MEDICAL PLASTICS NEWS COLOUR â€“ UNTAPPED POTENTIAL? How Colour Improves Design Without Compromising Patient Safety or Regulatory Compliance
ALSO IN THIS ISSUE: Sub Micron and Fibre Laser Welding Life Cycle Assessments of Polyols from CO2 3D Bioprinting: Sowing the Seeds of Life
ISSUE 11 March-April 2013 WWW.MPNMAGAZINE.COM
All Medical, All Plastics
US Medical Device Tax—page 5
Cover story—page 10 Laser welding—page 20
5. Editor’s Letter: Tax and Death Sam Anson writes about the US Medical Device Tax, including responses from the world’s largest manufacturers.
34. Product Focus: Urological devices Coatings to improve plastics and how Melitek has helped replace PVC with polyolefins for urological catheters.
6. On the Pulse: Industry news Milacron advances forward, scrutiny procedure alternative, lifecycle assessment of CO2-based polyols and defunct moulding energy efficiency guidelines.
37. Country Report: Israel As a producer, Israel has the highest number of medical device patent registrations per capita in the world. As a market it was valued at US$908 mn in 2012 with annual growth expected of 9.6% a year.
10. Material Diagnosis: Colour How colour improves device and packaging design without compromising patient safety or regulatory compliance. 20. End of Line: Welding High power fibre lasers, sub micron lasers and other welding advances. 26. Regulation Review: EU Sharps Directive This will come into force on May 11, 2013. Employers of users of medical sharps must ensure they comply. Schreiner MediPharm explain how sharps manufacturers can help. 28. Folio: Medtech infographic Eucomed have produced a fascinating infographic about Europe’s medtech industry in 2011.
Robotics and automation— page 49-53
31. Design 4 Life: Tickled pink Last year Gerresheimer acquired design bureau item. The team is going strong. 33. Doctor’s Note: Health economics Research finds that two manufacturers control hip prostheses supply to NHS.
38. Event Preview: MTI Expo Medtech Innovation Expo is being held for the first time in Coventry, UK, on April 10-11. The feature contains a review of the UK’s medtech industry statistics and news from the exhibitors. 49. Clean Machines: Robotics Automated pipetting and fluid delivery plus spring simulation during design and finished device quality checking for auto injectors. 54. Product Focus: RegMed 3D bioprinting, an arm of additive manfufacturing, enables the printing of polymer scaffolds seeded with human tissue stem cells, leading to synthetic growth of tissue and organs. We review the progress made and forecast development milestones to 2030 and beyond. 58. Events: Diary and Antec Medical plastics diary in April-May 2013 plus a preview of a dedicated medical plastics conference about resorbables at Antec in Cincinnati in April 2013.
Online and in digital 3D Bioprinting—page 54-57
Medical Plastics News is available online, at www.mpnmagazine.com, and in digital (on the iPad, mobile phones and computers). MARCH-APRIL 2013 / MPN /3
Tax and death have been said to be the only certainties in life for nearly three hundred years. The most famous quote was made by Benjamin Franklin, one of the founding “fathers” of the USA, in 1789, and later requoted by US author Mark Twain. Earlier utterers include Edward Ward, an English humourist in 1724 and playwright Christopher Bullock, also English, who wrote in 1716 “‘Tis impossible to be sure of anything but death and taxes”. On January 1, 2013, the US government enforced a new excise tax on sales of medical devices. The tax is charged at 2.3% of the sales price of all devices sold in the USA. Estimates point to a tax gain of US$2.5 bn in 2013 alone. It is part of the US Patient Protection and Affordable Care Act—aka the Obamacare healthcare reform or the Affordable Care Act— brought into US law in March 2010. Unsurprisingly, responses from manufacturers have been that of objection. Advamed, the USA’s largest medical device manufacturing trade association, is campaigning hard to persuade congress to repeal the tax. The organisation’s CEO said in February: “The device tax is already having a toxic effect on innovation, jobs and US leadership of the medical technology industry.” Addressing the Medical Devices LinkedIn group—an online network with 161,000 members—Republican Congressman Erik Paulsen pointed out that the tax antagonises government’s focus on manufacturing growth. He is also lobbying for a repeal. He also believes that America’s global leadership in medical technology is threatened by this tax, stating: “While other countries, especially in Asia and Europe, are providing tax incentives for medtech to research, invest, and manufacture, US policy makers are driving American innovators overseas.” Paulsen will be speaking at the group’s 10x Conference in Minnesota, USA, on April 29-30. Having known about the tax since March 2010, most medical device conglomerates made allocation for it in their financial plans for this year. In fact, a source told me that one of the world’s biggest manufacturers had overestimated the tax to such an extent that it, in effect, enjoyed a windfall this year. I asked twenty of the world’s largest OEMs to comment.
Most of them referred me to Advamed, saying they supported the repeal. Baxter pointed out that the Affordable Care Act was having an effect on the company in areas outside medical devices. A spokeperson told me: “We have estimated that the device tax will have about a US$30 mn impact on our 2013 financial results. Devices represent only a portion of our portfolio—many of our products are considered pharmaceuticals and biologic and biotech therapies. The most significant impacts of the Affordable Care Act, of which the device tax is just one piece, on Baxter over the last few years have been pharmaceutical industry fees, increased rebates to state Medicaid programmes for some of the company's drugs and biologics, and expansion of the 340B drug discount programme, all of which have been previously implemented.” Stryker, also supporting the repeal, said: “Stryker expects to owe approximately US$100 mn in the first year alone, equating to over 20% of our annual global R&D investments. We would rather put this money towards jobs, innovation, clinical research and other priorities which will create valueadded medical technology for patients while helping us partner with hospitals to deliver cost effective solutions.” In Europe, the effects are already being felt. Fritz Stein, head of medical at Swiss finished plastic device outsourcer Weidmann, explained that customers have been trying to pass the tax upstream by asking for lower prices for services. In late February 2012 he said: “While our revenues have not been directly affected, discussions with customers about prices are increasing. But the nature of manufacturing for healthcare is that there will always be pressure on prices, and we absorb this through operational excellence.” While a political war ensues in the White House and US industry, we must bear in mind that at the heart of the work being done is an extension of the reach of healthcare to Amerca’s poor. Obama’s goal is to help them get affordable access to healthcare through taxation, while industry wants to provide value-added healthcare through capital investment, clinical research, economic growth and the creation of jobs.
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MARCH-APRIL 2013 / MPN /5
INDUSTRY NEWS | Roundup
Plastics Machinery Manufacturer Advances Forward US plastics machinery manufacturer Milacron has made a spate of notable strategic moves in the last few months, some of which have reinforced its commitment to the medical and pharmaceutical sectors. Medical Plastics News can confirm that the European arm of Milacron’s extrusion machinery arm, Cincinnati Milacron, will join forces with Ferromatik Milacron, the UK subsidiary of Milacron’s European injection moulding machinery manufacturing outfit, to present a demonstration of a medical single lumen catheter tubing extrusion line at a joint open house event in Chesterfield, UK, in April 2013. Medical injection moulding machinery will also be on show at the event. The dedicated public demonstration of medical extrusion and injection moulding under one roof has been confirmed as a European first by Tim Appels of Dutch medical catheter manufacturing equipment supplier 2Spring who will also be at the event. The event follows an announcement in mid February 2013 that Milacron had acquired US hot runner technology manufacturer Mold Masters for US$975 mn. In November 2012, the company appointed a new sales and marketing VP, Shawn Reilly. Shawn was previously president of one of the USA’s largest
FEBRUARY 26, 2013 European Parliamentary Debate on EU Medical Device Legislation
pharmaceutical packaging manufacturers AndersonBrecon. At the time of Shawn Reilly’s appointment, Medical Plastics News asked him to describe the most exciting trend he had witnessed. Shawn responded without hesitation. The topic was biopharmaceuticals. Biopharmaceutical drugs are medical drugs which have been produced using biotechnology. According to Wikipedia, biotechnology—or biotech—is the use of living systems and organisms to develop or make useful products. The UN Convention on Biological Diversity defines biotechnology as “any technological application that uses biological systems, living organisms or derivatives thereof, to make or modify products or processes for specific use”. Wikipedia explains the difference between traditional and biopharmaceutical drugs. Most traditional pharmaceutical drugs are composed of relatively small molecules that bind to particular molecular targets and either activate or deactivate biological processes. Small molecules are typically manufactured through traditional organic synthesis, and many can be taken orally. In contrast, biopharmaceutical drugs consist of large biological molecules, such as proteins, which are developed to address targets that small molecules cannot easily
Serge Bernasconi, Eucomed CEO, said: “The EC’s [legislative] proposal is a step in the right direction [but] the proposed scrutiny mechanism is inappropriate because it does not contribute to patient safety and is essentially a duplication of reviews. We have suggested replacing the scrutiny mechanism with a systematic control procedure.”
March 1, 2013 Stryker Completes Acquisition of Chinese Orthopaedic Device Maker Trauson
“With the acquisition of Trauson we are well positioned to broaden our presence in China and to expand into the fast growing value segment of the emerging markets. We look forward to building on the company’s long history of success,” said Kevin A Lobo, president and CEO of Stryker.
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handle. Some examples of biopharmaceutical drugs include Infliximab, a monoclonal antibody used in the treatment of autoimmune diseases, Etanercept, a fusion protein used in the treatment of autoimmune diseases, and Rituximab, a chimeric monoclonal antibody used in the treatment of cancer. Due to their larger molecule size, and corresponding difficulty with surviving the stomach, colon and liver, biopharmaceuticals are typically injected. Modern biotechnology is often associated with the use of genetically altered microorganisms such as E coli or yeast for the production of substances like synthetic insulin or antibiotics. It can also refer to transgenic animals or transgenic plants, such as Bt corn. Genetically altered mammalian cells, such as Chinese hamster ovary cells, are also used to manufacture certain pharmaceuticals. Another promising new biotechnology application is the development of plant-made pharmaceuticals. Plastics, thanks to their versatility in design, inertness and low cost, are becoming the material of choice for manufacturers of biopharmaceutical drug delivery devices. In terms of delivery devices, many of the most advanced biopharmaceutical drugs require some exacting demands. Often, delivery devices must be highly accurate in terms of dosge.
March 4, 2012 UK Chancellor George Osbourne Visits Albis UK Representatives of the UK’s plastics industry reportedly voiced concerns to Mr Osbourne about skills shortages and the need for energy supply security. They asked for value added tax on “green” plastic products to be reduced to 5%, for the next fuel duty rise to be cancelled, and for further cuts in corporation tax.
March 14, 2013 500th Device to Use Invibio PEEK Cleared by the FDA, 80 in China Invibio director of regulatory affairs, Craig Valentine, said: “As demonstrated by these global regulatory milestones, PEEK Optima continues to set an industry standard for biomaterials biocompatibility and quality.”
ON THE PULSE
Shawn Reilly explains: “Medical device delivery systems which meet the requirements of some of the newest large molecule biopharmaceutical drugs requires sophistication in injection moulding, assembly and packaging. This presents a significant opportunity for medical plastics manufacturers to meet a growing need.” To give a flavour of just how sophisticated drug delivery device design and manufacturing can be, Shawn quoted
some examples: “Potent, highly toxic compounds like those used in oncology are delivered in units of 10-4 mg and therefore need highly accurate delivery.” “For self-treatments of chronic diseases, the device must be designed so that the chance of mis-dosing is minimised as far as possible. To achieve this and more, drug delivery devices consist of four or five components while maintaining complete integrity.”
It can take up to 15 years to develop a new medicine. The design and development of the delivery mechanism can start as many as six or seven years before the expected approval date. Medical Plastics News forecasts that as the plastics industry’s understanding of materials and mould design develops, the delivery mechanism will play a bigger and more crucial role in drug development.
control procedure that makes sure we increase the safety of all medical devices, which is in the end the collective objective of all stakeholders. We look forward to continuing our discussions finished its assessment. The proposed measure creates a false sense of security and with policymakers and other parties and are confident that patients in Europe will be the is essentially ineffective and inappropriate”. Serge Bernasconi, chief executive officer winners in the end.” On February 26, criticisms of the scrutiny of Eucomed, confirmed: “The proposed scrutiny procedure is a needle-in-a-haystack procedure were communicated to the EU’s Environment, Public Health and Food Safety approach which should be replaced by a (ENVI) committee via a hearing at Parliament. systematic procedure that prevents the needle from landing in the haystack in the Diagnostics first place. Only then will we successfully Together with Eucomed, under their increase patient safety and prevent newly merged banner of MedTech Europe, unnecessary delays of medical devices the European Diagnostics Manufacturers reaching patients.” Association (EMDA) has published a blog to Eucomed’s alternative, known as the help about people understand why in vitro systematic control procedure, reportedly consists of five critical measures and is said to diagnostics (IVDs) need their own regulatory framework. “more effectively achieve the common An earlier blog was published outlining objective of increased patient safety”. what members can expect from MedTech Mr Bernasconi outlined the proposed alternative as follows: “We suggest a systematic Europe in 2013.
Eucomed’s Alternative to “Inefficient and Inappropriate” Scrutiny Procedure process—after the notified body has Eucomed, Europe’s largest medical device trade association, has recommended an alternative process to the scrutiny procedure proposed in the new EU medical device legislation, designed to replace the current Medical Device Directive in force in the EU. The scrutiny procedure, proposed in late 2012 as part of new European regulation, has been criticised for being too intense and at risk of stifling innovation while forcing up the cost of manufacturing. Eucomed have slammed the scrutiny procedure saying that it is “random, ineffective and does not contribute to patient safety”. Eucomed goes on to say: “The proposed scrutiny procedure is inappropriate because it is a random sampling process of certain medical devices and the timing of the scrutiny occurs very late in the approval March 15, 2013 Clariant to Double Polish Masterbatch Production Capacity
Hans Bohnen, head of Clariant’s masterbatches business unit, said: “You cannot underestimate the meaning of this investment for the entire company. The market for masterbatches, though demanding, develops dynamically and a modern facility such as this will allow us to develop new solutions tailored to the specific needs of customers effectively.”
PREVIOUSLY ON MPNMAGAZINE.COM “We are excited to apply Sony DADC’s deep manufacturing expertise to confront one of the major challenges in the life sciences,” said Christoph Mauracher, senior vice resident of the biosciences division of Sony DADC. He added: “Organs-on-chips have the potential to revolutionise testing of drugs, chemicals, toxins and cosmetics.”
March 18, 2013 Sony DADC and Harvard Announce Organ-on-Chip Collaboration
04:04:2013 March 20, 2013 Milacron UK Medical Moulding and Extrusion Open House in April is European First Tim Appels of Dutch catheter manufacturing equipment suppler 2Spring said: “I have not seen medical injection moulding and extrusion machines being publicly demonstrated under one roof at the same time in Europe before.”
MARCH-APRIL 2013 / MPN /7
INDUSTRY NEWS | Roundup
Novomer Wins Race to Build First Large Scale Polycarbonate From CO2 Line USA-based Novomer, which describes itself as a “green chemistry” company, has announced it has completed the world's first large-scale manufacturing run of polypropylene carbonate (PPC) polyol, having produced over seven tonnes of finished product. Novomer says its polyols are designed to replace conventional petroleum-based polyether, polyester, and polycarbonate polyols. The polyols are based on the copolymerisation of carbon dioxide (CO2) and epoxides. Novomer claims that the resulting products contain more than 40% CO2 by weight. Medical Plastics News understands that breaking down CO2 into useable elements for polymer production requires a large amount of energy relative to traditional polymer production from petrochemicals. In 2011-2012, Novomer enlisted the help of Deloitte Consulting to complete a full cradle-to-gate life cycle assessment for the polyols in accordance with ISO14040, the international environmental management standard which contains the principles and framework for life cycle assessments. This study focused on carbon footprint and 12 other environmental impact categories, including acidification, respiratory effects, ozone depletion, and particulate matter formation. Novomer says the carbon footprint of its polyols has been calculated using standard cradle-to-gate life cycle inventory (LCI) boundaries, including: measurements for extraction of non-renewable resources and the growing and harvesting of renewable resources; transfer, storage and refining of these resources; conversion of these resources into energy; production processes; all relevant transportation processes; and management of all waste streams generated within the system boundaries. More details of the analysis are available from the editor. The analysis shows the production process for Novomer’s PPC polyols have a carbon footprint which is approximately three times smaller than that for existing polyether and polyester polyols used in
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flexible and rigid foams, coatings, adhesives, sealants and elastomers. The PPC polyol was scaled up and produced with US specialty chemicals company Albemarle at their manufacturing facility in Orangeburg, South Carolina, USA, using existing Albemarle equipment modified for PPC polyol production. The work was completed in conjunction with a grant of US$25 mn from the US government’s Department of Energy (DOE). “We are pleased with the results of this first run and thank the DOE for their support,” said Dr Ron Valente, Novomer’s vice president of Research. “This campaign clearly demonstrates the robustness of our catalyst and manufacturing process and we are confident in the ability to move to a larger scale as demand warrants.” “The process fits well into our Orangeburg infrastructure and only minor modifications were required to enable PPC production,” said David Decuir, Albemarle’s custom services business director. “We are very confident in our ability to commercially produce Novomer PPC polyol at our Orangeburg plant.” Germany-based Bayer MaterialScience (MS) has been working to develop its own plastics from CO2 production line since early 2011. The feedstock is CO2 captured as a waste byproduct from fossil fuel burning plants and other facilities in the energy sector. Polyether polycarbonate polyols (PPPs) have been being produced on a scale of kilograms at a specially constructed pilot plant at Bayer MS’s Leverkusen headquarters. Recently the project switched from batch to continuous production. As a next step, the scale-up to multi-tonne levels is being considered. For testing purposes, the CO2-based polyols are being processed into polyurethane flexible foam in the technical labs. This will also be the first target segment for these new products. According to an official company spokesperson: “The results are very promising—the new material has at least the same quality level as conventionally produced foam and can be processed with existing slabstock technology.”
He added: “We strive to come to market with our CO2-based polyols as from 2015 with mattresses and furniture being the first product application. A variety of industries have indicated interest in the new technology.” Comparing Bayer MS’s work with that of Novomer, the spokesperson said: “At first sight, our PPPs appear similar. But there are fundamental differences regarding the way the CO2 is incorporated into the polymer chain. That obviously results in different product properties.” Medical Plastics News asked Bayer to provide details of research it had done to assess the net environmental impact of its project to take into account the energy required in breaking down the CO2. Bayer MS said: “As part of the project, our partners at RWTH Aachen University in Germany are performing a comprehensive life cycle assessment (LCA). They are analysing the ecological impacts of the chemical CO2 utilisation for polyurethane production—for example the CO2 emissions and the energy balance. They are nearly done with the overall evaluations and we expect an announcement pretty soon. So far, the still unofficial results look very promising and the new technology is obviously ecologically favourable. Bayer MS continued: “That is mainly due to the fact that we are able to substitute a certain amount of oil-derived chemicals by CO2, and by this there are less CO2 emissions. The energy balance looks good as well because the petrochemicals we use—so called epoxides—have a lot of energy to enable the reaction with the inert CO2 in an energy efficient way. This means that the energy requirements for the new process are not higher than for the conventional process. Furthermore, we investigate the possibility to couple regenerative energies with chemical CO2 utilisation. This is done within another research project called CO2 rrect, which we are carrying out together with a range of partners from industry and academia.
ON THE PULSE
Revised Energy Efficiency Guidelines Welcomed But Are They Open to Manipulation? Europe’s association for plastics and rubber machinery manufacturers, Euromap, has revised its guidelines for comparing energy efficiency between various injection moulding machines. They now separate the guidelines into two parts—machine- and product-related consumption. Euromap’s statement on the revision is as follows. Energy efficiency has been an issue for the plastics and rubber machinery industry for quite some time. The EU Ecodesign Directive and, not least, customer demand for transparent and comparable energy consumption figures have brought fresh impetus to the subject. The existing Euromap 60 on the determination of the energy consumption of injection moulding machines was itself an important step forward in open debate on the subject but, despite the intensive measurement effort made, failed to provide the sought after comparability because factors such as the measurement parameters were not adequately defined. For that reason, the recommendation has now been thoroughly revised. In response to calls for comparable measurement results on the one hand and to take account of the variability of machines on the other, the recommendation has now been divided into two parts 60.1 and 60.2.
Product-related consumption: In addition to the rough classification of injection moulding machines, the second part of the new recommendation offers the possibility of transparency in product-related energy consumption for the manufacture of individual injection-moulded parts to customer specifications (with specified materials, tools and machinery). The key parameter here is the specific energy consumption in kilowatt-hours per kilogram (kwh/kg) of plastic processed. To this end, a method of measurement with defined terms of reference is provided, together with a model for documenting the results. This will allow customers to include energy consumption in the machine’s life cycle cost calculation at the tendering stage.
could potentially open the standard up to manipulation whereby mmachines could be tested at high production rates to gain better ratings.” Daniel Heinzelmann of German manufacturer Arburg echoed these comments, saying overall the revision is a positive step but there are still areas for improvement. “The definition of a brochure value is problematic because too many factors can influence a machine’s energy requirements and these cannot be recorded in a single value,” he said. Daniel added: “Although customers can compare machines from different manufacturers, it is not possible to determine the actual energy requirements of a specific process. It is almost impossible to compare different machine technologies. For example, the Arburg energy-saving system for hydraulic machines or servo-hydraulic systems can save more energy with longer cooling times than with short cycle times.” Daniel went on to say: “We welcome the introduction of efficiency classes as a first step in offering customers greater transparency. In this context, however, it is important to emphasise that energy requirements largely depend on the process. The energy efficiency classes only allow machines with the same machine technology to be compared. It is important to indicate the pump and motor outputs. When dealing with different machine technologies, energy requirements need to be determined on a process-specific basis in order to obtain meaningful results.” On March 12, 2013, Arburg announced the winner of its fifth energy efficiency award, German manufacturer of motors and drives AMK. Demonstrating Arburg’s commitment to energy efficiency, the award is given to one of Arburg’s suppliers each year and began in 2008. Medical Plastics News welcomes comments to the editor.
Comment: Medical Plastics News asked a selection of leading injection moulding machine manufacturers and experts to comment on the revised guidelines. Dr Karlheinz Bourdon, vice president of injection moulding technologies at Germany’s KraussMaffei Group, owner of the KraussMaffei and Netstal brands, said: “For a long time, we have pushed for the EM60 to be made more user-friendly. We have been heavily involved in the update and we will continue to support this guideline. In particular, the new two-stage configuration Machine-related consumption: The new based on machine classification and defined version gives customers an opportunity to specifications for product-related use with compare machines from different moulds meets the desire to have more manufacturers on the basis of uniform objective comparability.” parameters. It introduces an energy But UK-based independent injection efficiency classification based on two test moulding engineering consultant Robin Kent cycles that take the particular characteristics of Tangram Technology still sees potential of fast running machinery and very small shortcomings, which could make the machines into account. Keeping the guidelines open to manipulation by machine measurement effort required to a level manufacturers. He said: “While the revised acceptable to machinery manufacturers guidelines are a step in the right direction without the results losing any of their they assume that for screw diameters of information value is an important greater than or equal to 25 mm the specific consideration here. The efficiency classes energy consumption (SEC) in kWh/kg is identified serve as benchmarks allowing constant for all production rates and this can customers to make a pre-selection. Not least, be used to rate the machine. Results from the uniform classification enables increases in our own experiments on energy efficiency << Engineer Robin Kent efficiency to be put across clearly, including show the SEC is dependent on the to the political decision-makers. production rate (kg/h), especially for small says the guidelines may be machines.” He added: “These concerns open to manipulation. >>
MARCH-APRIL 2013 / MPN /9
COLOUR | Untapped Potential?
How Colour Improves Device and Packaging Design Without Compromising Patient Safety or Regulatory Compliance BY STEVE DUCKWORTH, HEAD OF CLARIANT’S MEDICAL AND PHARMACEUTICAL MASTERBATCHES BUSINESS UNIT
Designers of devices and pharmaceutical challenges are facing a growing dilemma—how to make their products functional but more appealing to the end user, the patient, whilst meeting an increasing set of regulations and guidelines impacting the materials they use. In addition, the spread of diabetes and respiratory diseases means appealing to a patient population with a diverging age and cultural mix. Increasingly, treatments become more self-administered where compliance to a regular regime is important, and over the counter (OTC) medicines are selected based on a “branding” principle. So perhaps there are design lessons from the personal care packaging (PCP) and consumer goods sectors? A well-designed and attractively coloured device can have a dramatic impact on the success of a drug. One such device, used to treat chronic obstructive pulmonary disease (COPD), won its manufacturer a Queen’s Award for Industry. By the end of 2010 over one billion units of the device had been sold and the revenue stream had been extended well beyond what might have been expected from patent protection. There are signs that the industry may change. New marketing executives at pharmaceutical companies are bringing their experiences from a mass consumer oriented business model. An example is a joint venture formed between Proctor and Gamble—with its strength in branding— and Teva, bringing its expertise in generic drug manufacture. Whilst colour is increasingly used for the safe identification of medical devices, designers have followed more traditional approaches when it comes to colour selection for aesthetics, staying with colours they consider to be “safe”. They have felt protected by a “food contact” 10/ MPN / MARCH-APRIL 2013
statement, unaware of the risk they faced from a routine change in supplier of a pigment or additive, even if the “chemical type” appeared the same. Even when they addressed the problem with a so-called “no-change” document, their supplier was probably unaware of changes that were likely to happen further up the supply chain. Unfortunately for device and pharmaceutical packaging producers, the situation has not improved. The regulatory authorities are more aware then ever of the potential impact of these changes on mechanical functions, on biocompatibility and on leachables into the drug. This heightened awareness can be seen manifesting as more scrutiny of materials during the FDA 510(k) process and more investigations by industry groups—for example on sources of leachables profile changes in metered dose inhalers (MDI) or parenteral drug packaging. As previously reported in Medical Plastics News, in 2011 an FDA guidance document stated: “Changes in material formulation of patientcontacting devices or device components may affect the biocompatibility of the device. These changes may also affect material properties and the safe and effective performance of a device. Therefore, a new 510(k) should be submitted for changes in material formulation for patient-contacting devices or device components.”
So do these restrictions force designers into an even more conservative approach? No, they don’t. However, understanding where risk comes from and dealing with this in the early stages of design are necessary if the industry is to move forward. If the risk of changes in materials can be managed, this can open new possibilities to use the experience from PCP. Fortunately at Clariant, we have understood what needs to be done to help manage risk of changes. Note I said manage, not eliminate. One thing to appreciate is the context of scale. While the healthcare segment is very specialised and technically advanced, it is very small in terms of demand for polymers, pigments and chemicals. Indeed, estimated demand from the healthcare industry for polymers is just 5% of global output while for pigments and additive chemicals it is less that 0.05%. So suppliers of these products are generally not interested in discussing “change control”, and regard the sector as too complex and not worth the investment. For a pigment, the usual specification and certificate of conformity (CoC) offered is a colour index and, in addition, a relatively simple regulatory statement, for example FDA food contact. Changes in process or specification therefore can take place with no consideration on the impact on applications further downstream. Going one step along the chain to compounding, raw materials represent 5065% of a manufacturer’s costs, which means that there is often a need to change between suppliers or optimise formulations. Incoming quality control may only include confirmation of the document from the supplier, and not testing. This is not good news if you are concerned about maintaining mechanical properties or an extractable and leachable profile.
<< Products from Clariant’s suppliers undergo thorough checks to ensure the risk of changes to ingredients or processes are managed. >>
After a decision in 2009 to change its approach to the healthcare sector, Clariant decided to invest and took steps to manage the risk of changes, finally resulting in the launch of its Mevopur healthcare brand in October 2010. In 2012 we formed a dedicated team focused entirely on the sector. There were four important elements to this reorganisation. Global Approach: Specialisation of three plants (out of over 50 in Clariant Masterbatches) located in the USA, Europe, and Asia under the ISO13485 quality system with change control protocols. This is important because, firstly, production of a medical device may be required in different regions or be transferred and, secondly, back-up supply is normally a requirement. Standardisation of raw materials—in terms of chemistry and supplier. This process involved the technical, product stewardship and supply chain functions of Clariant to assess each raw material not only on performance characteristics, but on regulatory criteria such as RoHS, Reach, BSE/TSE and so on, and whether the supply was available in each of the three sites. Without this the following element would make no sense. Establishing a “fingerprint” based on physical attributes such as the Fourier
transform infra-red (FTIR) spectrum, extraction (ISO10993 part 18) and biological evaluation (ISO10993 and USP parts 87, 88). Batch testing: Rather than accepting the CoC from the supplier, we decided that it is necessary to test each incoming batch because we believed (and this has been proven) that changes in the raw material can occur even though the CoC indicates the colour index is in specification. Fourier transform infra-red (FTIR) and Raman spectral analyses are used to give a rapid comparison to a chemical product’s fingerprint. As an example, FTIR analysis of samples of a typically used phthalocyanine blue pigment (pigment blue 15:3) from two suppliers shows a number of differences. Although the pigments from a colour perspective might appear to be the same, and have the same CAS registry number (a unique numerical identifier assigned by the Chemical Abstracts Service), the FTIR clearly shows they are not the same. If such a change is detected between incoming raw material and our fingerprint, then the batch is quarantined, and if necessary we then carry out further risk assessment based on following the test protocol for extraction and biological evaluation. As stated earlier, we at Clariant Masterbatches help to manage risk,
because it is not practical to expect pigment or chemical suppliers to introduce the controls that a healthcare customer might expect. By using the above approach we can help to minimise the risk being passed down the supply chain. Unfortunately, the industry has not yet fully understood where these risks can occur. There is a common belief that protection comes from an “FDA Food Contact” statement as well as testing which has been carried out on a masterbatch or compound two years ago, or in some cases even longer. Worse still, there are often attempts to correct the problem by imposing a new quality standard with change control on a product originally formulated ten years ago. In addition to these specific initiatives which manage risk, Clariant also helps designers via a range of offerings, including its ColorWorks colour centres, which have created tools that help designers select colours that are practical to process in plastics, and its ColorForward trends outlook. Conclusion: In answer to the question “colour—untapped potential?”, we say categorically: “Yes—why restrict yourself to white when you may be able to have Hora da Caiprinha Green or In Vino Veritas Red.”
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ON TREND | Colours in Biocompatible Polymer Compounds
Can Coloured Plastics Improve Patient Compliance? Here is a picture of one of the most advanced respiratory nebulisers available in the medical device industry—the I-neb produced by Philips Respironics. The device features some of the most impressive drug delivery technology combined with electronic data capture. A single highly engineered elastomeric valve enables two modes of intelligent delivery of drugs—tidal breathing mode (TBM) and target inhalation mode (TIM). A different mouthpiece is used for each mode. The TBM mode allows delivery via the patient’s normal breathing pattern with no restriction while the TIM mode restricts inhalation flow, ensuring low flow rate and longer and deeper breaths. The device is able to switch from the TBM to the TIM mode thanks to a small pin in a plastic moulded valve “seat” in the TIM mouthpiece which inserts into the valve when the mouthpiece is connected to prevent sealing during inhalation. A platinum mesh placed at a carefully engineered angle ensures drugs are delivered using the patient’s breath, rather than being force sprayed into the mouth. The device is such a big step forward in nebuliser technology that the Journal of Aerosol Medicine and Pulmonary Drug Delivery published a supplement dedicated to the various technologies contained within the device as well as to the clinical trials performed by the manufacturers. But there is a possible drawback of the I-neb, according to a Medical Plastics News source who is a clinician at a leading UK cystic fibrosis unit. The clinician guides her patients on how to use the device while trying to encourage compliance with their treatment regimes. “Our biggest challenge with the I-neb is getting patients to comply with their prescribed usage, especially children and young teenagers. The device is an essential daily treatment for my patients who are long term sufferers of cystic fibrosis. But it is bulky and a dull blue colour so many are embarrassed to get it out in front of friends away from the hospital,” the clinician told Medical Plastics News.
<< The I-neb was launched in 2005. The dark blue colour was chosen at that time to appeal to a wide range of patients, of different ages, in multiple markets. >>
When asked about whether she was aware that multicoloured options are available for drug delivery devices like the I-neb, the clinician said: “I had no idea. There is a general lack of colour in most drug delivery devices we work with. But if the I-neb was more colourful—perhaps integrating pinks for girls or silver for boys—this may improve compliance.” Commenting on the thinking behind the selection of the blue colour, a spokesperson from Philips told Medical Plastics News “We were concerned that a light colour would appear to “yellow” over the design’s lifecycle of five years, whereas this effect will be less apparent with a darker colour plastic.” They added: “I-neb was launched in 2005 and the colour was chosen at that time to appeal to a wide range of patients, of different ages, in multiple markets. We understand that patient compliance and adherence are big issues faced by healthcare professionals, which is why I-neb was designed to be small, light and quiet and to aerosolise medication quickly so patients have the benefit of short treatment times.” Medical Plastics News understands that for many device manufacturers, using multiple colours can involve added costs, which can be perceived as an extra regulatory burden, as each individual colour masterbatch must be tested and verified for biocompatibility. Continued on page 15 MARCH-APRIL 2013 / MPN /13
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But Medical Plastics News can report that since 2005 there has been significant development in the medical plastic industry with respect to the supply of multiple colour biocompatible masterbatches. The masterbatch division of one company in particular, Swiss specialty chemical manufacturer Clariant, has invested time and effort in a process which the company says guarantees the safety of its colour masterbatch products. Through its own “fingerprinting” service, Clariant says it controls its own supply chain so that it only uses chemical ingredients which have passed a thorough supply chain “control” check. If the company cannot ensure that its suppliers will not make changes to their manufacturing process with enough notice to allow Clariant to find a new supplier, particularly in pigment manufacturing, those products will not be passed by the company for medical and pharmaceutical grade masterbatch (see page 10-11 for more information). Trends in Colouring Plastics Larry Acquarulo, CEO of US medical polymer compounder Foster Corporation, has written exclusively for Medical Plastics News, as follows. Custom colours have always been used to define brands, differentiate features or improve aesthetics of medical devices. As the healthcare market expands and becomes more competitive, particularly in devices for home healthcare, custom coloured components used in medical devices are expected to increase. Today’s custom coloured plastics for medical devices are challenging material suppliers like never before. Colour selections, part sizes, functional additives and regulatory requirements have influenced the techniques and technologies required by custom compounders to meet today’s colour specifications for medical plastic components. Vibrancy: A wider range of colours in more vibrant hues are being used in medical devices as a result of several trends in healthcare. Market maturation in some segments has intensified competition and accelerated efforts to visually differentiate products.
<< Examples of biocompatible coloured plastics. >>
Technological advancements in innovative devices are also visually differentiated from traditional products using colours. The rise in home healthcare has shifted purchasing decisions from institutional buyers to individual consumers and the use of vibrant colours for product branding, similar to consumer products, has increased. More vibrant colours can require higher pigment loadings in plastics. Dispersion for colour consistency in thin wall parts: Many medical devices are becoming smaller and lighter to improve performance, portability, comfort and compliance. Small, thin-walled plastic components require exceptional pigment dispersion within the plastic raw material to ensure part-to-part and lot-to-lot colour consistency. Higher pigment loading for colouring performance additives: Medical device companies are also increasingly designing components with multiple attributes to improve product performance, consolidate components, and reduce costs. For example, antimicrobial additives are being incorporated into plastics to reduce bacterial infection in device components which contact body tissue for extended periods of time. Such additives can have inherent colours that must be overcome with higher pigment loadings to achieve the desired colour match for the component. Approved pigments: In addition to the technical challenges of colour compounding plastics, pigments which meet medical regulatory requirements, including USP VI approval, is a consideration. Not all pigments are approved to be used in medical devices.
For example, orange pigments which meet medical device regulatory approvals are difficult to obtain. Creating an orange colour match in plastic often requires selection of approved red and yellow pigments; however, a precise orange colour match by this indirect method may not be possible. Custom pre-coloured plastics: The use of custom coloured plastics for medical device components is increasing and has been accompanied by technical and regulatory challenges to meet desired colour specifications. Custom compounding of pigments into plastics using twin screw extrusion is often required to optimise dispersion of higher pigment loadings. Custom pre-coloured plastics are often preferred over masterbatches, which are added in concentrate form to non-pigmented plastic, to ensure consistency throughout the plastic prior to processing in components. Regulatory compliance in sourcing: Lastly, colour compounders with specific expertise in sourcing regulatory compliant materials are more likely to provide shorter material development times with less risk by selecting approved ingredients to achieve the desired colour match for the associated medical device class. Continued on page 16
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Ancient “Egyptian Blue” Pigment Points to New Medical Imaging Technology According to a report published in the Journal of the American Chemical Society, a bright blue pigment used 5,000 years ago is giving modern scientists clues about the development of new nanomaterials with potential uses in stateof-the-art medical imaging devices, remote controls for televisions, security inks and other technologies. The authors—Tina T Salguero, assistant professor at the University of Georgia’s department of chemistry in the USA, and her colleagues—point out that Egyptian blue, regarded as humanity’s first artificial pigment, was used in paintings on tombs, statues and other objects throughout the ancient Mediterranean world. Remnants have been found, for instance, on the statue of the messenger goddess Iris on the Parthenon and in the famous Pond in a Garden fresco in the tomb of Egyptian “scribe and counter of grain” Nebamun in Thebes.
<< The blue pigment used in ancient Egyptian artwork may foster development of new materials for medical imaging devices and other modern technology. >> The authors describe surprise in discovering that the calcium copper silicate in Egyptian Blue breaks apart into nanosheets so thin that thousands would
fit across the width of a human hair. The sheets produce invisible infrared (IR) radiation similar to the beams that communicate between remote controls and TVs, car door locks and other telecommunications devices. “Calcium copper silicate provides a route to a new class of nanomaterials that are particularly interesting with respect to state-of-the-art pursuits like near-IR-based biomedical imaging, IR light-emitting devices (especially telecommunication platforms) and security ink formulations,” the report states. The authors acknowledge funding from the University of Georgia. UK Masterbatch Manufacturer Reports Growing Demand UK-based colour masterbatch manufacturer Silvergate Plastics reiterates the idea that colours are in growing demand among medical device manufacturers. Silvergate sees colour as a universal language, with more colourcoded products being utilised to improve processes and procedures within the medical sector than ever before. Devices and products are being developed to not only do a specific task but also to improve decision-making and to save time while being aesthetically pleasing. In terms of regulatory compliance, Silvergate says its colour formulators are familiar with biocompatibility requirements related to ingredients according to the FDA and US Pharmacopaeia. The company explains its formulation process as follows. A combination of pigments is used to formulate any colour. Every pigment used within the colour must meet approved specifications such as those required by the FDA; as must the process aids and carrier system. This results in a reduced range of pigments that can be used within medical devices and products. However these limitations do not restrict the range of available colours. Across the colour spectrum, Silvergate says there are more than 20 million achievable shades, each of which is created by combining appropriate pigments. The colouration of plastics is achieved by determining the colour required, the polymer type and the purpose for which it is being used. A colour is created through the use of
pigments in varying degrees, enabling the company to achieve an exact colour match, even under such strict conditions. Silvergate says it appreciates that “getting it right first time can be a matter of life or death”, where finished products may be used both inside and outside the body. Consequently, the company has state of the art material control systems, which demonstrate without doubt the specified ingredients have been used in the correct amounts, for every material used. This provides absolute assurance and total peace of mind for the medical sector and, of course, the end user. PolyOne Celebrates US$3 bn Turnover and Launches OnColor iPad App Talking with Medical Plastics News at the recent Medtec Europe trade show in Germany in February, the new global marketing director for healthcare at specialist polymer compounds manufacturer PolyOne, Charles Kutchin, pointed out that the company was celebrating breaking the US$3 bn turnover mark. “We’re a US$3 bn company now” he told editor Sam Anson. A breakdown of revenues by sector in 2011 shows that healthcare represented 9% of PolyOne’s total sales. When asked about what sets PolyOne apart from other large polymer materials manufacturers, Mr Kutchin explained: “Our global manufacturing footprint is broad reaching. And this supports globalisation efforts of the major medical device OEMs and large contract manufacturers.” He added: “We have been growing strongly in Asia Pacific. And recently have expanded in Brazil.” When commenting on his approach to marketing during a period of rapid growth, Charles said: “Our global footprint is an important factor here. Close to 40 of our manufacturing sites worldwide are manufacturing to cGMP and many of them have ISO13485 certification. This is a strength we bring to the marketplace because our customers can expect that wherever we are operating around the world we are working to standardised quality procedures.” Continued on page 19
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Also in February PolyOne announced the release of a mobile app for accelerated product development and colour selection. OnColor Portfolio App for iPad, available for free download, is said to bring mobile convenience to the colour development process, enabling iPad users to evaluate colour ideas, to request samples, to submit custom colour requests, and to easily access information about PolyOne’s colour and additive technologies. “The OnColor Portfolio App is just the beginning of our ability to leverage mobile technology to generate tools that help streamline our customers’ product development process,” said Fernando Sanchez, global marketing director for PolyOne’s colour and additives division. “At the same time, these tools can expand the understanding of what is possible with colours and special effects when they are considered at the earliest stages of development.” A Question of Cooperation: Melitek and Clariant Team Up on Healthcare Polymers Melitek, a Danish compounder of polyolefin- and styrenic-based polymers dedicated to the healthcare sector, has announced that it has signed a cooperation agreement with the medical and pharmaceutical segment of the masterbatch division of Swiss chemical manufacturer Clariant. Under the agreement, Clariant will have access to Melitek's Meliflex brand, enabling it to sell medical compounds of polyolefins and styrenic-based polymers through its network, while Melitek will have access to Clariant's Mevopur masterbatches for use in its Meliflex compounds and for sale directly to its customers. This allows processors to have a single supplier and point of contact whilst keeping traceability. Thermoplastic elastomers (TPEs) are excluded from the agreement. According to the press release announcing the agreement, modification of polymers by colour, additives or blends and alloys, either as concentrates or compounds, is increasingly demanded across a wide range of medical devices and pharmaceutical packaging. The regulations for this sector are
increasingly needing more attention in order to meet requirements by controlling changes to raw materials and manufacturing processes. It goes on to say that the two partners have a similar understanding and approach to the needs of the sector, and have decided to work more closely together. In doing so, customers of each company can access a wider choice of options whilst keeping clear responsibility for change control and traceability. “In some situations the producers of the plastic components for medical devices demand both compounds and masterbatches”, said Steve Duckworth, head of medical and pharmaceutical masterbatches at Clariant. “This can be based on many factors such as batch sizes, process machinery capability and part design.” According to the press release, Melitek has been an established polymer compound supplier to the healthcare market and has machines capable of producing large lot sizes. It has deep experience and proven capability to meet the requirements of this market, and develop new solutions. Originally focused on PVC replacement with colourless olefin alloys, customer demand encouraged Melitek to develop compounds containing colours and additives. This demand developed the relationship with Clariant’s site in Sweden. Kim Laursen, managing director of Melitek, said: “The relationship with Clariant goes back many years, and we appreciate the common understanding of the market needs that Clariant has developed, which is essential for masterbatches which support the customer’s compliance to the medical requirements.” Steve Duckworth added: “The capability to offer a clear and auditable raw material chain, with control of changes is extremely important to the healthcare industry, and through this partnership we can give the customer the choice from a wide range of compounds and masterbatch, developed to address the needs of the healthcare market, irrespective whether the customer needs 25 kg or 25 tonnes of compound, or 100 kg of masterbatch.”
He went on to say: “This is an alliance model similar to the airline industry, where a combination of skills, equipment, network and a common quality goal combine together to meet a customer need. Likewise in the healthcare industry, the combination of skills of Melitek and Clariant with our deep understanding and dedicated resources will help customers to meet the new challenges they face.” Concluding enthusiastically, Laursen said: “The synergies coming from this cooperation are built on Melitek’s long expertise and dedication to the healthcare market in providing added value materials and supply solutions to customers. By this sales cooperation, we hope to grow even further in the colour compound market, offering more customers the advantage of pre-coloured compounds and masterbatches.” << Jesper Laursen, brother of Kim Laursen, is the co-owner of Melitek. >>
<< Steve Duckworth of Clariant says the Melitek partnership, which mirrors cooperative networks in the airline industry, will enable both companies to offer a clear and traceable raw material chain, with control of changes, something which is extremely important to the healthcare industry. For more on change control see pages 10-11 >> MARCH-APRIL 2013 / MPN /19
WELDING END OF LINE | High Power Fibre Lasers, Sub Micron Lasers and Other Welding Advances
Progress in Lasers Improves Polymer Joining Despite having been invented over 50 years ago in the USA, lasers in all of their many forms are still often perceived as an exotic energy source that is difficult for laymen to understand. But a new laser type and a new laser wavelength starting to be used in the medical device industry is changing that—the high power fibre laser. Dr Tony Hoult of laser welding equipment maker IPG Photonics in California introduces our first innovation. The high power fibre laser has been dramatically altering the face of the laser industry since 2001. In older technologies, lasers are assembled from many separate optical components and may be delivered to the workpiece via a fibre optic cable, a technology that has been around for more than 25 years. In the case of the fibre laser, however, the laser beam is actually generated within the fibre itself and all of the optical components are optically spliced together into one all-in-fibre beam path. The many advantages of this approach are easily understood by anyone familiar with optics. Going back to basics, a laser beam is simply a beam of light energy which can be focused down to a very small spot, and this property alone is responsible for many of the high power industrial applications for which lasers are used— like cutting and welding thick steels. In addition to this ability to focus on a very small spot is another property of a laser beam that is perhaps more responsible for their esoteric reputation— most laser beams produce light of a fairly well-defined wavelength. Most readers will be familiar with the concept of the wavelength of light. But when the discussion moves to the relationship between wavelength and energy—which is at the heart of all branches of physics—many non-scientists and even some engineers may disengage. 20/ MPN / MARCH-APRIL 2013
<< IPG’s fibre laser welding can be used to weld clear polymers together without the need for additives. The technology is particularly useful for transparent parts which require invisible weld lines. >>
However, this important relationship is central to understanding why clear polymers can now be laser welded without the complications of using additives, different colours or additional inks and dyes. This is illustrated in the news that IPG has worked with Eastman to invisibly weld pure Tritan copolyester without additives (see page 22).
Until recently, significant average power for laser materials processing in industry was only available from a very limited number of laser types, either solid state lasers emitting in the near infra-red 1.07 μm wavelength regime or carbon dioxide gas lasers emitting at the longer 10.6 μm wavelength regime. The advent of new versions of the standard industrial fibre laser now produce up to 120 watts of power at an intermediate wavelength regime known as the short wavelength infrared regime. The lower photon energy related to this longer wavelength, which is longer than the near infrared regime, has many important effects. Because specific photon energies are absorbed by particular molecular bonds via a resonance mechanism, this longer wavelength is absorbed differently by many different molecules. Of particular interest to us in the field of medical polymers is the improved absorption in the carbon-hydrogen (C-H) molecule, which is of course the background chain of all organic polymers. The end result of this is that absorption of this laser beam in clear polymers is greatly increased to the point at which highly controlled melting through the thickness of optically clear polymers is possible. The availability of this new wavelength at high average power has, therefore, led to a greatly improved and simplified technique for laser welding clear polymers for the medical device industry. IPG Photonics already has a dominant position in the market for conventional high average power fibre lasers for cutting metals. But in a recent development, IPG Photonics has shown that these lasers may now be used economically for the welding of polymers, of interest to the medical device industry. Continued on page 22
WELDING Continued from page 20
At the recent medical technology manufacturing trade show MD&M West in California, held in February, IPG demonstrated how Eastman’s clear Tritan copolyester can be invisibly welded without additives. Tritan, a relatively new material, has a balance of properties, including clarity, toughness and chemical resistance. It offers similar properties to polycarbonate but does not contain bisphenol A. Eliminating the need for additives may result in two benefits for manufacturers. One is a potential cost saving, the other is not having to make sure the additive has been tested for biocompatibility. Additionally, because the welding work is done via laser, no tools come into contact with the medical device material, making the process clean and controllable. Dr Hoult reiterates the benefits: “For medical device manufacturers, the benefits of this welding technique include fully hermetic leak-proof precision joints which have a smooth weld that will not entrap bio-burden.” Sterilisation of clear reusable durable devices made from Tritan copolyester is a critical consideration for manufacturers. Gary Hawkins from Eastman told Medical Plastics News that while they haven’t yet completed post ethylene oxide or radiation sterilisation laser weld quality or lap shear strength comparisons (they are due shortly), they expect post sterilisation performance of weld seals to be good based on experience with other welding methods. He added: “We have completed quality and lap shear evaluations after 120-hour exposure to isopropyl alcohol and sodium hyper chloride disinfectants and found strong performance.” Sub-Micron Laser Welding of Plastics Goes to 500 nm Recent developments by UKheadquartered TWI (The Welding Institute) and Vistec Lithography in the Netherlands have allowed welds with a width of 500 nm to be made in plastics. Medical Plastics News understands that these are the smallest welds ever reported in these materials. With the drive towards ever smaller scale complex plastic products such as biological analysis chips, chemical micro-reactors and electronics 22/ MPN / MARCH-APRIL 2013
products in plastics, there is a need for for the deposition of thin layers in high welding processes that meet these resolution patterns. When the laser is challenges. applied it will heat and weld only where Laser welding developments in the tracks of absorber are present, with the recent years have shown that the laser beam passing through the other areas with beam size can be used to limit the weld very little effect, hence protecting sensitive size. Welds of the order of 10 μm in parts of the products. width have been demonstrated using a There is potential for welds of even focused infrared laser beam of similar smaller dimensions as well as potential dimension. Welds much smaller than this for use in other plastics using similar are not possible using this technique due techniques. to the resolution limits inherent in Medical Plastics News would like to focusing a near infrared laser beam. thank Ian Jones, principal project leader An alternative technique has been for polymers at TWI for this information. investigated using precise patterning of laser absorber dye on the plastics surface to define the weld position. This has enabled joints to be made an order of magnitude smaller than this. The new method used electron beam lithography to apply laser absorber in precise patterns, mimicking the methods used to build microelectronic circuits. The absorber tracks were then used to generate welds between two plastic parts using laser heating. Polymethylmethacrylate (PMMA) substrates were coated with lithography resist material << SEM image of laser welded sample modified to absorb infrared in cross section. 0.5 μm welds radiation, and to be weld separated by 2.5 μm. The 0.5 μm wide compatible with the substrate. tracks have been welded to the top Developments were carried out to sheet of PMMA. >> use electron beam lithography to pattern the resist coatings. This left a high resolution pattern of laser absorbent tracks on the surface of the PMMA, enabling selective heating by a laser beam that was much larger than the tracks of absorber. Tests of the weld strength on larger scale samples with the same materials and techniques showed that successful high strength welds were produced. Although tests with simple linear patterns have been carried out to date, the potential for welding of high resolution complex patterned devices is clear. These could include small channels, which may << Laser welded PMMA sample have sensitive surfaces such that only the in cross section. Pillar tops edges of the channels must be heated or welded with low profile detailed areas with very complex welding channels in between. The tops requirements. The lithographic patterning of the 5-μm-wide pillars have techniques have been amply demonstrated been welded to the top sheet of within the scope of the electronics industry PMMA. >>
Rotating Fibre Optics Welding At Medtec Europe, held in February 2013 in Germany, manufacturer of laser production equipment Rofin, also based in Germany, showcased a rotating laser processing head which allows for circular laser processing of miniature workpieces sitting in a tray, or bulky parts whose size makes them unsuitable for mounting on a rotary axis. A synchronously rotating gas nozzle precisely delivers assist gas for circular weld seams. According to Rofin, typical applications include cannula, medical instruments and valves for assembling endoscopes. Desktop Galvo Fibre Laser Welding Fibre lasers were also on show at MD&M West at the stand of US manufacturer of welding equipment and laser processing systems, Miyachi Unitek. The company demonstrated its newest welding system, its Mu desktop galvo fibre laser welding system, as well as its LF series of fibre lasers. Miyachi describes the desktop welding system as follows. “It features the motion capabilities of a stage-based system in a highly compact footprint. Fibre and Nd:YAG compatible, the new system has an average power of up to 500 W, and high speed galvo motion. The Class 1 mini workstation is available in a number of configurations, one with a vertical door that provides quick access for loading and unloading. Options include through-thelens vision, extraction, and custom tooling. The Mu is also available as a Class 4 system, and may also be configured as a welding sub-system for machine integration.” For the LF fibre lasers, the company states: “The new LF series fibre lasers are ideal for micro spot and seam welding applications as well as fine cutting, with power levels from 100-500 W and a selection of beam qualities to suit each application need. A high definition large screen pendant enables quick and easy programming.” Laser Welding of Plastic Microfluidic Devices Frank Brunnecker, vice president of laser welding at German laser welding
<< Rotating fibre optics for circular weld seams on parts too small or bulky to be mounted on a rotary axis. >> equipment supplier LPKF has written about how his company has developed laser welding equipment for two microfluidic point of care diagnostic devices. The first is a device manufactured by the former medical plastic device manufacturer Wilden group, acquired by Germany’s Gerresheimer Regensburg in January 2007. LPKF’s technology has been used to laser weld a measuring system for combined DNA and RNA analysis (figure below). The system consists of an analyser and a one-way microfluidic cartridge. The latter is manufactured via injection moulding and joined by laser welding.
<< Nucleic acid analytics in a oneway cartridge from the former Wilden Group, now Gerresheimer Regensburg. >> Continued on page 24
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For many years, DNA and RNA analysis was a complex process that required fully equipped laboratories. Now, the microfluidic point-of-care â€œmini-labâ€? described above allows small research laboratories, surgery centres, clinics, and even food production facilities to dive in to rapid nucleic acid analysis. For example, if a patient is admitted to a hospital, the device allows DNA and RNA analysis to be carried out immediately by testing to identify the presence of any antibiotic-resistant pathogens. The heart of the whole system is its one-way cartridge. It consists of several injection-moulded components which are joined together by transmission laser welding. This cartridge contains all the necessary reagents, and carries out the actual test. The liquid sample passes along the long microfluidic channels, going through numerous processing steps along the way. At the end, the processed sample lands in the actual detection field. The technology for sealing the microchannels on the base of the cartridge is said to present a special challenge. The need for the nearly 2 m-long channel to be airtight is obvious. Moreover, the cross-sections of the channels must also guarantee the unimpeded flow of the sample through the maze-like network. Welding challenges: To join the one-way cartridge, a number of different technologies could have been used. Methods where energy is input in the form of friction, such as ultrasound welding, were deemed unsuitable right from the start because of the specification for absolute particlefree production. These methods produce debris which could block the width of the channels. Thermocouple welding was also deemed technically unsuitable because it cannot satisfy the need for very fine contours. After analysing all of the alternative technologies in detail, the choice was clear: transmission laser welding. Laser welding was the winner for several very compelling reasons: short cycle times, good options for process monitoring, reliability, high welding seam strength, and the fact that no additional materials were required. The technology is also perfectly suited for cleanroom applications. The second application is the Medios series from German diagnostics manufacturer Pes DiagnoseSysteme. Here, the complete diagnostics unit is located in one analytical device which takes up about as much space as a
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WELDING desktop printer. The diagnosis cartridges in this appliance are joined by transmission laser welding. For this application, the choice of material for the main component and the lower cover plate went to a polycarbonate (PC) to satisfy the medical and mechanical specifications. The upper cover plate is a two-component injection moulded part made of PC and a TPE. This is also joined to the main element by laser welding. The housing is made with either a black or transparent colour to absorb the laser energy. The transparent colour contains a special absorber tailored to the wavelength of the laser beam. The cover plate and the TPE in the front module are uncoloured and therefore transmissive to the laser beam. The functional and production-specific parameters were already taken into account during the design of the cartridge. A key aspect here is ensuring that the welding zone is completely accessible to the laser beam. The stringent requirements of the application itself mean that the microfluidic components which are to be joined together must be made with very high geometrical precision. After recently expanding production facilities, LPKF has enlarged its distribution capacities with the employment of two new experts—Thomas Eckert and Mario Gügel. The appointments are to provide consulting services to support the company’s growth in laser welding. Mario Gügel has experience in the assembly of new industrial installations as well as in their relocation—including industrial laser systems. He will strengthen the international customer acquisition and customer service activities, as well as assisting the LPKF branch office in the USA. Thomas Eckert’s previous customer service experience was in the technical field service team for the customers and distributors in Germany and Europe of a manufacturer of plastic butt-welding equipment. He will assist the German distribution team from his base in Hamburg, Germany, from where he will also provide customer support to clients in northern Europe.
<< Cartridges in the Medios diagnostics system from German manufacturer Pes DiagnoseSysteme are welded in a cleanrom by a laser. >>
Transmission Laser Welding Module Optimised for Cleanroom At Medtec 2012 German plastics joining equipment specialist Bielomatik highlighted the fact that its K3642 laser integration module, optimised for cleanroom class 7 and GMP grade C, allows laser transmission welding to be integrated into existing facilities. The company said that connecting the K3642 by Bielomatik to automated production lines and facilities, such as conveyor belts, rotary discs and so on, << Bielomatik’s K3642 laser is also comparatively simple. integration module, The laser unit is 300 mm optimised for cleanroom wide and is said to offer both class 7 and GMP grade C, high installation flexibility and allows laser transmission very good accessibility. The welding to be integrated into supply unit with laser source, existing facilities. >> control cabinet and pneumatic equipment can be installed remotely from the laser integration module. An IT connection via a range of interfaces including ethernet also ensures flexibility. Remote maintenance options are possible. The module can be equipped with either a diode or fibre laser in the performance range 25 W to 300 W (continuous wave, not taking into account the power reserve of approximately 20%) at the fibre optic termination. Said to be intuitively operated via touch panel and visualisation software, all process variables can be monitored and adjusted by setting their target levels and upper and lower limits. Retaining force, laser power and scanning speed can be controlled “dynamically”. Process data can be archived on a network drive, an SD card or a USB stick. The clamping and fixturing system consists of a pneumatic pressure cylinder and a two-column precision guide. Two points of rotation are used to position the clamping bracket and support for the mask exactly parallel to the capture tool. The clamping system uses reference-based position measurement with an accuracy of either 0.001 mm or 0.01 mm to facilitate the component/cover request and thus prevents unnecessary waste. During welding, the sinking depth is monitored exactly. Bielomatik says the tool can be changed manually in approximately five minutes. It is claimed by the manufacturer that the laser welding method “meets very high requirements for tight, particle-free and clean welded connections”. It goes on to say: “A flow-optimised, easy-clean stainless steel hood encloses the laser welding integration module and covers encapsulate lubricated parts of the machine, as well as those parts which emit particles”. MARCH-APRIL 2013 / MPN /25
REGULATION REVIEW EU SHARPS DIRECTIVE | Effective May 11, 2013
The Requirements of the EU Sharps Directive and What it Means for Manufacturers Aims The directive aims to ensure the safest possible working environment, to prevent sharps injuries and to protect healthcare workers and patients at risk. It recommends conducting risk assessments in all situations where there is potential for injury, or exposure to blood and other infectious material. Where such risks are identified, the directive recommends that either processes or devices must be put in place to reduce or eliminate the risk. It also requires the implementation of policies for risk assessment and prevention, training, information awareness and follow-up and response procedures.
On May 10, 2010, EU Directive 2010/32/EU was introduced to prevent injuries and bloodborne infections to hospital and healthcare workers from sharp instruments such as needles and lancets. Member states will have until May 11, 2013, to ensure that the provisions of the directive have been implemented into national legislation. The obligation is on the employer to ensure the safety and health of workers in every aspect related to their work with devices containing medical sharps. Sharps are defined as any device or object which is used to puncture or lacerate the skin.
Possible options for protecting sharps and needle stick injuries, in order of effectiveness 1. Elimination of unnecessary injections y 2. Providing medical devices with integrated safet mechanisms 3. Regulations and training programmes ge 4. Standard precautions, no recapping of the syrin 5. Personal protective equipment such as gloves
What this means for manufacturers Pharmaceutical and medical device manufacturers are not legally obligated to reduce the risk of needlestick injuries or to provide passive or active needle devices.
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Nevertheless, it will be important for them to react to the directive to fulfill the market requirements and keep up their sales opportunities. One company which is able to help companies looking to respond is German pharmaceutical label manufacturer Schreiner MediPharm. The company describes itself as a certified tier one supplier and development partner for the pharmaceutical industry. Medical Plastics News asked Schreiner MediPharm to provide details of how its products can help manufacturers of medical sharps. The company responded with details of its Needle-Trap, a label-integrated needle protection system for prefilled syringes. The system works by having a safety mechanism built in as an integral component of the label, securing the bloodcontaminated hypodermic needle after an injection. According to the company, Needle-Trap is easy to handle for healthcare professionals. The activation of Needle-Trap’s safety mechanism can be conducted with one hand only, allowing the other hand to be kept free for clinical procedures.
How to use the Needle-Trap Step 1 Preparation: First, fold the red needle trap toward the side by approximately 50-80° and remove the cap. Do not remove the cap before folding the trap. Step 2 Performing the injection: Perform the injection as usual. Step 3 Securing the needle: Secure the needle by placing the trap on a firm surface such as a tabletop using one hand. Then push down the trap. Step 4 Clicking: Bend the trap by more than 45° until the needle audibly locks (via a clicking sound) into the plastic part. Step 5 Disposal: Dispose of the secured needle in the nearest sharps container.
<< Photographic representation of the combined label and safe disposal Needle-Trap system. >> The capability of adding Needle-Trap to a prefilled syringe manufacturing line is apparently relatively painless (please excuse the pun). Conventional labeling equipment can be used with just minor modifications. According to Schreiner MediPharm, this is a quick and easy integration into existing processes which gives manufactures the possibility to react rapidly to the directive and the resulting market requirements. The company adds that additional costs of investments necessary are minimal. Thanks to the compact design there are no changes of secondary packaging required. Needle-Trap is adaptable to all standard syringe dimensions. The unique system design complies with occupational safety and health regulations (FDA 510(k) certification). The authorisation for medicinal products can be submitted as an adaption of the prefilled syringe label. << Schreiner MediPharmâ€™s NeedleTrap system has been developed to help manufacturers support their customers with the EU Sharps Directive. >>
In terms of the outlook for this sector, Schreiner MediPharm has been able to reach double-digital growth rates and is expecting this to continue. In the prefilled syringe market, experts are predicting an average growth rate of more than 9% over the next five years. Needle-Trap is said to be particularly useful for clinical trials because compared with passive devices it can be easily combined with a booklet label which provides essential information. Schreiner MediPharm says it fully supports manufacturers from the initial idea to production, creating customised solutions which optimise processes, reduce costs, and add value. Medical Plastics News would like to thank Susanne Zinckgraf at Austrian injection moulding machine maker Engel for putting us in touch with Schreiner MediPharm. MARCH-APRIL 2013 / MPN /27
Eucomed, Europeâ€™s medical device industry association, has produced this fascinating infographic about the industry in 2011.
DESIGN 4 LIFE Tickled Pink | Breast Tumour Marking Device Demonstrates Progress
Gerresheimer’s Item Acquisition Going Strong At the recent Medtec Europe show in strengths in product design and Germany in February, vital signs were development with Gerresheimer Plastic positive for medical plastic drug delivery Systems’ bundled manufacturing expertise. device manufacturer Gerresheimer’s recent Our customers profit from this combination. acquisition of item, a German medical Design for manufacturing (DFM) now device design bureau, which became commences in the product development effective as of February 1, 2012. Since the stage, which shortens development time, << Peter Wallrabe, Managing Director acquisition, item has been trading as an reduces development costs and mitigates of Gerresheimer item, with a visulisation independent subsidiary under the name project risk because there is no longer any of medical device design. >> Gerresheimer item. need for post-design, plastic-oriented Speaking to Medical Plastics News optimisation.” competencies at an early stage of the value Peter Wallrabe (see image right), managing Gerresheimer item’s portfolio of services chain. We aim to be involved in customer director of Gerresheimer item, said: “A extends from concept development to projects right from the initial product good example of our capabilities is this production-ready product. It includes concept onwards. new pink and white disposable device for advice and support in the early project At the beginning of 2011 Gerresheimer breast tumour marking (see below image) phases, assistance in design development, established the Medical Innovation Group, a which we designed and prototyped. It insurance of freedom to operate, plus team of specialists with interdisciplinary allows surgeons to easily identify the engineering, prototyping and production product development design and position of a breast carcinoma using a and logistics of samples for clinical studies. engineering competencies. minimally invasive procedure. We are Providing some background to The acquisition of the item medical pleased with the economic design of a Gerresheimer’s item’s services, Karin device design bureau has provided disposable product, combined with a high Strasser, director of marketing and Gerresheimer with a subsidiary that has level of ergonomics and the reassuring more than 10 years of experience in strategic communication at Gerresheimer Plastic form of a product which induces calm Systems, said: “What we want to do is a product development and the design of rather than anxiety.” tailor-made service package. Starting a pharmaceutical and medical products. The acquisition of item by Gerresheimer project with Gerresheimer Plastic Systems At the time of the acquisition of item, the has augmented the pharmaceutical and provides the customer with flexible options. Medical Innovation Group and item were medical product design and development If the customer wants to advance the merged to form Gerresheimer item. A team competence of Gerresheimer AG’s Plastic development of a product from an existing of around 20 designers and product Systems division. developers work there. Gerresheimer item is stage, optimise an existing product or As a full service provider, modify the configuration to suit polymer managed by item’s former managing Gerresheimer’s Plastic Systems Division processing, our teams at our technical director Peter Wallrabe. covers all stages of the development and competence centres in Wackersdorf and At the time of acquisition, he production chain. Peachtree City, USA, and our team within emphasised the benefits of the newly Explaining the thinking behind the Gerresheimer item in Münster, Germany, founded company for customers: “The new acquisition, Andreas Schütte, member of the company unites item medical device design’s are the experts.” Gerresheimer management board Services provided by Gerresheimer item responsible for the Plastic Systems division, said: “We apply our concept of Innovation management Market research and user surveys combining product IP management Technology landscapes and freedom to operate (FTO) analyses development and Industrial design; From design strategy to mock ups; manufacturing Usability design Optimal ergonomics for care givers and patient << This user friendly device for breast tumour marking was demonstrated by Gerresheimer’s new design bureau Gerresheimer item at Medtec Europe 2013. >>
Laboratory tested product functions
CAD simulations, production and assembly specifications
Rapid prototyping, rapid tooling and design verification
Small series and clinical sample production
Specification, risk analysis and design control
Basic development, manufacturer search and electronic design
MARCH-APRIL 2013 / MPN /31
DOCTOR’S NOTE Healthcare Economics | Researchers Report on NHS Supplier Portfolio
Just Two Manufacturers Control Most of Hip Prostheses Supply to UK’s NHS Dominant Suppliers Have 69% of the Market WORDS BY | DR CHARLOTTE DAVIES AND DR PAULA LORGELLY The purchasing behaviour of the UK’s state-funded National Health Service (NHS) has been attracting considerable attention of late with several key reports, including those by British billionaire businessman Sir Philip Green in 2010, the National Audit Office (NAO) in 2011 and financial services company Ernst & Young in 2012 , identifying wide variation in the purchase price paid by NHS hospitals for consumables (ranging from bed sheets to MRI diagnostic equipment). More specifically, the reports by the NAO and Ernst & Young have also identified that purchasing decisions are taking place at the fragmented, hospital level, somewhat counterintuitive to what one might expect when considering a large buyer such as the NHS. However, hospital purchasing is only part of the picture. The behaviour of the suppliers and the nature of their relationship with the NHS and the fragmentation in purchasing within the NHS are also relevant. This raises the possibility that the NHS could be leaving itself open to so-called “seller power”, whereby sellers are able to extract anticompetitive prices by cornering a majority of a particular market sector. This is well researched and understood in the pharmaceutical sector. However, medical devices have attracted much less interest until now. The authors used the prostheses implanted in primary total hip replacement surgery as a case study to investigate whether the supplying industry has the structural features necessary, although not sufficient, for the exercise of market power both at the national and hospital level. Further to this, they also focus their analysis on the pattern of purchasing at the individual hospital level in order to determine the level of specialisation hospitals have in their procurement of hip prostheses.
Finally, larger hospitals (in terms of In on-going research the authors are number of procedures) are less using a large national patient level dataset concentrated in their purchases, albeit only derived from the National Joint Registry slightly so. (NJR) for England and Wales and the The authors confirm the findings by the Hospital Episode Statistics (HES). From NAO and Ernst & Young that procurement these data, a hospital level panel for each in the NHS is not at all uniform. These results year 2004 to 2008 was constructed with also raise further questions, most notably, the hospital year (of surgery) as the unit of why do hospitals have such concentrated observation. This resulted in a total of purchasing patterns for hip prostheses? 2,281 hospital year observations, for Are hospitals exercising their buyer 278,063 patients. power by negotiating scale discounts (bulk They identified that at the national level, purchases), or is it the result of targeted only five manufacturers have a market share marketing or even market sharing, by the of consistently over 5%. However, more manufacturers? startling was the finding that two of the Clearly, it would be beneficial to have manufacturers consistently account for 69% information on price, however, this is not of the market over each of the years 2004 available within the dataset used and nor is to 2008. From these results they conclude it readily available within the wider literature. that the national market is highly Future work will include an indepth concentrated (very oligopolistic), with no investigation into the decision making significant entry of new firms and with very process regarding the procurement and stable concentration and stable market purchase price of hip prostheses, involving shares of the leading manufacturers. At the both the surgeon and hospital procurement hospital level, they find that procurement is departments. typically very specialised. A regression analysis of the determinants of hospital procurement << Dr Charlotte concentration reveals that hospitals have Davies is a health become more specialised in their economist at purchases since 2007, when the Norwich Medical previous government issued a School at the healthcare spending policy, payment by University of East results, which rewarded hospitals with Anglia, Norwich, budgetary resources in level with a UK. >> range of performance criteria. Procurement specialisation was also found to be higher in NHS foundation trusts (which have financial autonomy) as opposed to NHS trusts (which are financially managed by local health authorities). All regions were more specialised in their << Dr Paula Lorgelly is purchases than the UK’s capital a health economist at city, London, with some indication Monash University, of increased concentration Melbourne, Victoria, especially in localities around Australia. >> manufacturer headquarters. MARCH-APRIL 2013 / MPN /33
UROLOGICAL DEVICES Making Plastic Work | Preventing Tissue Damage
Coatings Prevent Tissue Damage by Hydrophobic Plastics in Acqueous Environment WORDS | SIMON ONIS, Principal Scientist, Biointeractions
Plastic urological devices are commonly used in global healthcare to perform a particular function or functions. Because of their relatively low cost, high throughput production and wide choice of starting materials, plastics provide a myriad of opportunity for medical device design. For example, applications range from very hard polycarbonate connectors to flexible silicone catheters. Plastics can be coloured, transparent or made radiopaque. The functional opportunities are varied. Examples include everyday patient support—for example intermittent and indwelling urinary catheters—diagnostic and investigative devices, such as cystoscopy cameras, and devices which help the treatment of disease or complications, like those for the removal of bladder stones or urethral stents for the dilation of urethral strictures. The interfacial properties of a plastic surface play an important role in determining its biocompatibility, ease of use and functioning lifetime. Promising plastics, which display ideal physical properties, can possess undesirable surface properties that can evoke harmful biological and chemical responses in the urological environment. The responses can result in device failure, thanks to occlusion, thanks to patient harm—for example device associated infection—and invariably thanks to intervention from a medical professional. The possible problems associated with plastic urological devices can limit their intended use and function while causing pain, discomfort and further trauma. Other examples of problems with plastic urological devices include: damage to surrounding tissue during complicated removal or placement of device, caused by friction associated with a hydrophobic plastic device in an aqueous environment; “misting” or accumulation of spherical water droplets on camera viewing panels; or biofouling due to deposition of salts, cells and protein onto the device surface. Modification of the device surface can improve its performance in numerous ways and coatings are generally a logical, cost-effective and convenient strategy for doing so. Most coatings are said to allow the bulk device properties to remain unchanged, whilst surface functionality is altered to result in a more biologically acceptable device and improved device function. 34/ MPN / MARCH-APRIL 2013
BioInteractions is a UK-based company which specialises in coatings for the medical device industry. Its coatings are licensed as a technology to major medical device manufacturers. BioInteractions’s coatings are polymeric in nature, not compromised by common sterilisation procedures and can be applied to a wide range of substrates of varying geometries and size, without affecting the bulk properties of the underlying device substrate such as flexibility and visual clarity. The main surface related problems facing urological plastics can be overcome by existing technologies in the BioInteractions portfolio. Its capability enables the company to combine technologies in order to give a multi-faceted approach to device compatibility through surface modification. BioInteractions has numerous technological platforms which alleviate the problems seen in urological plastics. Its lubricious coating provides a biocompatible surface which has a very low coefficient of friction, is instantly wettable, prevents misting or accumulation of fluid droplets and eases both device placement and removal, minimising patient discomfort and additional device related trauma. The company’s antimicrobial platform is polymeric and combines a non-leaching broad range antimicrobial with a hydrophilic polymer. The hydrophilic nature of the polymer minimises non-specific deposition onto the device and associated bio fouling. The non-leaching antimicrobial is long lasting and does not rely on leaching of the active component and associated problems (for example functional lifespan and systemic effect). Biointeractions says the technology has been clinically proven to reduce device related infections. Originally designed for blood contacting environments, Biointeractions’s advanced heparin technology platform is said to perform excellently in preventing thombus and platelet deposition (devices have been implanted for over a year with no evidence of fibrin sheaths). However, this platform also prevents cellular deposition and ingrowth, so is reportedly ideal on devices where these are problematic. The biostable polymeric drug delivery platform is a tailored therapeutic agent release technology which can deliver both hydrophilic and hydrophobic drugs in a controlled manner. Total elution of the drug is possible which helps in the economical aspects of this system. Possible applications of this technology in urological settings include controlled reduction in scar tissue formation after stent placement.
Melitek Highlights Alternatives to Soft PVC in Urological Catheters Inspired by a trend in the early 1990s in Scandinavia to replace soft PVC containing DEHP, Danish compounder Melitek decided to devote its operations to offer alternative materials. Some of the world’s leading urological catheter OEMs are located in Scandinavia and Melitek reports that these had a strong desire early on to replace soft PVC. Initially, the task of replacing soft PVC in urological catheters appeared to be easy, but much work had to be done to develop a sustainable alternative. In order to ensure the new alternative material would offer true environmental benefits over soft PVC, many materials were profiled via lifecycle assessment (LCA) studies to ensure only material with a good profile with respect to its impact on the environment could be considered. A life cycle assessment takes into account the impact of a product’s processes for manufacturing, marketing (including transportation and distribution), reuse and disposal. Melitek says the results were clear; the preferred material had to be polyolefin-based due to its good LCA profile. In addition, Melitek points out that polyolefins offer approximately 30% lower density compared with soft PVC, yielding less material consumption and waste. Once the optimal chemistry had been identified, Melitek developed a polyolefin-based elastomer that was specially designed for urological catheters in regard to excellent processing, kink resistance, easy tipping and punching properties while giving the users the characteristic feel of PVC. In addition, and most difficult, Melitek enabled a non-polar polymer to gain good coating properties for the hydrophilic gels typically applied on urological catheters. After more than five years of development and process optimising, a large OEM was able to introduce their new generation of PVC-free urological catheters using Melitek’s unique polyolefin-based elastomer. The new non-PVC catheter was initially introduced in some geographic niche markets, but after some years of favourable supply experience and market feedback, the new non-PVC catheters are said to be phasing out the older PVC catheters in the market. Melitek observes that the successes of the Scandinavian OEMs have lead to a wider trend of PVC replacement in the urological catheters market. Melitek offer a broad range of tubing materials for drug delivery systems, catheters, blood transfusion and dialysis under its Meliflex XT brand. According to Jesper Laursen, co-owner of Melitek: “The good chemical resistances of Meliflex make it superior to PVC for tubing used in administration of unstable solutions such as nitroglycerine or insulin as its absorption and migration rates are low. Furthermore, Meliflex demonstrates very good properties in peristaltic pump applications common in drug infusion and dialysis procedures.” The Meliflex brand of compounds includes those made from polyethylene, polypropylene, TPE, thermoplastic olefin (TPO) and cyclic olefin copolymer (COC).
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ISRAEL Country Focus | A Hotbed for Startups?
Did You Know Israel Produces the Most Medical Devices Per Capita in the World? WORDS | SAM ANSON
Israel is a popular destination for companies looking to gain an edge in R&D and innovation, thanks to a number of competitive advantages—a strong education system with a focus on life sciences and engineering, good economic ties to the USA and Europe, and a sense of local ingenuity. Triventures state that Israel is the birthplace of Given Imaging’s camera-inpill technology, of Syneron’s line of aesthetic lasers and of Teva, one of the world’s largest generic pharmaceutical companies. Medical Plastics News is aware of two key Israeli medtech trade shows, Medical Device Design & Manufacturing Industry (MDDMI) and Medax. MDDMI was last held on October 22, 2012, in Haifa, housing around 60 exhibitors. In his opening letter, the mayor of Haifa described the event as “one of the best opportunities According to Triventures, an Israeli investment company for presenting to the business community the advantages of the focusing on the country’s medtech sector, Israel’s culture of medical devices field in Israel in general, and in Haifa in innovation has produced a large number of start-ups and product particular,” adding that “Haifa has been a pioneer in this field ideas, particularly in medical devices. since Elscint developed its world-class computerised The company’s website states that there are over 1,000 life tomography systems” and that “Haifa is now benefitting from science companies in Israel, with more than 80 new companies the presence of world leaders in the industry, such as J&J, starting each year. The medical device subsector, in particular, is Philips Med, and GE Med”. He also pointed out Haifa’s close substantial, representing 55% of Israeli life science companies. proximity to research institutes such as the Technion-Israel Institute of Technology and the Rambam Health Care Campus as well as a brand new Haifa Notable Medical Device Transactions in Israel Life Sciences Park consisting in total of 85,000 sq m. TRANSACTION PRODUCT YEAR Medax, a similar sized show 2010 Roche’s acquisition of Medingo Diabetes: semi-disposable insulin patch pump 2010 with a co-located conference, is Medtronic’s staged-acquisition of Biocontrol Implantable electrical stimulation technology 2009 Medtronic’s acquisition of Ventor Second generation transcatheter aortic valve held each year in Tel Aviv. Event 2008 St. Jude Medical’s acquisition of MediGuide Sub-millimetre-sized sensors which enableminimally sponsors include large OEMs invasive intra-body navigation like Abbott, Coloplast, GE Medical’s acquisition of Versamed Respiratory: portable ventilator technology 2008 Covidien, Johnson & Johnson Johnson & Johnson’s acquisition of Omrix Surgical: Biologic-based haemostats 2008 and Teva. Boston Scientific’s acquisition of Remon Medical Wireless devices which monitor physiological parameters, stimulate tissues or organs, or activate other devices 2007 Selected recent news from Johnson & Johnson’s acquisition of Colbar Dermal filler, wrinkle correction, and alveolar bone selected Israeli manufacturers regeneration technologies 2006 includes the fact that Stryker’s acquisition of Sightline Endoscope technologies 2006 NeuroQuest has begun clinical Kyphon’s (Medtronic) acquisition of Disc-O-Tech Orthopaedic: minimally invasive vertebral compression Medical Technologies fracture products 2006 trials for a diagnostic blood test Edwards Lifesciences’ acquisition of PVT Catheter-based approach for replacing heart valves 2003 for Alzheimer’s and that Stimatix GE Medical’s acquisition of Elscint Imaging: nuclear medicine and MRI 1998 GIis is looking for partners to GE Medical’s acquisition of Elbit Medical Systems’ Imaging: cardiac ultrasound technology 1998 help develop its stoma device Diasonics division Johnson & Johnson’s acquisition of Biosense Electrophysiology mapping and ablation technology 1997 for patients who have had their Medtronic’s acquisition of Instent Coronary stent technology 1996 colon removed.
Israel is known to be a hotbed for medical technology start-ups and innovation. Life science exports are worth US$6 bn a year and the country ranks first in the world in terms of medical device patents issued per capita. As a market, US$908 mn worth of medical devices were sold in Israel in 2012 and this figure is projected to grow at an average of 9.6% a year to US$1.4 bn in 2017. A total of 80% of medical devices were imported in 2012, with 41.3% coming from the USA and Germany in 2011 (source Espicom).
MARCH-APRIL 2013 / MPN /37
Trade Show | UK Medical Technology Debut
Representing a £16 bn Industry Growing by £1 bn a Year At the time of going to press, a new free-to-attend medical technology trade show and conference, Med-Tech Innovation Expo, was due to open its doors on April 10-11, 2013, at the Ricoh Arena in Coventry, UK. One area of particular interest to the medical device manufacturing community is an area of the trade show floor dedicated to medical technology and bioengineering research from the UK’s leading universities. Recent innovations from the UK’s universities is published on the following eight pages accompanied by news from selected exhibitors. UK Medical Technology Posts Record Results, Says ABHI The UK medical technology industry has defied the continuing economic gloom to post record sales and employment, according to government figures released in December. The new data, compiled annually by the UK government’s Department of Business, Innovation and Skills (BIS), show that the medical technology industry’s turnover was £16 bn in 2011, an increase of £1 billion, or 6.25%, compared with the previous year. Association of British Healthcare Industries (ABHI) chief executive Peter Ellingworth (pictured) commented: “British medical technology is first and foremost a human industry; one where world class scientists have ideas to solve medical needs, engineers make these concepts a reality and people create the final products which we take to the world.” He added: “This creates opportunities for fresh thinking and constant innovation from the drawing board to factory floor, ensuring what the industry produces continues to be valued by customers.” The BIS statistics show that the medical technology is now the largest employer in the UK’s life science sector and the industry now directly employs 71,000 people. The industry is described as one which is geographically diverse, with employers situated as far afield as the highlands of 38/ MPN / MARCH-APRIL 2013
<< ABHI’s CEO Peter Ellingworth describes British medical technology as a “human industry” which “creates opportunities for fresh thinking and constant innovation”. >> Scotland and Plymouth in the south west of England. Large employers are also found in traditional sites of heavy industry including Hull in the English county of Yorkshire and North Wales. LifeScan Scotland—a member of the Johnson & Johnson family of companies—is one of the largest private employers in the highlands and islands of Scotland and is regarded as a leading medical device
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company and centre of excellence for those working in the field of diabetes. Over 1,000 people are employed at the company’s facility in Inverness. With a focus on future development, LifeScan is committed to “creating a world without limits for people with diabetes.” LifeScan is said to rely on outstanding research and development professionals, like those in Scotland, to realise this vision. Another UK device manufacturer, BD, is one of the largest employers in Plymouth and one of the largest users of medical plastics. Their plant manufactures a broad range of blood collection products and systems including BD Vacutainer blood collection tubes for haematology, coagulation and special chemistries, supplying the NHS in the UK, as well as countries across Europe and around the world. The Plymouth facility employs approximately 720 people. The medtech industry also supports a workforce across different disciplines, with R&D, engineering and manufacturing all taking place in the UK. One example of this is Eschmann, a medtech company with all aspects of its business taking place in the English county of West Sussex. Eschmann is the UK’s number one manufacturer of medical solutions in operating theatre tables and instrument decontamination (predominantly in primary care and dental environments). In the past year the company won a significant contract to supply operating theatre equipment in Iraq, proudly helping to rebuild the Iraqi health service. Eschmann as a company says it strives to prove that a tag-line of “British-made” stands for the highest quality, yet still cost-effective, manufacturing. Two companies celebrating a highly successful 2012 are The Binding Site and Physiological Measurement. Despite a challenging global economic environment that continues to impact Europe and the USA, 2012 has been very successful for The Binding Site Group with increased growth and sales, particularly in the Middle East and Japan, for a company already exporting over 90% of its products. CEO of The Binding Site, Charles de Rohan, said: “2012 was a year of continued investment for future growth and expansion. We made a significant investment in new staff, both in the UK and in our overseas
offices, in the areas of research, new product development and clinical education. We purchased new equipment to facilitate faster product development as well as initiating a manufacturing process review that is already yielding improved efficiencies in production.” Physiological Measurement is an awardwinning medtech company based in the English county of Shropshire that is also thriving despite the harsh economic climate. The number of staff on the payroll has doubled year-on-year since the company was founded in 2006, and all profits have been re-invested to continue growth. Jon
MED-TECH INNOVATION Pither, director of Physiological Measurement commented: “PML are an example of how innovative, private companies can bring significant benefits to NHS partner organisations. We deliver a vertically integrated model of care. Our Community Diagnostics services offer patients hospital-quality care close to home and this now extends into their home with telehealth, our innovative software also and enables all their results and images to be accessed by community clinicians and those in secondary care quickly, when required.” ABHI: Stand A3 www.abhi.org.uk
Renfrew Debuts New Children’s Wheelchair Design UK product design consultancy Renfrew, in partnership with the UK’s publicly funded National Health Service (NHS), recently unveiled modular children’s wheelchair Chair 4 Life (C4L), designed to address the unmet needs of disabled children and young adults. The C4L initiative was developed by the NHS’s National Innovation centre (NIC) in response to clear statements of clinical need from users, carers and health experts.
The priority need was identified by a government report to create a specification for a wheelchair that would be easily adaptable for a growing child, improve quality and provision of equipment, promote independence and improve a child’s quality of life. With close teamwork and engagement with users and key stakeholders, Renfrew’s inclusive design approach identified how best to address the usability problems to ensure that the chair design prioritised needs of the users and carers first, but also radically redefined possibilities for prescription, manufacture and supply. The resultant C4L presents the concept of a compact universal, modular wheelchair system allowing wide specification to cater for the physical and social demands of a user’s life, capable of addressing the needs of at least 80% of paediatric users aged 4 to 18 years for powered wheelchairs. Emphasis has been placed on producing a user centred design that adapts to an individual’s growing needs, with a seat and components that grow with the child, yet is compact and lightweight. Renfrew: Stand 15 www.renfrewgroup.com Continued on page 40
MARCH-APRIL 2013 / MPN /39
Continued from page 39
Trade Show | UK Medical Technology Debut
ASTM Releases New Packaging Dye Penetration Test Standard
According to independent medical device and packaging testing experts Anecto, based in Ireland, medical device companies need to be aware that a new packaging test method has been released, ASTM F1929-12 for dye penetration. This new revision to the standard now includes three dye application methods. Method A is the injection method, as per the previous revision, method B is the edge dip method and method C is the eyedropper method. Method C requires the package to have an unsealed area beyond the outer edge of the seal. Project manager at Anetco Noel Gibbons said: “These test methods are intended for use on packages with edge seals formed between a transparent material and a porous sheet material. They are limited to use on porous materials which can retain the dye penetrant solution and prevent it from discolouring the seal area for five seconds. This new version of the standard also clarifies the duration that the dye penetrant must be in contact with the sealed area.” Anetco: Stand 54 www.anecto.com
EU Electronic Labelling Reg in Force UK-based medical device consultancy Advena have shared their monthly regulatory update with Medical Plastics News. The update is usually only available to Advena’s customers. The lead item in the update is news that the EU electronic labelling regulation came into force on March 1, 2013. The rule allows manufacturers of certain types of medical devices and accessories to provide electronic instructions for use if they wish and lays down requirements which must be met in order for this to fulfil the requirements of the Medical Devices Directive. EU regulations are directly applicable in UK law and do not therefore need to be 40/ MPN / MARCH-APRIL 2013
transposed into domestic medical device regulations to take effect. The provision of instructions for use in an electronic form can be beneficial for certain professional users and the purpose of the regulation is to reduce the environmental burden and improve competitiveness by reducing costs whilst at the same time maintaining safety. There is even a suggestion that electronic instructions for use could improve levels of safety, given that electronic storage of information is less susceptible to loss, providing that sufficient safeguards are used. Advena: Stand 13 — part of the Medilink Stand www.advenamedical.com
Instron to Demonstrate Auto Injector Spring Simulator
Essex-based Anglia Ruskin University Medtech Campus Going Strong The newly formed Anglia Ruskin University Medtech campus, the construction of which was announced in May 2012, is going strong. The campus is a partnership between the university and three local councils in Essex in south east England—Chelmsford, Harlow and Southend on Sea. The goal is for the campus to house a cluster of healthcare companies, giving them access to academic and clinical networks, a test bed population of 3 mn patients, sources of funding, and crucially, a single point of access to all the resources required to deliver the development and uptake of business ideas across the healthcare system. Three sites are being developed across Essex, one in each council’s geographic area. As many as 120 acres of land has been identified in total to accommodate 1.7 mn sq ft of floor space. At the recent Healthcare Innovation Expo 2013, held in London in March, the MedTech cluster launched its business services package to attract companies to set up operations at the cluster. The organisers hope that the campus will act as a catalyst for innovation, supporting the commercial exploitation of ideas through a portfolio of services offered domestically and internationally. Anglia Ruskin University: Stand U5 www.anglia.ac.uk.com
US testing equipment manufacturer Instron will be demonstrating how springs for auto injector parts can simulated on its E1000 range of machinery. For more information about the application please turn to page 50 in the robotics and automation feature in this issue. Instron: Stand 17 www.instron.co.uk SynergyHealth Offer Gamma Radiation Indicators Of interest to manufacturers of plastic devices for which there is a chance of accidental multiple sterilisation will be UK-based sterilisation services company SynergyHealth’s gamma radiation indicators. The products will be of interest because there have been reports of growing concern among manufacturers of single use disposable plastic devices that hospitals may accidentally re-sterilise products. Resterilisation of plastic products not intended for such can lead to degradation of polymers and substandard—and sometimes dangerous—performance. SynergyHealth’s gamma radiation indicators change colour following gamma or e-beam sterilisation so that sterilisation operators can see whether a batch of products have been sterilised. SynergyHealth: Stand 43 www.synergyhealthplc.com
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Midas Acquires New Haas Machining Centre UK-headquartered reaction injection moulder Midas has published the following story on its website regarding its newly acquired Haas machining centre. “Back in 1997 Midas purchased our first CNC machine tool, it was a 1 m Haas VF3 that was over-badged by Mikron. Selected for its size, type, price and ease of use it was the machine that saw us enter the computer aided engineering era and as a result things changed forever at Midas. The days of multiple craft patternmakers working by hand from 2D paper drawings were numbered and we began the journey into CADCAM and unattended CNC machining. Then the door to complex machining, tight tolerances and rapid turnaround was opened to us. Now in December 2012 we see our old VF3 leave Midas to be replaced by a Brand New Haas VF4SS.
As part of our ongoing investment plan we felt 15 years was long enough for this machine and it was time to upgrade so the addition of another high speed VF4SS seemed logical. Our machine shop has multiple large machines ready to run 24 hours a day, seven days a week, cutting any material that's necessary to achieve the tightest of deadlines. As we look forward to seeing another shiny precision machine tool arrive we will be sad to see our first machine leave us, the last 15 years has seen many changes and much expansion happen at Midas, let's hope our new VF4SS brings us as much luck as our old VF3 has done.” Midas: Stand 1 www.midas-pattern.com Ensinger Publishes Updated Engineering Plastics Manual Ensinger, a Germany-headquartered manufacturer of semi-finished plastic stock
MED-TECH INNOVATION shapes including rods and sheets for machining applications, has published an engineering plastics manual. Encompassing 100 pages, the manual contains what Ensinger describes as “references collating specialist knowledge from every aspect of plastics processing”. The manual starts with an overview and direct comparison of materials based on their most important properties, modifications and fields of application. A colour-coded index links this introduction to more detailed information. In the chapters on material selection and further processing, users are provided with facts needed for the construction of components or for machining semifinished materials. This information has been formulated in clearly arranged graphs and diagrams and is backed up by a wide selection of application examples. Ensinger: Stand 15A www.ensinger-online.com Continued on page 42
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Trade Show | UK Medical Technology Debut Continued from page 41
Intertronics Announces Partnership With Liquidyn UK-based supplier of adhesives and associated dispensing equipment Intertronics has announced a new partnership for 2013 with Germany’s Liquidyn, a specialist manufacturer of high precision contactless micro dispensing equipment. Peter Swanson, MD at Intertronics, said: “The partnership with Liquidyn is a most valuable addition to our portfolio for dispensing of materials such as oils, greases, silicones, paint, flux and filled products, as well as adhesives. Once again as a company we are fulfilling the needs of our customers for high repeatability, high accuracy, high speed robotic compatible dispensing systems at reasonable cost.” A flagship product in the IntertronicsLiquidyn deal is the P-Jet CT—a newly introduced high accuracy jetting valve for contactless dispensing of low to medium viscosity fluids at frequencies up to 280Hz. Another is the P-Dot pneumatic system for jet dispensing of dots, beads and lines of medium to high viscous chemicals (including filled materials) in droplet sizes
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from 0.3 mm to 5 mm diameter, and at ranges of 2 mm to 10 mm. Intertronics say they are enthusiastic that the Liquidyn products will aid manufacturers yet again in streamlining production cycles, while enhancing quality and achieving reduced piece part costs. Intertronics: Stand 6 www.intertronics.co.uk
Cranfield Scientists Win £50,000 of Aptamer Business Support Scientists at UK-based Cranfield University have won up to £50,000 worth of business support from UK
biotechnology company Aptamer Solutions. Aptamer Solutions works with nucleic acid aptamers, novel synthetic DNA molecules which are a key component in macromolecular drug development. Cranfield were shortlisted for Aptamer Solutions’s feasibility and collaborative research competition and were invited to present their technology proposal at a workshop in York in December 2012. Cranfield are designing aptamers which will specifically target compounds such as toxins that play a significant role in causing septic shock, the number one cause of mortality in intensive care patients. Medical solutions can be contaminated with endotoxins that may also be present in drinking water. Cranfield’s aptamers will be used to develop point-of-care sensors for endotoxin analysis and can also be attached to filters to remove endotoxins from water and biological samples. The aptamer will also have the potential to be used as an endotoxin neutralising drug. Dr Sam Tothill, reader in Analytical Biochemistry said: “Winning this competition will allow my group to access
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this cutting edge technology and enable us to push the boundaries towards more innovative sensing technology and novel applications.” Cranfield: Stand U1 www.cranfield.ac.uk Measure Surface Roughness with Your Smartphone USA-based manufacturer of measurement equipment Mahr has developed an Android App which lets users measure common surface roughness parameters using their smartphones and other Android operating system devices. The MarSurf One App interfaces via Bluetooth with a Mahr RD 18 Drive Unit and probe to measure the most popular roughness parameters, including Ra, Rz, Rmax, Rt, and Rq. Resulting profiles can be zoomed using multi-finger gestures for instant analysis, saved, converted to PDF files, synched, or emailed for display and analysis on other devices such as PCs. “Using the MarSurf One App with your Smartphone is a very inexpensive and extremely portable way to obtain
surface roughness measuring capability,” said Pat Nugent, vice president Metrology Systems for Mahr Federal. The MarSurf One App can be downloaded from Google Play for Android. A free demo version is available for 7 days, and the full, licensed version can be purchased via the "buy button" for automatic download. Mahr says that no operator training is required as operational elements follow typical and well-known Android user interface styles. The MarSurf One App uses a standard R-profile filter and measures in accordance with DIN EN ISO 16610-21, the standard which specifies how to separate long and short wave components of a surface profile. Mahr: Stand 68 www.mahr.com
Tinius Olsen Introduces MP1200 Melt Flow Indexer Yuvraj Jaipal of Tinius Olsen has written on the company’s website the following report.
MED-TECH INNOVATION “We asked our global customer base what they liked and did not like about our previous generations of melt indexers, we listened to the feedback and implemented the best of the ideas in our MP1200 series. Tinius Olsen is proud to introduce the latest addition to its polymer testing line, the MP1200 Melt Flow Indexer/Extrusion Plastometer. The MP1200 features the latest in melt flow measurement technology and allows operators to quickly and easily set up and perform melt flow tests, according to ASTM D1238, ISO 1133-1, ISO 1133-2, D3364, and JIS K7210. Tinius Olsen: Stand 51 www.tiniusolsen.com Continued on page 44
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Trade Show | UK Medical Technology Debut Continued from page 43
Integrated Technologies Limited Wins Major Cancer Device Order and Establishes US Subsidiary Integrated Technologies Limited (ITL), a UK-based instrumentation design consultancy and manufacturer, has announced that it has won a major order to build, test and deliver UK-based device manufacturer Endomagnetics’ SentiMag instrument for the staging and treatment of a number of cancers. The system is based on magnetic materials rather than radioisotopes, and comprises the SentiMag instrument and its magnetic tracer Sienna+ to locate lymph nodes involved in the spread of cancer. The order, for 35 SentiMag instruments, represents the largest so far, demonstrating a high level of success and growing demand for the system. Established in the UK for over 35 years, ITL has built a solid reputation as the market leader in the design and manufacture of medical diagnostic and analytical instruments. Tom Cole, CEO of ITL, commented, “We support customers such as Endomagnetics throughout every
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this exciting technological advance. In March the company announced it had registered a US subsidiary, ITL (Virginia), in November 2012. ITL: Stand 14 www.itl.co.uk
stage of the concept, design, development, prototyping and manufacturing cycle. Being a relatively small company has distinct advantages when it comes to being dynamic and flexible.” The Endomagnetics’ solution provides much-needed flexibility and control in the fight against breast cancer. Melanoma and colorectal cancer sufferers are also likely to benefit from
MPA Founder Writes About UK Tax Relief on R&D Spend UK-based MPA Group is a firm of accountants and tax consultants specialising in helping innovative companies to take full advantage of the UK’s R&D tax relief scheme. Mike Price, founder of The MPA Group, was one of the first tax specialists to focus on R&D tax relief and the firm say it is, based on the latest data from the UK government, the fastest growing in the field. Many business owners are unaware that they qualify for R&D tax relief and they mistakenly assume that R&D is all about technicians in lab coats with clip boards measuring things. So far, as the scheme goes, R&D is
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really about product development and competitiveness. Mike says that if a business can answer the following questions then they are likely to have a claim. “Are you working on improvements to your products or services in order to make them more attractive to your customers? Do you meet previously unforeseen technical challenges (in a field of science) as you try to realise your improvements? Field of science is very broadly defined and will encompass most aspects of work in the plastics sector. Do you take risk and incur costs to overcome the obstacles? Is resolution of the problems not already reasonably accessible in the public domain?” Claims are said to average over £40,000 and can be backdated two years. The MPA Group: Stand 55a www.thempagroup.co.uk Nordson EFD Claims Industry’s Fastest Piezoelectric Jet Valves US headquartered Nordson EFD has
announced that they have more than tripled the speed of their Pico series of jet dispensing systems—from 150 Hz (cycles per second) up to a reported industryleading continuous 500 Hz, making the new and improved versions, so the company claims, the fastest piezoelectric valves available to the global manufacturing community. “Making our proven Pico valve technology even faster is the latest demonstration of our 50 years of commitment to developing innovative dispensing technologies which help our customers build their own products better, faster and more cost-effectively,” according to Ken Forden, Nordson EFD’s vice president and general manager. “The fact that the enhanced Pico valves can run continuously at such high speed will enable manufacturers to produce much more product in much less time.” Pico systems use piezoelectric jetting technology to apply adhesives, lubricants and other assembly fluids with exceptional speed, in amounts as small as 2 nanolitres. The company says that because Pico jet
valves do not contact the substrate, they are ideal for applying precise amounts of fluid on uneven surfaces or products with small components, tight tolerances or hard-to-access areas, such as today’s mobile handsets and medical devices. Nordson EFD: Stand 45 www.nordson.com Continued on page 46
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Continued from page 45
Primasil Silicone Update UK silicone compounder and processor Primasil have invested in an automated cutting machine. Coupled with mixing silicone compound on site in the UK, this allows Primasil to compete globally for punched silicone components with material specifically formulated for your application. The news follows the announcement that Primasil is registered with the FDA. At the recent Compamed event, Medical Plastics News learned that Primasil is able to produce silicone mouldings with a shimmer effect, which gives the silicones an attractive “reflective” appearance. Medical Plastics News understands that the effect is the result of the mould design and does not involve any additives, although Primasil have not been able to confirm this information. Primasil Silicones: Stand 41 www.primasil.com LPE Presents on Rapid Prototyping and Additive Manufacturing for Device Design At the time of going to press, Campbell Evans, sales and marketing director at Northern Ireland-based rapid prototyping bureau LPE (Laser Prototypes), was due to present a paper on the role of rapid prototyping and additive manufacturing for medical device designers at 1:30 pm on April 10. The presentation provides both existing and future users of 3D printing technology the opportunity to ask questions and discuss their thoughts on the role rapid prototyping plays within the medical device industry. The presentation focuses on previous projects for companies such as Brandon Medical, MR Solutions, Benedetti and Marvao Medical. Materials swatches and samples from the above mentioned prototyping projects can be viewed at Stand 10. LPE: Stand 10 www.laserproto.com ML Electronics Offer 3D Moulded Interconnect Devices UK-based manufacturer ML Electronics has written about its ability to integrate 3D moulded interconnect devices (MIDs).
3D MIDs are injection moulded thermoplastic parts with integrated electronic circuit traces. They offer a complementary technology to conventional printed circuit boards (PCBs) and are used for dental tools, insulin pens and pumps and hearing aids. Generally, PCBs consist of conductive pathways etched from copper sheets laminated onto a flat non-conductive substrate. The way that PCBs are manufactured—ie using a flat two dimensional substrate—means that designers of electronic devices are faced with design limitations because PCBs can only be two dimensional, mainly squares and rectangles. This means that devices either have to be conventionally shaped, or the space inside intricately shaped devices is not optimised.
Image courtesy of Cicor. 3D MIDs, by contrast, consist of a single moulded substrate into which the circuit of conductive pathways is integrated. Because the electronic aspect is integrated, the substrate can be moulded into interesting and unique shapes, offering space saving advantages for manufacturers. However, the benefits don’t stop there. Medical Plastics News understands that generally, thanks to extremely tight tolerances which can be achieved, structures as small as 150 μm are possible for small quantities. For larger production runs, ie greater than 1 mn, sizes of conductor tracks and the distances between them can be as small as 300 μm. Furthermore, conveniently shaped parts with less components make assembly cheaper and quicker while rendering the devices lighter in weight. A report about 3D MIDs was published in the May-June edition of Medical Plastics
News. Back issues are available on request. ML Electronics: Stand 16 www.ml-electronics.co.uk Dyne to Present Paper on Adhesion of Plastics Chris Lines, managing director of plasma surface treatment equipment supplier Dyne Technology, will be taking part in the two day conference at MedTech Innovation Expo. He will present a paper entitled Adhesion to Plastics in Medical Device Manufacture which will explain how his products can provide an alternative method for bonding, printing or coating plastics and rubber components. The paper will cover three main areas. First, it will look at why it can sometimes be difficult to achieve good adhesion to common polymers which tend to have a low surface energy. Second, it will investigate ideal surface properties for optimum adhesion. Third, he will look at ways of improving adhesion. Dyne: Stand 28 www.dynetechnology.com Oliver-Tolas Expands Michigan Facility Healthcare packaging manufacturer Oliver-Tolas has announced a US$1.3 mn investment at its facility in Grand Rapids, Michigan, USA. The investment includes a manufacturing area expansion, additional cleanroom installations and the modernisation and expansion of its packaging development and technology centre. The manufacturing area expansion has added 40,000 sq ft to the existing 140,000 sq ft of production space. There are also plans to install cleanroom capabilities for pouch production at the Grand Rapids facility and its sister facility in Feasterville, Pennsylvania. “For many years, we have been serving a specialised customer base who values sterile-grade materials produced in a cleanroom,” said Jeff Murak, VP of sales and marketing. “Now that customer base is growing to include a broad base of medical device manufacturers and we are excited to be expanding our cleanroom capabilities to meet the growing demand.” Oliver-Tolas: Stand 38 www.oliver-tolas.com MARCH-APRIL 2013 / MPN /47
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Robotics and Automation | Efficient and Fast High Volume Manufacturing
Specialist Automated Machinery for Handling High Volume Pipette Tips and Reaction Vessels German manufacturer of robotics Waldorf Technik has recognised the importance of automated high volume injection moulding systems, especially pipette tip manufacturing, by developing a dedicated automation machinery concept, Vario Tip. The concept is outlined in detail in a paper which is available from the editor at email@example.com.
<< Waldorf Technik’s Vario Tip automated equipment is specially designed for handling high volume plastic mouldings like those used for pipette tips. >> The paper recognises key technical challenges faced by manufacturers and outlines how its Vario Tip concept solves these challenges. In particular, it outlines how to achieve high specification quality requirements while ensuring optimum levels of productivity for what it describes as “massive” volumes. The paper summarises the challenges involved as follows. First, there are the challenges related to the specifications of the part itself with regard to dimensions, straightness and surface defects. Secondly, there are challenges with the handling and packaging which often demands traceability down to the cavity level. There is also a challenge with the operating environment to ensure contamination-free
Cleanroom compatibility means paying production which then brings with it a attention to the details which contribute battery of GMP standards. Last and to contamination so that no particulates certainly not least is the sheer volume are expelled into the atmosphere. It also associated with modern production means fully contained use of air or concept, having short cycle times and as elimination of air usage altogether. Equally many as 32, 64 or even more cavities. The important is ensuring low noise emissions sum of all of these factors adds a degree of to enhance the work area. Most of the difficulty which only an efficient and high performance drives incorporate reliable automation system can overcome. water cooled servo motors and linear It then goes on to say how its Vario Tip drives to reduce the radiant heat concept, which has been internationally expelled into the machine room. After all, patented, can be used to develop a heat dumped in the cleanroom is only solution to these challenges. The process removed with expensive air conditioning begins with getting a definition of the and water cooled heat exchangers are process—in other words, establishing a much more efficient and operate at a clear picture of the needs of a new robotics system—understanding the cost of fraction of the cost. The Vario Tip concept allows for a quality, the environment, and productivity vision inspection system to check, reject and efficiency. and even replace with like cavity numbers if Once this has been framed, the solution desired; all before population of the racks can be tapered to a manufacturer’s needs. so that only top quality parts are placed in This involves understanding the capabilities the rack for processing. and technical specifications of Waldorf’s The concept can be adapted to include robots. The description, according to the the packaging of the rack into the so called paper, is that this involves “high speed, “selling unit packages”. This may include precision take-out devices to remove parts everything from “bulk pack” to multi-tier from the mould with a minimum of racks in a blister pack with customised foil encroachment on the mould open time. sealing. Waldorf Technik say their technical Extremely dynamic acceleration and solutions to these requirements are as many deceleration is made possible through the and varied as the customers who use them. use of lightweight yet stable alloy and composite materials. In many cases, the dynamic motion allows a certain amount Table 1: Steps for Defining of overlap of the mould and robot motion Waldorf Tecknik’s Vario Tip Process to safely minimise the mould open time.” The paper goes on to say: Cavity specific handling throughout the process “The configuration and features Production of pipettes with and without filters of the cell are very much Vision inspection of the finished pipettes application specific and while Check dimensions, flash black spots, run-out and filter placement many pipette solutions share Reject defective parts some common attributes, each Replace with “like cavity” good parts system is custom tailored to the Placement of pipettes in racks Variety of racks possible customer’s needs for product Maintain cavity integrity mix, secondary operations, Placement of bar code label or radio frequency identification (RFID) tag handling and packaging needs Palletising of racks and labelling.” Placing in stacks or blister packs It also makes mention of Sealing of selling units cleanroom compatibility and Labelling consideration of the production cell’s footprint. Continued on page 50 MARCH-APRIL 2013 / MPN /49
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Continued from page 49
Maximising Yields on Automated Dispensing Lines Dispensing equipment manufacturer Nordsen EFD has kindly provided the following information about how to maximise yields on automated dispensing lines. Adhesives, lubricants and other assembly fluids are used to build a wide variety of medical devices. On automated production lines, these materials are often applied with pneumatic dispense valves. Although dispense valves may be a small part of the overall assembly line, choosing the valve that is most appropriate for a specific application can significantly increase yields while reducing the number of rejects and while cutting assembly costs. Valve integration can be streamlined and production lines kept running at maximum efficiency both by carefully matching the valve to both the application and the fluid being applied, and by using a dedicated valve controller to simplify setup and operation. Matching the valve to the application: Although it is possible to achieve similar results with different valves, some designs will perform better than others in specific applications. A diaphragm valve, for example, is a good choice for UVcure adhesives because this design will minimise turbulence which could produce bubbles in the fluid. There are no seals to wear out and leak, and the fast, clean cutoff will eliminate drips that could cause functional or cosmetic damage to parts. For reactive fluids like cyanoacrylate or “super glue,” the same diaphragm design with wetted parts made of an inert ultra high molecular weight polymer will keep fluid from curing inside the valve. When making very small deposits or dispensing watery fluids like solvents, a needle valve is typically recommended. Because the needle seats in the tip adapter, there is virtually no dead fluid volume remaining between shots. A well-designed needle valve with self-adjusting packings to compensate for wear can provide tens of millions of trouble-free cycles before maintenance is required. For thicker fluids and filling applications, a piston valve with an adjustable flow control will provide good results. The piston design produces a faster flow rate than diaphragm and needle valves, and a
snuffback action as the valve closes will << A selection prevent fluid from dripping or oozing of Nordson between cycles. EFD’s dispense These are just three general-purpose valves in designs. Other configurations include action with precision spray valves for critical coating plastics applications, aseptic valves for dispensing including sterile fluids, and piezoelectric valves disposable capable of speeds as fast as 500 cycles contact lens per second. trays (topt) Valve controllers maximise accuracy and a and efficiency: Once the valve has been respiratory selected, the most effective way to mask integrate it into the assembly line is with a component dedicated valve controller. (bottom). Pneumatic dispense valves use a >> combination of fluid pressure, valve open Factors such as drug time, and tip size to determine the amount viscosity, needle of fluid applied. Higher pressures, longer diameter and the type of lubricant used all open times and a larger tip will produce play a role in determining the rate of drug larger deposits; lower pressures, shorter delivery, which is the key variable of times and smaller tips will result in smaller interest. Different springs can be simulated deposits. Once initial setup has been and the effects analysed using Instron’s completed, valve open time can be adjusted in increments as small as 0.001 s to machine, along with the appropriate control software. finely tune the size of the fluid deposit. Manufacturing personnel sometimes ask why a dedicated valve controller is recommended, when they could actuate the valve by indexing or other mechanical means, or by linking it to an existing << The rate of drug delivery in an auto programmable logic controller (PLC). The injector is controlled by the spring simplest explanation is that a dedicated mounted behind the syringe. >> controller is the easiest, most accurate way to adjust valve open time, and it puts this << Instron has capability right at the dispensing station. By developed testing supplementing—rather than replacing—a technology which PLC, a valve controller can provide several allows designers important benefits. to simulate Instron Machine Simulates Spring in Automated Testing of Auto Injector Prototypes US-headquartered testing equipment manufacturer Instron has developed a dynamic test method which replicates an auto injector spring—the ElectroPuls. The company has stated that the technology will be useful for designers as it offers them a way around the problem of having to iteratively test large numbers of springs when developing new auto injector device designs. As a result, the development is expected to save significant time and reduce a perceived level of tedium traditionally involved with auto-injector pen design.
different springs without needing physical specimens, accelerating the process of testing prototypes. >> Instron have developed this application in response to the trend for more and more patients being treated at-home. With this, medical device companies are catering to an increasing demand for safer, more user-friendly biomedical solutions. According to Instron, the company’s recommended control software is clever enough to handle complex problems related to the idea that any tests need to Continued on page 53
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%NGCPCPFGHƂEKGPVEspecially in sensitive sectors such as medical technology or optics, equipment must be 100% reliable. This begins with production of the relevant high-quality plastic parts. With us as your partner, you are always on the safe side: thanks to many years of experience with clean room applications and specially equipped ALLROUNDER injection moulding machines – also available as unique stainless steel versions. We ensure your product quality and
ARBURG GmbH + Co KG Postfach 11 09 · 72286 Lossburg Tel.: +49 (0) 74 46 33-0 Fax: +49 (0) 74 46 33 33 65 e-mail: firstname.lastname@example.org (GB) ARBURG Ltd. · Tachbrook Park Drive · Warwick CV34 6RH · Tel.: +44 (0) 1926 457 000 · Fax: +44 (0) 1926 457 020 · e-mail: email@example.com
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Robotics and Automation | Efficient and Fast High Volume Manufacturing Continued from page 50
increased, making the test significantly more take into account the fact that the machine Input and output of the capillaries are efficient. Testing can, however, be is simulating a spring where the applied flexible. The Epson Scara robot puts the performed manually at any time if required. filled capillaries on a sample carrier, installs load and injection time are key variables. When used in combination with Zwick’s Instron solves this control challenge them in a disposable cartridge or deposits testXpert II testing software, the system is using Modal Control, an advanced feature them for shock freezing into an integrated able to fulfill FDA requirements on of the 8800 controller which creates a Dewar vessel in liquid nitrogen. Handling, electronic records and electronic signatures dispensing and QC functions of the “composite” channel to allow the applied stipulated in title 21 CFR Part 11 of the load to vary with actuator position. The pipetting platform can be combined with code of federal regulations. user needs to specify the initial preload each other and programmed in various and spring stiffness in order for the system sequences, which makes it possible to adjust << This equipment to adjust itself based on the actual load to new tasks and products at any time. allows auto injector For the production of such medical seen by the syringe. The resultant load and manufacturers to products, it is important that relevant batchsystem displacement data is acquired by test their products related data, like for the 8800 controller at a rate of up to 5 kHz. for quality control. example the capillary A force vs time graph is produced and Automation is diameter or drop size dispensing time and stall force of the enabled thanks to and the appertaining syringe is calculated. The user can then computer controlled camera images can be determine if the chosen parameters for software and robotic recorded and archived. spring stiffness and preload have yielded feeding systems. >> an ideal auto-injector dispensing time for a << Epson’s Scara given drug. cleanroom robot Automated Camera Controlled has been used by Pipetting of Fluids During Zwick’s Automated Testing of Xenon for a cameraAssembly Finished Auto Injectors controlled pipette US manufacturer of manufacturing German testing equipment dispensing robots Epson has published a case study manufacturer Zwick has written about its equipment designed to manufacture illustrating how its Scara robots have equipment for the automated testing of cartridges for in-vitro diagnostics. >> been used for the automatic pipetting of finished auto injectors for quality control droplets of fluids during the manufacture applications. The prime considerations of cartridges for in-vitro diagnostics in a Fipa’s Sprue Gripper “Senses” Low when testing these products are cleanroom. Tolerance Sprue Positions reproducibility of results and reduction of The robots have been used by Xenon German manufacturer of end of arm operator influence. The standards relating based in Dresden, Germany, which makes tooling Fipa is offering customers a new to quality assurance tests on insulin pens and carpules are EN ISO 11608 Parts 1 to 3. automation equipment for assembly, testing sprue gripper, the GR04.101A. According and automated packaging. Xenon have to the company’s CEO, Rainer Mehrer, a Zwick’s system is based on a Zwicki-Line built a camera-controlled automated key feature of the gripper is its large sensor Z0.5 TN table top testing machine with pipetting system for the manufacturer of additional torsion drive. This allows the area for improved sprue detection and the cartridges with a footprint of just one various operations of the pen to be tested control, which allows the gripper to adapt square metre. using a single device. The testing machine to low tolerance sprue positions, regardless During automated pipetting of measures the dosage setting, injection force, of the position of the sprue in the mould. substances, Epson says that a dosing needle stroke and plunger-rod thrust in one The gripper exhibits a strong gripping must be positioned accurately, even if the continuous process. Test methods on the force, 22 N, to encourage a secure grip at two test axes can be modified and combined target cannot yet be defined exactly. In fast cycle times. It is coated with a robust addition, it must be possible to implement as required. If tests are to be performed with Hartcoat treatment which gives a long cycle such a task effectively and affordably. a cartridge installed, an optional laboratory life and high wear resistance. Thanks to its According to the case study, Epson’ s scale option which measures the insulin dose compact construction, low weight and large Scara cleanroom robot carries a mobile delivered can be fitted. jaw opening, Fipa says the new gripper can camera that can inspect the different areas Automated specimen feed can be easily be integrated with existing Fipa and makes it possible to correct positions. achieved using Zwick’s roboTest R handling gripper modules. Even if the target part is not always system (see image in middle column) plus << Fipa’s latest positioned in exactly the same place, the autoEdition2 automation software. The gripper can camera work makes it possible to move to pens are fed into the testing machine from pick up a sprue dosing or gripping positions accurately. A the magazine (capacity up to 50 from a low second camera carries out quality controls. specimens) and the test is started. Variation tolerance It checks whether the filled drop is in the in test results caused by operator influence mould. >> correct position and has the required size. is eliminated and specimen throughput MARCH-APRIL 2013 / MPN /53
PRODUCT FOCUS | Artificially Growing Human Tissues
Polymers Help Sow the Seed of Life Bioprinting Sirris, Belgium’s national research institute, has provided information on bioprinting—the ability to print various biological materials and cells along with tissue scaffold materials. It credits the Wake Forest Institute for Regenerative Medicine in Winston Salem, North Carolina, USA, as a leading research institute on the subject. Sirris is a leading centre for additive manufacturing—the ability to print layers of various materials such as polymers, ceramics and metals into intricate three dimensional objects. Bioprinting is an arm of additive manufacturing. In general, resorbable polymer scaffolds are printed using stereolithography and then injected, or seeded, with stem cells from the target organ. Additive manufacturing is crucial to the process because it allows an individual product to be made from a single data file. The data file is taken from a CT scan of the patient’s organ, providing the required geometry to give a perfect fit. The goal of printing biological materials is to produce functional cells, tissues and organs to repair, replace or enhance biological function that has been lost by disease or injury. The method is seen by many as the most promising solution to meeting high demand for suitable organs for transplantation. To illustrate the gap between demand and supply, the number of available kidney donors in the USA stood at around 5,000 in 2003 while the number of patients needing a kidney transplant was around 55,000. The average cost of a single kidney was US$30,000 (source Sirris). In terms of livers, there were 114,300 people waiting for a transplant in 2012. To give you an idea of how new this technology is, the method used for bioprinting, stereolithography, was invented in 1984. But it was not until 2004 that the first technology to engineer 3D tissues with cells and without the help of a scaffold was developed. In 2006 trials were undergone to implant the world’s first “3D printed” artificial bladders into seven patients. Medical Plastics News has not been able to confirm whether these trials were successful. To follow were the first 3D printed
Regenerative medicine and tissue engineering are mainstream areas of scientific research. In the USA alone at least US$200 mn is given each year to research institutions in public funding. Specialist polymers play a crucial role as materials for synthetically manufactured organs like the skin, trachea, bladder and liver, as well as artificial blood vessels and nerve guides. Resorbable polymers are used to make the cell scaffolds on which the organs are grown.
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nerve guides in 2009 and blood vessels without the use of a scaffold in 2010. And in 2011 and 2012 scientists built the first patches of cardiac and lung tissues as well as the first artificial trachea to treat cancer. Looking forward, Sirris expects bioprinting to be capable of producing simple tissues for implant in a couple of years, albeit for clinical research purposes. Lobs or pieces of organs should be possible by 2030 or possibly longer. To demonstrate the 3D printing procedure, Sirris quotes the artificial bladder produced and implanted in 2006 from the Wake Forest Institute for Regenerative Medicine. The process was called the Orthotropic Neobladder Procedure. Transplantation was successfully done that year on seven patients although whether there was a follow up has not been identified. Other successful examples include the development of an artificial liver using a 3D printed collagen skeleton seeded with human liver cells. The scaffold is then placed in a bioreactor to give it nutrients and oxygen and stimulate cell growth.
<< Left: An example of living cells produced via 3D “bioprinting”. >>
<< Right: An artist’s impression of the possibilities of bioprinting. >>
The world’s first artificial trachea was built using additive manufacturing at the University of Karolinska in Sweden. The trachea can be used to replace cancerous trachea. The material used is a synthetic nanocomposite polymer. A portable skin printing system was successfully tested on mice in 2011. It uses living cells to create tissue-engineered skin grafts to cover burn wounds and is expected to be used to treat injured soldiers in the battlefield to stop bleeding without having to wait for an ambulance. Fibroblasts and keratinocytes are printed directly on to skin. Suspensions with cells are mixed with fibrinogen, type 1 collagen and thrombin at the moment of application.
REGENERATIVE MEDICINE In terms of bioprinting equipment, modified 3D printing materials at the same time to produce constructs with locally machines are used, including those from inkjet printing differing physico-chemical properties, thereby offering a further companies Canon, Epson, HP and Lexmark, as well as USA-based improvement to biomimicry strategies aiming at matching the companies Sciperio, Therics, Envisiontec, Neatco and Sandia NL. natural milieu of the tissue to be regenerated when designing a Researchers expect there to be ethical and moral arguments scaffold. Most recently, a few open source systems have been also against organ printing, particularly from the perspective of developed, promising to abate the initial investment costs. cell cloning. Soon, Sirris aims to be able Outlook: Despite these to use a bioprinter to print successes, a number of living tissues. challenges are posed to the Lorenzo Moroni, assistant biofabrication community to professor at the University of empower extrusion based RP Twenteâ€™s tissue regeneration platforms. department in the A better control over the Netherlands, has kindly heating and extrusion provided the following mechanism is needed, so that account of additive also thermoplastic polymers manufacturing of with a lower thermal stability resorbable scaffolds. like PLA and copolymers can Three dimensional tissue be easily processed without scaffolds are porous materials concerns over degradation which are able to interact during fabrication. New with cells to let them biomaterials are also needed, proliferate and form a able to display tuneable targeted tissue or organ. The surface properties for a more choice of the most optimal dynamic interaction with cells. additive manufacturing (AM) When mimicking the native technology depends often architectures of tissues and on the desired resolution of organs is considered, a better the scaffoldâ€™s struts, the control over the layer-by-layer production speed, the process should be achieved, versatility in working with allowing the deposition of different biomaterials, and materials on curved surfaces the surface properties of without the need of the scaffolds. supporting structures. << Examples of CT and MRI scanned anatomical models As distinguished from all the Production speed is also of (a, c, e) and correspondent anatomically-shaped concern when envisioning a other AM technologies, extrusionfabricated 3D scaffolds. (a, b) meniscus; (c, d) vertebra; large production of off-the-shelf based rapid prototyping (RP) (e, f) finger joints (taken from [italics start] Journal of scaffolds or of large scaffolds systems offer a control over these Biomaterial Science [italics end], Polymer Edition, Vol with anatomical shapes for parameters at the micron scale, 19, No 5, pp 543â€“572, published in 2008) >> personalised implants. In this without being limited to the roughness of the initial powder respect, the continuous material used in other platforms like development of open source 3D printing and selective laser sintering, or the photosensitivity of systems will facilitate these improvements, as it will be easier to the material required in stereolithography and two-photon access mechanical and electronic components, as well as the polymerisation. software governing the technology than currently available Extrusion-based RP systems have been extensively used to commercial systems. fabricate custom-made scaffolds and modulate their mechanical References are available on request. properties with encouraging results. Several thermoplastic polymers are, in this respect, today available for processing. These Resorbable Polyurethanes Medical Plastics News has learned that in 2010 USA-based comprise poly e-caprolactone (PCL), polylactic acid (PLA), Biomerix was looking into the use of bioresrobable polyurethanes polytrimethylcarbonate (PTMC), polyethylene oxide for dual functional dressings to improve wound healing, terephthalate-co-poly butylene terephthalate, particularly for diabetic ulcers and pressure sores. The researchers polymethylmethacrylate-co-butyl methacrylate, and copolymers hope to use the polyurethane technology to develop dressings thereof, among others. which can be used in negative pressure wound therapy (NPWT) This printing technology has progressed from single-head to while also acting as a scaffold for tissue regeneration. multi-dispensing systems which allow depositing different Continued on page 56
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PRODUCT FOCUS | Artificially Growing Human Tissues Continued from page 55
The broader impacts of this research are in a variety of applications in tissue regeneration and repair for general, cardiothoracic, and plastic surgery; trauma, sportsmedicine, and fracture healing. The novel scaffold technology will be developed within the framework of large scale foam manufacturing methods using industrial foaming and thermal reticulation techniques. This will also reduce the cost of the biomaterial and substantially impact healthcare spending across a broad range of clinical application areas in the US. The Biomerix team was awarded a grant of US$200,000 by the USA’s Small Business Innovation Research (SBIR) award in 2010. In September 2012, Biomerix established a strategic distribution agreement with US cell culture technology supplier Synthecon for Biomerix’s three dimensional cell culture scaffolds. In February 2013, US thermoplastic polyurethane manufacturer Lubrizol announced that it had developed bioresorbable polymers based on a polyurethane chemistry. When asked whether the announcement was linked to the biomerix project or something similar Lubrizol declined to comment. When commenting on Lubrizol’s resorbable polyurethane, Tilak M Shah, CEO and CTO of USA-based processor of medical polymers and bioresorbable materials Polyzen said: “I am somewhat familiar with Lubrizol’s bioresorbable material on a polyurethane platform. They were working on it for a while very quietly until now, and I guess are now ready for the commercial launch.” Regarding Biomerix’s technology, he said: “I am not familiar with
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Bimerix’s grant work. Biomerix’s current wound dressing is based on bio-stable polycarbonate urea polyurethane. The grant is specifically for bioresorbable dressing, so it’s a good possibility they are working with Lubrizol’s bioresobable on urethane platform, which would create a similar foam scaffold.” Spider Silk Garners Growth for Cells According to a report on Qmed.com, researchers from Tufts University in Boston, USA, and the CNRS Institut de Physiques de Rennes in France have written about how implantable devices made from spider silk can spur regrowth of human tissue as they degrade. The report states: “The researchers created the optical devices by pouring purified silk protein solution into moulds for microprism arrays. The speed at which the implants dissolve can be controlled by regulating the water content of the protein solution. Upon drying, the solution dries and forms a material resembling reflective tape.” It goes on to say: “The researchers experimented with embedding the material with gold nanoparticles. When implanted in mice, these implants were illuminated with green laser light, thus heating the implants for use in thermal therapy to combat bacterial infections or destroy malignant cells. At the same time, the implant's optical properties enabled the scientists to monitor the process.” And: “The researchers also experimented with embedding the material with the cancer drug doxorubicin. The drug remained stabile even when the material was heated to 60°C.”
REGENERATIVE MEDICINE Polycarbonates in Bone Repair Scientists at the University of Southampton, UK, have created a new method to generate bone cells which could lead to revolutionary bone repair therapies for people with bone fractures or those who need hip replacement surgery due to osteoporosis and osteoarthritis. The research, carried out by Dr Emmajayne Kingham at the University of Southampton in collaboration with the University of Glasgow, also in the UK, and published in the journal Small, cultured human embryonic stem cells on to the surface of plastic materials and assessed their ability to change. Scientists were able to use the nanotopographical patterns on the biomedical plastic to manipulate human embryonic stem cells towards bone cells. This was done without any chemical enhancement. The materials, including a biomedical implantable polycarbonate, offer an accessible and cheaper way of culturing human embryonic stem cells and presents new opportunities for future medical research in this area. Professor Richard Oreffo, who led the University of Southampton team, explains: “To generate bone cells for regenerative medicine and further medical research remains a significant challenge. However we have found that by harnessing surface technologies that allow the generation and ultimately scale up of human embryonic stem cells to skeletal cells, we can aid the tissue engineering process. This is very exciting.” He added: “Our research may offer a whole new approach to
skeletal regenerative medicine. The use of nanotopographical patterns could enable new cell culture designs, new device designs, and could herald the development of new bone repair therapies as well as further human stem cell research.” The study was funded by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC). This latest discovery expands on the close collaborative work previously undertaken by the University of Southampton and the University of Glasgow. As previously reported in Medical Plastics News, in 2011 the team successfully used plastic with embossed nanopatterns to grow and spread adult stem cells while keeping their stem cell characteristics; a process which is cheaper and easier to manufacture than previous ways of working. Dr Nikolaj Gadegaard, Institute of Molecular, Cell and Systems Biology at the University of Glasgow, said: “Our previous collaborative research showed exciting new ways to control mesenchymal stem cell—stem cells from the bone marrow of adults—growth and differentiation on nanoscale patterns. This new Southampton-led discovery shows a totally different stem cell source, embryonic, also responds in a similar manner and this really starts to open this new field of discovery up. With more research impetus, it gives us the hope that we can go on to target a wider variety of degenerative conditions than we originally aspired to. This result is of fundamental significance.”
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EVENTS medical plastics diary | APRIL-MAY 2013
Plastics trade show April 10-11, 2013 Malmö, Sweden
Medtech trade show April 10-11, 2013 Coventry, UK
Medical plastics open house April 16-17, 2013 Chesterfield, UK
Antec plastics conference April 22-24, 2013 Cincinnati, USA
Regenerative medicine conference April 25, 2013 Sheffield, UK
Medtech trade show May 1-2, 2013 London, UK
Medtech trade show May 15-16, 2013 Lyon, France
Plastics trade show May 7-10, 2013 Kielce, Poland
Plastics trade show—Chinaplas May 20-23, 2013 Guangzhou, China
World’s Largest Technical Plastics Conference Dedicates Afternoon to Medical Plastics The Society of Plastics Engineers (SPE) has earmarked an entire afternoon of its upcoming flagship technical conference, Antec, to medical plastics. Antec will be held in Cincinnati, USA, on April 22-24, 2013. The title of the session is New Technology Forum on Polymers in Health. The contents have been compiled thanks to a joining of forces between the SPE’s Medical Plastics Division, the Engineering Properties and Structures Division and the New Technology Committee. Of the topics to be discussed will be exciting applications made possible with their use. The session will look at how innovation is being done using novel polymers and how the frontiers of regulatory agencies are being challenged and redrafted based on emerging polymers and new applications. On the subject of resorbable polymers, Medical Plastics News asked Len Czuba, former president of the Medical Polymers Division, to recount the most impressive medical plastic technology he’d seen in recent times. The editorial team were glad to hear his response was about a device we had earmarked as a landmark development in the industry —Abbott’s brand new fully resorbable Absorb polymer stent. The stent was approved for sale in Europe last year while clinical trials in the USA began in January 2013. Absorb is a drug eluting fully bioresorbable vascular scaffold for the treatment of coronary artery disease, which is a narrowing of one or more arteries that supply blood to the heart. Absorb is 58/ MPN / MARCH-APRIL 2013
made of polylactide (PLA), a naturally dissolvable material that is commonly used in medical implants such as dissolving sutures. Absorb works by opening a clogged vessel and restoring blood flow to the heart similar to a drug eluting metallic stent, the current standard of care. Absorb then dissolves into the blood vessel, leaving behind a treated vessel that may resume more natural function and movement because it is free of a permanent metallic implant. James Oberhauser, polymer R&D manager at Abbot Vascular, will be presenting a paper entitled The Application of Bioresorbable Polymers to Vascular Medical Devices at the Polymer Applications in Health session at Antec along with Boston Scientific and 3M. At the time of going to press, in addition to James’s presentation, the preliminary line-up was as follows: Putting Electrospun Nanofibres to Work for Biomedical Research, by Younan Xia of Georgia Tech; Resorbable Polymers: Melt Processing, by Larry Thatcher of TESco Associates; Differentiating Biological Response to DES Polymers, by Barbara Huibregtse, biotechnology director at Boston Scientific; Value Driven Engineering and US Global Competitiveness, by Frank Douglas; and Global Regulatory Guidelines for the Design and Development of Medical Devices, by Scott Sardeson, international regulatory manager at 3M.