oxygen exposure to a minimum while the device is packaged.

The oxidative degradation of UHMWPE starts during the gamma or ebeam irradiation process. The process results in free radicals, enabling oxygen to sink into the UHMWPE polymer chain.

Once the oxidation has been initiated, it

cannot be interrupted. The reaction continues inside the packaging and increases due to the extra oxygen constantly entering through blister walls.

A recent trend is for manufacturers to incorporate vitamin E into crosslinked UHMWPE implants to get a better resistance to oxidative degradation. It should be noted that while the use of vitamin E does reduce the rate of oxygen degradation, it does not completely suppress it so oxygen barrier packaging is still required.

According to Velox, the copolymer is very easy to thermoform and is selfsealable with heat.

<< In addition to preserving oxygen sensitive implants made from UHMWPE, Barex is used for nicotine therapy product packaging. >> COCs Improve Polyolefin Temperature and Water Resistance and Avoid Curling Medical packaging processors are reportedly using Topas’s cyclic olefin copolymer in combination with polyethylene and polypropylene to impart improved temperature resistance into standard films for packaging. It is also being used in extrusion coating to give improved water resistance—the resin has four times the water vapour barrier of LDPE. Thanks to an inherent stiffness, the material also reduces shrinkage which helps to avoid film curling.

<< Topas COC can be combined with polyolefins to improve packaging properties. >> 22/ MPN / SEPTEMBER/OCTOBER 2012

Aclar Fluoropolymer Films for Heat and Humidity In late 2011, USAheadquartered Honeywell Specialty Materials, part of diversified manufacturing group Honeywell International, introduced a new grade of fluoropolymer-based barrier film, Aclar UltRx 6000, for the hottest and most humid climates.

Product Focus | PACKAGING According to Honeywell, the film, which is made from polychlorotrifluoroethylene (PCTFE) fluoropolymer, can also reduce the size of drug package sizes by up to 55% compared with traditional materials.

The material has already been widely used as a laminate on PETG and PVC films by ACG Pharmapack, a leading Indian manufacturer of pharmaceutical packaging films.

Transparent Coloured Sterile Pill Bottles Contain 54% Clear Nylon Biopolymer A 2009 report on Omnexus.com describes transparent sterile pill bottles being made from Arkema’s high purity Rilsan Clear G830 Rnew biobased nylon resin. The resin contains 54% biopolymer.

The key achievement here is that biopolymers are renowned to be cloudy, yet the manufacturer of the bottles, USAbased packaging firm TricorBraun, has managed to maintain a 91% light transmittance while reducing cycle time compared with cyclic olefin copolymers (COC) by 15%. According to the report, the bottles’ other physical properties, including sterilisation performance and crack resistance, are comparable to standard products.

Bio-based Ingeo PLA Polymer Used in First Aid Kit A biobased film has been used to overwrap a first aid kit by USA-based packaging film manufacturer Clear Lam. The film is made from modified Ingeo polylactic (PLA) made by USA-based biopolymer manufacturer Natureworks.

The PLA polymer is modified so that 40% of its content is made from the bio-based polymer. According to Clear Lam, the film is processable at high speeds and can be printed with up to ten colours. Clear Lam uses Ingeo PLA in a number of nonmedical applications, including breathable and high barrier bio-based films.

Dow Launches Health + LDPEs for Blow Fill Seal In April 2010 US chemical manufacturer Dow launched a range of LDPE grades for the healthcare sector called Health +. Two grades are specifically designed for blow fill seal applications, namely Dow LDPE 91003 and 91020 Health + polymers.

Bormed Medical HDPEs Deliver Improved Moulding Flow Rates In June 2011 Austria-headquartered polyolefins manufacturer Borealis launched its new high flow Bormed HE9601-PH high density polyethylene (HDPE) grade.

According to Borealis, the new HDPE grade delivers a flow rate improvement of up to two-and-a-half times that of comparable alternatives thanks to its melt flow rate (MFR) of 31. This enhancement enables higher speed injection moulding of applications ranging from two-part syringe plungers to caps and closures.

In addition to the potential for faster production and increased throughput, the faster flow allows for operation at decreased pressure and temperature.

This lowers both energy and mould maintenance requirements and gives a cost advantage.

The new grade is an addition to Borealis’s wide range of Bormed speciality polyolefins. In moulding, PP is available as a homopolymer, a block copolymer and a random copolymer. HDPE and LDPE are also available. LDPEs are noted for their suitability for BFS applications. Almost all the grades have drug master file (DMF) numbers.

In film extrusion, PP grades are available as a homopolymer, random copolymers, a terpolymer and a soft PP which is a random heterophasic copolymer PP. A speciality polyolefin for drug delivery applications is also available—known as Steripeel.

To help with regulatory issues over material changes, Borealis offers its polyolefin customers an option to arrange a long term supply commitment and a pre-notification prior to deletion or modification.

Styrene Butadiene Copolymers “A Halfway House” In a report published in March 2011, US petrochemical company Chevron Philips claims that its K Resin styrene butadiene copolymers are a half way house in terms of price for medical packaging products between polyolelfins and polycarbonates.

Being less dense than clear alternatives is what gives K Resin its price advantage Continued on page 24

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PACKAGING Continued from page 23

apparently, as less is required for comparable levels of toughness. Another bonus is that it is processed at lower temperatures, reducing energy costs. The company claims that clarity is better than with standard polyolefins.

The drawbacks of the product are as follows. It is not sterilisable by autoclave sterilisation. Chemical and crack resistance may not be strong enough for some applications. It cannot be used in contact

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with plasticised PVC as the plasticisers can migrate into SBC, resulting in destructive results.

Additives in SBC have been known to react with certain devices, including implantable lenses, and diagnostic packaging.

Polycarbonate Film: For Intricate Device Packaging According to US-based medical film manufacturer Tekra, polycarbonate has

become an increasingly attractive option for thermoformers looking to achieve steam or dry heat sterilisation. It has favourable properties in terms of high tensile strength, durability, dimensional stability and elasticity requirements.

Also, it has deep draw thermoformability options which means that complex shapes and sizes can be accommodated.

The material is particularly useful for protective packaging for intricate devices, opthalmics, implants, diagnostics and specialty products.

Copolymer Grades from DuPont for Medical and Pharmaceutical Films USA-headquartered chemical science company DuPont offers a range of products, including: n Surlynâ&#x20AC;&#x201D;an ionomer heatseal copolymer resin used as a sealant or structural layer together with ethylene vinyl alcohol (EVA). It is commonly used in all kinds of sachets such as those for condoms; n Bynel specialist modified polyolefin adhesive resins for barrier structures; and n Elvax ethylene vinyl acetate (EVA) for nutritional pouches and colostomy bags.

Tritan and Eastar Copolyester and Ecdel Elastomers US plastic and chemical manufacturing firm Eastman claims that its Tritan copolyester has transformed the medical industryâ&#x20AC;&#x2122;s outlook on clear and sterilisable medical grade polymers. The resin is designed to replace traditional copolyesters, polycarbonates and acrylics which years ago were developed as a replacement to glass.

Tritan copolyester is a popular option for manufacturers of dialysis filtration casings, where impact resistance, transparency and sterilisability are important. There is also a Tritan grade which is suitable for thin walled applications.

Eastman reckons that Eastar copolyester sheet has been an industry standard in rigid thermoformed medical packaging for more than 20 years. Eastar copolyester can also be used in

24/ MPN / SEPTEMBER/OCTOBER 2012

Product Focus | PACKAGING demanding flexible packaging applications like monolayer fluid bags. The resin can also be combined with an Ecdel elastomer film in a multilayer structure.

Medical Packaging: Background Medical packaging and components can be divided into four categories—thin wall (or flexible), rigid, blown bottles and containers, and caps, closures and other seals.

Thin wall packaging refers to lightweight flexible packaging that is generally disposable. Rigid packaging, by contrast, is hard and tough—designed to protect contents from impact punctures.

Packaging Standards According to the USA’s Institute of Packaging Professionals, the FDA recognises as many as 14 medical packaging standards—including 12 test method standards, a standard terminology guide and a steering document for packaging design and evaluation (table 1). These standards make up the backbone of the medical device packaging industry—much of which is served by plastic materials.

<< Table 1: American Society for Testing and Materials (ASTM) Standards Recognised by the FDA. >> Description

Reference Number

Description

Reference Number

Bubble emission test to determine leaks in flexible packaging containing headspace gas

ASTM D3078:1994

Exposure chamber test to determine microbial barrier properties of a porous material (test results can indicate potential of material to contribute towards loss of sterility)

ASTM F1608:2000

Impact and vibration tests to ensure device is not damaged during shipping

ASTM D4169:1999

Guide to accelerated aging tests of sterile packages (used to check shelf life claims)

ASTM F1980:2002

“Tail holding” force test to measure seal strength of flexible barrier materials

ASTM F88:1999

Burst and creep test for flexible package seals within restraining plates. Test can simulate sterilisation and low pressure conditions such as high altitudes.

ASTM F2054-07

Definitions of standard terminology relating to flexible barrier packaging

ASTM F17-08 (replaced ASTM F132705 in 2007)

Leak test for pressure decay in ASTM flexible packages F2095-07e1

Dye penetration test to determine two-way seal integrity in porous packaging

ASTM F1929:1998

Bubble test for detecting gross leaks in packaging

ASTM F2096-11

Burst and creep test to ASTM determine resistance of F1140:2000 seals to internal pressurisation—no restraining plates. Test can simulate sterilisation and low pressure conditions such as high altitudes

General guide for designing and evaluating medical packaging. Includes details on safety, barrier properties, durability, package and seal integrity, visibility and appearance, processing, printing ink properties, and package performance

ASTM F2097-10

General procedures for testing the integrity of porous barrier medical packages

Requirements for packaging of terminally sterilised used medical devices

ANSI/AAMI/IS O 11607-97

ASTM F1585:2000

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This picture, from Netherlands-based specialist mould maker Axxicon Moulds Eindhoven, shows the injection moulding process of a microfluidic substrate for a lab on a disc in vitro diagnostic (IVD) point-of-care test device. Intricate levels of detail are moulded into the substrate using a proprietary process. Axxicon Moulds Eindhoven enables the manufacturing of lab on a disc and lab on a chip in cooperation with diagnostics and life sciences companies, from prototyping to mass production.

The company’s skills are not only required to replicate microstructures, but also to adhere to precise measurements, made possible by a laboratory with highly specialised equipment like a Zeiss Prismo Super ACC (Accuracy) navigator measuring machine as well as an atomic force microscope and an optical microscope.The depths of the microstructures vary from 50 μm to 200 μm whilst the width varies from 50 μm to a few millimetres. The roughness of the bottom of the structures is 0.08 μm Ra. The roughness of the surface is of optical quality (about 2 nm).

FOLIO

INDIA

Investing in India?

Timing is Everything

WORDS | SAM ANSON

On paper, India should offer the international medtech industry huge opportunities as a potential manufacturing base.

According to the World Diabetes Foundation, with 50.8 million at the last count, India has the highest number of diabetics in the world, followed by China with 43.2 million. Furthermore, according to a recent report by the USA-based IMS Institute for Healthcare Informatics, growth in pharma sales in emerging markets—including India—is estimated at $157 bn over the next five years.

But when visiting the country, established suppliers of medical moulding equipment have found only a small domestic sector compared with the size of the country’s population. And these moulders, all Indian companies, are only supplying the basic needs of the industry. Christoph Lhota, head of medical at Engel, explains “Our experience of India’s small medical moulding sector is that it mostly supplies commodity products like syringes and infusion sets, labware, diagnostics and disposables. In terms of moulding for advanced medical devices, such as insulin pens and inhalers, there is as yet very little activity.”

The Indian medical device market, estimated by UK-based medical business intelligence firm Espicom to be worth US$2.7 bn in 2011, procures its advanced products via import from the USA and Europe. These products are bought by private hospitals servicing the growing wealthy middle and upper classes. But despite being in the top 20 markets in terms of absolute size, India’s per capita annual spend on healthcare remains at just US$2—a third that of China.

Nigel Flowers, managing director of injection moulding machine manufacturer Sumitomo (SHI) Demag’s UK subsidiary explains: “The device market is heavily dominated by US and European suppliers; a significant proportion of devices are imported rather than manufactured locally. This is due in the most part to the high regulatory hurdle associated with foreign direct investment which manufacturers must clear before setting up operations in India. In addition to this, private medical practices generally demand products made in the US or EU as a mark of quality.”

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So why the reliance on imports? As inferred by Nigel, investors in India face a barrage of regulatory hurdles when looking to set up operations there. There are strict rules limiting foreign ownership and control of companies to Indian citizens, although there are reports that this has been slightly relaxed recently.

Furthermore, excessive red tape involved in setting up new companies makes the process complicated and laboursome.

Added to this, the rules of foreign investment are also complex, making getting up to speed with the processes difficult and time consuming.

That said, the Indian government is aware of its problems with excessive bureaucracy and has taken steps to simplify the process in recent times.

And along with senior members of the healthcare industry, it is aware of the opportunities available if the country can foster an internationally competitive domestic manufacturing industry.

But the industry is starting from a small base. Having had contact with many existing Indian moulders, Richard Gane, project manager at Swiss medical mould maker Kebo shone a light on the challenge facing the government: “We went over to India earlier this year hoping to be able to provide our mould making services to new customers but we could only conclude that we were a bit too early. We are used to supplying complex, high value and high precision moulds to large OEMs but most Indian medical moulders do not need these yet. Their customers have lower quality requirements than those in the USA or Europe as a result of less stringent regulations in the Indian domestic healthcare industry. Richard summarised: “The country is like China was ten years ago.”

A recent article in The Times of India explained the Indian medtech situation nicely. The headline, Marching in Medicine but Trailing Along in Technology, suggests that the healthcare industry has a well supplied pool of qualified clinicians, many of which have medical experience in US and European hospitals, but a limited supply of domestically manufactured devices. The report quotes three experts in the field who testify to this—two hospital CEOs and Dr GSK Velu, the managing director of Trivitron Group, one of the biggest of India’s manufacturers and importers of medical devices.

Underlining the incentive for the healthcare sector to stimulate domestic manufacturing, Dr Velu states that the healthcare industry could save 30-35% on spending of devices by manufacturing everything in India.

But according to one of the hospital CEOs, the problem is that there isn’t a government department dedicated to device manufacturing, meaning that “medical technology is nobody’s child when it comes to formulating rules”.

There are signs that things are starting to move in the right direction for the Indian medtech industry, however. According to a July report in India’s Business Standard newspaper, Trivitron and Medtronic have begun talks for a strategic investment by Medtronic into Trivitron’s medtech manufacturing park in Chennai on India’s south east coast. Trivitron is in the process of expanding revenues generated from device manufacturing from 35% to 80% at the expense of importing and distributing operations. It should be noted that Medical Plastics News has not confirmed the report of the negotiations with Medtronic.

On August 22, 2012, an Indian owned subsidiary of USAbased drug delivery component supplier West Pharmaceutical Services, West Pharmaceutical India Packaging, began construction of its new moulding facility located in Sri City, India.

The plant, located on 784,000 square feet of land (72,800 square metres—approximately ten European football pitches) will become part of West’s global supply chain for its pharmaceutical packaging components.

And on August 31 – September 2, 2012, Indian healthcare provider and founder of the first commercial hospital in India, Indian Apollo Hospitals group, held an international conference in Hyderabad about “transforming India’s healthcare industry”.

The conference featured a range of international speakers from 70 countries and covered innovations in IT for healthcare as well as regulating to improve patient safety.

The Swiss trade association Medtech Switzerland is organising a trade mission to Delhi, Bangalore and Mumbai on October 15–17, 2012. The trip is supported by financial services specialist Ernst & Young, presumably to help interested parties understand India’s complex investment regulations.

The trip includes visits to manufacturers in Bangalore and Mumbai. The ones in Bangalore are electronic monitoring device maker BPL Healthcare, class III implantables producer Medived, and monitoring device maker Opto Circuits. The visits in Mumbai are to clinical trials lab SIRO Clinpharm, dental, orthopaedic, gynaecology, cardiology and anaesthesia equipment maker Dhanwantari Medical Systems (DMS) and cardiology and gynaecology equipment manufacturer Maestros Mediline Systems.

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STERILISATION

Room Temperature Sterilisation of Plastic Medical Devices with Nitrogen Dioxide Nitrogen dioxide (NO2) sterilisation is a new process. First FDA approval of NO2-sterilised devices is expected in the first quarter of 2013. The developer, USA-based Noxilizer, describes plus points as: room temperature processing at ambient and low pressures; vacuum processing for faster sterilisation; low concentrations required; short processing cycles; room temperature sterilant storage; and similar validation and control methods to traditional sterilisation. Dr Evan Goulet of Noxilizer discusses applications of NO2 in polyetherimide, silicone rubber and cyclic olefin copolymers (COCs).

olyetherimide (Ultem), silicone rubber, and cyclic olefin copolymers (COCs) are used in devices because of their desirable properties and relatively good biocompatibility. The NO2 sterilisation process maintains these properties while providing rapid and effective sterilisation of a wide range of microorganisms.

Ultemâ&#x20AC;&#x2122;s characteristics include chemical and temperature resistance, high strength and durability. It provides a similar challenge to NO2 sterilisation as does stainless steel. This is evident in figure 1, which shows the reduction of biological indicator (BI) population on both stainless steel and Ultem as the NO2 concentration in the chamber is increased and exposure time is held constant.

P

In order to derive these results, coupons of Ultem and stainless steel were inoculated with spores of the bacterium Geobacillus stearothermophilus and exposed to the NO2 sterilisation process. Stainless steel is a typical carrier material for BIs in many sterilisation processes, including NO2, due to its resistance to reaction with the sterilant. Reactions between the sterilant and the carrier material can inhibit lethality, and one can

see from the rate of lethality there is little interaction between the Ultem and the NO2. Ultem coupons were also exposed to 50 NO2 sterilisation cycles, and there were no observed changes in materials properties as measured by tactility, hardness, and surface finish.

Pure silicone rubber (polydimethylsiloxaqne, or PDMS) exhibits a challenge to NO2 sterilisation that is similar to that of Ultem or stainless steel. It is relatively inert in terms of reactivity with the sterilant. However, additives are often used in silicone to impart colour or improved mechanical properties. These additives can increase the challenge to sterilisation that is presented by the silicone rubber, as can be seen in figure 2. Red silicone rubber (o-ring material) and blue silicone rubber (cable sheath material) were compared to PDMS. One can see that the PDMS carriers were sterilised, while 33% of the red silicone carriers and 100% of the blue silicone carriers were positive for bacterial growth after the cycle. The difference in response of the silicone materials was due to the additives in the different formulations.

These results indicate that the coloured materials require a different set of cycle parameters than PDMS. This indicates the importance of individually screening materials and devices to determine the appropriate cycle parameters to ensure sterilisation in the most challenging location on the devices.

Sterilisation of COCs proceeds rapidly, similar to stainless steel, due to the inert nature of the polymer with respect to the NO2 sterilant. COC components remain clear with no colour change after exposure to the NO2 sterilisation process.

Additionally, the NO2 gas does not permeate the COC material during the sterilisation cycle, which allows for rapid aeration of the sterilant. This means that residuals from the sterilisation cycle are low. When COC syringe barrels that have been exposed to the Noxilizer sterilisation process are filled with ASTM Class I water, the water remains within the standard limits of â&#x20AC;&#x153;water for injectionâ&#x20AC;? when analysed for sterilant residuals.

SEPTEMBER/OCTOBER 2012 / MPN /31

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ASSEMBLY

Considerations for Automated Assembly of Drug Delivery Devices

<< Cleanroom production at Gerresheimer >> Following the news in September that Gerresheimer Medical Plastics Systems (MPS) had successfully transferred manufacturing of price sensitive products like inhalers and lancets to an FDA-inspected plant in China, Sam Anson persuaded the companyâ&#x20AC;&#x2122;s chief technical officer Manfred Baumann to kindly share his notes on automated assembly of drug delivery devices.

Q: What are the main considerations when designing a drug delivery device for automated assembly?

A: Drug delivery devices are often pre-assembled at a supplier, with the filling and final assembly steps being carried out at a pharmaceutical company. The device should be designed to allow partial assembly and testing before filling. Final assembly post filling should be simple and quick.

Manufacture, assembly and filling must be considered at the product concept stage. Getting it right first time can save a manufacturer millions for high volume products. Many design principles for automated assembly are similar to those for manual assembly but designers need to understand that there are sometimes conflicting trade-offs between functionality, aesthetics, ease of moulding and ease of assembly.

Q: And what about at the detail design stage?

A: A simple design is easy to assembly. Combine components wherever possible using twin shot or over-moulding. Design the device for assembly from one side where possible. Where not possible, reduce the number of re-orientation steps. Assess prototypes for ease of assembly as well as functionality.

Components should have appropriate tolerances for assembly.

Worst case tolerance analysis may be needed. Incorporate design features to reduce tolerance requirements, for example crush ribs, springs, chamfers and tape fits, particularly with injection moulded parts which are not rigid. Consider requirements for automated inspection at each assembly step.

Electronic components should be designed as sub-assemblies to be inserted ito the device during the assembly process.

Q: What about metal-plastic joins?

A: Metal must be free of contaminants and material combinations must be checked using finite element method (FEM) simulation.

Q: Which joining and marking processes are integrated and how are the components tested?

A: Joining operations such as ultrasonic, vibration and laser welding, thermoforming, cold calking and adhesive bonding as well as laser marking are integrated into the assembly lines.

Testing is an integral part of the process. A test procedure is implemented after every assembly step. The device can only move on to the next assembly step if it passes a test of the previous step. Designers build step by step testing into their product designs. Packaging is integrated at the end of the line via normal packaging equipment, robots and labelling machines.

Q: What are the most technically demanding lines and what are the normal volumes produced from them?

A: The most demanding lines are those for cleanroom class 7 which have to follow GMP guidelines. Normal volumes are around 50 million pieces per year.

Q: Are there any specific design considerations for prefilled devices?

A: For pre-filled devices, design for filling is often critical (but sometimes not fully appreciated). Devices should ideally be designed for rapid filling using standard or near standard systems. Adequate access should be provided to the drug container. This access must have a large enough opening for filling while the drug container may be a separate component.

Continued on page 34

SEPTEMBER/OCTOBER 2012 / MPN /33

Drug Delivery | ASSEMBLY Continued from page 33

Q: What are the main challenges in automated assembly of drug delivery devices?

Q: Where has the most technological development been in automated assembly in the last five to ten years?

A: The biggest development has been the integration of testing procedures into an assembly line. Other gains have been faster speed to reduce costs, better cleanability and arrangement by cleanroom classes including air ducts for particle-free assembly and linking of production from injection moulding machines directly into assembly lines. With integrated testing, this allows a part to be moulded, assembled and testing without interruption or human interference.

A: There is not a permanent availability of lines. The machinery is very specialist and there are long lead times. Furthermore, when considering international expansion, as we have done in China, we need an international level of service from our line manufacturer. This is not always possible.

In terms of designing for automated assembly, there is still room for improvement in getting an assembly oriented design to be instilled in designersâ&#x20AC;&#x2122; minds. Serial assembly steps must already be integrated at the time of device development for complex assemblies of more than 30 components.

Due to a sometimes slow response in the assembly machinery supply chain, it can be difficult to make adaptations to a device once in production as quickly as some manufacturers would like.

A faster response from machinery manufacturers would allow a faster response to device changes by assembly companies.

<< An injection moulding cleanroom at Gerresheimer Medical Plastics Systems. >>

34/ MPN / SEPTEMBER/OCTOBER 2012

In terms of testing, I would like to see more integration of electronic and functional testing of the device being integrated into the assembly line. This is important as devices become more electronically oriented.

ASSEMBLY Q: Looking forward, where should assembly machinery manufacturers focus their improvements?

A: For me, the most important improvements should be as follows: reduced construction time for assembly lines; simultaneous engineering; a quicker response time on component changes and design changes; qualification and validation applications should be ready during conceptual line design; provision of service for lines during production ramp up; an overall improvement in the availability of assembly lines; simple geometries for components; a reduction in complexity of the assembly process; test specifications should be made available after the end of the construction phase; technologies should be developed to allow assembly companies to produce higher volumes in narrower spaces; and suppliers should qualify the line according to customer requirements. << Manfred Baumann is the chief technical and chief operating officer of Gerresheimer Regensburg in Germany. >>

<< Gerresheimerâ&#x20AC;&#x2122;s cuvette production line in Kuessnacht, Switzerland, uses some of the most advanced automated assembly equipment in the plastics industry. >>

SEPTEMBER/OCTOBER 2012 / MPN /35

36/ MPN / SEPTEMBER/OCTOBER 2012

Cover Story | COMPAMED 2012

COMPAMED

Resilia Kem One Showcases Phthalate Free PVC Compounds Under New Ownership Structure In July 2012 new vinyls manufacturing giant Kem One was established. The Kem One group of companies was formed following the acquisition of Arkema’s vinyls group of companies by Swiss family owned investment firm Klesch Group.

A key company involved in the deal is Italy-based specialist medical PVC compounder Resilia. The company has been named as the group’s biomedical headquarters. Prior to them showcasing their biomedical PVC compounds at Compamed on November 14-16, 2012, Sam Anson spoke with Marco Toscano, general manager at Resilia and head of Kem One’s Biomedical department, and Sophie Suc, chief communications officer. Sam wanted to find out more about the new organisation and, specifically, what biomedical PVC customers can expect as a result of the acquisition.

Q: Marco, tell me how Resilia customers can expect to benefit from the new structure?

Marco Toscano: As headquarters for the Kem One group’s biomedical department, our customers will be able to take great advantage of the new Kem One structure.

Kem One is open about its interest in healthcare and is supporting the ambitious development targets of Resilia, which embodies the driving force for high value products of the innovative vinyl division.

Q: Sounds exciting. Tell me more about Resilia and why it has such a strong reputation as a supplier of PVC compounds for healthcare applications.

Marco Toscano: Resilia is based in the town of Samarate, located near the international airport of Milano Malpensa in Italy. Several years ago the company started a programme to focus solely on the healthcare sector as a top priority market.

At the beginning of 2011 Resilia became the first vinyl compound producer in the world to acquire ISO13485.

The company operates under a mission of always putting the customer as its top priority, and with safety being the absolute first concern.

Continued on page 39 SEPTEMBER/OCTOBER 2012 / MPN /37

COMPAMED Continued from page 37

Q: That’s what I’d heard too. You have a great reputation. Patient safety is obviously paramount when manufacturing materials. Tell me more about how you achieve this?

Marco Toscano: We have a biological lab which provides customers with a “toxicity free” declaration for each batch produced. At the same time, we maintain ABC segregation of both production departments for maximum efficiency.

Q: There is a lot of concern over phthalates in the healthcare industry at the moment. How do you help your customers who are worried about this?

Marco Toscano: On the side of product innovation, Resilia is continuously working on different paths, thus providing customers with reliable solutions to incoming requirements, always carried out in the name of safety, which remains the milestone of our activity.

Years of experience have now given to Resilia the highest capability in phthalate-free vinyl compound formulation and production, thanks to important and fruitful cooperation with some of the most important plasticiser producers.

Q: Thanks Marco. We have an article on DEHP on pages 6-13 to which your technical director Andrea Zanichelli contributed, so thanks for the input there.

What other areas of product innovation are you working on?

Marco Toscano: We have some state of the art technologies coming from Kem One’s biomedical department in the form of strategic innovations in the field of plasticiser free solutions for delicate applications with zero migration requirements.

Resilia laboratories are also focused on the development of ad hoc formulations for special rigid vinyl blends which in selected applications can replace high value polymers, such as PC, PETG and transparent ABS (or MABS), thus generating very important savings and efficiency improvements for the customer.

Some of the most important multinational medical devices companies are already profiting from this key competence.

We also have a new solution for the medical packaging market. The product will be presented at the Compamed exhibition. All I can say for now is that it offers a radically new approach to this market segment, leading to a concrete and immediate advantage to the customer.

Q: Sounds intriguing. I’m very curious. What should people do if they are interested in your new solution for the medical packaging market?

Marco Toscano: If people are interested they should come to our stand at Compamed. We are ready to talk about this new product, verify the customer’s potential interest and evaluate the possibility to research together as part of a common project.

Q: Fascinating. I can’t wait to visit the stand. Sophie, can you tell us a little more about the Kem One group as a whole. It’s a chemical company dedicated to vinyls if I understand correctly, isn’t it?

Sophie Suc: Yes Sam. Kem One is a new fully integrated company in the vinyl sector. It offers its customers everyday commodity products as well as new “tailormade” vinyl solutions for innovative applications. By combining the know-how of its experts in PVC manufacturing, formulation and transformation, Kem One positions itself as a true partner able to fully accommodate its customers’ growth.

Q: You have a turnover of over €1 bn. What are the main manufacturing processes that generate this revenue?

Sophie Suc: Kem One’s business stretches from the extraction of salt and the production of chlorine, soda and their derivatives, to the manufacture of PVC, its formulation into highly technical vinyl compounds and its further processing into profiles and tubes.

The company employs 2,600 people at 22 manufacturing sites, primarily in Europe but also in Asia and North America. It is Europe’s third-largest producer of PVC and possesses numerous strengths for growing and becoming the integrated vinyl solutions leader in southern Europe and the Mediterranean basin.

Q: Marco, what an amazing structure to be part of.

What are Resilia’s prospects for international growth?

Marco Toscano: On the side of growth consolidation, the important American and Asian markets will be areas of strategic development, above all in the fields involving new solutions and high value products. We will also hope to be profiting from the already consolidated presence of our important production units operating in Vietnam and Mexico.

The management team of Resilia is already focusing on a sustainable development programme, which forecasts that the Kem One biomedical department will have a presence in important healthcare exhibition events overseas.

Resilia: 8b/H20 www.kemone.com SEPTEMBER/OCTOBER 2012 / MPN /39

Exhibitor News | COMPAMED 2012

INJECTION

MATERIALS Tritan Copolyester Clarifies Digital Cardio Monitor

The casing, lens and connectors of an advanced wearable digital cardio monitoring device have been made from Tritan copolyester, made by USA-based resin manufacturer Eastman. Thanks to the material’s physical properties, the device is resistant to chemicals and has optical clarity and good impact strength. “[The manufacturers] wanted to be able to throw the device on the ground,” says Scott Clear, formerly vice president of the product development firm involved in the device, USA-based DD Studio.

“Hospitals are very harsh environments,” says Jim Moon, CTO for Sotera, the OEM making the product. “Blood, vomit [and] drugs will be spilled on this device. It will be dropped and banged against bed rails. So you have to find a balance with respect to the material that makes the product rugged, highly cleanable and having smooth surfaces for patient comfort.”

Eastman: 8a/P04 www.eastman.com

Porous Plastic Used in Protein Capture Assay for Cancer Research

Sintered porous plastics from UK-based porous plastic materials manufacturer Porvair have been used in a chromatin immuno-precipitation (ChIP) assay—a device which captures antibody-tagged DNA protein complexes associated with cancer. To enable the device to trap the proteins, the plastic in the device has had certain other proteins chemically bound to it.

Porvair: 8a/F08 www.porvairfiltration.com

TPE Specialist Wittenburg Opens Facility in The Netherlands Dutch compounder Wittenburg is proud to announce the opening of a purpose built production and R&D facility in Zeewolde, The Netherlands. According to the company, the investment will enable it to meet the most stringent quality requirements of existing customers. It will also enable it to continue to supply products for highly regulated and risk adverse TPE applications into the long term.

Wittenburg has a strong presence in the medical and pharmaceutical delivery device industries, particularly in TPEs for infusion systems.

Wittenburg: 8a/P31 www.wittenburgbv.nl

40/ MPN / SEPTEMBER/OCTOBER 2012

Bayer Showcases Aliphatic Polyurethane Foam

Onsite Micro Moulding of Inhalator Filters with 80μm Detail

Germany-headquartered Bayer MaterialScience will be showcasing a new aliphatic polyurethane foam based on Baymedix FP reactive foam technology.

The raw material enables the production of very smooth and conformable foams that are non-yellowing, thus maintaining their white colour over time.

Their high absorption rate, together with fluid retention capability, fits the moisture management requirements of advanced wound dressings very well.

Epurex Films, a subsidiary of Bayer MaterialScience, offers films made from thermoplastic polyurethane under the Platilon trade name.

They are tailor-made for use as soft, thin-film protective coverings and are characterised by controlled water vapour transmission, high flexibility and a matt surface.

Bayer will also be showing its range of thermoplastic materials, such as Bayblend M850XF—a blend of polycarbonate and acrylonitrile-butadiene-styrene (ABS).

A micro moulding machine from Austrian injection moulding machine manufacturer Wittmann Battenfeld will be producing a micro filter made of POM with an 80 μm grid and a part weight of 1.1 mg (pictured) at Compamed. The part can be used in inhalators and will be made on a MicroPower 15/10 machine.

Bayer MaterialScience: 8b/H30 www.materialscience.bayer.com

Wittmann: 8b/F03 www.wittmann-group.com

Tamper Proof Red and White Twin Shot Fluid Bag Cap Combines PC and TPE

German contract moulder and assembly firm Spang & Brands will demonstrate its capabilites in complex high precision twin shot moulding with a sealing component it has developed for fluid bag systems.

The component, a tamper proof cap, features a red polycarbonate ring connected to an ultra soft TPE cap. The cap can be ultrasonically welded to the collar of the port of a fluid bag using ultrasonic welding. The cap, which Spang & Brands claims provides a 100% reliable seal, is sterilisable via steam and gamma rays.

Spang & Brands: 8a/M33 www.spang-brands.de

COMPAMED

MOULDING Axxicon to Highlight Lab on a Chip Mould Making Prowess

Netherlands-based specialist optical media mould maker will show its prowess in the precision design and production of tooling for microfluidic consumables. The company describes itself as a key enabler for producers of these products and offers services including consulting, tool design, production and automation.

Key product areas include lab on a chip and disc diagnostic devices.

Axxicon Moulds: 8a/D34 www.axxicon.com

Apple Highlights Micro Moulded LSR and Fluoroelastomer Miniature Seals USA-based contract moulder Apple Rubber Products will be featuring seals and custom moulded parts in biocompatible LSR, ethylene propylene and Viton fluoroelastomer at Compamed this year.

According to the company, parts are manufactured in a class 7 certified cleanroom.

Products can be inspected using the company’s automated optical microscopy inspection equipment. The company will also be introducing a new interactive web site.

Apple Rubber: 8b/F20-8 www.applerubber.com

Sony DADC Collaborates on Sony Cyto Cell Sorting Equipment Sony DADC Biosciences, an independent Austria-based bioscience subsidiary of global entertainment equipment manufacturer Sony Corporation, has announced that it is collaborating with the newly formed Sony Medical Business Unit (MBU).

The objective of the collaboration is to develop and manufacture smart consumables for Sony’s new generation of advanced cell sorting instrumentation systems, SH800, which was launched in June 2012.

Sony DADC: 8a/G03 www.sonyDADC.com

Phillips-Medisize Opens European Design Centre Newly merged finished device contract development and manufacturing firm PhillipsMedisize, headquartered in the USA, has concentrated engineering forces for Europe in a new Design and Development Center in The Netherlands. The centre will develop pharmaceutical, medical device and combination products for OEMs from the first drawing right through to the finished product. President and CEO Matt Jennings said: “The opening of the European Design Center is in keeping with our strategy of providing our customers regional access to our global capabilities.”

Phillips-Medisize: 8a/H15 www.phillipsmedisize.com

SEPTEMBER/OCTOBER 2012 / MPN /41

Exhibitor News | COMPAMED 2012

COMPAMED

EXTRUSION Real Time Data Loop Yields High Precision Silicone Peristaltic Pump Tubing

The Performance Plastics division of Franceheadquartered materials manufacturer Saint-Gobain has developed a proprietary extrusion process which is able to produce silicone tubing to highly precise dimensional tolerances.

The new process, Compass, incorporates closed loop process controls and real time data acquisition to improve dimensional control and reduce lot-to-lot variability.

The closed loop system continually monitors the finished tubing, including aspects such as inner and outer diameter and concentricity and will automatically adjust the settings at the extruder to ensure that the process is always within the targeted dimensional range.

This data can then be provided to the customer as part of the certification data package for the production run.

Saint-Gobain has recently announced it will discontinue production of DEHPplasticised PVC in June 2013.

Saint-Gobain Performance Plastics: 8b/L08 www.medical.saint-gobain.com

Parker Hannifin Develops Aliphatic Polycarbonate Polyurethane Tubing

The Engineered Polymer Systems (EPS) division of Parker Hannifin Corporation, the USA-based manufacturer of motion and control technologies, has launched its first polyurethane product series for biomedical use.

The series is made from a range of proprietary aliphatic polycarbonate-based (ALC) polyurethanes—which Parker describes as high purity materials with improved chemical resistance and biodurability.

The tubings are targeted at the catheter market and available in a range of durometers to meet specific application needs.

Parker says that use of polyurethane materials for short-term implantable devices is increasingly attractive to device manufacturers due to their biocompatibility and absence of plasticisers.

Parker’s medical grade polyurethanes are manufactured in an ISO13485 facility in an ISO Class 7 clean room.

Parker Hannifin: 8a/M13 www.parker.com

Vesta Adds Silicone Dip Casting, Tipping and Flaring and Heat Shrink Tubing

USA-based tubing manufacturer Vesta has broadened its capabilites. It now offers silicone dip casting following its acquisition of USA-based dip casting specialist Simatrix in November 2011. Vesta can further support its customers’ supply chain efficiency and precision finishing needs through its recent addition of tipping and flaring capabilities and the introduction of a standard heat shrink product line.

Vesta: 8a/R23 www.vestainc.com

Teleflex Medical OEM Expands Manufacturing Facility

On September 14, 2012, USA-based custom developer of minimally invasive devices Teleflex Medical OEM opened a newly renovated and expanded facility in New Hampshire, USA. The multimillion dollar expansion adds 10,000 sq ft (929 sq m) to the facility, which includes additional research and development facilities and a larger extrusion centre.

Kelpac Opens Extrusion Lines in Ireland USA-based Kelpac Medical, a manufacturer of medical device tubing and packaging, has announced the opening of a new extrusion plant in Ireland.

The new facility, which has been certified compliant with ISO9001:2008 standards, will provide regional logistics efficiencies to medical device manufacturers in Ireland and throughout Europe.

The opening of the Ireland facility expands Kelpac’s global footprint to seven locations worldwide, including four in the USA, one in Singapore and one in Costa Rica.

Kelpac: 8b/G20-5 www.kelpacmedical.com

Raumedic Works With Moldflon High Temperature PTFE Thanks to a cooperation agreement between German plastic device development expert Raumedic and plastics specialist ElringKlinger, also based in Germany, Raumedic is working with high temperature PTFE for the first time.

Dr Ralf Ziembinski, director of Raumedic’s extrusion and tubing business unit, said: “With ElringKlinger’s development of Moldflon, it has become possible for the first time to process PTFE thermoplastically, which creates entirely new product possibilities in medical engineering.”

Raumedic: 8a/F28 www.raumedic.com

Teleflex Medical OEM: 8a/L27 www.teleflexmedicaloem.com SEPTEMBER/OCTOBER 2012 / MPN /43

Exhibitor News | COMPAMED 2012

PACKAGING Weidmann Overmoulds RFID Tags in Medical Devices

Swiss contract moulder Weidmann Plastics Technology will showcase the benefits of integrating radio frequency identification technology (RFID) tags into moulded components for medical devices via overmoulding.

RFID is a technology which enables products to be identified automatically using a chip which can be identified using radio waves without the products needing to be handled or removed from their location.

The technology allows manufacturers to automatically trace their stock while gathering and recording their whereabouts.

RFID has been around for a number of years but Weidmann is able to integrate an RFID chip directly into a plastic device, eliminating wet labelling—a traditional means of affixing the chip to the surface of a product.

The overmoulding process involves the chip being placed into a mould and then molten plastic being injection moulded around it up to a maximum temperature of 200°C. Weidmann: 8b/K17 www.weidmann-plastics.com

Multivac Presents New Packaging Machine for Sensitive Pharmaceuticals A new machine to be launched at Compamed by Germany-headquartered packaging equipment manufacturer Multivac is claimed to be a solution for the packaging of sensitive pharmaceutical and biotech products.

Thanks to Multivac’s famous “drawer” system, requirements are met for frequent, reproducible and rapid format changes. The system has also been extended to include complete cutting tools, which are usually used in pharmaceutical applications for the single-piece cutting of the sealed packs.

Multivac: 8a/H01 www.multivac.de

Ramac to Demonstrate Blister Packaging Machines

For just-in-time packaging of small to medium sized production volumes, Danish machine manufacturer Ramac will present various configurable models of its workstation for combined blister forming and sealing.

Ramac: 8b/K08 www.ramac.dk

44/ MPN / SEPTEMBER/OCTOBER 2012

COMPAMED

DIAGNOSTICS SteriPack Opens US Facility in Florida and Expands Irish Test Lab Ireland-based contract medical device packaging converter SteriPack has opened its first North American manufacturing facility in Florida, USA. The new plant is ISO13485 certified and will manufacture products in a class 8 cleanroom, duplicating its sister companies in Ireland, Poland and Malaysia to service the North and South American markets. SteriPack USA will offer a range of cleanroom manufactured packaging products, including pouches, header bags, die cut lids and rollstock.

SteriPack: 8a/M01 www.steripackgroup.com

Amcor Shows Packaging Films and Laminates UK supplier of packaging films and laminates Amcor Flexibles will be showcasing a range of materials including high barrier materials, forming films, peelable systems, laminates, bespoke converted pouches and die cut lids with options available for all sterilisation methods.

Representatives will be available to discuss all aspects of packaging requirements, including material selection, pack design, package optimisation and validation support services.

Amcor: 8a/E14 www.amcor.com/healthcare

Orgentec Demonstrate ‘Walk Away’ Infectious Disease Diagnostics

Germany-headquartered Orgentec Diagnostika has introduced six new tests for the diagnosis of infectious diseases. The new tests detect antibodies against Chlamydia trachomatis and Chlamydia pneumoniae. In addition, these test systems make it possible to differentiate between acute, latent, and chronic infection.

Orgentec Diagnostika: 3/A92 www.orgentec.com

Aline is Growing USA-based contract manufacturer of microfluidic diagnostic devices, Aline, has recently completed a move to a new facility. The company has upgraded and enlarged its cleanroom, created an applications lab, and implemented automation for pick and place assembly as well as UV bonding.

Upcoming automation enhancements include automation of its core lamination processes to support several client programmes. In June 2012 the company was certified to be compliant with ISO9001:2008

by Germany headquartered standards agency TÜV Rheinland.

Aline: 8B/G20-1 www.alineinc.com

SEPTEMBER/OCTOBER 2012 / MPN /45

Exhibitor News | COMPAMED 2012 TESTING & INSPECTION

END OF LINE CONNECTORS MACHINING

Vision Engineering Launches DimensionOne

Desktop Laser Marker Can be Used in Automated Production Line

Vision Engineering, a UKheadquartered producer of microscopes and measurement systems, will present its new mark-up and dimensioning software solution DimensionOne. The software allows pictures to be annotated directly onto the monitor and dimensions taken on screen.

Vision Engineering: 8b/M03 www.visioneng.com

Intertek Establishes Medical Device Polymer Testing Toolbox UK-based testing and certification bureau Intertek has launched a medical device polymer testing toolbox. The toolbox comprises tests for inspection as well as migration of extractables and leachables.

Inspection methods include microscopy, spectroscopy, spectrometry, and rheological, lubricity and mechanical property measurements.

Migration testing includes gas chromatography mass spectrometry (GCMS) and liquid chromatography mass spectrometry (LCMS).

Rofin, a German producer of laser manufacturing equipment, has launched a revised version of its desktop laser marking system EasyMark.

The new version can be incorporated as a module into an automated production line.

According to Rofin, the new model incorporates the latest diode-pumped or fibre laser technology and powerful yet intuitive software makes it an ideal all-in-one laser marking system for a wide variety of applications.

The software, Visual Laser Marker (VLM), offers a comprehensive range of marking functions, fonts, and pre-defined laser setups.

The standard configuration comes with a laptop (Windows 7), the VLM software, programmable z-axis, pilot laser and camera observation, and is available in October 2012.

Rofin Baasel: 8a/G19 www.rofin.com

Intertek: 16/G10-5 www.intertek.com /med-pharma

SnapQuik Connectors Offer Alternative to Luers in Small Bores USA-headquartered Colder Products Company, a manufacturer of connectors for plastic tubing, has developed a new brand of connectors for small bore medical applications. The brand, SnapQuik, offers an alternative to luer fittings.

According to the company, SnapQuik connectors are ideal for applications such as airinflated cuffs, surgical devices and monitoring equipment.

The connectors deliver high flow fluid transfer in a small profile and deliver an audible click sound to signal that a reliable connection has been made.

Colder Products: 8a/E02 www.colder.com

Mednet Introduces Blood Pressure Cuff Connector

Germany-based distributor of medical device components and other medical related products Mednet has introduced a new connector to the European market from USA-based manufacturer Value Plastics.

The connector, branded BPL, incorporates a quarterturn design that is commonly used in blood pressure applicationsâ&#x20AC;&#x201D;particularly blood pressure cuffs. Features include a 10-point grip and a winged male fitting.

Mednet: 8a/H14 www.medneteurope.com

46/ MPN / SEPTEMBER/OCTOBER 2012

Carville Works with Physicists on Quality Assurance Phantoms for 3D X-Rays

UK specialist plastic machining company Carville has been working with medical physicists within the UKâ&#x20AC;&#x2122;s state funded health service, the National Health Service (NHS), to develop a new range of quality assurance (QA) phantoms.

Phantoms are specially designed objects used in medical scanning and imaging devices to evaluate analyse and tune performance.

The new phantoms are for use with conventional 2D and new 3D tomosynthesis X ray systems. Carville already manufactures ISO cubes for oncology applications such as mammography screening.

The new phantoms are manufactured in variable thicknesses and contain either 99.9% pure aluminium foil or a grid matrix of steel balls.

These phantom developments are ongoing with the latest batch of bespoke tomosynthesis test phantoms due for delivery to the NHS in October 2012.

Carville: 8a/N15 www.carville.co.uk

DOCTOR’S NOTE

Orthopaedic Surgeon Shines Light on Textured PEEK Implants WORDS | SAM ANSON n an interview with Medical Plastics News, facilitated by the UK’s Healthtech and Medicines Knowledge Transfer Network (KTN), leading UK knee surgeon Prof Simon Donell has highlighted a key issue for consideration by developers of implantable textured PEEK joint replacements.

The issue concerns the drive to impart nano-sized grooves, crevices and dimples onto implant surfaces to encourage stem cells to embed in and around the implant and encourage the bone to grow around the implant when in vivo.

Developers of textured implants hope that by succeeding in this, they can improve an implant’s compatibility with the surrounding joint, lengthen the life of the implant and reduce the risk of revision operations for loosening, where the implant has debonded from the bone.

When asked about textured implants, Prof Donell explained that in theory the technology is a great idea. However, he expressed reservation, saying it is easy to get carried away with technology before its efficacy has been properly tested and assessed, particularly with respect to how implants are normally handled by surgeons during surgery.

I

<< Injection moulded PEEK with a nanopatterened textured surface. >>

“When a medical device concept is originally conceived, it is easy for innovators to become so focused on one particular technical detail or goal that they forget that the device must be practical for usage by a clinician whose main priority may be to perform their operation quickly and efficiently.

He explained: “Sometimes in an operating theatre environment there isn’t the time to handle an implant with a great deal of care. There are times when an orthopaedic surgeon may need to apply force to an implant, for instance by using a hammer, in order to get it into the right place. As such, any changes to a device’s surface, including textures, must be able to withstand this.”

Simon explained that he would advise anyone working on research into implantable orthopaedic devices to test their technology by simulating the handling of the device by a surgeon during an operation as well as the performance of the device in vivo.

Medical Plastics News presented this feedback to one of the UK’s leading researchers on nanopatterned PEEK implants, Nikolaj Gadegaard at the University of Glasgow, UK. Nikolaj explained that this kind of information closed a gap in his research.

“We have developed a process whereby nano-sized grooves can be imprinted on to a PEEK implant during injection moulding to encourage stem cell adhesion and bone cell growth around the implant” said Nikolaj. “We have reached a stage where we are ready to take our technology to in vivo testing and Prof Donell’s feedback is invaluable to ensure our goals are aligned with what the leading surgeons want.”

Following the interviews mentioned in this article, Prof Donell and Nikolaj Gadegaard have made contact regarding in vivo test procedures to simulate Nikolaj’s textured nanopatterned PEEK moulding process.

<< Consultant orthopaedic surgeon Prof Simon Donell is a knee specialist working at Norfolk and Norwich University Hospital, UK. He works within the Healthtech and Medicines KTN as an clinical adviser to industry. >>

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DESIGN 4 LIFE GATHERING AND INTERPRETING DATA DURING PRODUCT DEVELOPMENT IS A CRITICAL PROCESS. SOFTWARE-BASED TOOLS ALLOW ENGINEERS TO UNLOCK GIGABYTES OF VIRTUAL EXPERIMENTS. BUT THERE IS A TEMPTATION TO GENERATE OCEANS OF UNNECESSARY DATA, WHICH ULTIMATELY HINDERS DEVELOPMENT. BOB KETELHOHN, SENIOR MECHANICAL ENGINEER AT FARM, A US PRODUCT DEVELOPMENT FIRM, PROVIDES SOME TIPS ON HOW DATA CAN BE USED WISELY.

Utilising Design Data Wisely

Engineers love data, but programme << Figure 1: managers can grow frustrated when Maximum principal buried by graphs, presentations and strain plot notes simulation rainbows. Irrespective of the magnitude but not product, volumes of data are useless direction. >> without a proper specification framework to filter and process key attributes.

Conversely, the right data in the right << Figure 2: hands at the right time makes all the Vector principal difference to product success. plot shows direction and Product Requirements Document magnitude of the A development team needs to focus three principal on specific product functionality, and a strains, key for product requirements document (PRD) is strain gauge the source of that focus. The PRD, written placement and by cross-functional departments, provides the foundation to build on and reigns in alignment. >> scope creep. Working without a PRD is absolutely the slowest and most expensive way to develop a product.

In a perfect world, every programme would start with a detailed PRD, but this is not << Figure 3: an option for true innovation. In cases where the outer limits of a revolutionary Strain gauges technology are not explicitly definable, the development team will still need effective applied to test processes to reach definitive milestones. specimen. >> Finite Element Analysis Cost will always be a heavily weighted factor in product development. Prototyping loops are expensive in terms of both capital and time. Concepts must be scrutinised and either fail or graduate quickly.

A powerful tool to reduce the number of prototyping loops is finite element analysis (FEA). Virtual testing delivers results, both good and bad, fast. Data is shown plain as a rainbow on the computer screen, but is it fact? If concept A predicts X stress and B 1/2X with the exact same setup, you are moving in the right direction. The question then becomes one of reality. Are the true stress levels at X or 10X? There are many ways to validate FEA simulations. The decreasing cost of 3D printers allows concepts to be up and testing in hours.

Whether a part is printed or machined, both will have the same high stress location when tested in identical setups, but different ultimate loads based on material. The challenge escalates when your prototype fails in ways you did not expect. Failure load and location are only one data point in a complex system.

Strain gauges provide real-world data for validating FEA simulations. The key to using strain gauges is to confirm your gauge application and data gathering process on something simple, like a bending beam. Perform the hand calculations, confirm the calculations with an FEA run, then hang some weights and match your gauge readings to the calculations. Strain gauges are immensely useful for tuning FEA constraints and uncovering inappropriate setup assumptions.

Development teams will still need to iterate between the FEA setup/results and gauge readings, but at least will have a physical data path to correlation. Strain gauges are cheap; apply them liberally.

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EVENTS medical plastics | DIARY 2012

Fakuma plastics trade show October 16 - 20, 2012 Friedrichsafen, Germany

SOFCOT 2012 — French Society of Orthopaedics and Trauma annual conference November 12 - 16, 2012 Paris, France

Thermoplastic elastomers conference November 13 - 14, 2012 Berlin, Germany

Finished medical devices trade show November 14 - 17, 2012 Düsseldorf, Germany

Medical Devices Leaders Forum November 28 - 30, 2012 Berlin, Germany

The Economist Global Healthcare Summit November 29 - 30, 2012 London, UK

Medical Devices Summit Europe November 13 - 14, 2012 Dublin, Ireland

Medtech trade show November 14 - 16, 2012 Düsseldorf, Germany

Healthpack Europe December 3 - 4, 2012 Dublin, Ireland

Review of MedTech Polymers Conference, Chicago, September 2012

by Len Czuba, CEO Czuba Enterprises On September 10-12, 2012, a new medical plastics conference took place in Chicago, USA. It was introduced and sponsored jointly by the USA-based plastics magazine Plastics Today and the conferencing arm of device manufacturing magazine MD&DI . The conference replaced the MD&M Chicago trade show which was moved in early 2012 to McCormick Place Exposition Center into a Springtime timeslot.

The editors and staff of Plastics Today did a good job of gathering leading speakers to this new programme and in spite of this already crowded area of technology, this conference and an outstanding programme drew a strong attendance.

The two-and-a-half day programme began with a preconference workshop which focused on bioresorbable polymers.

Three leading internationally recognised speakers presented a good overview of the topic and the panel discussion which allowed attendees to further gain insight into this rapidly expanding area of specialty medical polymers. The conference sessions were titled: n Market trends and opportunities; n Regulations and compliance; n Development and applications of medical grade polymers; n Design and manufacturing of polymer-based medical devices; and n Business development strategies.

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Speakers from leading medical devices manufacturers were featured, including: n Johnson & Johnson’s Ethicon; n Abbott; and n Medtronic.

Supplier companies that participated as presenters included: n Invibio; n Purac; n DuPont Canada; n Bayer; n Solvayl; and n NuSil. The programme was rounded off with a friendly exposition area, several networking activities, panel discussions and case studies. Attendees were able to meet with colleagues from other major companies in the industry, exchange contact information and share their experiences, both good and bad.

I very much enjoyed this event and felt that the organisers did a great job pulling together a fine programme which drew strong support by attendees from the industry. And even though I frequently have complained that there are too many conferences being held in this technology space, I would choose this event as one on my must-attend list.