MPN
MEDICAL PLASTICS NEWS
ALBIS UK CUTS DEVELOPMENT TIME FOR ULTRASONIC SURGICAL SCALPEL ALSO IN THIS ISSUE: Mediplas Preview Multishot Injection Moulding A Guide to Antimicrobials Pharma Polymer Extrusion
ISSUE 7 July/August 2012 WWW.MPNMAGAZINE.COM
MPN
All Medical, All Plastics
Contents 5. Editor’s Letter: Editorial independence Following the Leveson Enquiry, MPN promotes its editorial independence. Page 11
6. On the Pulse: Industry news Medial plastics recycling, UK industry growth and Recently on MPNMagazine.com. 11. Material Diagnosis: Antimicrobials A factual guide to antimicrobial medical plastics written by Sam Anson.
Page 20 Page 28
16. UK Focus: Introduction An introduction from Peter Ellingworth, chief executive of ABHI. 16. UK Focus: Injection moulding Profile of Owen Mumford. 19. In the Zone: Contract manufacturing A sublingual (under the tongue) drug delivery device. 20. Cover Story: ISO10993 colour compounding Albis UK cuts development time for ultrasonic surgical scalpel. 23. Regulation Review: UK focus Selling to the NHS.
Page 51 Page 61
24. Design 4 Life: The IEC 60601 A tool to help you cope with mandatory emissions data for electronic device certification. 26. Doctor’s Note: Clinical help The HealthTech and Medicines KTN as a funding facilitator.
28. UK Focus: Pharma polymer extrusion Sam Anson reports from the University of Bradford’s Centre for Pharmaceutical Engineering. 32. End of Line: Laser marking Laser marking additives are a scratch proof alternative to inks and can be activated without contact and automatically. 35. UK Focus: Mediplas Nearly 50 medical plastics exhibitors are profiled, including those in materials, injection moulding, extrusion, end of line and testing. 48. Clean Machines: Multishot moulding Bill Welch, CTO of Phillips-Medisize, and John Berg, Marketing Director of MGS Mfg Group, give insight into this black art. 57. Product Focus: Minimally invasive devices Catheter coatings — antithrombosis, antimicrobial, lubricious and drug delivery — and hydrogel urological catheters and stents. 64. Folio: High resolution images Objet’s demonstration of medical 3D printing plastics and B Braun’s drug eluting balloons. 66. Events: Diary and roundup Mediplas free conference, first ever World Medtech Forum and Scandinavia’s medical plastics conference.
Online and in digital Cover image designed by Sam Hamlyn. Content courtesy of Albis UK and SRA Developments.
Medical Plastics News is available online, at www.mpnmagazine.com, and in digital (on the iPad, mobile phones and computers). JULY | AUGUST 2012 / MPN /3
MPN | EDITOR’S LETTER
MPN | CREDITS
editor | sam anson advertising | gareth pickering art | sam hamlyn
MPN — Proud to be Editorially Independent On July 6, 2011, the UK’s prime minister, David Cameron, announced to Parliament that an enquiry would be established to investigate the culture and ethics of the British press following accusations that employees of the News of the World newspaper and other journalists had engaged in phone hacking, police bribery and exercising improper influence in the pursuit of publishing stories. The enquiry, led by senior British judge Lord Justice Leveson, finished collecting evidence on June 26, 2012. Among the witnesses interviewed were the prime minister himself, the two previous UK prime ministers, as well as senior executives at the publisher of the News of the World and other leading journalists and celebrities. Although the enquiry is still to make any firm conclusions, the entire process was televised to allow members of the pubic to make their own conclusions. Despite the enquiry lasting over seven months, the focus was almost entirely on the mainstream press — business to business (B2B) journalism remained largely untouched. Indeed, a Google search of the witness statements unearths just one reference to B2B publishing — from Lord Rothermore, the executive chairman of the Daily Mail and General Trust, (DMGT) publisher of the Daily Mail and the Mail on Sunday — two of the mainstream papers under investigation by the enquiry. The reference to DMGT was that it generates 74% of its operating profits from B2B activities — including a majority ownership stake in Euromoney Institutional Investor plc, the publisher of leading B2B title Euromoney Magazine, as well as 70 more. Euromoney has a monthly print circulation of 25,000. Still, the enquiry has stirred debate among journalists. For example, the
Press Gazette, a leading digital website for journalists, has launched its own Journalism Manifesto, which it describes as a pledge to tell the truth, to stop “special favour interests” and implement a ban on “copy approval”. Among other things, the manifesto criticises the practise of editors allowing advertisers to pay to gain preferential mentions in editorial as a consequence of their commercial spend. As an advocate of editorial independence, I am proud to pledge that our editorial policy at MPN is one of complete editorial independence. All articles have been researched, written, and edited solely with the readers’ interest in mind. The main objective is to give them balanced and relevant information to help them on their quest for manufacturing safe and cost effective medical plastic parts which, ultimately, improve a patient’s wellbeing. In this issue, examples of this include my independent guide to antimicrobials on page 11, the development of pharma polymer extrusion on page 28, the fundamentals of multishot mould design on page 54, and the breakthrough of hydrogel urinary stents and catheters on page 62. Any mentions of advertisers in an article is coincidental — although I do inform the sales manager, Gareth Pickering when I commission an article in case the author wishes to supplement the editorial with an advert. Mediplas On a separate note, MPN is proud to be the official media partner of the brand new UK medical plastics trade show Mediplas. A preview of the show and the associated free conference, which is organised by the same company that publishes this magazine, begins on page 36. I urge those who can attend to come along.
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© 2012 Plastics Multimedia Communications Ltd While every attempt has been made to ensure that the information contained within this publication is accurate the publisher accepts no liability for information published in error, or for views expressed. All rights for Medical Plastics News are reserved. Reproduction in whole or in part without prior written permission from the publisher is strictly prohibited.
BPA Worldwide Membership ISSN No: 2047 - 4741 (Print) 2047 - 475X (Digital)
JULY | AUGUST 2012 / MPN /5
ON THE PULSE | Recycling
Plastics from Hazardous Sharps:
The Green Shoots of... Recycling WORDS | SAM ANSON
The healthcare industry lags behind other sectors in terms of plastic recycling — heavy regulation forces hospitals to incinerate biohazardous waste. But surging through the smog of burnt plastic comes ecoFinity Life Cycle Solution, an award winning closed loop recycling scheme from BD in the USA which recovers, recycles and reuses up to 70% of a facility’s sharps waste. Sam Anson, a self confessed recycling nerd, spoke to Ranjeet Banerjee, vice president and general manager of BD’s Medical Surgical Systems unit — the man behind their scheme.
A Late Developer Conventionally, the question of how to handle medical sharps waste has always been simple — incinerate anything hazardous and send the rest to landfill. Environmentally responsible healthcare professionals have probably queried this broad-brush approach. But in terms of plastics recycling, the industry lags far behind other sectors, particularly food and drink packaging and electronic goods — which both have wellestablished recycling schemes. What observers may not realise is that there are significant economic benefits to plastics recycling which are yet to be untapped in the healthcare industry. A healthy price for recycled plastic allows compounders to purchase sorted clean plastic flakes from waste management companies, melt them down, repelletise them and still make a healthy profit when they’re sold on for use in non-medical applications. And the large volumes involved in the medical industry mean that additional costs required for the sterilisation of biohazardous waste can comfortably be incorporated into the margins. That said, in order for a supply chain like this to flourish, plastic must be diverted from the waste stream as soon after use as possible. Achieving this involves a change of culture in persuading regulators and hospital
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managers to allow recyclers to handle sharps waste and other medical plastics. Green Revolution The new scheme from BD (Becton Dickinson and Company) is inspirational. Sharps waste is collected, disinfected, shredded and reprocessed and the regenerated plastic pellets are utilised as material to manufacture << BD ecoFinity is the new plastic products which do not brainchild of BD. >> need to be made from virgin plastic. But what is perhaps most astonishing is the sheer scale of BD’s progress. Ranjeet Banerjee confirms: “In just one year our BD ecoFinity programme has collected over one million pounds [454 tonnes] of material destined for landfill or incineration.” Some of the recycled plastic is being used to manufacture new BD Recykleen sharps collection containers (see far right image).” The programme has been in operation for almost three years but it started from a relatively small base. Ranjeet explains: “BD aims to give our customers comprehensive solutions. We want to offer them products of a high standard clinically which incorporate environmental benefits without incurring incremental costs. Our BD ecoFinity recycling programme offers an eco-friendly improvement to existing supply agreements.” Robust and Reliable — A Safe Process The biggest barrier to the scheme was a perceived risk among healthcare professionals around toxicity. Ranjeet’s attitude to this is reassuring: “To do this well and to do it reliably requires expertise, and it must be done extremely carefully. We have invested a lot of time and care working with our waste management partner in ensuring that the process is robust and is carried out safely. As I said earlier, our goal was to create an environmental solution without compromising cost or clinical safety.” When selling medical sharps to its customers, BD
ON THE PULSE
348,500 pounds [159 tonnes] of sharps regulated medical waste collected and processed since their pilot scheme began in August 2011.”
<<The BD ecoFinity programme was recognised with an award at the Society of Plastics Engineers (SPE) Global Plastics Environmental Conference (GPEC) in Atlanta, USA, in late 2011. >>
offers to arrange for them to be collected after disposal using a similar process to the customer’s current process. After collection, the waste is disinfected, shredded and the plastics are granulated into confetti-like “flakes” before being melted down and compounded into new pellets. Rapid Adoption Judging by the volumes recovered already, the scheme is enjoying rapid uptake by BD’s customers. “Some of our biggest customers are already on board,” said Ranjeet. “Rady Children’s Hospital in California was the first to adopt it. DaVita, a leading provider of kidney care in the USA, have enrolled, and New York City-based Montefiore Medical Center, a prestigious leading healthcare institution, has had over
<< BD Recykleen Sharps Collectors are made with a minimum of 50% recycled material — collected using the ecoFinity programme. >>
Outlook: Green Shoots BD is undoubtedly leading the way here. But it’s a clear understanding of plastic recycling and the medical device market that has got them to where they are. Ranjeet says: “Our partner, Waste Management Inc, has brought a lot of expertise to the table, and we continue to add to our team. We have people who have tremendous technical competencies in plastics and in life cycle analysis (LCA).” So what’s next for BD on the eco–front? Ranjeet believes in “greening” medical products. “We are working from a mantra of reduce, reuse, recycle — we are reducing the amount of material which goes into our products, we are identifying where we can reuse valuable natural resources in our manufacturing sites — three of our sites in the US are producing products with 100% renewable electricity — and we are providing a real option to recycle through BD ecoFinity.” BD is an active member of USA-based members group Practice Greenhealth, one of the sponsoring organisations of the Healthier Hospitals Initiative. The Healthier Hospitals Initiative is a US-wide association with the goal of encouraging healthcare organisations to consider sustainable business models with an awareness of their impact on the environment. The BD ecoFinity Life Cycle Solution is a trademark of BD which has been registered with the US Patent and Trademark Office. BD Recykleen is a trademark of
BD.
JULY | AUGUST 2012 / MPN /7
ON THE PULSE | News from the industry
The UK’s Medical Plastics Industry Goes from Strength According to forecasts from UK-based business information publishers Global Business Intelligence (GBI), demand for medical polymers will grow by an average of 9.8% between 2009 and 2015. This follows average annual growth of 7.2% from US$650 mn in 2000 to US$1.2 bn in 2009. A breakdown of the global market published in December 2010 shows that North America leads the demand for medical polymers with a share of 42.2%, followed by Europe with a share of 30.1%, Asia with a share of 22.8% and, with vast potential, the rest of the world with a share of 4.9%. Acceleration in annual average growth is being generated by two factors. First, demand for medical devices is on the up anyway thanks to the aging population in Western nations and from improvements in standards of healthcare services in developing regions. In addition, however, the use of plastics in medical devices is also increasing, replacing metals, glass and other traditional materials. Fuelling this growth are advancements in polymer technology. Properties such as transparency,
June 12, 2012 Plastics in Medical Devices Conference Reaches Successful Conclusion Len Czuba, CEO Czuba Enterprises, said: “This event in my opinion clearly established the Plastics News PMD conference as one of the leading must-attend programmes for device engineers. I am looking forward to next year!”
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July 12, 2012 Medical Device Directive Updated Following PIP Scandal
mechanical performance, electrical conductivity resistance and ease in forming and joining have increased the appetite for plastics in the medical industry. A small snapshot of the UK medical plastics sector shines a light on some of the best progress in medical polymers. Custom designed, patient-specific implants can now be made by the laser sintering process from high performance plastics like PEEK from the UK’s Invibio Biomaterial Solutions. Bespak Medical, also based in the UK, is steering the drive in device design and product innovation ranging from drug delivery devices to point of care diagnostics consumables. Advanced Medical Solutions Group, again in the UK, is developing and providing leading edge technology to the global wound care markets using a range of novel alginate biopolymers, hydrophilic polyurethane foams and hydrocolloids. And Carclo Technical Plastics in the UK, with its emerging technologies division, is formulating material solutions and technologies to the medical device and associated industries.
Mike Kreuzer, the technical and regulatory executive director at the UK’s Association of British Healthcare Industries (ABHI), commented: “This is an important and long-awaited development that is a significant step towards full traceability and improved patient safety around the globe.”
July 12, 2012 Medtech is Top of the Pile in £250 mn UK Government Funding
Vince Cable, the UK government’s business secretary, said: “Innovation is a key part of our plan for growth and the Technology Strategy Board is actively supporting industries where the UK is one step ahead of the competition. We already have some great industrial success stories, like our aerospace, energy and healthcare industries where innovations have been effectively translated into commercial use.”
ON THE PULSE
to Strength
It is pleasing to hear that Mediplas 2012 is coming to Birmingham, UK, this year on September 25-26. A series of free technical seminars are being held, ranging from Medical Grade Polymers, Materials Selection, Design & Prototyping, Advanced Processing and Regulatory Affairs. This is a timely opportunity for participants to encourage technology adoption and a “must attend” for those involved in advanced technologies related to medical plastics. The show is co-located with TCT Live, MM Live UK 2012, NANO
Live 2012 and MEMS Live 2012; which demonstrates the grassroots move towards the realisation that convergent technologies is the way of the future. For further details, see www.mediplasuk.com. In addition, HealthPack Europe is coming to Dublin, Ireland, on December 3-4, 2012. The event is a conference dedicated to issues and new technologies in the area of medical device packaging. Dr Austin Coffey is a lecturer at Waterford Institute of Technology Ireland and a visiting professor of Future technologies at the University of Applied Sciences, Upper Austria. He is the current president and councillor of the European Medical Polymers division of the Society of Plastics Engineers (SPE).
<< For further details on Mediplas 2012 visit www.mediplasuk.com >>
PREVIOUSLY ON MPN MAGAZINE.COM July 15, 2012 Arkema Divests Vinyls and Creates KEM ONE, a €1 bn Giant
According to Marco Toscano, general manager of Italian PVC Compounder Resilia and Healthcare division manager said: “It is a milestone for us. Resilia, as the corporate centre for healthcare at KEM ONE, will participate in the investment programme, further emphasising its global approach in the view of added value for our customers.”
July 16, 2012 Clariant Rebrands
Dr Rai Rolker, Clariant’s head of corporate communications, said: “We want to become the global leader in specialty chemicals — competitive, innovative, and sustainable, with outstanding value creation for all of our stakeholders and partners. An open and constructive dialogue with the media and society is a special priority to us in this.”
11:08:2012 July 25, 2012 Mediplas Announces Speaker Programme
Notable speakers include Mehdi Tavakoli, technical director HealthTech & Medicines KTN, Chris Dyke, director at Medilink, Sean Lyons, senior R&D engineer Bausch & Lomb, and Dr Finbar Dolan, technical director at Lake Region Medical.
24 JULY | AUGUST 2012 / MPN /9
ANTIMICROBIALS
WORDS | SAM ANSON
A FACTUAL GUIDE to
Antimicrobial Medical Plastics ntimicrobial plastics are polymer compounds with the ability to kill or inhibit the growth of bacteria on their surface. Demand for such products is on the up because they are seen as an important component for healthcare institutions attempting to reduce the incidence of healthcare associated infections (HAIs). Conventionally, the most common application area for antimicrobials are non-invasive class I devices like wall guards, soap dispensers and other furnishings. But antimicrobials are being used for a growing range of infection prone invasive devices — particularly catheters, connectors and other accessories. Coatings are an established way of making devices antimicrobial (see page 57) but they are reputed to being prone to getting scratched off. There is a fast growing range of FDA compliant biocompatible antimicrobial polymer compounds which are fully mouldable and extrudable and available in a wide variety of polymer compounds.
A
Organic or Silver When selecting an antimicrobial compound a designer must choose whether to use an inorganic or organic additive. Inorganic additives are made from silver or another metal while organic additives are chemicalbased.
Recently, inorganic silver-based compounds have become a popular choice for use in medical devices. Manufacturering involves loading tiny silver particles on to glass or zeolite supports. Then, once processed, the entire surface of the plastic part has the desired antimicrobial effect. The silver is permanent and doesn’t run out — its physical nature is the feature which provides the antimicrobial effect. Traditional organic antimicrobial additives, such as triclosan, are manufactured in the same way. However, they work in a different way. The organic “active” chemical reacts with the microbes at the surface. As this occurs, the “used” chemical is replaced with more chemical from inside the part. In other words, the antimicrobial additive migrates through the plastic to the surface as it is used up. Organic additives are well established chemicals and their efficacy against bacteria — including the ones which have been identified to cause the majority of HAIs — are well known. Furthermore, their efficacy is highly effective per gram. You only need a small concentration of additive to achieve an acceptable level of antimicrobial performance. However, their processing properties are not as favourable as silver — they have limited heat stability and dwell times in the mould. Furthermore, there are questions as to the safety of some of these chemicals. Continued on page 12
JULY | AUGUST 2012 / MPN /11
Antimicrobials | A FACTUAL GUIDE Continued from page 11
According to Wikipedia, as of July 2012, the safety of triclosan was under investigation by the FDA. Silver-based compounds are more expensive than organic compounds as they require a heavier loading of additive to achieve the same performance. But manufacturers like the idea that silver is an inert substance and may be “safer” when in contact with, or inside, the body. The other advantage of silver-based compounds is that they are more heat stable and can be processed at high temperatures. They are also a lot more “colour-friendly” which means that a broader range of coloured biocompatible compounds is available. Antibiotic Drugs in Antimicrobial Silicones There is promising research into the incorporation of antibiotics into silicone elastomer compounds. Silicone elastomers, exhibiting high free volume, weak intermolecular forces, and superior biocompatibility, are in many ways ideal candidates for drug delivery as the free volume allows active pharmaceutical ingredients (APIs) to diffuse through the matrix and be released through the surface of the part. According to USA-based silicone compounder NuSil, silicone formulations can be customised in a variety of ways to facilitate a specific process of fabrication while also achieving key mechanical and drug elution properties. Product examples include catheters with antibiotics, contraceptive intra-vaginal rings (IVRs) and intra-uterine devices (IUDs), pacemaker leads with an anti-inflammatory active ingredient, and transdermal skin patches that range in application from treating high blood pressure (with vasodilators) to pain management (with opiates). Recent collaboration between silicone manufacturer Momentive Performance Materials and silicone processor Specialty Silicone Fabricators (SSF), both based in the USA, has resulted in new technology that allows silicone-drug mixtures to be vulcanised rapidly and at low temperature via brief exposure to UV light. As part of their research, SSF combined Momentive’s new 60 durometer UV curable liquid silicone rubber with 1.0% of doxycycline, a tetracycline antibiotic. The silicone-drug mixture was homogenised by SSF using non-contact mixers that provided centrifugal shear as well as high intensity acoustical energy. The mixture was then placed between 2 PMMA plates and exposed for 40 seconds to UV radiation emitted from a microwave powered D lamp. This process produced a 2” x 2” x 2 mm sheet. Durometer measurement of 59 confirmed complete cure of silicone-doxycycline elastomer. More recently SSF and Momentive have begun evaluating LED arrays as the UV light source. Initial results suggest that,
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<< A catheter spike made from Evonik’s Cyrex Protect antimicrobial acrylic-polycarbonate blend. >> when compared with lamps, the narrower range of UV wavelengths produced by LED arrays further reduce the time required for the vulcanisation of antimicrobial silicone-drug components. Testing of Antimicrobial Plastics At present there is not one single test for determining the efficacy of antimicrobial plastics. That said, ISO 22196:2011 specifies a method for evaluating the efficacy of antibacterialtreated plastics, although it is rarely quoted by suppliers in the industry. The internationally accepted standards are the ASTM 2149 and the JIS Z2801. The ASTM method employs a dynamic contact method where an antimicrobial sample is immersed in an inoculated solution with resultant bacterial growth of colonies remaining on the surface versus a control after removal of the plastic sample. The JIS method measures the kill rate of colony forming units (CFUs) inoculated onto the surface versus a control. In both cases, the results are measured in terms of the log kill rate — which measures the percentage of bacteria killed over a certain period of time. The standard minimum is log 4, or 99.99% of bacteria, although device manufacturers are demanding log 5 (99.999%) and even log 6 (99.9999%). These tests must be done carefully to ensure repeatable and reliable results, and the testing protocols must be carefully reviewed to ensure that results are a fair reflection of the efficacy of the antimicrobial material/device, and not the result of poor control of the test variables. This includes proper selection of base CFU concentrations in inoculation solutions, usually in the range of 150,000-300,000, as well as proper nutrient levels in
ANTIMICROBIALS
<< Examples of common parts which are made from Cryolite Protect acrylic compounds. Source: PolyOne. >> the growth environment. In the extreme, some tests claiming antimicrobial efficacy have done so by using low CFU concentrations in the inoculum, or by starving bacteria by providing low nutrient levels.
It is also important to test a variety of bacteria types, as they may respond differently to antimicrobial agents, with some being more resistant than others. This should include a mix of grampositive and gram-negative organisms, as they each have different structures and characteristic responses to environments that differ from one another. In all cases, replicates of the efficacy tests should be conducted to confirm performance because of the observed variability in test results. It is very difficult to achieve high levels of repeatability and reliability, and these replicates can be very helpful not only in confirming the efficacy of performance but also the quality of the test lab conducting the analyses. For testing of long term efficacy, performance is directly related to the usage expectations regarding contact and field of effectiveness. In the case of disposable devices such as IV set components, typical time of use and exposure range from 24 to 96 hours. Any testing should include re-inoculation at specified periods during the efficacy test period to simulate repeated Continued on page 14
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Antimicrobials | A FACTUAL GUIDE Continued from page 13
exposures as is the case during actual use. In addition, there is an expectation of shelf-life and effective performance of the device once it is placed in use. To ensure that expectations are met, the component or material provider should have information that confirms performance over in-use time periods for usage and for expected shelf-life/storage periods. Regulation Consumer applications and antimicrobial agents are regulated by the USA’s Environmental Protection Agency (EPA) as pesticides. In both cases, companies providing these products, as well as the products themselves, must be registered with and authorised by the EPA. Medical devices using antimicrobial plastics should be evaluated according to the current draft guidance published by the FDA, Draft Guidance for Industry and FDA Staff - Premarket Notification [510(k)] Submissions for Medical Devices that Include Antimicrobial Agents, which was initially published in 2007 and last updated in February 2012. At the time of going to press, this guidance document was not finalised. But it does include a broad range of criteria and insight into issues of concern, such as balancing the need for antimicrobial
performance with the possibility of creating more resistant bacterial strains.
Selected Antimicrobial Plastic Suppliers EVONIK Evonik makes two brands of antimicrobial plastic compounds — Cyrolite Protect acrylic compound and Cyrex Protect acrylic-polycarbonate blend. Both products feature inorganic antimicrobial additives and are specifically designed for FDA regulated Class I or Class II medical devices covered by 510(k) pre-manufacturing notification (PMN) submission. Both are tested according to the JIS Z 2801 protocol against a variety of microorganisms commonly found in healthcare facilities and have achieved an efficacy level greater than log 4. They are compatible with many materials including ABS, polycarbonate, and methyl methacrylate-acrylonitrilebutadiene-styrene-polymer (MABS), and can be easily bonded to PVC tubing and films. BASF BASF’s range of antimicrobial compounds are sold under their Hygenetic brand. One grade is Hygenetic 6025 ST 656C, which is a styrene-butadiene block copolymer biocompatible compound with a silver-based antimicrobial additive. The compound achieves a reduction in CFUs of greater than log 4 in the JIS Z2801 tests for nine types of bacteria. Of these, six are log 5. BASF also offers a custom compounding service for silverand triclosan-based additives in polycarbonate, TPU, LSR, polystyrene and other polymers. POLYONE PolyOne offers a wide range of organic and silver antimicrobial compounds. Recently its specialist medical compounder NEU partnered with USA-based medical catheter micro extruder Microspec to deliver antimicrobial solutions for complex medical tubing. CLARIANT Clariant offers Mevopur ISO10993 biocompatible antimicrobial compounds featuring Switzerland-based Sanitized’s MedX range of silver antimicrobial additives. According to Steve Duckworth, head of medical and pharmaceutical at Clariant, they can offer a fully traceable product flow — an important advantage to reduce the risks associated with changes in raw materials further down the supply chain. The traceability for the end customer also means he can avoid the provisions of the European biocide directive. Clariant’s specialism is compounds for coloured and transparent antimicrobial devices.
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ANTIMICROBIALS
RTP USA-headquartered custom compounder RTP Company offers organic and silver antimicrobial compounds. The company recently partnered with Spainâ&#x20AC;&#x2122;s NanoBioMatters to offer Bactiblock silver compounds. RTP Company has engineered antimicrobial masterbatches and compounds for olefins, ABS, PC, PC/ABS, PA, PS, TPU, TPE, POM, PBT, PVC, PET, and some fluoropolymers. BIOMASTER UK-based Biomaster offers its silver-ion antimicrobial additives in biocompatible masterbatch form. According to the company, the technology has been tested to the relevant ISO standards and has been proven to reduce the growth of a range of harmful bacteria by up to 99.99% (log 4). It has been used for spinal implants and is suitable for PEEK.
Credits Peter Colburn, director, business development, innovation and technology at Evonikâ&#x20AC;&#x2122;s Acrylic Polymers division, for advice on the details of antimicrobial testing and standards. Mike Chappell, colour and additive marketing specialist, RTP Company. Danielle Peak, marketing technical writer, NuSil Technology. Mark J Paulsen, business development director, Silicone Specialty Fabricators (SSF). Larry Johnson, global healthcare marketing director, PolyOne.
<< Oxygen masks are a common application for antimicrobial plastic compounds. >>
NUSIL USA-based silicone compounder Nusil works with inorganic silver additives and active pharmaceutical ingredients (APIs). It has extensive experience in the compounding of APIs and silvers with silicone elastomers.
Note that research undertaken in the writing of this report was done so by the editor independently. At no time was there outside influence from advertisers or other parties with a vested interest in the content.
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An Introduction from the Association of British Healthcare Industries (ABHI) The UK medical technology sector, which is made up of over 3,000 companies, makes a significant contribution to the UK economy with a combined turnover of around £15 billion and 64,000 employees. The sector is predominantly made up of SMEs which employ less than 250 people each. In terms of turnover, the largest section of the industry is single use technology, followed by wound care and Peter Ellingworth, management, orthopaedic devices and Chief Executive professional services. In total, the UK produces about 500,000 different medical devices, which range from syringes and wheelchairs through to pacemakers and X-ray machines. The Association of British Healthcare Industries (ABHI) is the industry association for the UK medical technology sector. Its purpose is to promote the rapid adoption of medical devices to ensure optimum patient outcomes throughout the UK. Its strategic review focuses on advancing access to medical technology with its core mission centring on championing the benefits and use of safe and effective medical technologies to deliver high quality patient outcomes. ABHI advocates policies which allow members to operate in favourable business environments in the UK market and international markets with appropriate regulations, standards, ethics and principles. It represents companies whose output makes up for around 85% of the industry’s total.
INJECTION MOULDING Saves Healthcare Billions MPN Profiles Owen Mumford’s OEM Custom Solutions Division WORDS | SAM ANSON The development of capillary blood sampling and drug delivery devices — which can be used to manage chronic conditions in a patient’s own home — has over the last 20 years helped to reduce the length of time a patient spends in hospital. Injection moulded components have played a big part in this. They have enabled products to be easy to use, disposable and affordable. One of the leading suppliers of capillary blood sampling and drug delivery devices is UK-headquartered Owen Mumford. The company, which has been making medical devices since 1952, is divided into two main business areas. One division sells Owen Mumford branded capillary blood sampling and drug delivery devices to healthcare professionals in Western Europe, the USA, Australasia, South Africa and Asia. The other main area of the business provides custom design and development services for medical devices and consumables for some of the world’s top pharmaceutical and diagnostic partners.
<< Owen Mumford achieves very tight component tolerances to produce its insulin pens, which must meet stringent dose accuracy requirements. >>
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UK FOCUS << The plastic mechanism in this auto injector overcomes needle phobia by hiding the needle and enables self-injection of medication. >> Being a player in the pharma delivery sector demands the highest levels of quality and compliance. Owen Mumford’s managing director, Jarl Severn, explains: “The demand from large pharma companies ensures we maintain the highest levels of compliance and that every product meets exacting standards at all stages of production — from design through to manufacturing, quality control and distribution.” He adds: “We are used to being audited and assessed by some of the world’s leading pharmaceutical and diagnostic companies as well as third party accreditation bodies including the FDA, the MHRA [Medicines and Healthcare products Regulation Agency in the UK] and the Swiss testing and regulatory bureau SGS (Société Générale de Surveillance).” Andy Vardé, director of research and development, says that the expertise is evidenced by the technically advanced nature of their products: “Our devices comprise highly engineered mechanical parts made from specific engineered polymers. To maintain the performance of these parts, we keep a close eye on our material selection. We use advances in material technologies to maintain and improve the mechanical features of our products, and this drives further precision and reliability across our range of devices.” The company’s two types of drug delivery devices — auto injectors and injector pens — are both advanced in terms of injection moulding technical prowess. Owen Mumford’s auto injector, designed to make it easier for patients to self-administer injectable medication, gives an injection of a drug from a syringe by inserting the needle and injecting the syringe’s contents automatically into the skin. The device, which can be disposable or reusable, has revolutionised the selfmanagement of diseases. The needle remains completely hidden before use which overcomes the main cause of needle phobia — the actual sight of a needle penetrating the skin — thereby encouraging patient compliance. Owen Mumford manufactures a wide range of auto injectors to be used across a range of different therapy
areas for patients with conditions such as rheumatoid arthritis and multiple sclerosis (MS) as well as hormone injections for human growth treatment. Ergonomically designed devices are also available for patients with dexterity issues. The pen injector is a reusable pen injection device for use with cartridges. Originally designed for people with diabetes, they feature a variable dosage mechanism to allow a patient to change the dosage depending on his or her insulin need at the time. The variable dose mechanism is particularly precise as individual doses can be as small as 10 microlitres. Achieving this in design and manufacturing requires highly accurate workings on mould tool design as well as inspection, processing and finished part testing. Owen Mumford’s single-use capillary blood sampling devices have a pre-set safety needle which is held in position and fitted with a spring under compression. The devices have a shelf life of five years, so the mechanical component and spring must be capable of storing this energy for that amount of time without affecting its reliability — no mean feat. According to Jarl Severn, a big driver of demand for injector devices is the development of biologic drugs, which are drugs that have been prepared using a biological process. “More and more of the new drugs are biologics, which because of their complex nature cannot be made into tablets and so have to be delivered subcutaneously, requiring more innovative and intuitive devices to facilitate injection in the home environment.” << These lancing devices contain metal springs in a plastic casing which must store energy for up to five years. >>
JULY | AUGUST 2012 / MPN /17
In the Zone | CONTRACT MANUFACTURING
SELF-ADMINISTERED DRUG DELIVERY:
Under the Tip of Your Tongue There has been a shift in demand for single use drug delivery devices made from plastic. In conjunction with a pharma customer, UK-based device manufacturer Europlaz has developed a new tamper proof sublingual delivery system — originally developed for opiate-based drugs — consisting of six fully recyclable injection moulded parts. The device, SubEuro, is a sterilised single use dispensing canister for the sublingual (under the tongue) spray of micro sized droplets of reformulated drugs. The sublingual method enhances drug delivery compared with an injection as the mucosal membrane under the tongue allows direct access to the bloodstream. Europlaz manufactures SubEuro in a 10,000 (ISO class 7) cleanroom. The six parts are easily assembled — either manually or through automated processes. According to Europlaz, it was important that the finished device was non-reusable and tamper proof to alleviate the risk of infection and cross contamination. One of the main benefits of the device is that it prevents refilling and reuse by poorly educated clinicians, counterfeiters and other registered drug companies. The SubEuro device was developed initially for an opiatebased drug — the tamper proof aspect is so one controlled dosage can be securely administered and addicts cannot access the drug to develop a stock. A small plug within the device is dispatched on first use making the spray mechanism useless thereafter. The outer device is tamper evident and disassembly proof. This also means that the intended drug cannot be removed and replaced with a different drug. It is not uncommon for poorly educated clinicians to attempt to refill single use devices, even when there are clear markings that the device is single use, because they are so accustomed to doing so. But the design of the SubEuro makes that impossible. Occasionally device waste can be sold to be repackaged and remarketed by a different company – usually in the Far East. However, once this device is empty it cannot be sterilised and re-filled by another drug company. This aspect of the design offers piece of mind to the drug manufacturer that no other substance can be administered by their branded device. Some materials used in device manufacture, especially polymers, can absorb chemicals from the drug formulation, which can then gradually leach from the material over time. In order to avoid this, Europlaz selected a medical grade plastic which conforms to US Pharmacopoeia XXIII Class VI and ISO10993 then carried
out a two year, real time, stability programme to ensure patient safety. Part of the beauty of the design of this device is that it can administer a controlled dosage in a secure and definite way. If the spray is held to the mouth and used, there can be no doubt that the patient has received the exact amount needed and he/she cannot deceive the administrator in any way. The new device has just three operational steps, making it easy to use. It also has a special mechanism designed to release a plume spray, which offers maximum sublingual coverage, and a droplet size of between 15 and 30 microns, any smaller and there is a risk the drug could be inhaled. This easy approach makes the device suitable for infirm or incapacitated patients. The device has been used in proof of concept and clinical trials and was labeled outstanding. Licensing is available worldwide on an exclusive or non-exclusive basis for therapeutic drug delivery. Own branding and customisable options are also available from Europlaz.
<< Patents for the SubEuro sublingual delivery device are granted in the UK, Europe, South Africa, Australia and Canada. A patent is pending in the USA and Japan. >>
JULY | AUGUST 2012 / MPN /19
Cover Story | MATERIALS
COLOUR COMPOUNDING TO ISO10993 AND MOLDFLOW ANALYSIS Deliver Excellent Results for the Lotus Surgical Scalpel
Specialist biocompatible polymer distributor and compounder Albis UK has proven its technical prowess in engineering polymers. Working in partnership with SRA Developments, the UK-based designer and manufacturer of the new Lotus surgical scalpel (pictured), Albis added significant value by making important corrections to mould design. It was also able to deliver colour-coded biocompatible materials — a key requirement of surgeons nowadays —thanks to its licensed UK-based capacity for compounding ISO10993-certified biocompatible materials. The scalpel is used by surgeons to cut and seal soft tissue quickly and easily, keeping blood loss to a minimum. According to SRA, the Lotus uses torsional ultrasound to direct powerful compression energy into the target tissue, resulting in secure coagulation and fast cutting. Colour-coded plastic parts are a crucial part of the device’s appeal — including a pioneering ergonomic “palm fit” design with spring-loaded trigger as well as easy-to-use functional features like finger activation buttons and a simple rotation wheel for curved rotating shears. The scalpel is used in many surgical specialties but is particularly well suited to laparoscopic (keyhole) surgery. At the device design stage, SRA approached Albis UK for assistance in material selection. The Albis team undertook a full assessment of the device, an essential part of working with the medical industry, to fully understand any regulatory requirements. The Lotus scalpel was to be recognised under the Medical Device Directive as a Class IIb device needing to undergo sterilisation by ethylene oxide (ETO) and be certified biocompatible to ISO10993. Various parts were to be colour-coded to help the surgical team quickly and accurately select the correct version of the device according to the nature of the planned operation. SRA were looking for colours which were already ISO 10993 certified as well as advice on the best polymers to use from an engineering perspective. Given that the Lotus project involved a particularly complex design with a number of polymer engineering challenges, Albis was involved at every stage of the
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design process — from design concept, material recommendation, mould tool design, tool trials, product launch and process optimisation. This included work for the handle, the rotation wheel, the activator and front buttons, the trigger, and the snap fit actuator (see table). In terms of colour compounding, Albis UK is licensed to compound a wide range of polymers from Bayer MaterialScience, Styrolution and LanXess, whilst retaining accreditations and standards attached to the individual grade. These standards include ISO10993 and USP Class VI biocompatibility, as well as other approvals. It achieves this by manufacturing to the pre-set formulation given by the licensing agreement with its producer partners. These formulations include nominated pigment feedstock and additives. Manufacturing to these formulations overcomes a key problem associated with using un-pigmented or natural polymer and coloured masterbatch. It removes the risk that an additive which has not been tested by the formulation owner — considered a contaminant under FDA regulations — gets into the compound and invalidates warranties associated with the base material. In addition, Albis UK has access to the special feedstocks specified by the original producer in its formulation. These feedstocks are able to withstand the high shear rates involved in the compounding process. Non-licensed compounders, using a standard feedstock, risk introducing high shear rates which in turn can break down the polymer chain and affect the performance of the material. In the case of the Lotus scalpel, the material selections were Bayblend PC/ABS and Makrolon PC from Bayer MaterialScience, selected for their key performance characteristics. The highlights of Albis’s involvement for each part, as well as the highlights of the materials, are described in the table.
<< Moldflow diagrams clockwise from left: Handle, front button, trigger, handle button, rotation knob. >>
Part
Albis UK was established in 1966 and operates close to the UKâ&#x20AC;&#x2122;s motorway network from a manufacturing and distribution centre in Knutsford, Cheshire. In addition to the products and services mentioned in the table, the company distributes the following ISO10993 and USP Class VI certified polymers: APEC PC-HT and Desmopan TPU from Bayer MaterialScience; Pocan PBT and Durethan PA6 from LanXess; Lustran ABS from Styrolution; Purell PP and PE from LyondellBasell; Eastar, Durastar, Provista and Tritan copolyesters from Eastman; Ultraform POM and Ultradur PBT from BASF; and Udel PSU, Radel PPSU, Avaspire PAEK and Ketaspire PEEK from Solvay Specialty Chemicals. Of these brands, Makrolon, Pocan, Lustran, Purell, Eastar, Durastar, Provista, Tritan, Ultraform and Ultradur have Drug Master File (DMF) listings. Thanks to these approvals, using these materials in devices offer significant shortcuts in future approvals. Albis UK is part of the international Albis group of companies which has manufacturing facilities in Germany, the UK, and the USA, with a Chinese operation opening in early 2013.
Material
Highlights
Bayblend PC/ABS M850XF in white
1) Albis had concerns with potential sink marks and filling issues caused by ribs on the handle. Flow analysis was used to correct gate position. Part was modified successfully (see image). 2) Bayblend selected for its impact strength, flow and rigidity as well as being solventbondable for assembly. 3) Bayblend is also ETO sterilisable.
Rotationa l control knob
Makrolon PC 2858 in various colours
1) Advice on gate location overcame concerns about sinking and jetting to give good visual surface. 2) Makrolon selected for dimensional stability which is good for overmoulding with a TPE. 3) Biocompatible colours were important.
Handle activator and front button
Makrolon PC 2858
Trigger
Makrolon PC 2858
Gate position was crucial to eliminate the potential of voids which are a potential weak spot and to give a uniform surface for subsequent two shot moulding.
Snap fit actuator
Makrolon PC 2458
Wall section required a grade of Makrolon with extended flow characteristics. This was recommended and selected.
Handle
Moldflow analysis was used to overcome the potential for weld and flow lines on the visual area as well as eliminating gas traps on the tool.
JULY 2011/ MPN /21
Regulation Review | UK FOCUS
SELLING TO THE NATIONAL HEALTH SERVICE:
Procurement Changes Generate Opportunities for Medtech Suppliers
BY VASSILIS SERAFEIMIDIS, PA CONSULTING GROUP he latest procurement guidelines for the UK’s state-funded National Health Service (NHS) mark a further step forward towards a more simplified, integrated procurement system that will deliver benefits for both suppliers and buyers. With a total procurement spend of more than £18 bn a year, the NHS has huge potential to use its buying power to secure good deals from its suppliers. However, its current fragmented approach — in which 358 hospitals pursue their own individual contracts — means this potential is not being realised. As a result, many hospitals are paying different prices for the same goods and failing to secure the efficiencies they are required to make in the current challenging financial situation. This situation will only get worse with the envisaged transformation of the health system. There are many advantages of a more centralised and collaborative procurement system both in the efficiencies it can deliver and in the management information it provides about purchasing trends, supplier performance, and so on. That information, along with the detail of what other purchasers are paying, helps managers to understand the broader picture and then use that data to negotiate further with suppliers. According to leading UKbased business consultants PA Consulting, collaborative buying of commodities in the public sector can achieve around 15-20% worth of savings. For suppliers too there are advantages in that a more consolidated system means they can provide information and services in a standard form. It should also drive the development of more e-procurement and more efficient administrative and payment systems.
T
The UK government is also proposing to provide more transparency in the process and this should help small and medium sized enterprises gain access to contracts. Instead of having to market themselves to every individual health provider, they will be able to see what services buyers are looking for and access contracts through a single portal. There is also a specific commitment to encouraging innovation and the new approach aims to create an environment where healthcare providers can engage with suppliers and actively look for innovative solutions and develop new products. For this approach to work, it will require engagement from all parties. There will be resistance to more collaboration from individual hospitals that are used to having the freedom to procure from suppliers with which they have an established relationship. So it is important that the case for collaboration is made strongly and that the benefits are clearly highlighted to convince procurement teams of the advantages as old habits die hard. There is still a long way to go before the NHS achieves a truly integrated procurement system. However, the financial pressures on hospitals means that they will be increasingly looking for opportunities to make savings and to look at collaborative procurement. This, combined with the pressure from government to go down this route, means that progress is now more likely and that we will see real change in the way the NHS procures a whole range of equipment. So suppliers will need to be ready to meet the challenges of increased transparency but also to seize the very real opportunities that a more integrated approach will offer. Vassilis Serafeimidis is a procurement expert at UK-based business consultants PA Consulting Group.
JULY | AUGUST 2012 / MPN /23
Designing for the IEC 60601: CO2 Emission Data Mandatory Medical Plastics Beat Metals in Independent CO2 Emissions Life Cycle Assessment he International Standard for Environmentally Conscious Design of Electronic Medical Equipment (IEC 60601-1-9) is considered to be the global On June 1, 2012, the third edition of benchmark for the IEC 60601: Medical Electronic companies Equipment came into force in the EU designing and Canada. The regulation requires sustainable designers to submit environmental medical data about a electronic device during equipment. It requires certification. But understanding the manufacturers to environmental impact of products is consider the a complicated process and one with environmental which even the largest companies impacts of their have struggled. Now, however, devices thanks to the LCA Calculator — a throughout the simple tool from UK-based design product life cycle. consultancy IDC — compliance with The difficulty the data requirements can be the standard achieved for just £300. poses for many medical device companies is that despite long standing awareness, they have little or no experience dealing with issues relating to the environmental impact of their designs — with the tools and information required to comply with the standard not readily available.
T
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Sponsored by:
Design 4 Life | PLASTICS BEAT METALS
Obtaining useable data about the impact of these stages and the processes within them has proven to be a major problem, as confirmed by a recent conference paper by Brouet et al representing global pharma companies (including, GSK, AstraZeneca, Novartis, Pfizer and Merck) in which they concluded that the medical industry was behind other industries with its adoption of sustainability. UK-based device design consultants, Industrial Design Consultancy (IDC), have been working to overcome these difficulties in order to help companies understand and manage their environmental and sustainability issues. IDC has developed a series of tools which manufacturers can use themselves to ensure they comply with legislation for product life cycle and design for the environment, including IEC 60601-1-9. One such product is the Life Cycle Assessment (LCA) Calculator (www.lcacalculator.com), a tool which helps designers gather data about the environmental impact of the components in their device from a cradle-to-grave perspective. The cradle-to-grave approach considers every stage of the component’s life, including
<< Four materials were compared — aluminium, polycarbonate, ABS and polystyrene. >>
<< Figure 1 and 2: A comparison of CO2 emissions for polystyrene, polycarbonate and ABS in (a) the same generic part and (b) in a 1 kg sample of material shows significantly reduced emissions. Percentages show the reduction in emissions compared with aluminium. >>
manufacture, transport, use and disposal. The analysis for the manufacturing stage takes into account an LCA of the materials from which the component is made, as well as how the material has been processed (including injection moulding or extrusion). The data in the database is from EcoInvent, which claims to be the world’s leading source of life cycle assessment (LCI) data. Analyses can be saved, copied and compared against comparable products or potential new designs and results can be exported as Excel data or a pdf report. To demonstrate the tool, IDC put together a case study exclusively for readers of Medical Plastics News. The company took a generic plastic case and compared the carbon dioxide (CO2) emissions of a selection of polymer materials — polystyrene, polycarbonate and ABS — and compared them with virgin aluminium. The results, shown in figure 1, demonstrate that all three plastics offer significantly lower CO2 emissions compared with aluminium. The use of polystyrene reduces emissions by 84%, polycarbonate by 68% and ABS by 83%. IDC also compared 1 kg samples of the same materials. The results, shown in figure 2, show that all plastics still offer reduced emissions, although the scale is smaller. According to IDC, the reason why the results for the 1 kg sample are different than those for the generic part is that the density of the materials are different. This means that for some materials, a smaller weight is required to make the same part.
JULY | AUGUST 2012 / MPN /25
Doctor’s Note | CLINICAL HELP
The KTN: Public Funds for UK SMEs WORDS | SAM ANSON
The HealthTech and Medicines Knowledge Transfer Network (KTN) is a UK government funded (via the Technology Strategy Board) group of business professionals involved in healthcare and medical technology industries. The network, which is free to join, offers suppliers and developers an opportunity to connect with end users of healthcare and medical technology products — particularly clinical specialists and senior medical research professionals. The network is a facilitator for channelling public funds from the UK and EU governments into healthcare related R&D via collaborative and single company research and development projects. It is a key “translator” for the recently announced BioMedical Catalyst — a £180 mn
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fund made available by the Technology Strategy Board and Medical Research Council (MRC) to stimulate technological development in the UK healthcare sector. The network also aims to connect partners by organising regular UK networking events and international technology missions. Its third goal is to foster a culture of openness to sharing knowledge and innovation in the industry in the form of an up-to-date website and relevant and reliable news. The website, www.healthktn.org, is easy to navigate and is quick and responsive. After joining the site, you can populate your profile with a picture and biography and then interact with other members of the group. The idea is similar to other networking sites like LinkedIn and
Case Study –
Facebook, but with a strong focus on innovation and UK business growth. The network covers six board categories of healthcare, as follows: bioprocessing biological medicines, medical devices and diagnostics; regenerative medicine; stratified medicine; detection and identification of infectious agents; and assisted living. Within these categories, there are a total of 20 official groups. The most notable of these for manufacturers of medical plastics are highlighted in table 1. Table 1: Notable official groups of the HealthTech and Medicines KTN Advanced Wound Care
Healthcare Associated Infections (HAIs)
Biomedical Surfaces
Medical Devices and Diagnostics
Cardiovascular Devices
Medical Devices Clinical Studies
Dental
Orthopaedics
Drug Delivery
Regenerative Medicine (tissue engineering)
Detection and Identification of Infectious Agents (DIIA)
Urology
A Public Funding Success Story in Tissue Engineering In 2003, the KTN was given £1 mn from the EPSRC to support new innovative projects. Part of that money went to help a team of researchers, led by Professor Bill Bonfield, develop silicone substituted hydroxyapetite for use as a synthetic bone graft. The project was worked on jointly with The University of Cambridge, the Orthopaedic Research Unit at Addenbrooke’s hospital as well as another orthopaedic surgeon from Aberdeen Southend hospital. At the time, a small company called Apatec was established. The funding helped bring together the relevant experts to give Apatec the information it needed to develop one of its products. In 2010, just eight years later, Apetec was sold to Baxter Healthcare for around US$300 mn. People interested in joining the network and applying for funding should come along to the relevant industry events to meet as many people as they can in order to start to put together their business case. They can also look at the KTN’s funding maps (www.healthktn.org.uk/supportmap) which describe the innovation landscape within the UK and how the existing infrastructure can help deliver more impactful proposals and projects.
AN EXAMPLE OF A CLINICIAN INVOLVED IN THE KTN Name: Professor Simon Donell Specialism: Orthopaedic Location of work: Norfolk and Norwich University Hospital NHS Trust Experience:
Plastics play an important role in the network’s nominated priority areas — assisted living; DIIA, including diagnostics; regenerative medicine, biopharmaceuticals and bioprocessing; medical devices and diagnostics; stratified medicine and high value manufacturing. Examples of plastic-related projects include polymer materials for cell scaffolds in regenerative medicine, plastic-based point-of-care diagnostics, such as lab-on-achip devices, hand-held monitoring devices like glucose monitoring insulin pens and blood pressure monitor, new plastic compounds for the packaging of bioprocessed drugs and the formulation of certain insoluble pharmaceuticals using polymer based substances (see also page 28).
Wyeth phase 1 drug trial on injectable BMP in tibial fracture 2004 -2006 Wyeth phase 2 drug trial BMP in tibial fracture 2004 – 2007 DePuy post marketing surveillance knee joint replacement 2005 – 2012 DePuy PhD studentship immunology study on metal ions in hip replacement 2012 - current Amgen phase 2 two drug trials on hip and tibial fractures 2009 - current Orthox Ltd Technology Strategy Board developing therapeutics 2 (regenerative medicine) translational project awaiting start.
JULY | AUGUST 2012 / MPN /27
University of Bradford | PHARMA POLYMER EXTRUSION
Plastics in Drug Forumlation: University of Bradford Leads the Way in Pharma Polymer Extrusion WORDS | SAM ANSON
The University of Bradford is home to one of the leading centres of polymer research in the UK — the Polymer Interdisciplinary It’s clear that the range of Research Centre (IRC), which applications for medical includes the universities of plastics is broad reaching and Leeds, Sheffield and Durham growing. But did you know as members. Bradford is also that plastics are used as home to the Centre for excipients in novel life-saving Pharmaceutical Engineering drug tablet formulations? Science (CPES), a hotbed of Certain plastics, pharmaceutical innovation for pharmaceutically accepted industry. A fusion of research polymers, are being used as between the two departments has given rise to matrix materials to carry a leading position in pharma insoluble active polymer research, according pharmaceutical ingredients to Dr Adrian Kelly, a senior (APIs), presenting HIV and lecturer in polymer cancer patients with new and engineering and co-founder more efficient treatments. of the centre. The process used to prepare these formulations is Why Use Polymers in Drug something with which we are Formulations? all familiar — hot melt Many newer APIs, such as extrusion. those for HIV retroviral and cancer treatments, have extremely poor bioavailability. Poor bioavailability refers to the fact that even though an API is known to successfully treat a certain disease, its physical properties prevent it from being administered orally. In many cases, this is due to the API’s poor solubility, which means it cannot be easily absorbed by the body after being swallowed. Bioavailability also refers to the behaviour of the API in the stomach. Once dissolved, the API must be able to permeate across the gastro intestinal tract to be absorbed in the blood. Conventionally, excipients used to carry APIs and form tablets have relied on the solubility of the APIs, thus the development of some new drugs has been limited. Tablets have needed to be large to carry enough dosage of the API to allow for the limited absorption in the gut. 28/ MPN / JULY | AUGUST 2012
Pharma Polymer Materials Extruding these APIs with pharmaceutical grade polymers — for example methacrylates, celluloses, polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) or polyethylene oxide (PeO) — creates a solid solution or dispersion of the drugs, which can be used to make a tablet in the normal way. In simple terms, the solid dispersion allows formulators to incorporate insoluble APIs into tablets which will behave in the same way in the gut as tablets containing normal, more soluble APIs. Four selected suppliers of pharma polymers for poorly soluble APIs are Germany-headquartered BASF and Evonik, USA-based Dow Chemical and Japanese company Shin-Etsu. BASF describes its range of pharma polymers as solubilisers. The materials are sold under the following brand names — Kolliphor, Soluplus, Kollisolv and Kollidon. All four brands cover a range of polymer types. BASF claims to have “extensive expertise and cutting-edge tools” to help customers find answers to their solubilisation problems and interested formulators are
advised to get in touch directly. Evonik describes itself as a leader in polymer-based excipients for oral dosage forms. Its brands in this area are Eudragit, Resomer and Lakeshore Biomaterials. The latter was acquired from USA-based SurModics in November 2011. Dow Chemical’s brands include cellulosic polymers Cellosize, Ethocell and Methocel as well as its PeO Polyox. Shin-Etsu claims to be one of the world’s top chemical companies. It produces a variety of cellulose derivatives and supplies to several customers for use in pharmaceutical applications in addition to the construction, paint and food industries. Shin-Etsu began the production of cellulose derivatives for pharmaceutical applications in 1962 under the trade name Metolose, and one of the major pharmaceutical applications is film coating around tablets. On July 3-4, 2012, the CPES co-hosted a technical seminar with Shin-Etsu on solid dispersions. Delegates from worldwide pharmaceutical companies travelled to Bradford to learn more about Shin-Etsu products and processing as well as characterisation technologies in operation at the university. Continued on page 31
<< ABOVE: ThermoFisher Scientific’s lab scale pharma polymer extruder is certified according to FDAregulations to be used with pharma polymer extrusion. >>
<< LEFT: The Polymer IRC and the Centre for Pharmaceutical Engineering at the UK’s University of Bradford. >> JULY | AUGUST 2012 / MPN /29
University of Bradford | PHARMA POLYMER EXTRUSION Continued from page 29
Extrusion Machinery The extrusion machinery required for the processing of these polymers with APIs is highly specialised. A wellknown supplier of this equipment is USA-headquartered ThermoFisher Scientific. The machines are conceptually the same as those used widely in the plastics industry — that is to say the normal parallel co-rotating twin screw extruder. Modifications, however, are that all moving parts, including the screw, the barrel, the feeding components and the gears, are made from surgical grade stainless steel. The grade of steel allowed is regulated by the US Food and Drug Administration (FDA), to ensure that when in contact with the drug there is no leaching of metal or other unwanted materials. In addition, the design of the machine is easy to dismantle and free from nooks and crannies where material can collect, allowing thorough cleaning to be performed. All functionality of the machines must be tested, documented and certified according to a user requirement specification (URS) and a functional design specification (FDS). Customers must show these documents to the FDA to demonstrate that the technique they are using for their formulations is qualified to the correct standards. Temperature controls on the machinery must be highly accurate as most APIs are very sensitive to high temperature. The normal processing range, depending on the formulation, is 80-180°C, but typically no higher than 180°C. There are two models of pharma polymer extrusion equipment — lab scale (pictured on pages 28-29) and production size. Research at the CPES At the CPES in Bradford, Dr Kelly has a 16 mm diameter ThermoFisher Pharmalab laboratory extruder with a configurable length to diameter ratio (L:D) of between 15 and 40:1. He also has a bench top Haake Minilab recirculating conical twin screw extruder and two small Dr Collin single screw extruders for producing sheet, tube and fibre. Dr Kelly uses this equipment to understand new extruded formulations and assess existing technologies. To do so, he needs to be able to characterise the properties of these materials to a high level of detail. These characterisations can be broken down into three categories — thermal analysis, rheological characterisation and pharmaceutical performance properties of the drug. Thermal properties such as glass transition temperature (Tg), melt temperature (Tm) and
degradation characteristics are measured for the polymer, the API and mixtures of both, before and after extrusion. These tests provide an insight into the miscibility of the materials — how well the substances mix together — and their morphology; whether they have a crystalline or amorphous nature. Rheological tests measure the flow behaviour of the formulation to allow an extrusion process window to be mapped. Hot melt extrusion lends itself well to process monitoring — which is encouraged by the FDA, reflected by their publication of a process analytical technology (PAT) initiative in 2005. This can be done using a variety of techniques, including near infrared (NIR), Raman or UV visible spectroscopy. At Bradford, in-line rheological and ultrasonic process monitoring techniques are also being investigated. The properties of the finished drug’s performance include an assessment of four aspects: the release rate of the API in the stomach — which can be controlled by the type and quantity of polymer used; the bioavailablity; the stability of the API in storage under certain environmental conditions; and the purity and toxicity of the drug. Mechanical properties of the extrudate are also important as they influence how readily the material can be milled into powder for subsequent tabletting. Examples of successful trials Three notable successes have been developed using polymeric solid dispersions — USA-headquartered Abbott Laboratories’s Kaletra HIV tablets and Isoptin SRE fast onset ibuprofen tablets and UK-headquartered Astra Zeneca’s Zoladex injectable breast and prostate cancer treatment.
<< Abbott Laboratories’s Kaletra HIV retroviral tablets was approved by the FDA for oncedaily dosing in April 2010. >>
JULY | AUGUST 2012 / MPN /31
End of Line | UK FOCUS
Additives for Laser Marking Leave
No Trace At a recent UK-based conference, PDM 2012, the regional technical services and applications manager at Gabriel-Chemie UK, Greg Hammond, presented an educational seminar about laser marking. His The printing and presentation included decorating of plastic information about the devices gives end users different marking effects crucial information about a available, the product. Laser marking is composition of dark and particularly handy as it light marks, colours and allows manufacturers to transparent markings. Gabriel-Chemie is an decorate devices without ISO13485 Austrianequipment coming into headquartered plastic contact with the product, refining specialist with six thereby giving an additional compounding extremely clean finish. facilities in Europe, including Kent in the UK. Laser marking relies on reactive additives in the plastic to enable permanent decorations to be made on the surface of plastics with a controlled laser beam. Because there is no change to the surface, sterilisation at high temperatures is possible. And according to Gabriel Chemie, no other process manages this so easily. Furthermore, only through the use of laser additives can nylons, polyolefins, polyacetates, plastified PVC, SEBS and TPU be marked as part of the normal production process without compromising quality. The marking performance of more or less self-inherent laser markable plastics such as polycarbonate, PPSU, PPS, PEEK, PET, PBT and styrenics can be further improved through the use of laser additives. Advantages of the method comprise: contactless marking of plastic parts, including soft, rough, tiered and curved parts; elimination of ink and pretreatment; decorations can be changed easily and quickly; permanent wear-, light- and chemical-resistant finish; and forgery-proof, short run individual designs. The method uses laser pulses, which enable all types of marks — including logos, lettering, serial numbers and data-matrix codes — thus guaranteeing complete traceability of patientspecific data on a long-term basis. In order to achieve the best marking contrast possible, engineers at Gabriel Chemie recommend that materials should be optimised with the addition of 2-3% of laser additives. The wavelength required for marking (around 1,064 nm) can be 32/ MPN / JULY | AUGUST 2012
generated by three different light or diode-pumped laser systems — the neodymium YAG laser, the neodymium vanadate laser and the fibre laser. Compared with the lesser used wavelengths of 355 (UV), 532 or 10,600 (IR) nm the most common wavelength range of about 1,064 (NIR) nm provides the following advantages: - Affordable initial laser investment and ongoing operating costs; - Increased marking contrast; - Choice of a dark or light mark via laser additive formulation; - Faster layout change and cycle times; and - Deepest beam penetration for markings below the surface. According to Philip Watkins, managing director of GabrielChemie UK: “Laser marking is proving increasingly popular for plastic parts in medical device applications where security, innovation and visual appeal are paramount. We offer a wide range of laser marking additives for polymers and it remains essential to choose the right polymer and additive to achieve the required results.
<< The scales and logos on these plastic products are examples of laser marked decoration. >>
JULY | AUGUST 2012 / MPN /33
SHOW preview Birmingham, UK, 25thâ&#x20AC;&#x201C;26th SEPTEMBER
mediplas makes history The opening of Mediplas at the UK’s National Exhibition Centre (NEC) in Birmingham on September 25, 2012, will mark an historic moment in the UK plastics industry. It is the first time that a plastics trade show has been dedicated to medical processors. For me, what’s most impressive is the broad range of technologies available. As of August 1, as many as eight materials suppliers had signed up, including specialist distributors and compounders. In injection moulding, stands had been booked by six brands of machine makers, six contract moulders, two mould makers and a variety of suppliers of hot runner systems, temperature control equipment and mould simulation and optimisation software. In other areas there are two exhibitors in extrusion, three in machining, two selling testing equipment, six selling equipment for end of line applications (including two plasma) and five involved in recruitment, industry networking and/or communications. The MM Live show next door will also be of interest. With strength in medical, the show offers visitors information about micro moulding as well as 3D MIDs, nanowelding and polymeric microtubes. And visitors interested in rapid prototyping will gain invaluable insight by visiting the TCT Live show, also located next door.
seminar programme Tuesday 25th September 2012
Polymers in the Medical Industry 10.15
Chairperson’s Welcome:
Tavakoli, Technical Director, Healthcare & Medicines KTN 10.25
KEYNOTE: Future Demands for Medical Plastics - A Predictive Overview
11.10
Polymers in the Medical Industry
11.40
Challenges for (Bio)Polymer Sterilisation within the Medical Device Arena
Chris Dyke, Connectivity Director, Medilink Derek Watts, Sales & Product Manager, Distrupol
Dr James Kennedy, Lecturer & Senior Research Fellow, Athlone Institute of Technology
12.10
Delivering Plastics Solutions to the Healthcare Industry Dr James Stern, Application Market Manager, Borealis
Plastic Processing in the Medical Arena Chairperson:
Gareth Pickering, Medical Plastics News 1.30
Development of Contact Lens Properties Through Innovative Processing & Material Design
2.00
To Mould or to Machine — Which Process is Best for your Application?
2.30
Polymer Processing From a New Prospective - The Microextrusion
3.00
How Two-Shot Moulding Adds Value to your Medical Device
Dr Seán Lyons, Senior R&D Engineer, Bausch & Lomb
Ross Fraser, Sales & Marketing Director, Carville
Simone Maccagnan, Sales Manager, Gimac Microextruders Andy Tettmar, Technical Sales Director, Hymid Multi-Shot
Sam Anson Managing Editor Wednesday 26th September 2012
Materials Selection Austin Coffey, Lecturer, Waterford Institute of Technology
Chairperson: 10.15
KEYNOTE: Medical Plastics Selection and Specification and the Current Regulatory Environment
11.00
Designing Molecularly Imprinted Polymers for the Analysis and Controlled Release of Corticosteroids
Dr Finbar Dolan, Technical Director, Lake Region Medical
Dr Laurence Fitzhenry, Post-Doctoral Researcher, Waterford Institute of Technology
11.30
Special Effects in Thermoplastics for Patient & Operator Safety Dr. Ton Hermans, Marketing Manager Healthcare, Innovative Plastics, SABIC bv
12.00
Laser Surface Modification of Polymers to Enhance Adhesion Andy J Wilson, EngD Research Engineer, University of Surrey/TWI Ltd
Testing, Regulations & Legislations Chairperson: Dr James Kennedy, Lecturer & Senior Research Fellow, Athlone Institute of Technology 1.30
Testing, Regulations & Legislations for Polymers Used in Medical Applications
2.00
Choosing the Correct Analytical Instrumentation for Solving Chemical & Polymer Science Problems
Tim Hulme, Principal Consultant, Smithers Rapra | Smithers Pira
John Dale, Global Medical Business Scientist, Intertek Chemicals and Pharmaceuticals Division
2.30
Accelerated Ageing of Medical Plastics Dr Dorian Dixon, Lecturer, University of Ulster
Register to visit online at www.mediplasuk.com
36/ MPN / JULY | AUGUST 2012
TO TO
Exhibitor Highlights connect with an exciting range of exhibitors On the show floor, Mediplas will play host to over 50 exhibitors who aim to bring you the most innovative and dynamic technologies available on the market.
Albis (UK) Ltd bfa solutions ltd Biesterfeld Petroplas Ltd Boy Ltd Carville Ltd Classic Industries Cotsworld Plastics Dalau Limited Data Plastics Ltd Distrupol Ltd DS Brookes Ltd Dyne Technology Ltd EFI Ltd Engel UK Ltd Ensinger Ltd Ewikon Ltd
M18 L22 M23 L37 L26 M26 M28 M22 L34 N31 L21 L28 N25 M21 L18 M19
Fibracon â&#x20AC;&#x201C; Insoll Machined Plastics Glazpart Greiner Bio-One Ltd HB Therm Hellyar Plastics Henniker Scientific Ltd KEBO AG Krauss Maffei (UK) Ltd Listgrove Martech Medical Med-Tech Innovation Medical Plastics News Magazine Medilink UK Mould Technology Magazine Netstal Ltd Netzsch-Geratebau GmbH
L27 M38 M31 L20 N30 M32 M41 L19 M42 N23 P37 M37 P37 P41 L20 N37
Nexeo Solutions Plastics UK Ltd N24 OGP (UK) Ltd N29 Precision Moulds & Tools Services L25 Premier Moulding Machinery L24 Quadra Solutions N28 Society of Plastics Engineers (SPE) P35 Sumitomo (SHI) Demag Plastics Machinery (UK) Ltd M29 Techsil Ltd L31 Telsonic UK Ltd L38 Ticona UK Ltd N26 Wilde Analysis Ltd N28 Wittenburg M25 Xtrutech N17 Zwick Testing Machines Ltd M30
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Exhibitor Profiles | MEDIPLAS 2012
materials customers on the best route forward. Ensinger — L18 www.ensinger.co.uk
Ticona Shows Plastics for Drug Delivery, Orthopaedics and Other Healthcare Markets Ticona, the global engineering polymer arm of Celanese, will exhibit materials for inhaler and drug injection delivery devices, orthopaedic implants and other healthcare applications. According to the company, in drug delivery its polymers enable inhalation and injection devices to function safely, smoothly, quietly and reliably. In orthopaedics, Ticona has a 50year history of supplying the implant market. It claims to currently provide material for over 90% of the world’s hip and knee replacement procedures. Ticona — N26 www.ticona.com
Stock Shapes Shape Up for Growth Since being established in 1987, stock shape manufacturer Ensinger’s UK operation has rapidly grown to include five additional branches throughout the UK – Waterlooville, Manchester, Bishop’s Stortford, Scotland and Birmingham. Semi finished products can be further processed to meet individual requirements. Specialist technical staff are available to advise and work with
Total’s Lumicene PE and PP Represented by Hellyar Metallocene polyethylene and polypropylene made by Brussels-headquartered resin manufacturer Total Petrochemicals under the brand Lumicene will be represented at Mediplas by UK distributor Hellyar Plastics. Hellyar Plastics offers Lumicene from UK stock on extended stock holding agreements to ensure the product is available exactly when required. Next day delivery is also possible when a quick response is needed. Hellyar also have a polymer compounding facility in Whitstable, Kent. Hellyar Plastics — N30 www.hellyar.co.uk
Biesterfeld Exhibits Borealis, Chevron Philips and DuPont Polymers Borealis, Chevron Philips and DuPont will be represented at Mediplas by distributor Biesterfeld Petroplas, part of panEuropean distributor Biesterfeld Plastic. The company believes that its partnerships with these suppliers give it access to their technical expertise and product knowledge. According to Biesterfeld Petroplas, this enhances the level of support it can offer customers, and compliments the service provided by its own technically minded sales team.
Distrupol Claims Widest Medical Polymer Range Polymer distributor Distrupol claims its product portfolio is widely regarded as being the largest range of medical polymers. According to the company, all medical polymers are compliant with the requirements of one or more of the following: United States Pharmacopeia (USP), International Standards Organisations (ISO) cytotoxicity, US FDA approvals or Drug Master File (DMF) listings. Distrupol — N31 www.distrupol.com
Biesterfeld Petroplas — M23 www.biesterfeldplastic.com
TPE Specialist Wittenburg Opens Facility in The Netherlands Dutch compounder Wittenburg is proud to announce the opening of a purpose built production and R&D facility in Zeewolde, The Netherlands. According to the company, the investment will enable it to meet the most stringent quality requirements of existing customers. It will also enable it to continue to supply products for highly regulated and risk adverse TPE applications into the long term. Wittenburg has a strong presence in the medical and pharmaceutical delivery device industries.
Albis UK Supplies ISO10993 Certified Grades Albis UK, a distributor and compounder under license for the UK and Irish markets, will show its 10993 range of biocompatible materials. It also offers custom developed solutions with own branded compounds and masterbatches under the Altech and Alcom tradenames. Technical support is provided by a team of field-based technical engineers providing expertise on material selection, application development and tool design. Supplier partners include: Bayer MaterialScience, Lanxess, BASF, Styrolution, LyondellBasell, Solvay, Eastman, Cereplast, and Azoty Tarnow.
Distributor Connects OEMs and Processors Claiming to be a global leader in thermoplastic distribution, Nexeo Solutions connects healthcare OEMs and processors with quality products. The company claims to help companies select materials, meet safety and compliance requirements, and ensure supply continuity. Services include specialised technical service, application problem solving and personalised attention. Customers can benefit from local sales representatives, a broad product line, a local inventory, a dedicated stocking programme and a flexible and frequent delivery service.
Wittenburg — M25 www.wittenburgbv.nl
Albis (UK) — M18 www.albis.com
Nexeo — N24 www.nexeosolutions.com
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Exhibitor Profiles | MEDIPLAS 2012
injection moulding
Tiebarless Engel Allows Automation Freedom Injection moulding machine maker Engel UK will demonstrate its unique tiebarless clamp system. The advantage of having no tiebars is the ability to fit larger moulds within a given machine size. Secondary benefits include freedom for automation solutions, faster mould change times, and a lower crane height necessary to load the tool. Engel claims to be the UK market leader in terms of the value and number of machines sold. Engel UK — M21 www.engelglobal.com
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Netstal Brings Precision Moulding to Mediplas Switzerland-based injection moulding machine maker Netstal claims to be a specialist and technology partner for injection moulding systems and services for the production of highly complex and precise medical and technical parts. Since 1945 Netstal has successfully installed over 35,000 high performance, high precision injection moulding solutions. Netstal says it is a professional partner in consultancy, technology, development, project management, training and support. Netstal — L20 www.netstal.com Boy to Demonstrate Micro Moulding UK-based Boy Limited will demonstrate a Boy XS to
medical specification, producing a poly-L lactide (PLLA) osteosynthesis plate — a plate used to mend broken bones. The part, with a shot weight of 0.1 grams, will show the control that the XS offers to be able to manufacture a micro part under cleanroom conditions. Total consistency and reliability is obtained by the special 12 mm plasticising unit combined with Boy’s branded Procan Aplha control system. Boy Ltd — L37 www.boy.ltd.uk
Machines for Repeatability, Says Krauss German plastic processing machine maker KraussMaffei says its injection moulding machines are designed and engineered to deliver versatility and high levels of repeatability in a very small footprint. Machines range from 35 to 4,000 tonnes and feature microprocessor control, cleanroom capability and a wide range of options. KraussMaffei — L19 www.kraussmaffei.co.uk Sumitomo Demag UK Shows Medical Device Expertise Sumitomo (SHI) Demag UK will
Exhibitor Profiles | MEDIPLAS 2012
injection moulding
be showcasing its expertise in medical device manufacturing, which spans 30 years, with case studies and example applications. The company’s IntElect all-electric machines are particularly suited for medical device production in cleanrooms, owing to their repeatable, clean and precise direct drives. Another plus is that all-in-one turn-key automated lines, including FDA compliance, are available from a single source. Sumitomo (DHI) Demag — M29 uk.sumitomo-shi-demag.eu
innovative approach to finishing of mouldings in the design and manufacture of plastic components. Using its specialist knowledge of design, tooling and finishing requirements, Glazpart claims its surface and aqua foiling effects is market leading. The effects can be used to match other components and introduce wood grain effects — including Irish Oak — as well as technical surface treatments like a carbon fibre appearance. Glazpart offers a full component manufacture service — from concept and design to tooling fabrication, component manufacture and surface finishing. Glazpart — M38 www.glazpart.com
Contract Moulder Glazpart Imparts Special Effects Glazpart will demonstrate its
Swiss Multi Cavity Specialist Parades Hot Runner System Swiss specialist multi cavity
mould maker Kebo will demonstrate its own in-house designed and manufactured hot runner system at Mediplas. According to the company, the technology is a major factor in Kebo’s success in managing mould making projects for medical devices, drug delivery devices and laboratory products. Apparently, Kebo’s comprehensive know-how of the entire injection moulding process, enables customers to achieve the highest precision in production and economic efficiency, as well as the maximum longevity of their equipment. Kebo — M41 www.kebo.com
Zhafir All Electric Moulding Machines and FASI Auxiliaries Shine at Mediplas UK-based machinery distributor Premier Moulding Machinery (PMM) will be showcasing the German built Zhafir all electric machines from China-based injection moulding machine maker Haitian. The range encompasses the Venus series (400 to 4,100 tonnes) and the innovative Zhafir Mercury series with the tie bar free concept. PMM specialises in providing complete moulding
Hall 3A 41 Stand M
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Exhibitor Profiles | MEDIPLAS 2012
injection moulding solutions based around the Zhafir machinery, with Taiwanbased FASI material handling and temperature control equipment and China-based Max-Robot automation equipment. PMM — L24 www.pmmuk.net
PM&T to Show Moulds for Lancets, Cannula Hubs and Inhalers Mediplas visitors interested in learning about specialist medical mould making will be able to speak to experts at UK-based Precision Moulds and Tools (PM&T). The company’s promotional literature includes details of a 96-impression tool for a lancet device operating in a vertical moulding machine, a fourimpresssion tool to produce cannula hubs, and a 16impression tool for making
actuator components in an inhaler. Precision Moulds and Tools — L25 www.precisionmoulds.co.uk
Multi Tip Hot Runner Concept for Syringes The UK arm of Germanyheadquartered hot runner systems maker Ewikon will show its HPS III-MH nozzle multi tip hot runner concept. It is suitable for direct side gating of parts as well as for compact valve gating with distances between cavities as close as 6 mm. Especially advantageous for the
production of syringes or pipettes with demanding requirements regarding dimensional accuracy is a version with 60° degree tip angle because it helps to eliminate core deflection caused by the melt pressure. Ewikon — M19 www.ewikon.com
EFI Develops Specialised Medical Hot Runner Controller In recognition of the demanding nature of medical moulding, UK-based supplier of hot runner temperature control systems EFI has developed what it considers to be the most advanced and complete hot runner controller package available on the market. It has focused its technical development to meet the exacting requirements of the modern medical moulding facility, including aspects of consistency, accountability and traceability. EFI — N25 www.efisystems.eu Swiss Family Makes 4,000 Temperature Control Units a Year, and Counting Claiming to be the leader in its sector, Swiss family-owned temperature control equipment manufacturer HB Therm will bring innovative “Swiss made” temperature control technology to Mediplas. The company produces over 4,000 units per year and has subsidiaries in Germany, France and Japan. Furthermore, it has more than
42/ MPN / JULY | AUGUST 2012
40 further national agencies, making the company an international supplier. HB Therm — L20 www.hb-therm.ch
Autodesk Simulation DFM Software Released At Mediplas, UK-based simulation specialists Wilde Analysis will present Autodesk Simulation DFM (design for manufacture) software. DFM provides plastic part designers with real time feedback for manufacturability, tooling and component cost, and environmental impact whilst they model within their existing CAD environments. Wilde Analysis — N28 www.WildeAnalysis.co.uk BFA Presents π_Inject Moulding Optimisation Software Switzerland-based software developer BFA Solutions will present its π_Inject software to the UK medical plastics sector. According to BFA, π_Inject gives moulders well-arranged production and process information to allow analyses and the recognition of potential for optimisation. π_Inject’s special features include an overall equipment effectivess (OEE) analyser and data set handling. Additional
Exhibitor Profiles | MEDIPLAS 2012
injection moulding equipment can be included, like material feeding, automation lines and other systems. The system is available on mobile devices. BFA — L22 www.bfa.ch
Finished Product Outsourcing Option is a Classic USA-based specialist medical moulder Classic Industries will demonstrate its skills and what it describes as a “commitment to excellence and efficiency”. With more than 580 employees at seven production facilities around the world, including one in Durham, UK, Classic Industries can provide OEMs with
contract services in design, manufacturing, assembly, packaging and logistics services. Advanced engineering and project management capabilities include design, process development, cleanroom manufacture, complete part validation, assembly, printing, welding, packaging and logistics. Classic Industries — M26 www.classicind.com
Data Plastics Announces Fruits of Investment UK-based medical injection moulder Data Plastics will promote its recently enhanced manufacturing capability — including a coordinate measuring machine (CMM) for fast quality checks; a Mars moulding machine; an HP 3D printer; an expanded and upgraded ISO13485 class 7
cleanroom; PEEK moulding capabilities; three-axis pick and place robots; close-looping of moulding machines to minimise waste; and atmachine blender systems able to add colour and blend materials. Data Plastics — L34 www.dataplasticsmedical.co.uk
OEM Partner Greiner Bio-One Promotes Custom Services Greiner Bio-One will show its custom moulding services at Mediplas. As an OEM it is a long-standing partner to the life sciences industry. Partners and customers include pharma, diagnostics and medtech companies. Its specialisms
range from the ‘simple’ branding of an existing product to unique, customised developments. The company describes its service as stateof-the-art injection moulding technology. Greiner Bio-One — M31 www.gbo.com Martech Medical to Present Moulded and Extruded Products USA-based Martech Medical will present its range of contract moulding and extrusion services for finished product manufacture. Products include standard and custom moulded components, as well as ancillary products such as peel-away introducers, TuohyBorst adapters, vessel dilators, needles, guide wires, and over the needle (OTN) catheters. Martech Medical — N23 www.martechmedical.com
Hall 3A Stand M30
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Exhibitor Profiles | MEDIPLAS 2012
people and communications and sharing collaborative success stories from its members. Medilink — P37 www.medilinkuk.com
Medilink Unravels NHS Procurement at Mediplas Healthcare industry networking group Medilink will launch its quarterly guide to NHS procurement at Mediplas. Apparently, the guide, which is in digital format, breaks down the many routes into the NHS — a market estimated to be worth £20 bn — and identifies hardto-find procurement opportunities. It will include regular updates on the UK government’s new commissioning scheme, structural changes as well as hyperlinks to NHS buyers. Medilink UK will also be giving live demonstrations of its tenders and sales leads service
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Media Platform Announces Med-Tech Innovation Expo 2013 Med-Tech Innovation, a leading media platform serving the UK and Irish medical device design, research, innovation and engineering community, will be present at Mediplas. The company will be providing details of its new event for 2013 — the MedTech Innovation Expo. Med-Tech Innovation — P37 www.med-techinnovation.com
Free Copies of Mould Technology Magazine Mediplas visitors will be able to pick up a free copy of UKbased injection moulding magazine Mould Technology. According to the publisher, the magazine provides a vast wealth of technical information to its readers which helps in the manufacture of polymer moulded products, especially for the medical industry. Features cover prototyping, mould design, mould making, injection moulding, and the handling of the final plastic part. Mould Technology Magazine — P41
www.MouldTechnology.co.uk
Mediplas Hosts Plastic Recruitment Experts Listgrove Visitors looking for recruitment in the plastics industry will be pleased to know that UKbased Listgrove will be on site to help. With more than 35 years of experience, Listgrove describes itself as a specialist recruitment and human resources (HR) services provider to the plastics, polymer, packaging, petrochemical and chemical sectors. Services include executive search, volume selection, interim appointments, outplacement and career transition, management coaching, competency frameworks, assessment and development, retention and rewards, and redundancy and relocation. Listgrove — M42 www.listgrove.com
Exhibitor Profiles | MEDIPLAS 2012
extrusion testing
DS Brookes Showcases Medical Extrusion Machinery DS Brookes, the home of Davis Standard Extrusion Systems Europe, will showcase its portfolio of medical extrusion machinery. The company is the UK’s largest supplier of bimetallic barrels and extrusion screws for plastics and rubber processing. It is also the European home for the provision of spares and support for Davis-Standard machinery. This includes the former extrusion machinery businesses of Betol, Francis Shaw Plastics, Floataire and Kabel Teknik. DS Brookes — L21 www.dsbrookes.com
Versatile Twin Screw Extruders in 19, 24 and 35 mm UK-based extrusion machinery supplier Xtrutech will show its range of twin screw extruders designed for R&D in the areas of thermoplastics, biopolymers, medical plastics and pharmaceuticals. According to the company, the company’s XTS 19 bench top line is ideal for smaller samples while the XTS24 and XTS35 R&D lines are suitable for scale-up to production and processing of larger samples ranging from 2-100 kg per hour. Xtrutech — N17 www.xtrutech.com
Zwick Offers Specialist Medical Device Testing Equipment Medical device designers at Mediplas will be interested to know that Germanyheadquartered testing equipment supplier Zwick Roell is offering advice about standard and bespoke testing solutions. The company collaborates with an extensive range of industrial customers and academic establishments. Zwick’s equipment for evaluating finished medical devices includes injector pen action testing, catheter strength testing, as well as standard tests for wear and impact resistance, tensile strength and fatigue. Zwick Testing — M30 www.zwick.co.uk
Netzsch Demonstrates Thermal Analysis and Thermophysical Properties Testing Leading supplier of thermal analysis systems Netzsch Instruments, part of worldwide Netzsch Group, will be on hand to show thermal analysis techniques and thermophysical properties testing systems. Thermal analysis methods include differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and dynamic mechanical analysis (DMA). Thermophysical properties testing techniques include laser flash for thermal diffusivity, from which thermal conductivity can be calculated. Netzsch Instruments — N37 www.netzsch-thermalanalysis.com JULY | AUGUST 2012 / MPN /45
Exhibitor Profiles | MEDIPLAS 2012
end of line The company is ISO 9001 accredited. Carville — L26 www.carville.co.uk
pump. As a result, Dyne says the unit can be installed and operational within minutes. Dyne Technology — L28 www.dynetechnology.co.uk
Henniker Showcases Plasma Surface Treatment Equipment UK-based supplier of plasma surface treatment equipment Henniker is showcasing its range of plasma surface treatment. The product range encompasses low cost benchtop treaters to high throughput batch and in-line machines to rent or buy. They also offer customisable products, a free proof-ofconcept service, and comprehensive surface testing facilities. The equipment not only provides a solution to basic surface adhesion problems, it can also impart specific functionality to medical devices, including permanent hydrophobic, hydrophilic and low friction properties. Henniker Scientific — M32 www.plasmatreatment.co.uk
Dyne Excited About VacuLab Benchtop Plasma Unit, Says MD UK-based plasma equipment supplier Dyne Technology will demonstrate its portable benchtop VacuLab laboratory vacuum plasma unit. According to the company, the unit is a cost effective solution to the problems of improving surface wettability and surface energy. It requires a 240 volt, 13 amp power supply and is equipped with its own vacuum 46/ MPN / JULY | AUGUST 2012
“Ideal Venue” for Live Welding Demo, says Telsonic The UK division of Swiss ultrasonic joining and cleaning equipment supplier Telsonic has said that Mediplas represents the ideal venue for its technology. The company will demonstrate live its proprietary Soniqtwist technology that enables delicate seals and membranes as thin as a micron to be welded successfully within devices using ultrasonics without the risk of damage or perforation. Other technologies on show include a unique torsional welding technique, hot air-cold staking (HACS) equipment, ultrasonic cleaning technology, and a handheld ultrasonic welding unit. Telsonic — L38 www.telsonic.co.uk Automated 3D Parts Measurement Lines Up UK-based supplier of more than 350 coordinate measuring machines (CMM) OGP UK will demonstrate its ability to measure components made from plastic using advanced 3-D contact and non-contact video-based measuring machines. With multi-sensor technology, up to five previous separate measurement devices are incorporated into a single machine, including high precision video optics with sophisticated LED lighting and touch probe, tactile and laser scanning sensors. OGP UK — N29 www.ogpuk.com
Techsil to Launch Panacol UV Curing Adhesive UK-based adhesives and sealants supplier Techsil will launch Vitralit 70741F UV curing adhesive for metalplastic bonding. Other product highlights include: Vitralit 1702 for tubes, valves and filters; Structalit 701 for endoscopes; Cyanolit 732F for delicate bonding of coloured plastics and stainless steel; FDA-compliant RTV615 and RTV100 silicones from Momentive; soft silicones for orthopaedic liners, gels for wound care and scar management; and UV curing equipment from German specialists Honle. Techsil — L31 www.techsil.co.uk
machining
Carville Carves Out Complex Machined Components Since it manufactured the world’s first haematology manifold for a blood diagnostic application in 1980, UK-based plastic machining specialist Carville has gone from strength to strength in complex plastic components for medical applications. The company will demonstrate these strengths with micro fluidic products such as diagnostic manifolds and quality assurance phantoms.
Dalau Turns PTFE to Mediplas Visitors UK-based plastics machining firm Dalau, which describes itself as a specialist in the precision machining of all engineering plastics, will demonstrate its broad range of services. The company supplies PTFE pistons for a new DosePro needle-free injection device, developed and launched by Zogenix Inc in the USA. Dalau has a drug master file (DMF) registered with the FDA. Dalau — M22 www.dalau.com Fibracon to Feature ISO10993 Plastics From Quadrant UK-based machining company Fibracon-Insoll will feature materials from Germany’s engineering stock shapes supplier Quadrant. It will also show its manufacturing service for plastic machined components made from PTFE, PEEK, Vespel (DuPont), Torlon (Solvay) and other engineering polymers. Sales director Mike Fryer comments: “Quadrant’s range of life science grades of medically compliant advanced polymers are utilised in artificial hips and knees, all offering full lot traceability, biocompatibility and ISO 10993/USP Class-6 compliance”. Fibracon-Insoll — L27 www.fibracon.com
CLEAN MACHINES
DESIGNING FOR MULTI-SHOT MOULDING
An Elegant Solution FOR REDUCING COST A STRAW POLL ON THE MPN LINKEDIN PAGE SHOWS THAT THE THE AWE-INSPIRING INTELLIGENCE THAT BRINGS US MULTISHOT MOULDING TECHNOLOGY IS A RELATIVELY NEW CONCEPT IN THE MEDICAL DEVICE INDUSTRY. THE TECHNIQUE IS AN EFFICIENT ALTERNATIVE TO OVERMOULDING AND CAN SIGNIFICANTLY REDUCE THE STEPS REQUIRED IN ASSEMBLY, THEREBY SAVING LABOUR COST AND TIME TO MARKET. SAM ANSON CAUGHT UP WITH THE VICE PRESIDENT OF ENGINEERING AND CHIEF TECHNOLOGY OFFICER OF PHILLIPS-MEDISIZE — PROBABLY THE LEADING MEDICAL MULTI-SHOT MOULDER IN THE WORLD — TO FIND OUT MORE. << Figure 1: This five-shot Negri Bossi injection moulding machine, supplied by Negri Bossi UK, is used to make toothbrushes in Italy. >>
Q: Bill, I’ve heard two different definitions for what multi-shot moulding means. Can you clarify for our readers please? A: Sure. In most countries, multi-shot moulding refers to an injection moulding process whereby more than one material is injected to produce a single part in a single mould — the part stays in the mould until it’s finished. Q: What are the benefits of designing products for this technique? A: Designing for multi-shot moulding can be very beneficial for a device manufacturer. For a small upfront investment in a multi-shot mould, OEMs can realise savings in manufacturing costs per item thanks to fewer assembly steps. At the same time, multi-shot moulding gives designers the chance to give surfaces a superior fit and finish, particularly on interfacial areas. Q: A multi-shot mould sounds intriguing. Can you give our readers an overview of how the process works? A: It involves different types of plastics being moulded on top of, or around, one another. The machine you use must have a separate barrel for each material, or shot. So for twin-shot moulding, the mould needs two barrels feeding into it and for three- and four-shot moulding, it needs three and four, respectively. The mould itself has mechanical actuation that moves parts of the mould to enable each barrel to add material until the part is finished [see fundamentals of multi-shot mould design on page 54]. Q: What specialist machinery is required? A: Our three- and four-shot machines have been specially designed with modifications for our own specialist purposes. Our preferred suppliers are Austria’s Engel and Germany’s Arburg. The optimum approach for multi-material moulding is normally dictated by part geometry and mould cavitation. Ideally, a manufacturer will have multiple machines sizes and injection barrel configurations to enable the best match between the tooling approach and the machine. At Phillips-Medisize we operate a number of different machine configurations, depending on the part being produced.
Continued on page 51
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<< Figure 2: A close up of a twin shot machine from Engel. >>
CLEAN MACHINES
Continued from page 48
In terms of two-shot moulding, we have machines with both parallel and perpendicular barrel configurations. The advantages and disadvantages of each are detailed in table 1. Our three-shot moulding machines are typically set up with a vertical third barrel in combination with two parallel horizontal barrels. And our four-shot machines have an additional micro moulding barrel which is attached directly on to the tool rather than the machine. Q: Tell me about the most complex mould you’ve seen. A: We have a three-shot drug delivery “patch” device which, for me, is a fantastic application of multi-shot technology (see figure 3). The top housing of the device is made of three different materials in a single mould. Functionally, the three materials create the outer shell, a soft-touch button, an LCD viewing window, and a light pipe for an LED. During final assembly, the top housing mates with a two-shot bottom housing to create a compact, fully sealed drug delivery “patch” system that protects the electronic delivery system inside. Q: Impressive stuff. Tell me about your multi-shot moulding capabilities with silicone? A: This is probably the area where we’ve had the most success in the past two to three years. We’ve developed assembly-free sealing components for devices with difficult water- or air-tight seals that previously relied on form-in-place gaskets. We are able to create the seal material using a second shot of silicone to give an extremely high quality seal for devices containing liquids under compression.
Table 1: Pros and cons of perpendicular and parallel barrel configurations on multi-shot moulding machines. Barrel Configuration
Advantages
Perpendicular
- Better serviceability for multi-material systems that utilise liquid silicone rubber (LSR). - Can use the machine for single-shot plastics if needed. - Can inject at parting line, allowing for cold runners without a sprue.
Parallel
- Generally allows for more appropriate sprue location. - Better floor space usage. - More compact auxiliary placement next to moulding machine. - More simplistic tooling designs, more like a conventional machine. - Could conceivably run two single shot tools, side by side. - Typically larger tiebar spacing that allows a larger mould base to fit between the tiebar, with no constraint of a side-entry perpendicular barrel.
Disadvantages - Requires more floor space. - Manifold systems require a 90° change in flow direction, making the manifold more complex.
- Limits mould size compared to perpendicular barrels, for rotary platen tooling applications. Example: a small part may need to be built into a larger mould than needed because the parallel spacing would dictate that. - Lack of centre-tocentre barrel standards limits ability to relocate tools to other suppliers.
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CLEAN MACHINES
“Our four-shot machines have a micro moulding barrel attached directly on to the tool rather than the machine.”
Continued from page 51
Q: In which areas of the industry are using this today? A: In diabetes care, our technology has been used for disposable pumps whereby multi-shot is used to bring the two halves of the pump together and create a seal. We’ve made promising progress working on the insulin pump system in the new OmniPod, the world’s first tubing-free wireless and waterproof insulin management system. In surgical care, our sealing solutions are used in catheter-based devices to ensure they are leak proof. We also have some advanced sealing solutions in drug delivery devices using both thermoplastic elastomers and silicones which are extremely exciting but are not yet on the market and I am therefore not able to discuss them – you’ll have to wait and see!
<< Figure 3: Geometry this complex can’t be done with assembly. Multi-shot moulding eliminated assembly costs for this drug delivery device, while providing a sealed one-piece surface for easy cleaning. >>
<< Figure 4: In this application, the multimaterial solution is used to minimise assembly by integrating a button, lens, sealing, and a soft-touch grip. Phillips-Medisize Vuecoat can be used to digitally apply hardcoat in-line with the moulding machine to the polycarbonate lens, for UV and scratch protection. >>
Background: Phillips Medisize is an early adopter of multi-shot technology. It embraced the technology when it first came out in the early 1980s, led mainly by innovation in the automotive industry on backlighting for radio faceplates. The technology became popular in medical devices in the late 1990s as OEMs integrated soft-touch surfaces into devices for improved comfort and grip.
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FUNDAMENTALS
of Multishot Mould Design IN A SINGLE SHOT MOULD, RESIN IS INJECTED INTO A CAVITY, THEREBY FILLING IT WITH MOLTEN POLYMER. THE TWO HALVES OF THE MOULD SPLIT OPEN AND THE PART IS EJECTED. IN MULTISHOT MOULDING, TWO OR MORE RESINS ARE INJECTED INTO THE MOULD TO CREATE A MULTIPLE MATERIAL PART. BUT FOR EACH ADDITIONAL SHOT, SPACE MUST BE CREATED IN THE MOULD TO ACCOMMODATE THE ADDITIONAL RESIN. PUT SIMPLY, STEEL MUST MOVE AFTER EVERY SHOT TO MAKE NEW SPACE FOR THE NEXT RESIN. JOHN BERG, MARKETING DIRECTOR AT US MULTISHOT MOULD MAKER MGS MFG GROUP, EXPLAINS THE FUNDAMENTALS OF THE SPECIALISED MECHANICS INVOLVED.
<< The core side of this rotary platen multishot mould rotates 180° during each cycle to allow a second shot of resin to be moulded over the top of the first shot. >>
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here are three principal ways of creating space in a multishot mould — common core, core and cavity steel change, and core toggle.
Common Core In a common core multishot mould, two materials are injected simultaneously. This is achieved by having the cavity side of the mould (the right hand half in the image) being split into two halves — the top and bottom four cavities. One of these is for the first shot of material and the other is for the second. Once the first shot has produced a part in the top half of the mould, the mould opens and the parts remain on the core side of the mould (the left hand side in the image). A rotary platen, or turntable, mounted to the platen of the injection press, rotates the core side of the injection mould 180° to align the parts with the bottom half of the cavity side of the mould, ready for the second shot. The mould closes and the second shot of resin is injected into the mould. After cooling, the mould opens and the part is ejected. The design of the steel on the cavity side for the second shot mirrors exactly that of the cavity steel for the first shot. As a result, new part geometry can be incorporated into the design to add a feature — for example, a grip line of soft-touch material on a handheld device. Depending on the characteristics of the part, additional shots may be added with or without an additional stage of steel movement or rotation.
CLEAN MACHINES Core and Cavity Steel Change This method enables moulders to add features to the core side of the part — something which is not possible with the rotary platen method. The part component produced by the first shot can be nested into the second shot, allowing material to be injected in, around and through the first shot. The method uses a rotating indexing stripper plate built in to the mould to lift parts made from the first shot from the first shot core steel after injection. The parts are not ejected, but are transported via the rotating indexing plate to the second shot core steel position. Indexing plates use simultaneous first and second injections just like the rotary platen method. Core Toggle This method is unique in that it does not use any type of rotation. Instead, actions to move steel are designed and built into the mould itself. Rather than opening after the first shot, the mould stays closed and internal actions move elements of the core and/or the cavity steel, creating new geometry between shots. Injection is sequential so cycle time is the total of the two shots — which is twice as long as the two previous methods. However, in the core toggle method, all cavity and core stacks create a finished multiple-material product every
cycle — which is twice as productive as the previous two methods. The previous two methods can only produce half as many parts per cycle because the first and second shots occur simultaneously. It should be noted that core toggle has significant geometry design limitations. All three methods allow designers to combine two or more resins. They can be combined in two ways — chemical bonding or through a mechanical or interlock bond. Chemical bonds can be created when one material molecularly grafts to another, or when heat and pressure create a “melt” bond between resins. A mechanical or interlock bond uses designed geometry features of the first and second shots to lock resins together. In the case of a “melt” bond, which is considerably less robust than true chemical bonding, mechanical bonding can be added to increase the life and performance of the mating areas. An interlock bond, with two or more non-bonding resins, is used to create in-mould assembled products with built in functionality, for example, rotation, slide actions, tamper evidence, and so on. Other multishot tooling systems include combinations of the previous three techniques, as well as rotary stack, rotary spindle, shuttle, moulding and robotic transfer. The geometry of the part, its performance requirements, budget and even existing press capabilities dictate which approach designers will use.
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Hall 3A Stand L19
MINIMALLY INVASIVE DEVICES
Coatings for Catheters By Dr Alan Rhodes, Senior Scientist, BioInteractions Ltd CATHETERS HAVE BEEN USED EXTENSIVELY TO PROVIDE ARTERIAL AND VENOUS ACCESS, DRAINAGE AND INFUSION CAPABILITIES AND TO ALLOW IMAGING AND DIAGNOSTIC PROCEDURES TO TAKE PLACE. THE SUCCESS OF SUCH PROCEDURES IS TESTAMENT TO THE WIDE VARIETY OF MATERIALS THAT ARE AVAILABLE, WHICH ALLOWS FAVOURABLE MECHANICAL PROPERTIES TO BE ENGINEERED INTO CATHETERS, AIDS PROCESSING AND HELPS MINIMISE ECONOMIC CHALLENGES FACED BY DEVICE MANUFACTURERS. HOWEVER, CATHETERS CAN FACE SIGNIFICANT CHALLENGES WHEN USED IN A BIOLOGICAL ENVIRONMENT, FOR EXAMPLE, BIOFILM FORMATION, WHICH CAN LEAD TO BACTERIAL INFECTION.
he interfacial characteristics of a component’s surface play an important role in determining its biocompatibility. Promising materials, which display ideal bulk properties, can be hindered as a result of undesirable surface properties that can evoke harmful biological responses. Coatings, therefore, represent a logical, cost-effective and convenient strategy for modifying the surface of a medical device, allowing the bulk composition to remain unchanged, whilst surface functionality is engineered to afford a more biologically acceptable characteristic. Broadly speaking, the major adverse issues affecting catheter use, include thrombosis (blood clots), infection and difficulties associated with insertion and removal. UKbased coating manufacturer BioInteractions has developed a variety of novel coatings specifically aimed at reducing such complications in an efficient and costeffective manner. Four of these coatings — Astute antithrombosis, Avert antimicrobial, Assist lubricious and Adapt drug delivery — are profiled in this report. Astute improves a catheter’s heamocompatibility by preventing thrombosis. Avert is an antimicrobial which helps to prevent infection. Assist gives devices a lubricious surface which eases friction for smooth entry and removal of devices into and out of a lumen. And Adapt is a coating which can control the release of drugs.
T
Astute Advanced Heparin Coating Astute is described by Biointeractions as an advanced heparin coating. It has been specifically designed to minimise non-specific protein binding, platelet adhesion and thrombus formation and is, therefore, ideally suited for minimally invasive applications that are in contact with blood. By combining both non-thrombogenic and antithrombogenic components on the same polymer backbone, the coating provides a multifaceted approach to haemocompatibility. The nonthrombogenic components, poly(ethylene glycol) (PEG), sulfates and sulfonates are co-polymerised with the anti-thrombogenic component, heparin, to provide triple endothelial-like action. The Astute coating has been evaluated in-vitro using << Figure 1: An uncoated sample of polystyrene (top) has promoted substantial platelet adhesion when exposed to plastic rich plasma (PRP), whereas the coated sample (bottom) has retarded this adhesion. >>
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Catheter Coatings | MINIMALLY INVASIVE DEVICES Continued from page 57
“Astute improves a catheter’s heamocompatibility by preventing thrombosis.” flow cytometry and radiolabelled platelets, whereby a 95% reduction in platelet adhesion was measured in comparison to an uncoated sample. This result has also been observed using scanning electron microscopy (SEM) (see figure 1). An in-vitro blood loop study was employed to find out how the Astute coating affects platelet activation. In this test, coated and uncoated polyurethane (PU) catheter samples were compared and platelet activation markers PF-4 and β-thromboglobulin were assessed via an enzyme linked immunosorbent assay (ELISA). A 92% reduction in platelet activation was observed for the coated samples in comparison to the uncoated ones. The in-vitro blood loop study also revealed a lack of occlusion within the coated device as evidenced by a well-maintained flow rate throughout the duration of the experiment. The biologically active component of Astute, heparin, has been specifically incorporated into the coating, to take an active role in thrombo-resistance. Chromogenic assays, which measure Factor Xa inhibition, can be employed to determine the activity of the immobilised heparin. The Astute coating currently displays one of the highest heparin activities on the market, with a value ranging from 250-300 mU/cm2. In order to evaluate the efficacy of the Astute coating in-vivo, a number of evaluations were performed, including thrombus formation and device occlusion. An ovine model was selected and 6 sheep were used. Random placing of coated and uncoated PU catheters in the left and right internal jugular veins was carried out and implantation was for a 30-day period, during which time simulated dialysis sessions were performed. Gravimetric analysis after the study revealed a 98.4% reduction in thrombus mass for the Astute coated samples, with no occlusion (Figure 2). << Figure 2: Uncoated and coated PU catheter samples explanted from sheep after 30 days. >>
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MINIMALLY INVASIVE DEVICES The Astute coating process is simple, water-based and uses no harsh solvents. Coating is carried out at room temperature, in less than 30 minutes, using a dip or flow based coating protocol (dependent on device) and is applicable to most substrates.
<< Figure 3: Avert spectrum of activity (4 h and 18 h incubation) compared with uncoated. >>
Avert Antimicrobial Coating As well as thrombosis, implantable devices are also prone to bacterial colonisation, which can occur on the device itself or on proteins that are adsorbed onto the device surface. Such proteins provide a breeding ground for bacteria, which can colonise and form a biofilm. Biofilm formation makes antibiotic penetration more difficult and can necessitate the use of higher doses. The Avert surface active antimicrobial coating provides a dual functional approach to preventing biofilm formation. The active component, poly(hexanide), is combined with a non-thrombogenic, highly hydrophilic component, poly(ethylene glycol) (PEG), to provide a stable, non-leaching system. This helps minimise protein deposition, as well as providing the surface active component that works on a contact kill mechanism (the polarised antimicrobial agent induces separation of the bacterial membrane, which causes exposure of the cell contents and bacterial cell death). The coating provides broad-spectrum activity against both gram positive and gram negative bacterial strains, including MRSA (Figure 3). Avert has also shown efficacy against yeast and fungi. As the coating is non-leaching, the longevity of activity is well maintained, with less than 20% reduction in activity after 4 weeks. As the antimicrobial agent is non-leaching, the risk of systemic toxicity is also minimised.
â&#x20AC;&#x153;Avert is an antimicrobial which helps to prevent infection.â&#x20AC;? Continued on page 60
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Catheter Coatings | MINIMALLY INVASIVE DEVICES
Continued from page 59
â&#x20AC;&#x153;Assist gives devices a lubricious surface which eases friction for smooth entry and removal of devices into and out of lumen.â&#x20AC;? As the coating is non-leaching, the longevity of activity is well maintained, with less than 20% reduction in activity after 4 weeks. As the antimicrobial agent is non-leaching, the risk of systemic toxicity is also minimised. << Figure 4: Assist Lubricious coating is suitable for use with Foley urinary catheters. >>
Assist Lubricious Coating The advancement of catheters through the tortuous pathways of the body is restricted by frictional forces that act between the device surface and the surrounding tissue. Such restrictions can lead to patient discomfort, prolonged procedures and an increased risk of tissue damage. The Assist enhanced lubricious coating has been developed to provide exceptional lubricity and hydrophilicity and incorporates a rapid coating and curing protocol to afford the final coated device. The coating combines lubricious and nonthrombogenic components on the same polymer backbone and is based on poly(vinyl pyrrolidone) (PVP). Additional functionality is incorporated into the polymer during the synthesis stage to provide flexibility and adhesive properties. A UV-crosslinking agent is also copolymerised into the polymer, which allows for rapid UV curing of the coating. Typically, a one-step coating is employed and UV-curing takes less than 1 minute. The coating becomes highly lubricious when wet, with a coefficient of friction less than 0.05. A stable durable coating is afforded through chemical linking to the device surface. Suitable substrates include PU, PVC, silicone, nylon and latex, amongst others. The coating is well suited for devices such as percutaneous transluminal angioplasty (PTA) catheters and Foley catheters. Adapt Drug Delivery Coating Site-targeted drug delivery, for example from drug eluting stents or drug eluting balloons, offers a number of advantages over oral administration of therapeutic agents. These advantages include prolonged deposition of the active agent directly into the vessel wall at high concentrations and at the time of injury. Also, systemic concentrations are minimised, thereby reducing the risk of remote systemic toxicity. The Adapt biostable drug delivery platform is a biocompatible, non-biodegradable
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MINIMALLY INVASIVE DEVICES
â&#x20AC;&#x153;Adapt is a coating which can control the release of drugs.â&#x20AC;? polymeric coating, which has been specifically designed for the controlled elution of therapeutic agents in a controlled and site-targeted manner. Synthesised from both hydrophilic and hydrophobic monomers, the amphiphilic (water loving and fat loving) Adapt system provides exquisite control over drug release and can be easily tailored, through simple adjustment in the monomer ratios, to afford customised release profiles and bespoke physical properties. The adjustable nature of the Adapt system means that a variety of drugs can be employed, for example the immunosuppressant rapamycin and the chemotherapy drug paclitaxel. About the author: Dr Alan Rhodes is a senior scientist working in research and development within the Medical Biomaterials group at BioInteractions, a UK-based manufacturer of biocompatible coatings.
<< Figure 5: Biointeractions's Adapt drug delivery coating can be used for drug eluting balloons. >>
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MINIMALLY INVASIVE DEVICES Hydrogel Stents and Catheters | MINIMALLY INVASIVE DEVICES
“Perfect” Non Stick Aqueous Hydrogel DISCOVERED FOR UROLOGICAL CATHETERS AND STENTS According to some sources, catheter and stent manufacturers are crying out for the perfect material to stop devices sticking to human tissue. Existing technologies and materials are cumbersome, some urological sources say, and coatings are expensive and involve extra manufacturing steps. CEO and founder of Q Urological, Scott Epstein, claims to have developed the “perfect” material — a non-stick aqueous hydrogel biomaterial — and has a patented processing method to boot. USA-based Q Urological Corporation, a wholly owned subsidiary of the Boston Scott Corporation, has developed a patented manufacturing process which produces a family of very high aqueous content, 100% all hydrogel catheters and stents. The products are made from the company’s trademarked “nothing sticks to it” structural hydrogel biomaterial pAguamedicina. This new manufacturing process utilises a family of polymer compositions, including reinforced, radiopaque, and absorbable compositions. Q Urological has received FDA approval for its pAguamedicina Pediatric Ureteral Stent, and is working to obtain FDA clearance for additional upper and lower urinary drainage products for adults later this summer. Devices comprised of pAguamedicina biomaterial consist of mostly water when fully hydrated with normal saline, closely emulating body fluids and mimicking human tissue. More importantly, devices made from the highly saturated material with less than 10% solids, exhibit significant mechanical characteristics. For example a 5F catheter with a
<< A pediatric ureteral stent made from pAguamedicina which has been in human urine for seven days. >>
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0.030 inch (0.762 mm) lumen can be stretched 300% without failure. Additionally, significantly reduced friction can be expected contributing to lubricous outside and inside surfaces which aid in delivery, in passage over guidewires and, in general — combined with the very soft nature of the device — provide a very plausible atraumatic implant. Q Urological pAguamedicina devices are not coatings. The catheter or stent is comprised totally of saturated hydrogel and in that manner there is no coating to erode, or become void of solution. And while hydrophilic coatings are widely used, according to Scott, they are typically expensive, can be unreliable and when configured with an antimicrobial or drug delivery system, exhibit a specific useful life that will expire (for more on coating, see pages 57-61). Q Urological has what the company calls “antifouling” technology, whereby “nothing sticks” to the material. According to Scott, this provides “extremely bio-compatible medical devices that continue to maintain an aqueous configuration”. Scott believes that, while almost all peer reviewed sources in the urology industry literature suggests that “the ideal material has yet to be implemented”, pAguamedicina devices will change that premise, addressing bio-film formation, of which primary needs include reduction of: (1) ureteral stent encrustation and (2) urethral catheter and stent infection. Pursuing these claims Q Urological Corporation will focus on product performance not addressed within the scope of typical 510k approvals — specifically, diminished bio-films on (< 30 day) implanted ureteral and urethral stent and catheters. And while FDA guidelines for product approvals associated with ASTM F1828 and F623 procedures do not address bio-film, in terms of pain and discomfort complications widely exhibited by predicate devices, many of which received FDA approvals by conducting in-vitro testing in water rather than human urine, Q Urological feels their all 100% hydrogel pAguamedicina catheter and stent technology which was tested in human urine will exhibit significantly better performance than predicate product. Thereafter, there are plans to focus this technology on vascular applications that exhibit similar benefits, focusing the same “antifouling” properties that keep bio-films from adhering. It is anticipated that there will be a diminished likelihood of red blood cells attaching to a device in-vitro — for example addressing distal tip thrombosis. Similarly, devices exhibiting reduced boundary layer friction and better fluid dynamic properties would be very beneficial.
Hall 3A Stand M29
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FOLIO CONTAINING SEVERAL 3D PRINTED PARTS, THIS PUMP DEMONSTRATES SOME OF THE APPLICATIONS WHICH ARE POSSIBLE WITH 3D PRINTING. THE BASE OF THE PUMP IS PRINTED IN A GREEN ABS-LIKE MATERIAL FROM ISRAEL-BASED OBJET. THE MATERIAL CLOSELY SIMULATES THE PROPERTIES OF ABS-GRADE ENGINEERING PLASTIC BY COMBINING HIGH-TEMPERATURE RESISTANCE WITH GREAT TOUGHNESS. THE FLUID VESSEL IS PRINTED IN A RIGID CLEAR TRANSPARENT MATERIAL (OBJET VEROCLEAR) AND THE TUBING IS PRINTED IN A BLACK RUBBER-LIKE MATERIAL (OBJET TANGOBLACKPLUS). OBJET IS A MANUFACTURER OF 3D PRINTING SYSTEMS AND MATERIALS.
FOLIO
B BRAUN VASCULAR SYSTEMS PRESENTS THIS DRUG ELUTING BALLOON FOR PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY (PTCA). COMMONLY KNOWN AS CORONARY ANGIOPLASTY OR SIMPLY ANGIOPLASTY, IT IS ONE THERAPEUTIC PROCEDURE USED TO TREAT THE STENOTIC (NARROWED) CORONARY ARTERIES OF THE HEART FOUND IN CORONARY HEART DISEASE. PLASTIC FEATURED IN THE BALLOON MUST BE ISO10993 REGISTERED AND ALSO MUST BE TESTING TO PHARMACOPOEIA STANDARDS TO ENSURE THERE IS NO LEACHING.
EVENTS medical plastics | DIARY 2012
Medtech innovation conference September 11, 2012 London, UK
Medical plastics trade show September 25 - 26, 2012 Birmingham, UK
Medical devices trade show September 26 - 27, 2012 Modena, Italy
Orthopaedic implants and instruments trade show September 12 - 13, 2012 Zürich, Switzerland
Medtech conference and exhibition September 25 - 27, 2012 Lucerne, Switzerland
Medtech trade mission to Saudi Arabia September 29 - October 4, 2012 Riyadh and Jeddah, Saudi Arabia
Medical plastics conference September 25 - 26, 2012 Boston, Massachusetts, USA
Medtech trade mission to Boston, USA September 25 - October 3, 2012 Boston, USA
Medical plastics and drug delivery device conference October 9 - 10, 2012 Copenhagen, Denmark
Mediplas Announces First Ever World Medtech Lineup for Free Conference Forum in Switzerland s many as 19 speakers will present at the free-toattend conference at medical plastic trade show Mediplas at the NEC in Birmingham, UK, on September 25-26, 2012. Highlights will include: Future Demands for Medical Plastics by Chris Dyke, connectivity director at UK-based medtech networking group Medilink; Polymer Processing from a New Perspective — The Micro Extrusion by Simone Maccagnan, sales manager at microextrusion machinery manufacturers Gimac in Italy; Modification of Polymers to Enhance Adhesion by Andy J Wilson, research engineer at the University of Surrey and TWI Ltd, both based in the UK; and Testing, Regulations and Legislations Used in Medical Applications by Tim Hulme, principal consultant, Smithers Rapra and Smithers Pira, also in the UK. Mediplas is being organised by Rapid News Commuications Group, the same company that successfully revived one of the oldest plastics trade shows in the world, Interplas, in 2011. Mediplas visitors will get free parking, free wifi and free access to neighbouring shows TCT (rapid prototyping and additive manufacturing) and MM and Nano Live (micro and nano manufacturing).
A
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The World Medtech Forum, a conference and exhibition for medical device technology companies sponsored by MPN, has announced the programme for its Center of Attention, a conference for orthopaedic, dental and medical devices. The event will take place on September 25-27, 2012, in Lucerne, Switzerland. A total of 20 exhibitors had signed up to the trade show at the time of going to press.
Scandinavia’s Medical Plastics Leaders to Meet in Copenhagen On October 9-10, 2012, Copenhagen will play host to two conferences, one about medical plastics, the other about drug delivery devices. The medical plastics conference is the 24th edition of the conference. Scandinavia’s leading technologists in the industry are expected to attend.