MPN EU Issue 61 by MPN Magazine

EUROPEAN EDITION

MEDICAL PLASTICS news A FRAMEWORK FOR MANUFACTURERS CONDUCTING HUMAN FACTORS STUDIES FOR PLATFORM DEVICES USING CLEANROOMS TO CREATE A REPEATABLE ENVIRONMENT FOR MICROMOULDING STERILISATION: HEAVY METALS — THEY’RE NOT ALL ROCK AND ROLL

ENGEL demonstrates it has what it takes to deliver BIG with precision, flexibility and speed ISSUE 61

July - August 2021

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CONTENTS July/August 2021, Issue 61

Regulars 5 Comment Corrine Lawrence unashamedly plugs this year’s Med-Tech Innovation Expo, Interplas and tct3SIXTY events. 6 Digital spy 12 Cover story A case study highlighting how ENGEL accommodated a partner’s rapid response to producing nestand-tub packaging for vaccine vials. 26 08:2021

Features 8 Packaging: The full package Jean Marc Galves, Berry Global’s new healthcare division lead, on how the company is expanding its presence in healthcare applications. 9 Cybersecurity: Mitigating cybersecurity risks in the IoT TurnONVPN’s Brad Smith advocates for a safe, secure, and censor-free internet for all.

10 Human factors engineering: Testing devices without a speciﬁed user population Owen Mumford’s Finola Austin outlines a framework for manufacturers conducting human factors studies for platform devices. 14 Cleanrooms: On repeat Joshua Haston of Connect 2 Cleanrooms explains how cleanrooms can achieve greater degrees of accuracy to reliably repeat the production of micro parts. 19 Materials: Determining polymer compatibility with harsh healthcare disinfectants — Part II LNP Copolymers’ senior business manager, Nithin Raikar, focuses on testing for compatibility among different materials, such as industry standard PC blends and advanced PC copolymers. 22 Sterilisation: Heavy metals — they’re not all rock and roll Michaël van der Jagt of Parx Materials argues that some antimicrobial and antibacterial materials could lead to catastrophic resistance problems.

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editorial content producer | corrine lawrence corrine.lawrence@rapidnews.com advertising | caroline jackson caroline.jackson@rapidnews.com

Editor’s Comment

vp sales & sales talent | julie balmforth julie.balmforth@rapidnews.com

C O R R I N E L AW R E N C E

head of studio & production | sam hamlyn graphic designer | matt clarke junior designer | ellie gaskell publisher | duncan wood Medical Plastics News Europe Print Subscription – Qualifying Criteria UK & Europe – Free US/Canada – £249 ROW – £249 Medical Plastics News NA Print Subscription – Qualifying Criteria US/Canada – Free UK & Europe – £249 ROW – £249 FREE on iOS and Android devices Subscription enquiries to subscriptions@rapidnews.com Medical Plastics News is published by: Rapid Life Sciences Ltd, Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE T: +44(0)1244 680222 F: +44(0)1244 671074 © 2021 Rapid Life Sciences Ltd While every attempt has been made to ensure that the information contained within this publication is accurate the publisher accepts no liability for information published in error, or for views expressed. All rights for Medical Plastics News are reserved. Reproduction in whole or in part without prior written permission from the publisher is strictly prohibited.

THREE IN ONE

ove them or loathe them, it would appear the B2B trade fairs are back after a ‘year out’. I’ve done my fair share of shoe-eroding, interhall aisle pounding — about 20 years of it — so you’d probably assume I’m emitting a small groan in response to a waning enthusiasm. Well, you’d be wrong; I am, in fact, a full-on trade fair lover, particularly this year, which represents a departure from my old stomping ground, the pharmaceutical industry. Birmingham has never looked so alluring — three events in one! (I haven’t been out much since the easing of lockdown, and I might be a little over excited.) Med-Tech Innovation Expo, Interplas and tct3SIXTY will be throwing open their collective doors to welcome in the best of their respective industries … and I get to meet them. Medical Plastics News organises and sponsors the Mediplas Pavilion in Interplas. This zone provides a focus for medical manufacturing, bringing together industry experts to offer practical advice from initial concepts and design ideas, through to materials and process optimisation. In addition, the medical plastics session of the Advancing UK Plastics Conference will feature three speakers, covering the design of plastics in medical devices to support

patient safety; improving patient compliance through innovative drug delivery; and functional materials. We might be a niche industry, but medical plastics has fingers in several pies, as our presence at the three aforementioned events demonstrates — we occupy corners within each of the wider medical technology, plastics and 3D printing industries. Having survived the pandemic and the mayhem it wreaked, many companies are now keen to show off, first-hand, their capabilities and innovations, a good number of which have been enhanced, extended or discovered as a direct response to the demands exerted by COVID-19. These events are your chance to put your company front and centre in the eyes and minds of prospective customers. Technology and know-how are important, yet much of business is secured via the people aspect — who do you feel you can trust and work with? Tradeshows and conferences frequently provide the starting point for such relationships. If you haven’t yet secured your place, there’s still time. You can register online at: www.med-techexpo.com; www.interplasuk.com; and www.tct3sixty See you in Birmingham!

BPA Worldwide Membership ISSN No: 2047 - 4741 (Print) 2047 - 475X (Digital) WWW.MEDICALPLASTICSNEWS.COM

DIGITAL

ACQUISITION UPDATE

spy EXPANSION UPDATE

www.elmet.com

Elmet begins expansion of its production facility in Austria www.skyrora.com www.aptar.com

here was good reason to celebrate on 23 July in Oftering, Austria. With the first turn of the shovel, Elmet officially launched the project to expand its existing company premises to increase production capacity and to create larger premises both for the mould-making division and for all the office staff. “We have been planning to expand for some time. But we had to put these plans on hold for a while due to the COVID19 pandemic. Now the time has come to face the future again with active enthusiasm,” said Kurt Manigatter, managing director of Elmet. Construction work is due to be concluded by June 2022. It will enlarge the production area by approximately 3,000 m² and the office space by 1,300 m². “We are investing in all areas. The mould-making and applications engineering departments will also be enlarged to meet the increasing demand for moulds, production systems, and dosing technology,” explained Manigatter. The company’s expansion plans reflect the continuous growth in the field of liquid and solid silicone. At the same time, the Upper Austrian company is giving its sales management a broader footing. The globally active key account managers are now grouped into three business units: dosing technology, tooling & turnkey, and part production.

Aptar to acquire 80% of Chinese producer of injectable drug delivery components

ptarGroup is set to acquire 80% of the equity interests of Weihai Hengyu Medical Products, a Chinese manufacturer of elastomeric and plastic components used in injectable drug delivery. The acquisition supports Aptar’s strategic priority to strengthen capabilities in highgrowth economies such as China, and enhances the company’s ability to respond to changing local market needs, including regional manufacturing, a wellintegrated supply chain and close proximity to customers and their patients. By adding local manufacturing

capacity, this acquisition positions Aptar to capitalise on the growth potential in the Asian region, while further strengthening the company’s ability to serve local and global customers in the injectable drug market with best-in-class products and services, competitive lead times and technical support, all while leveraging Aptar’s global network. Under the terms of the agreement, Aptar will have the option to acquire the remaining 20% of the equity of Hengyu upon the fifth anniversary of the closing of the initial majority equity investment.

PACKAGING UPDATE

www.pelibiothermal.com

PELICAN BIOTHERMAL REBRANDS TO PELI BIOTHERMAL

emperature-controlled packaging company Pelican BioThermal is unifying its brand across the globe. The company will now be known worldwide as Peli BioThermal. After growing its BioPharma Division through acquisitions from 2012 to 2014, Pelican Products, Inc. of Torrance, CA rebranded the division Pelican

BioThermal in the Americas and Peli BioThermal in Europe. The names aligned with Pelican’s existing brands and created a consistent market-specific presence for Pelican, but the work of Peli BioThermal and its customers is now increasingly global. “Customers who use our products and services operate

in many different markets across the world,” said David Williams, President of Peli BioThermal. “One name creates consistency for them and firmly positions us as a brand they recognise and trust, regardless of location.” Peli BioThermal’s unified global brand heralds its evolving direction. The company will launch an additional portfolio

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of offerings, including thermal shippers, rental programs, outsourcing services and new technology that connects all aspects of the cold chain for their customers. The company will also add new service centres to support the expanded offerings, growing its global network.

DIGITAL SPY

DEVICE UPDATE

www.sleepcogni.com

Sleep therapy start-up secures nearly £500K investment to advance its device

n innovative, UK-designed sleep therapy solution with global ambitions has raised more than £475K in the first week of a crowdfunding campaign. SleepCogni, a hand-held, data-supported device for people suffering from insomnia, has so far attracted funds from 157 different investors in this latest fund raise which combines venture capital investment and crowdfunding. SleepCogni helps insomnia sufferers break cognitive cycles that prevent sleep. Co-founded by Sheffield-based entrepreneur Richard Mills and Dutch chronobiologist and sleep expert, Dr Maan van de Werken, the device enables users to self-manage their insomnia, a condition which affects one

in three people across the world. The current crowdfunding investment round follows last month’s successful clinical trials at Sheffield Hallam University where SleepCogni produced “extraordinary” results, significantly reducing clinical insomnia after just 7 days. Earlier in June, the device was registered for medical use by the FDA. Funds from the latest investment round will go towards a software platform upgrade, recruitment of a new SleepCogni business development team, and beta testing of the device at four sites, two in the US and two in the UK. SleepCogni is then set to roll out its device to 130 clinics, including of one of the largest sleep care management groups in the US.

SUSTAINABILITY UPDATE

www.bormiolipharma.com

Bormioli Pharma pledges more low environmental impact materials by 2025

ormioli Pharma, an international manufacturer of glass and plastic containers for pharmaceutical use, has announced plans to use 50% sustainable raw materials, such as recycled plastic, bioplastics and glass from recycled sources in its products by 2025. With this commitment, the company will triple its current 16% use of materials with low environmental impact. According to a survey conducted by Bormioli Pharma on its customer base, more than 90% of companies in the pharmaceutical sector consider the quest for new sustainable packaging solutions a priority. This attention has already translated into an increase in sales of bottles, closures and accessories made from recycled or biobased

materials, which reached +50% in 2020 and +130% in the last 3 years. The company already offers 10 low-impact product ranges, including plastic containers obtained from polymers from highly selected separate waste collection. As far as bioplastics are concerned, Bormioli Pharma markets containers made from residual fibres such as sugar cane or corn starch, some of which are completely compostable. Other solutions are currently being developed and tested, such as the creation of an innovative plastic made from carbon emissions recovery, the introduction of ecodesign guideline that encourage a lower use of virgin materials, simplification of components and enhanced recycling.

talking

POINT

www.junkosha.com/en/news/54

JOE ROWAN, PRESIDENT AND CEO OF USA AND EUROPE, JUNKOSHA Junkosha has launched its Technology Innovator of the Year Award. What can you tell us about this initiative? Junkosha is on a mission to find an individual or team working within industry or academic research that deserves recognition for their innovative work in the delivery of Interventional Medical procedures or Microwave and mmWave technologies. To be eligible to win, all entries must be received by the end of September 2021. Our new award will be adjudicated by a panel of highly respected judges chosen for their industry credentials. Who can apply? We are looking for innovators in the fields mentioned who are embracing rapid change and are driven by the desire to make a lasting contribution in their field. To win this award, entrants will need to demonstrate how they meet some or all of the following criteria: • Explain how their work will enable customers to drive new/existing applications • How they are using technology in new ways • Provide information about what will be the ultimate benefit(s) • How the innovation will make a lasting contribution to society • How they are potentially developing a breakthrough that will require a leap in understanding or could ‘create a new category’. What’s the prize? The winning candidate or team will be judged and announced in March 2022, whereby they will be awarded $25,000 to invest in their worthwhile project. Is this award a one-time only endeavour? Junkosha’s new Technology Innovator of the Year Award will be a yearly awards programme, with the intent to offer entrants the opportunity to showcase their new innovations for many years to come.

PACKAGING

MPN SPOKE WITH JEAN MARC GALVES, BERRY GLOBAL’S NEW HEALTHCARE DIVISION LEAD, TO FIND OUT HOW THE PACKAGING COMPANY IS EXPANDING ITS PRESENCE IN HEALTHCARE APPLICATIONS.

FULLPACKAGE

THE What in the medical plastics industry has drawn the eyes of Berry Global? Berry has a long history in the healthcare industry, and creating a better patient experience through unique innovations is what differentiates us. Today, we are a global leader in pharma packaging and medical devices with more than 15 healthcare-focused sites in the US, EU, China, India and Mexico. Our newly formed global healthcare division will support new investments and partnerships in the space. Aside from the pandemic, what events have taken place within the market that has led to such growth? The healthcare industry is in the midst of a global transformation and demand for a better healthcare experience from an expanded pool of consumer-patients is increasing. Global healthcare costs are also expected to double during the next 7 years with an ageing baby boomer population. Our growth is driven by new products to improve quality of care and reduce costs. A great example of how we’re designing with the patient in mind is our digital inhalation devices. Our dry powder inhaler technology includes sensors and digital capabilities that enable connection to apps and the cloud. Our newest inhaler, RS01X, connects through Bluetooth to the Respiro app developed by Amiko to provide reminders, personalised insights and inhaler technique tips. Patients can share their data with healthcare providers, in person and digitally, to enable collaborative and data-driven treatment adjustments.

Which equipment or technology are you placing your primary investments in? Our global investments focus on digital capabilities, child-resistant and senior-friendly packaging solutions, and airless and preservative-free technologies. We’re allocating resources and capital to bring more innovative patient-centric drug delivery solutions and digitalisation capabilities for medical device packaging. New investments include ISO Class 7 to Class 8 cleanrooms for manufacturing. How does Berry hope to continue to meet sustainability targets? Sustainability is not new to Berry; it is at the core of our innovations. We’ve been a trusted partner in closed loop sustainable solutions for many years; for example, we recycle contact lens cases and reuse them successfully in the same application. We also offer one of the lightest OTC healthcare packaging portfolios, which reduces plastic use and saves on GHG emissions. Which of your products are the current market leaders? We lead in nasal, eye care, dermal, pulmonary and diagnostics healthcare. Some of our key innovations include: Risdrop — an eye dropper technology with a unique nozzle that dispenses uniform drops of the same size and weight to ensure the right dosage every time. It was recently recognised with an award during CPhI China. Palmsoft — a child-resistant, senior-friendly closure technology. It creates a soft rubber feel to the top of the closure to make it easier to open for seniors and anyone with arthritic conditions. Politainer — offers a unique closed filling system for healthcare applications so it creates a mess-free operation and minimises the risk of contamination. The Politainer collapses as the product is used, which helps to ensure complete emptying of the container with minimal residue. The collapsed PE container is fully recyclable, which aids in disposal. RS01 inhaler device — a patented capsule-based, refillable single-dose dry powder inhaler which is the worldwide standard for this category of devices. In addition to performance, safety and compliance, the RS01 design was designed for sustainability – it’s lighter weight and uses fewer components than previous generation devices. AirFree OTC — our Vega Ecosolution sustainable airless dispensing range is available in five different capacities from 50 mL to 500 mL, all light and 100% made out of plastic. The oxygen barrier protection in the bottle protects a formula’s active ingredients and allows for fewer needed preservatives.

Our global investments focus on digital capabilities, child-resistant and senior-friendly packaging solutions 8

CYBERSECURITY

MITIGATING CYBERSECURITY IN THE IoT

RISKS

BRAD SMITH, A TECHNOLOGY BLOGGER AND RESEARCHER AT TURNONVPN, ADVOCATES FOR A SAFE, SECURE, AND CENSOR-FREE INTERNET FOR ALL.

ccording to a recent analysis by The Insight Partners, the medical plastics market is set to grow at a 7.7% CAGR during the next few years.1 For some market sectors, that growth will be at an even higher rate. Although this opens tremendous opportunities for medical advancements, it also creates some real risk. As medical plastics become more advanced, giving doctors access to realtime patient data — and giving patients the upper hand in circumventing medical emergencies — information is constantly on the move. This ongoing data exchange can provide an in-road for a hacker with malignant intentions. Not only is each patient at risk of having their data skewed or corrupted, but each institution receiving that data is at risk of having their network infiltrated and compromised. If your network is adequately protected, you can help avoid a breach. At the same time, the medical IoT is growing, as is our technology for storing data. More databases than ever are moving to cloud-based storage, which provides greater storage capacity and allows medical professionals to access to the patient information they need, wherever they are. Unfortunately, these clouds don’t always have sufficient cybersecurity in place, leading to successful breaches.² Once cloud-based storage has been compromised, its data is also at risk. In addition, any user logging into the cloud to retrieve data can open up their network to the same hacker. A single poorly protected cloud can quickly expose many different networks and all the other sensitive data they hold. It’s no wonder, therefore, that people and companies have begun to pay more attention to how they’re protecting their sensitive data. Medical plastics are already used daily by medical professionals and healthcare providers. With new advancements on the horizon, we’ll likely see even more of these plastics making their way to providers and patients. Now is the time to improve cybersecurity protocols before any data is lost or exposed. It’s not just data that is at risk from insufficient cybersecurity protocols — with the increase in digital hospital equipment, devices using a compromised network can also be tampered with. Although we often think of the ramifications of lost patient data and how they can be used against the patient for identity theft or fraud purposes, the risk of ransom situations for the hacked institutions is also very real.

medical device or access sensitive customer data. This not only affects the operation of the product but also the reputation of the company. Hackers remain at the forefront of technology, and it’s no secret that cyberattacks have been on the rise. With a 158% increase of ransomware in the past few years in the US, there’s no sign of it slowing down.³ We’ll likely always need to adjust our cybersecurity protocols to keep sensitive data safe. For now, the best thing the medical plastics industry can do to keep their products, consumers, and patients safe, is to take the cyber threats seriously — and protect their products and their networks as fully as they possibly can. NB Content developed in partnership with ExpressVPN. References 1. https://www.globenewswire.com/en/ news-release/2021/04/20/2213476/0/ en/Medical-Plastics-Market-to-Growat-7-7-CAGR-to-Hit-USD-44-669-63Million-by-2027-Impact-of-COVID-19Pandemic-and-Global-Analysis-by-TheInsight-Partners.html 2. https://www.govinfosecurity.com/ union-benefits-administrator-says-datadeleted-in-hack-a-16872 3. https://www.theguardian.com/ technology/2021/jun/14/age-of-thecyber-attack-us-digital-destabilization

Fortunately, there are two small changes you can make that will strengthen your cybersecurity: • Install a Virtual Private Network (VPN). Using a VPN for network encryption scrambles any sensitive data as they travel through cyberspace. This makes the information — including log-in information and passwords — more difficult for hackers to decipher, leaving your network and your patients’ data better protected. nsure staff use secure passwords and multifactor authentication for all • E their devices and accounts. On top of strong passwords and keeping them safe from others, multifactor authentication adds another layer of security to your accounts: it requires users to go through an extra step of identity confirmation on a personal device. Designers of medical IoT should always keep in mind the aforementioned potential threats such as hacking and data stealing. Make sure security protocols are in place for data collection and storage. Once a device or a database is hacked, the criminal can affect the functioning of connected WWW.MEDICALPLASTICSNEWS.COM

HUMAN FACTORS ENGINEERING

FINOLA AUSTIN, HUMAN FACTORS ENGINEERING MANAGER AT OWEN MUMFORD, OUTLINES A FRAMEWORK FOR MANUFACTURERS CONDUCTING HUMAN FACTORS STUDIES FOR PLATFORM DEVICES, TO HELP ANTICIPATE THE NEEDS OF FUTURE CONSUMERS AND MEET BEST PRACTICE COST-EFFECTIVELY.

he development of medical devices must incorporate usability testing to ensure devices function as intended, while ensuring the safety of patients and other users. This requirement is established in industry standards and regulation. The EU Medical Device Regulation, which came into effect in May 2021, has a stronger focus on human factors testing than the preceding Medical Device Directive.1 The regulation demands that manufacturers must reduce the risks related to ergonomic features of a device as far as possible. It is therefore essential to assess device use with the various potential users, including medical professionals, lay users (such as carers) and patients; the latter category in particular may have a range of possible needs, depending on their condition. In addition, manufacturers will need to consider factors such as the intended use environment, training needs and the prior experience of end users. Drug delivery device manufacturers may find it challenging to conduct such testing for platform devices such as auto-injectors and safety syringes. Platform devices are purposely designed to accommodate a range of formulations for different therapies; there is, therefore, a broad group of potential end users whose needs must be addressed. The challenge for manufacturers is to demonstrate that their platform device can be used safely and effectively by a wide user population, which will also include people with different levels of physical and cognitive abilities. Testing

TESTING DEVICES WITHOUT A SPECIFIED USER POPULATION strategies and user recruitment will have to be carefully thought out to ensure sufficient representation and risk mitigation. The following steps provide a sound starting point for planning an inclusive strategy for a drug delivery platform device. DECIDE ON INITIAL SAMPLE SIZE Current standards advise that early development stages should include 5–8 participants per distinct user group, to reveal any major usability issues.2 The sample size may not necessarily provide further insight: one study showed that doubling the sample size from 5 to 10 subjects only increased the mean percentage of usability problems identified from 85.6% to 94.7% (Table I).3 A less formal test with easier-to-access participants, such as members of the device manufacturer’s company, can precede this initial testing. It is recommended, however, that manufacturers aim for a wide group of representative participants as early as possible, so that issues are identified and resolved early during device development. IDENTIFY USER GROUPS The number of user groups for platform device testing is likely to be higher than for drug delivery devices with specified intended users or defined therapy areas. Owen Mumford uses a framework that divides subjects into seven user groups (Table II), encompassing the factors that may affect how a device is used. The first four groups cover categories of people who may use

W W W. M E D I C A L P L A S T I C S N E W S . C O M

HUMAN FACTORS ENGINEERING

the device or aid a patient in using the device. The remaining three groups cover perceptual, cognitive and action abilities; that is, abilities that can affect how a user operates a device. Ideally, each use-impairment group should be mutually exclusive, to ensure that the device features are thoroughly tested within each group.

PLAN CAREFULLY As there may be a wide range of potential users of a platform device, it is critical to have a comprehensive sampling strategy that will help to anticipate safety and efficiency issues as cost-effectively as possible. The steps above can be used to guide a strategy that is tailored to manufacturers’ specific requirements. The plan should also consider how many studies are needed, the most appropriate stage of development to conduct studies, and the appropriate level of prototype fidelity. This thorough approach ensures confidence in the final drug delivery device for manufacturers and their potential pharmaceutical customers.

BROADEN GROUP DIVERSITY To fully understand how and why issues may arise with device use, it may be valuable for the sample groups to include secondary characteristics, such as gender, ethnicity and hand dominance. For instance, if the ‘Action ability’ group mostly comprises patients with neurological conditions such as Parkinson’s, adding patients with biomechanical impairments such as repetitive injuries will make the sample more representative and may reveal additional areas for improvement. Furthermore, there may be commercial reasons to broaden user groups, to meet specific business objectives or demonstrate a minimum representation of a specific comorbidity, for example, to ensure users are included for key markets or segments critical for commercial success. PREPARE VALIDATION SAMPLES After completing initial testing phases and addressing any issues, validation testing must be done to confirm that user needs have been met, risks mitigated and that there are no serious use concerns with the device. For this stage, US and UK regulators recommend 15–20 participants per user group, as this is considered large enough to account for any differences between users within the defined population. This final testing is critical to reassure prospective pharmaceutical customers that the device design has incorporated the needs of their intended user groups.

REFERENCES 1. https://eur-lex.europa.eu/legal-content/EN/ TXT/?uri=CELEX:02017R0745-20200424 2. https://www.iso.org/standard/69126.html 3. https://link.springer.com/article/10.3758/ BF03195514

Table I: Percentage of total known usability problems found in 100 analysis samples (rounded to 1 decimal place). Number of users tested

Minimum % usability problems found

Mean % of usability problems found

Standard Deviation

Standard Error

85.6

9.3

0.9

94.7

3.2

0.3

97.1

2.1

0.2

98.4

1.6

0.2

99.0

1.1

0.1

Table II: Human factors sampling strategy. Minimum sample size Group

Description

Small study (e.g., early-stage evaluation)

Large study (e.g., late-stage evaluation)

1. Adults

Adult aged 18 years plus; no upper age limit.

2. Juveniles

Persons aged between 8 and 17 years.

3. Caregivers

Lay caregivers who help another person to administer their injected medication.

4. Healthcare Professionals (HCPs)

HCPs who administer injected medication to patients (e.g., nurse, pharmacist, GP).

5. Perceptual ability

Persons with visual impairment. Plus at least one with auditory impairment.

6. Cognitive ability

Persons with a range of moderate cognitive impairment (e.g., ADHD, autism, dyslexia, learning disability).

7. Action ability

Persons with a range of physical (upper limb) impairment (e.g., RA, Parkinson’s, MS).

Total

COVER STORY

ENGEL DEMONSTRATES IT CAN DELIVER BIG WITH PRECISION, FLEXIBILITY AND SPEED TO ACCOMMODATE A PARTNER’S RAPID RESPONSE TO PRODUCING NEST-AND-TUB PACKAGING FOR VACCINE VIALS.

ll-electric, high-performance machines by ENGEL combine efficiency with precision. The decisive factor prompting Röchling Medical to invest in eight e-motion machines was the overall package, including digitalisation. In the production of nest-and-tub systems, the two largest machines, each with a clamping force of 5000 kN, impress with self-regulating temperature control processes. Nest-and-tub systems provide packaging for liquid pharmaceuticals in the form of vials or prefilled syringes. COVID-19 has led to a massive increase in global demand, as vaccine vials are also offered in this packaging form. For Röchling Medical at its Brensbach, Germany site, nest-and-tub systems are a new application which demands flexibility from injection moulding production. Focused on vials, five sizes of nest inserts are currently produced at Röchling on two new all-electric ENGEL e-motion injection moulding machines. The same applies to the standardised

tubs for all nest sizes, which require the highest clamping force of 5000 kN across the entire range of parts. To set up the moulds flexibly, the two machines intended for this application were ordered in size 500 and designed identically. “In the near future, the two 5000 kN machines will be in action 24/7 for nest-and-tub production,” says Marco Treuner, Technical Project Manager at Röchling Medical. EXTRA FEATURES BOOST EFFICIENCY IN THE CLEANROOM The nest-and-tub packaging dimensions are standardised to accommodate different filling and sterilisation systems by different suppliers. Throughout the filling and production process, vials remain in the nest, thus avoiding falling over or colliding with each other. The vials are well protected in the nest’s honeycomb structure. For 50 mL tubs, there are 16 vials per nest. The lower the filling quantity, the more vials there is room for in a package, and the more honeycombs the nest inserts have. POM is used for this demanding component geometry. This economical material reliably withstands cleaning and sterilisation before the filling process. But due to its pronounced shrinkage during cooling, POM places high demands on the stability and repeatability of the injection moulding process. Added to this is the mould design, which has many long, closely spaced cores. “We need very rigid mould mounting platens and particularly small centring diameters to avoid overmoulding, even with the very large platens of the e-motion 500,” says Treuner. The e-motion machines come with highly rigid platens as standard. ENGEL designed the platens with a particularly small centring diameter of 80 mm specifically for the nest-and-tub application at Röchling. The two e-motion 500 injection moulding machines in cleanroom design (easy-to-clean surfaces, closed lubrication systems and some more features reducing particle emissions) are equipped with a linear robot from the viper series and GMP-compliant belt conveyors — both of which ENGEL developed and produced. In addition, tailored solutions for Röchling make the large machines even more efficient than their standard counterparts. The cable ducts are enclosed, smaller cable bundles are routed in hoses, and the control cabinets have their own heat exchangers to prevent air turbulence at this point. Because the nest components are too unstable to stack when they are taken off the mould, additional U-shaped belt conveyors were installed above the clamping unit as a post-cooling section. Only 15 minutes after part removal, the viper robot picks up the components from the post-cooling conveyor and cycles them out via the larger belt conveyors for stacking in boxes. SMART TEMPERATURE CONTROL Constant temperature control is crucial for the dimensional accuracy of the demanding POM parts. Treuner explains: “We have to ensure repeatable quality as early as possible in the production process.” Quality controls (QC)

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occur several times at the Brensbach plant and at the customer’s site. If the customer is in the US — as is the case with the current order — sufficient time elapses between production and QC, and the recrystallisation process (shrinkage) is finished by then. At Röchling, part ageing is simulated in parallel over 6 months using a heat-ageing process. For precisely repeatable temperature control, Röchling Medical took a step toward digitalisation. Both machines use iQ flow control — ENGEL’s smart temperature control assistant. Equipped with six e-flomo temperature control water manifolds and six temperature control devices from the ENGEL e-temp series, the system relies on the software to control and regulate itself over the entire production batch, keeping the conditions constant. The temperature difference acts as a control variable for dynamic individual circuit temperature control. In the ENGEL solution, the injection moulding machines and the temperature control devices communicate with each other via OPC UA. In this way, iQ flow control can adapt the pump speed in the temperature control devices to the actual demand. This interaction combines temperature stability with high productivity and energy efficiency. “We can already see, in the short time after the start-up, that the pumps are running at just under 30% output instead of constantly at 100%,” reports Treuner. The decisive factor for the investment in iQ flow control was the POM material (it requires a very stable process to receive a constantly high product quality and dimensional accuracy), yet the company is benefitting from the significant energy savings. The energy consumption displays of the e-motion machines support the processor in systematic energy management.

MEDICAL MACHINES TAKE PRIORITY The two 500 models form part of the comprehensive package. All eight new e-motion machines with clamping forces of 1600, 2800 and 5000 kN are used for pharmaceutical packaging, diagnostics and medical technology cleanroom applications. In addition to the nest-and-tub systems, Röchling Medical also uses ENGEL machines to produce racks for pipette tips and microtiter plates. As a competence centre for injection moulding technology, the Brensbach plant combines injection moulding production, assembly and mould making. All-electric drive technology is the factory standard to avoid oil in the cleanroom. In addition, fast machine motion is crucial: the nest parts have cycle times of up to 40 seconds, and the tubs require a cycle time of 10 seconds. Triggered by COVID-19, the two 5000 kN machines were subject to enormous time pressure. “We adjusted our processes at the beginning of the pandemic and prioritised medical machines in all plants,” says Holger Kast, sales engineer at ENGEL Deutschland’s Stuttgart site. “For the Röchling project, we also accelerated order processing and postponed the red tape.” Getting the machines operational as quickly as possible was aided by ENGEL who delivered them in two parts, at no extra charge. “Our airlock is too small for a fully assembled 5000 kN machine,” explains Treuner. “If we had to open up the cleanroom to take in the machines, this would have involved a production stoppage of a week.” This would have affected several because there are more than 10 production cells in the large cGMP cleanroom.

When it comes to complex production cells, there are few companies who can achieve that at speed

Finally, by getting the complete production system from one single source means all components are perfectly matched to one another. “In ENGEL, we have a central point of contact, and we communicate directly,” says Lehmann. “Right from the outset, the entire production cell was perfectly planned, and all the components were precisely tuned. ENGEL made it easy for us. When it comes to complex production cells, there are few companies who can achieve that at speed.”

CLEANROOMS

JOSHUA HASTON, TERRITORY ACCOUNT MANAGER AT CONNECT 2 CLEANROOMS EXPLAINS HOW CLEANROOMS CAN SUPPORT THE ACHIEVEMENT OF GREATER DEGREES OF ACCURACY TO RELIABLY REPEAT THE PRODUCTION OF MICRO PARTS.

Creating a repeatable environment

FOR MICROMOULDING

or injection moulders, upgrading plastics manufacturing with a cleanroom to gain access to medical markets is a common move and a natural progression pathway. Cleanroom providers typically provide ISO 14644-1:2015 class 7 cleanrooms for such occasions. Having a class 5 cleanroom installed, however, brings additional benefits. MICROMOULDING Biplas Medical — a technical injection moulder in South Wales — had an ISO class 7 cleanroom installed when it introduced clean production in 2018. Earlier this year, the company took cleanroom production to another level when it needed an ISO class 5 cleanroom to house a micro-injection moulding machine to facilitate an Innovate UK grant project. Biplas Medical had joined a European consortium to develop a cancer diagnostics device, which, as it turned out, is produced using the smallest moulding ever made. The larger parts produced by the micromoulding machine for a different project weigh approximately 3–4 g. By comparison, the parts required for the Innovate UK grant project weigh less than 0.1 g. These parts are so small that quality control (QC) inspection requires a microscope and camera. The cleanroom ISO standard (146441:2015) dictates there can be no more than 10,200 particles of size 0.3 µm per m³ of air within an ISO class 5 cleanroom.1 To give an idea of scale, human hair has an average diameter of 100 µm and smoke particles are 1 µm. Achieving a microscopic level of environmental control is critical when producing micro parts as any contaminants would completely stop the products from working. Since investing in the ISO class 5 cleanroom, Biplas has received micromoulding contracts for dentistry components and a two-shot biotechnology component that separates fluids and cells as they pass through the product. Both parts cannot be produced in conditions any higher than ISO class 5.

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CLEANROOMS

BENEFITS OF CLEAN PRODUCTION A cleanroom creates a reliable and repeatable environment with controlled levels of airborne particulate. For manufacturers, this consistently clean production environment improves yield by reducing the number of parts that are rejected after QC inspection. Since the introduction of its first cleanroom in 2018, Biplas Medical has reduced its scrap rate and increased its scope of supply by being able to offer packaging services. Clients also benefit from this value-added service, as components that are cleanroom packed and double-bagged are much easier to transfer into a cleanroom; they are also more reliable as is less chance of contamination causing defects. TRAINED STAFF Often, the biggest contamination risk in a cleanroom is people. Operatives need to be trained to develop skills and knowledge in this specialised area of the market. A cleanroom is a large investment; it is, however, only one component of a contamination control strategy. If behaviours aren’t learnt and adhered to then staff pose a contamination risk to the end product. Once trained, a workforce will be aware of the appropriate behaviours that will control the introduction, generation and retention of particles, in line with ISO 14644 standards.

The challenge with creating a clean environment for medical plastics is that moulding machines produce contaminants during a cycle

CLEANROOM DESIGN FOR PLASTICS MANUFACTURERS The challenge with creating a clean environment for medical plastics is that moulding machines produce contaminants during a cycle. A favoured solution is to part-enclose the machine in a clean environment so that the tool face is protected by clean air, but the hopper remains external to the environment. Purpose-built modular cleanrooms can be profiled around machinery, or designed with clean canopies that can be integrated directly with the machine. Canopies with retractable fan filer units can facilitate quicker tool changing procedures, thus reducing production downtime. It is still possible to achieve a classified environment with full machine coverage. To achieve particle counts according to the levels dictated in ISO 146441, the cleanroom must introduce enough clean air to remove the contaminants produced by the process when operational. REFERENCE 1. https://www.iso.org/standard/53394. html

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Pore size measurement of porous materials PORVAIR SCIENCES’ DAVE COWIESON, MATERIALS SCIENCE MANAGER, KEN NZERIBE, MATERIALS SPECIALIST, CHARLIE BRIGGS, MATERIALS TECHNICIAN COMPARES CAPILLARY FLOW POROMETRY WITH MERCURY INTRUSION POROSIMETRY FOR DETERMINING PORE SIZE DISTRIBUTION. Porous materials demonstrate advantageous filtration characteristics which provide precise solutions in myriad applications ranging from large-scale industrial filtration (e.g., water or air filtration) to targeted separation and purification processes in pharmaceutical applications such as sample preparation, drug discovery, drug delivery. Understanding the distribution of pore sizes in porous materials such as porous plastics is crucial to selecting the right porous characteristics for effective filtration and separation performance of the porous material in application. There are two main methods of measuring pore size distribution (PSD): capillary flow porometry (CFP); and mercury intrusion porosimetry (MIP). In both cases, liquid (Porofil, a fluorocarbon liquid), is used for CFP; mercury is used for

MIP) is used to fill the porous structure; for CFP, the liquid fills the structure first and is expelled under increasing pressure whereas for MIP, the material is placed under vacuum to remove the air trapped in the pores of the material before liquid mercury is forced into the pores under increasing pressure. CFP CFP is a pore size characterisation technique that uses liquid expulsion to measure of the size of pores that completely penetrate through a porous network, so-called ‘through-pores’. A liquid is used to wet out and fill the pore structure thus displacing the air present. The wetting liquid is subsequently expelled by force using pressurised gas (air is used for CFP, and nitrogen is used for MIP), and a simple inverse pressurepore-size relationship

established. Gas pressure is applied and slowly increased expelling the largest pores first at low pressure and then smallest pores as the pressure increases (Figure 1). With this technique, a low surface tension liquid at low vapour pressures is used to minimise any potential evaporation during the measurement. The increase in airflow through the structure is used to measure this process, and generates a ‘wet curve’ on a graph. Once all the liquid has been expelled, the process is repeated, this time measuring the airflow through the structure with increasing pressure across the dry material to form a ‘dry curve’ graph superimposed on the wet curve. Data from the wet and dry curves can then be used to calculate the throughpores present in the material shown as a PSD

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for the material. Typically, manufacturers quote the range of pore sizes, from the minimum pore size to the maximum. This is suitable if the pore size of the sample follows a normal distribution where the mean tends towards the centre of the curve, but this is often not the case as the sample can either lean to the maximum or minimum points. Porvair Sciences quotes a minimum, maximum and mean flow pore (MFP) size from this distribution, providing a better understanding of the PSD of the material. As this distribution is based on air flowing through the structure, the mean must be quoted as MFP rather than a mean based on pore diameter. This is a key difference between these two techniques but, in most cases, MFP can be considered as a mean pore size. Porous structures contain a small percent of

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LEFT: Figure 1: a) An illustration of CFP. Through-pores of decreasing size empty as the pressure is increased across the sample, first pore number 1, then 2, and finally 3. b) Typical wet and dry run measurements (flow vs. pressure) and typical pore flow distribution (pore diameter vs. flow). dead-end or blind pores, and depending on the thickness of the porous structure, the percent of dead-end pores can increase. Deadended pores are those that terminate partway through the material; this characteristic is important to understand as CFP can only measure the pores that allow fluid flow through the structure from one side to the other. It cannot measure the dead-end pores, which will influence the resulting PSD. CFP measurements must be made on discshaped samples. Although bespoke housings can be offered for specific dimensions there are limits on dimensions that can be measured using CFP.

MIP For MIP, mercury is used to fill the pore structure by first placing the porous material under vacuum to remove the air present in the pores which would otherwise interfere with the intrusion of mercury into the porous structure. In addition, gas pressure is applied to allow the mercury to fill the pore structure. The material is inserted into a penetrometer, which is then installed in a pressure chamber in the porosimeter, evacuated, and backfilled with mercury. The penetrometer comprises a cylindrical section large enough to accommodate samples typically <10 mm in diameter/length. Large pores which are directly accessible at the surface are intruded into first and, as the pressure increases, ever-smaller pores accessible at the surface or connected to pores already filled are consequently filled

as illustrated in Figure 2. The volume of mercury intruded into the pores can be quantified via the electrical response calibrated against known volumes of mercury, and a graph of the volume of mercury intruded against the pressure required to push it into the pore structure is generated. By relating the pressure of intrusion to the size of the pore being filled, a PSD plot is generated. MIP measures all the pores within the structure including the dead-ended pores to give a more detailed and accurate measurement of the porous structure. The choice of mercury contact angle will greatly affect the calculation of PSD measurement obtained from MIP — a contact angle which provides a PSD comparable with that generated by the CFP method can be adopted; this, however, must be reported

BELOW: Figure 2: a) An illustration of MIP. Pores of decreasing size are filled as the pressure on the mercury is increased: first pore number 1, then pore 2, then 3, then 4, and finally 5. b) Typical raw volume vs pressure curve and pore size distribution curve.

alongside the PSD data. The MIP technique can be used to measure any sized sample (including complex shapes) provided it can be cut down to fit into the penetrometer used for the measurement. Although CFP and MIP yield different pore size distributions, each has their own benefits. It is important to understand the differences when comparing the pore sizes of different materials; it is also essential that the same technique is used for any direct comparisons. Materials with a large proportion of dead-ended pores will have very different particle size distribution when measured with the two techniques. Samples can be remeasured using CFP technique unlike MIP. MIP is destructive — measured samples must be discarded after measurement due to the entrapment of mercury in the pores during intrusion. CONCLUSION Fluid flow-through applications such as chromatography often require particle/ contamination filtration. Where pores of interest are through-pores, CFP is the appropriate method to predict the performance of an ultrafiltration or microfiltration media, or simply to better understand how a material will affect fluid flow. In drug delivery and dispensing applications such as eyedroppers or nasal sprays where bacterial prevention is necessary, both methods are relevant. MIP accurately measures PSD including dead-end pores to predict bacterial filtration efficiency and CFP is used to predict how the material will affect fluid flow in application.

enquiries@porvairsciences.com www.porvairsciences.com

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MATERIALS

Determining polymer compatibility with harsh healthcare disinfectants — Part II WITH THE SPATE OF NEW, HARSH DISINFECTANTS BEING USED IN HEALTHCARE SETTINGS — PRIMARILY IN RESPONSE TO THE COVID-19 PANDEMIC — DEVICE MANUFACTURERS NEED TO CONSIDER NEWER MATERIAL SOLUTIONS WITH IMPROVED CHEMICAL RESISTANCE TO WITHSTAND THE CUMULATIVE EFFECTS OF CLEANING. NITHIN RAIKAR, SENIOR BUSINESS MANAGER, LNP COPOLYMERS FOCUSES ON THE TEST FOR COMPATIBILITY WITH HEALTHCARE DISINFECTANTS AMONG DIFFERENT MATERIALS, SUCH AS INDUSTRYSTANDARD PC BLENDS AND ADVANCED PC COPOLYMERS. TESTING FOR COMPATIBILITY WITH HEALTHCARE DISINFECTANTS SABIC evaluated the compatibility between CRX and incumbent materials with 12 leading surface disinfectants widely used to clean devices. Disinfectants used in these products include quaternary ammonium compounds, sodium hypochlorite (bleach), hydrogen peroxide, and ethanol (also referred to as ethyl or isopropyl alcohol). Leading disinfectants such as PDI SaniCloth wipes and Diversey Virex wipes are published on the US Environmental Protection Agency (EPA) list which meet their criteria for combatting SARS-CoV-2, the novel coronavirus that causes COVID-19.1 Several of these disinfectants are listed in Table I. Data shown in the table are based on SABIC’s compatibility criteria scale. The materials tested were a PC/ABS blend, a PC/PBT blend and four PC copolymers from SABIC’s LNP ELCRES CRX resin family. Two of the ELCRES CRX grades are semi-crystalline copolymers, the other two are amorphous copolymers. RESULTS: BROAD CHEMICAL COMPATIBILITY OF PC COPOLYMERS Test results show that all four PC copolymers demonstrated broader compatibility with the selected disinfectant chemical products than the PC/ABS blend. Further, the semi-crystalline PC copolymers surpassed the PC/PBT blend in compatibility with Sani-Cloth AF3 and Virex TB wipes, considered among the most aggressive products on the market.

Specifically, the PC/PBT blend did not meet the compatibility criteria for elongation at break for these two disinfectants. TESTING FOR RESISTANCE TO EXTERNAL STRESS In addition to the ESC test, SABIC conducted a high-speed puncture test on selected material samples before and after exposure to one of the disinfectant chemicals. The purpose of this test is to reveal fracture patterns — either ductile or brittle fractures — as a gauge of impact resistance and toughness. Brittle fracture means that over time and prolonged exposure, the material tends to become more susceptible to stress cracking under application of an external force. Ductile fracture indicates a material with more toughness; that is, more

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MATERIALS

energy is needed to initiate a crack and there is a lower tendency for crack propagation.

Classification: Internal Use

PC/ABS HIGH SPEED IMPACT TESTING PC/ABS High Speed Impact Test 3000 2500 2000

Brittle Fracture

1500

Force (N)

For this test, the PC/ABS blend was compared with one of the amorphous PC copolymer materials. Each sample was tested with the high-speed puncture tool before and after exposure to PDI Sani-Cloth AF3 wipes for 3 days. At comparable conditions, data from this testing were used to determine differences in impact force and energy for the materials before and after chemical treatment of the moulded parts.

Crack Propagation

3 Day 500 0

1000

2000

3000

4000

-500 -1000

Time (ms)

Material

Temp (C)

PC/ABS PC/ABS

275 275

Chemical Treatment

Force (N)

Energy (J)

1245 1342

3.52 3.98

Control 3 Day

PC/ABS 3-day exposure to SANI-CLOTH ® AF3

PC/ABS unexposed

Average Impact data – High Speed Puncture Test (ASTM D3763)

BRITTLE FRACTURE LOWER PEAK FORCE, LOWER PEAK ENERGY 1

Classification: Internal Use

RESULTS: DUCTILE VS BRITTLE FRACTURES When the PC/ABS blend sample was exposed to Sani-Cloth AF3 wipes for 3 days and then subjected to the high-speed puncture test, brittle fracture was observed (Figure 2).

CRX1414 HIGH SPEED IMPACT TESTING CRX1414 High Speed Impact Test 3000

2500

Force (N)

2000

In contrast, the amorphous PC copolymer sample exhibited ductile fracture under the same conditions, with higher force (N) and energy (J) associated to initiate a crack in the puncture test (Figure 3).

1500 Control 1000

3 Day

Ductile fracture

500

1000

-500

2000

3000

4000

5000

Time (ms)

CRX1414 3-day exposure to SANI-CLOTH ® AF3

CRX1414 Unexposed

Average Impact data – High Speed Puncture Test (ASTM D3763) Material

Temp (C)

Chemical Treatment

Force (N)

Energy (J)

CRX1414 CRX1414

300 300

Control 3 Day

2420 2603

18.9 20.6

DUCTILE FRACTURE HIGHER PEAK FORCE, HIGHER PEAK ENERGY 1

Classification: Internal Use

AMORPHOUS PC COPOLYMER

SEMI-CRYSTALLINE PC COPOLYMER

PC/ABS

0.6

PC/PBT

1.0

CRX5421 RESIN

1.5

CRX9421 RESIN

1.5

CRX1414 RESIN

0.8

CRX9411 RESIN

Diversey Oxivir® TB

Trichlorosocynuric Acid

Cavicid e® CaviWipes1

SANI-CLOTH® prime

PRODUCT

SANI-CLOTH® plus

Ap plicat ion: Sat urat ion m et hod

SANI-CLOTH® AF 3

Exposure condit ion: 23 C

SANI-CLOTH® HB

St rain level: 1% st rain

Exp osure d ays

SABIC ESC Met hod: per ASTM D543

SANI-CLOTH® Bleach

CHEMICAL RESISTANCE AGAINST TYPICAL HEALTHCAR

Mold shrinkage (%)

Figure 3 does not show any change between the unexposed sample and the chemically treated sample following the high-speed puncture impact test. There is, however, a noticeable difference between the PC/ABS and the CRX1414 copolymer in their failure modes. The PC/ ABS sample shows significantly more radial cracking and would be classified as a brittle failure, whereas the CRX1414 copolymer has minor radial cracking and would be classified as a ductile failure.

Although ESC data and puncture test results are effective screening tools, the performance and interpretation of end-use testing are important

Brittle Fracture

Control

1000

σy ε b

σy ε

This information should be used as indicative only. This is essentially a ranking test and is not intended to provide data to be Therefore, extensive testing of the finished part is strongly recommended. The performance and interpretation of end-use te

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MATERIALS

Classification: Internal Use

PART DESIGN AND MOLDING PROCESSING ARE IMPORTANT FACTORS TO MAXIMIZE CHEMICAL COMPATIBILITY Minimize molded-in stress through good design principles (part geometry and gating)

MATERIAL SELECTION & SCREENING

Mechanical and Environmental Stress Cracking (ESC) Testing

PART DESIGN/ SIMULATION

End use part testing to determine suitability of material in application environment

MOLDING & SECONDARY OPERATIONS

PART TESTING / ENVIRONMENT

Minimize polymer degradation through manufacturing processes

ABOVE LEFT: Figure 2: Results of high-speed puncture test with PC/ABS blend. LEFT: Figure 3: Results of high-speed puncture test with amorphous PC copolymer. ABOVE: Figure 4: Synergistic approach to optimising resistance to harsh chemicals.

Proper selection of plastics for medical device housings and enclosures will continue to be a focus to help hospitals control HAIs and improve patient safety

σy ε b

REAGENTS).

IPA (70 %)

σy ε b

PLASTICS DETERMINATION OF RESISTANCE TO ENVIRONMENTAL STRESS CRACKING (ESC) METHOD) OR ASTM D543 (EVALUATING THE RESISTANCE OF PLASTICS TO CHEMICAL

Et hanol

Virex® TB

εb

CIDEX® OPA Solution

Virex® II 256

RE CLEANING AGENTS

σy ε b

e used for design or performance prediction. esting are the end producer’s responsibility.

Compatibility Criteria Yield stress Elongation at Color rating Retention, break retention,

Compatible Marginal Not compatible

αy (%)

Εb (%)

> 90 80 – 89 < 79

80 – 139 65 – 79 < 64 or > 140

Although ESC data and puncture test results are effective screening tools, the performance and interpretation of end-use testing are important. Extensive testing of the finished part is, therefore, strongly recommended. MATERIAL SELECTION SETS THE STAGE Proper selection of plastics for medical device housings and enclosures will continue to be a focus to help hospitals control HAIs and improve patient safety while at the same time reducing operating costs from premature failure of costly equipment. There is a need for advanced materials with improved chemical resistance that can extend the useful life of devices and equipment exposed to frequent cleanings. Once a material has been chosen, other factors affecting ESC come into play. Part design and processing are important to maximise chemical compatibility. Close attention should be paid to good design principles for part geometry and gating to minimise weld lines and avoid sharp corners to reduce areas of stress concentration. Basically, any initial stress points in the part design will become weak links for chemical attack; thus, poor part design can negate good material selection. As illustrated in Figure 4, a combination of informed material choice, good design principles, and processing and secondary operations that minimise stress can help device makers improve the performance and durability of equipment exposed to today’s healthcare disinfectants. REFERENCE 1. https://www.epa.gov/pesticideregistration/list-n-disinfectants-useagainst-sars-cov-2 NOTE LNP and ELCRES are both Trademarks of SABIC or its subsidiaries or affiliates.

SABIC’s ESC method evaluates retention of the following properties compared to a control from 3 to 7 days @ 1% strain:

LEFT:Table I: Test results for compatibility with healthcare disinfectants. (This information should be used as indicative only. This is essentially a ranking test and is not intended to provide data to be used for design or performance prediction. Extensive testing of the finished part is, therefore, strongly recommended. The performance and interpretation of end-use testing are the end producer’s responsibility.)

• tensile stress at yield αy • tensile elongation at break εb 1

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STERILISATION

PLENTY OF MATERIALS BOAST ANTIMICROBIAL AND ANTIBACTERIAL PROPERTIES, CHARACTERISTICS WHICH HAVE BEEN IN PARTICULARLY HIGH DEMAND OF LATE AS THEY CAN SIGNIFICANTLY REDUCE THE SPREAD OF INFECTION AND DISEASE. MICHAËL VAN DER JAGT, CEO OF PARX MATERIALS ARGUES THAT THE BEHAVIOUR OF THESE MATERIALS COULD LEAD TO CATASTROPHIC RESISTANCE PROBLEMS AND WHY, SAFE, HOLISTIC ADDITIVES ARE ESSENTIAL FOR OUR FUTURE PROTECTION.

ntibiotic resistance represents a significant threat to global health. Less effective antibiotics are making a growing number of infections, including pneumonia and tuberculosis, more difficult to treat. The threat of antibiotic resistance is so prevalent that the World Health Organisation (WHO) states in its Antimicrobial Resistance Global Report on Surveillance that without urgent action, we are heading towards an era in which common infections and minor injuries can kill.1

HEAVY METALS THEY’RE NOT ALL

The antibiotic resistance problem is largely attributed to the overprescription and overuse of antibiotics, rather than the overuse of antimicrobial additives in materials. Resistance against material-based antimicrobials, however, also poses a real threat. MATERIALS MATTER The term ‘antimicrobial’ describes anything that is used to prevent and treat infections in humans, animals and plants. This includes antibiotics and the additives used in materials for applications reliant on hygiene, including medical devices. Similar to antibiotic resistance, antimicrobial resistance occurs when bacteria and fungi develop the ability to survive the biocides designed to kill them. As a result, the bacteria survive and grow, passing on the genetic changes that made them stronger, becoming potentially life threatening. Most of today’s antimicrobial materials are made using silver ions — an additive that is incredibly effective at killing bacteria. Although heavy metals such as silver, mercury, arsenic and copper have been used as antimicrobial agents for thousands of years, this doesn’t mean they are safe or sustainable. TOXICITY RISKS In the mid-20th century, organic antibiotics replaced most of these heavy metal-based additives. Yet, the past few decades have seen a resurgence of interest in using silver as

a topical antimicrobial agent; for instance, silver sulfadiazine (SSD) is often used in wound healing bandages for burns. But just as mercury, arsenic and copper were replaced due to their toxic threat to the human body, silver poses a similar risk. SILVER’S SUSTAINABILITY PROBLEM Despite the wealth of information published on metal toxicity, metal-containing additives are commonly used in consumer goods. In fact, the antibacterial properties of silver ions are often used as a marketing too. Similar to antibiotic resistance, could such common use of metal-containing antimicrobials lead to a loss in effectiveness? The answer is yes. Unfortunately, this is already the case for silver- and copper-resistant bacteria, as demonstrated in research on “Efficacy of multiple metals against copperresistant bacterial strains” by the University of Arizona.2 The 2012 study demonstrated that several copper-resistant bacterial strains were also resistant to silver and a combination of both metals, suggesting a shared resistance mechanism.

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STERILISATION

What is more concerning, perhaps, are the precise mechanisms by which silver ion-containing antimicrobials kill microbes, and their ultimate effect on the human body and the environment, which remains unclear. The only certainty is that, to kill the bacteria, these ions must migrate from the material in question, ultimately leaching into the environment and/or the human body. THE ALTERNATIVE Using heavy metal ions for antimicrobial applications is unsustainable — for human health, the environment and for the efficacy of the materials themselves. A different, more holistic approach is therefore essential for our future protection. The industry must depart from heavy metal additives and instead use materials with an intrinsic immune system; that is, materials that mimic the natural antimicrobial mechanisms of human skin. By mimicking the body’s own antimicrobial properties, the method can make plastics and polymers resistant to bacteria attachment and proliferation. Parx Materials has developed a proven technique to achieve this biomimicry by incorporating a trace element that is found naturally in the human body. Saniconcentrate exhibits mechanical and physical properties that are bio-inspired, rather than reliant on toxic heavy metals. Using a trace element of zinc, the additive replicates the natural defence mechanism of the human skin. Bacteria are not attacked or killed; instead, they simply cannot attach and proliferate, allowing them to live out their natural lifecycle and die without spreading infection. This is a mechanism that the human immune system relies on. Crucially, it is also one to which bacteria do not build up a resistance. Saniconcentrate does not contain biocides, silver, nano materials or toxic substances. Unlike many other additives, it does not migrate from the material. The technology is already in use and has shown outstanding results in trials. A recent study evidenced that Saniconcentrate protects successfully against COVID-19, seeing a 99% reduction in the virus after 24 hours.3 NO MORE MIGRATION Another major concern about heavy metal additives is migration. Consider silver ions as an example. To be effective, ions are transported into bacteria cells to prevent cell division. This is achieved by binding to their DNA. The ions block the bacterial respiratory system, destroying energy production and essentially suffocating the bacteria until it is destroyed.

TAKING A HOLISTIC APPROACH As we enter an era in which hygiene and cleanliness is crucial, we must consider the risks of mass deployment of heavy metal additives. They threaten our health, our environment and increase the risk of antimicrobial resistant bacteria. Despite their efficacy, using heavy metal additives is simply not sustainable. To protect ourselves in the future, we must take a holistic approach to preventing the spread of bacteria. And what better method than replicating the immune response already found in the human body? Particularly for the medical plastics and medical devices realm, in which protecting against antimicrobial resistance is essential for long-term health.

Using heavy metal ions for antimicrobial applications is unsustainable — for human health, the environment and for the efficacy of the materials themselves

Although incredibly effective at killing bacteria, silver-based additives require ions to migrate from the material to work. This means the antimicrobial properties of the material will eventually wear off. It also means the silver ions are released into our environment, our oceans and in some cases, our bodies. This is particularly concerning given that the most common applications of antimicrobial additives — food packaging, medical devices and personal protective equipment — are all examples of high-risk products. What’s more, with an increasing demand for antimicrobial materials amid the COVID-19 pandemic, the public will be exposed significantly more to materials containing migrating silver ions.

REFERENCES 1. https://apps.who.int/iris/bitstream/handle/10665/112642/9789241564748_ eng.pdf?sequence=1&isAllowed=y 2. O. Torres-Urquidy and K. Bright, “Efficacy of multiple metals against copperresistant bacterial strains,” J. Appl. Microbiol., 112, 695–704 (2012). 3. https://www.parxmaterials.com/latest-news-about-parx-materials/ saniconcentrate-proven-to-reduce-coronavirus-on-surfaces-by-up-to-99per-cent-without-harmful-toxins

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ADVERTISEMENT FEATURE Figure 1: Survival studies of SARS-CoV-2 and other coronaviruses on the surface of various materials.

SANITISING TPE SURFACES THE RECENT DEMANDS ON THERMOPLASTIC ELASTOMERS HAVE PRESENTED MANUFACTURERS WITH SPECIFIC CHALLENGES REGARDING STERILISATION. MARFRAN SRL HAS RESPONDED BY DEVELOPING SOLUTIONS BASED ON BACTERIOSTATIC SUBSTANCES. The pandemic has brought many changes to our lifestyle, some of which are destined to remain for many months: the greater use of personal protective equipment (PPE) in the professional sphere is certainly the most evident example. The current trend in opting for reusable devices rather than their disposable counterparts is bringing the need for devices and materials that allow easy and effective sanitisation of the devices. TECHNICAL CHALLENGES All materials commonly used to produce reusable PPE, including thermoplastic elastomers (TPE), must face two technical challenges: the sterilisation temperature

increase compared with other products; and the widespread employment of multiple sterilisation cycles. Even when properly and repeatedly sterilised, germs and bacteria can still live on the surfaces of these materials. An additional challenge is, therefore, to design materials that are less hospitable for all those germs and bacteria which, if not adequately limited, can constitute a serious danger to human health. THE BACTERIOSTATIC EFFECT In 2015, MARFRAN srl (at that time Francesco Franceschetti Elastomeric srl) registered a patent on the use of ustic acid in TPE compounds as an antibacterial (WO 2016/020774 A1), the

effectiveness of which has been proven by numerous tests conducted on various compounds. Although ustic acid is sustainable (it is obtained from some lichens), it also introduces processing and operation temperature limits. Thanks to some collaborations, MARFRAN srl has more recently developed solutions based on bacteriostatic substances which, due to being inorganic, can be used at higher processing temperatures making them more suitable for TPE compounds with a higher molecular weight. The bacteriostatic effect prevents a bacterial biofilm forming on the surface of the devices, making even common detergents effective for sanitisation and

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autoclaving more effective and lasting. The effectiveness of the bacteriostatic treatment of MARFRAN compounds was confirmed by evaluating the antibacterial activity conducted according to ISO 22196: 2011. The bacterial strains chosen for the test with MARFRAN. MED 40A — a medical TPE compound suitable for autoclaving even at 134 °C are the following: • GRAM negative ⇒ Escherichia coli • GRAM positive ⇒ Staphylococcus aureus The results obtained are quite positive considering the hardness of the chosen compound:

ADVERTISEMENT FEATURE • Antibacterial activity against Escherichia Coli (GRAM negative) according to ISO 22196, R = 3.2 ⇒ 99.9% • Antibacterial activity against Staphylococcus Aureus (GRAM positive) according to ISO 22196, R = 1.8 ⇒ 98.4% REDUCED VIRAL LOAD During the current pandemic, the material has shown its ability to reduce the viral load present on the surface. Numerous studies have highlighted the ability of the SARS-CoV-2 virus to survive on the surfaces of various materials, even for several days. Figure 1 summarises studies done in the first half of 2020 relating to the survival of the coronavirus on surfaces. The result obtained is a reduction of about one decade of the viral

population per unit area (TCID50/cm²) in the first 8 hours. This behaviour makes any sanitisation or sterilisation process much easier and more effective. From this first series of tests, the advantages of the bacteriostatic treatment of MARFRAN TPE compounds are evident, and can be summarised as follows: • Effective against GRAM negative bacteria • Effective against GRAM positive bacteria • Significantly contributes to the abatement of the SARS-CoV-2 superficial viral population • Thermally stable • Suitable for contact with food • Non-cytotoxic, usable in the medical field • Does not affect the mechanical characteristics of the material.

The use of bacteriostatic treatment in MARFRAN compounds is in continuous development. The company has, for example, applied bacteriostatic treatment to work clogs (Figure 2), thus developing MARFRAN E CDP, an excellent permanent antistatic compound. The specific resistivity of volume and surface of less than 1*10^9 ohm*cm remains unchanged even in the presence of bacteriostatic treatment. Sterilisation/sanitisation is a continuous focus of development for MARFRAN srl, a company that always follows the real needs and requirements of customers and their applications.

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BELOW: Figure 2: Bacteriostatic treatment finds application in many personal protective devices such as work clogs.

Ground-breaking medical cooling device appears at Tokyo 2020 Paralympics

A Paralympian will be using a medical cooling device incorporating a cooling vest to regulate his body temperature in Tokyo.

Paxman, the developer, uses cooling technology to help cancer patients keep their hair during chemotherapy.

The lightweight miniature cooling device circulates a coolant through a specially designed cooling vest.

The device has been tested extensively, including successful heat chamber testing at Loughborough University.

08:2021 BASF’s Irgastab improves high clarity of medical polypropylene

orean chemical company, LOTTE Chemical, has produced polypropylene (PP) required for medical applications using BASF’s Irgastab, a non-discolouring processing stabiliser. With the rollout of COVID-19 vaccinations worldwide, the need for syringes made from PP has increased exponentially. The medical PP has been applied to the LDS (low dead space) syringes developed by a medical syringe manufacturer in South Korea. These specialised products are designed to minimise the amount of a drug left in the device after injection, which leads to

reduced vaccine wastage. As a result, LDS syringes are in huge demand globally as it is estimated to enable 20% more people to get the dose with the same amount of vaccine. “Irgastab serves to ensure that medical PP remains safe and suitable for use,” said Hermann Althoff, senior vice president, Performance Chemicals Asia Pacific, BASF. “It provides processing stability without discolouration to PP during compounding and injection molding, which is vital for LDS syringes as the materials need to be certified for high clarity.”

NEW BIOCOMPATIBLE UV ADHESIVE FOR SOFT PLASTICS

anacol has developed a new plastic bonder that is certified to USP Class VI biocompatibility standards for medical device assembly applications. Materials used to create infusion lines, catheters, and similar medical devices may include TPU, TPE, PEN, polyamides, Pebax, ABS and PEEK. Some combinations of these thermoplastics and thermoplastic elastomers can be difficult to bond. After assembly, these materials are challenged by torsional stresses at the points of transition between the soft tubing and the hard connector. Panacol developed the adhesive Vitralit UV 7030 to specifically address these complex issues.

The adhesive is a onecomponent, solvent-free UV curable acrylic adhesive. It can be cured with light energy in the broad UV-A spectrum, or with LED systems that produce either 365 or 405 nm wavelength. This adhesive cures in seconds at layer thicknesses of a few 100 µm, ensuring high bond strength immediately after UV exposure. A key feature of Vitralit UV 7030 is its high elongation at break, >250%, combined with good tensile strength. When exposed to black light, the adhesive fluoresces, which enables visual process control. Vitralit UV 7030 is suitable for typical sterilisation processes including gamma, EtO and autoclave.

Evonik expands its biomaterials portfolio through acquisition

vonik has acquired German biotech company JeNaCell, expanding its biomaterials portfolio to provide biotechnologically derived cellulose. The nature-identical material developed by JeNaCell is used in medical technology and dermatology for the treatment of wounds and burns

as well as in hydroactive skin care. Evonik recognised JeNaCell’s potential in 2015 and invested in the start-up through its own venture capital arm. Following the complete takeover, JeNaCell’s portfolio will be integrated into Evonik’s health care business. The company

accelerates the portfolio shift of its Nutrition & Care division towards system solutions and expands the division-wide technology platform of natural materials for medical technology. The share of system solutions in Nutrition & Care is to be increased from 20% today to more than 50% by 2030.

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CYROLITE® has been working in hospitals and

Lipid-resistant, BPA-free, and highly transparent: CYROLITE® acrylics are the reliable invisible helpers in hospitals and labs.

labs for more than 40 years. Thanks to their excellent properties, our high-performance acrylics are perfect for use in a wide range of medical devices. CYROLITE® is highly transparent and easily processed into intricate parts. It can be reliably sterilized using most common methods and is BPA- and DEHP-free. This has impressed both patients and healthcare professionals alike: CYROLITE® meets the requirements of USP Class VI, ISO 10993-1, and REACH. You can find more details at www.cyrolite.com.

MPN EU Issue 61

Articles inside

Cybersecurity: Mitigating cybersecurity risks in the IoT

Cleanrooms: On repeat

Cover story

Packaging: The full package

Cleanrooms explains how cleanrooms can achieve greater degrees of accuracy to reliably repeat the production of micro parts.