Cover story

Q&A

ENGEL DISCUSSES HOW INTEGRATED SOLUTION CAN BOOST EFFICIENCY AND HOW AUTOMATED PRODUCTION OF OPHTHALMIC PRODUCTS CAN BE DONE IN THE SMALLEST POSSIBLE WORK AREA.

Connected to a cleanroom, Aptar Radolfzell produces an innovative multiple dosing system for the administration of eye drops. The dosing system is microbiologically sealed and does not require any preservatives. In production, high precision needs to be combined with effi ciency. For series production, ENGEL supplied two new production cells, each consisting of e-victory injection moulding machines and integrated easix articulated robots.

In Germany alone, millions of applicators for eye drops are used. The symptoms for which liquid medications are dripped into patients’ eyes are manifold. What all eye drops used to have in common was unavoidable contact with bacteria after opening. The systems commonly seen on the market are therefore often single applicators whose contents can only be used for a few hours after opening. Aptar Radolfzell, an Aptar Group Inc. company, produces a sustainable alternative: a multiple-use dosing system with bottles of 5 and 10 ml capacities. As a self-contained system, it provides the necessary protection against microbiological contamination that reliably prevents premature expiration of the drug. “Our applicator delivers the drug drop by drop and is free from preservatives. That is the added value of the system,” says Ingo Korherr, production manager at Aptar Pharma, summing up. “The advantages here are that this is not a one-off application, which is not ecological and produces a lot of waste. The multiple dosage system can be used for several weeks, and it is more ergonomic to apply at the same time,” adds Ralf Fichtner, site manager at Aptar Pharma in Eigeltingen in southern Germany.

In ophthalmology, one of the Aptar Group’s product lines, the strategy of manufacturing all plastic parts in-house, has been successfully implemented. This has largely been achieved with ENGEL manufacturing systems.

TIE BAR-LESS CLAMPING UNIT ENSURES HIGH-PRECISION MOULDING The ophthalmic squeeze dispenser (OSD) consists of a total of seven plastic parts with varying degrees of complexity and one metal part. To produce the applicator and the spray pins, capital was invested in two new production cells for the Eigeltingen location; this is Aptar Radolfzell’s second production location in addition to Radolfzell.

The applicator with a diameter of 15 millimetres is produced from polypropylene (PP) in a 32-cavity mould equipped with a partial hot runner on an ENGEL e-victory 740/220 injection moulding machine with a clamping force of 220 tonnes. The total shot weight is 30.5 grams. An ENGEL e-victory 50/90 with a clamping force of 90 tonnes produces the spray pin from TPE with a total shot weight of 1.97 grams in a 16-cavity full hot runner mould. Both parts are productcarriers, i.e., they come into contact with the medication.

Where the plastic parts are highly fi ligree, complex at the same time, and are also produced in a multi-cavity mould, hybrid e-victory injection moulding machine with an electric injection unit and servo-hydraulic clamping unit often off er benefi ts. The reason for this is the tie-bar-less clamping unit, which provides suffi cient space for large multi-cavity moulds even on machines with comparatively low clamping forces. Patented force dividers distribute the clamping force evenly across the mould mounting platens, ensuring consistently high moulding precision across all cavities. These were the factors that tipped the scales at Aptar in favour of capital expenditure on machines from the e-victory series. As ENGEL sales representative Jürgen Fridrich adds: “What was required up front was very high repeatability, shot for shot, and very high availability of the entire production cell in each case.”

“Let’s not forget the very strict demands on the mould and the part, which necessitate a high level of precision – requirements which the e-victory series meets in full. The servo-hydraulic clamping unit side from ENGEL runs like clockwork,” says Andreas Gräber, manager of injection moulding services at Aptar Pharma.

Ralf Fichtner adds: “We process polyolefi ns, especially PP and PE. There are certainly more dimensionally stable plastics. The tolerance range with two decimal places in which we manufacture our parts, requires very high precision of the mould, the injection moulding machine, and the entire process. Polyolefi ns with this precision are certainly not standard, and this is exactly what we specialise in. The challenge is to achieve this precision in a cost-eff ective way in multi-cavity moulding with a high level of process stability.”

INTEGRATED CONTROL UNIT FACILITATES CHANGE TO ARTICULATED ROBOT The production process is fully automated and 100% monitored. SPC checks of the parts are also an integral part of the process. After completing the respective injection moulding cycle, the parts are removed by ENGEL easix articulated robots, including separation of the cavities, which is important for traceability. In other applications at Aptar, ENGEL linear robots handle the parts.

The fact that the control unit for the ENGEL robots is fully integrated into the control CC300 control unit of the ENGEL injection moulding machines, made the change to articulated robots particularly easy for Aptar. “One major advantage is that I can see everything on the machine display and do not have to walk around the machine. Of course, I have the hand-held unit for the process settings and teach-in, but that is a one-off thing, otherwise I can control everything from the machine, and it is very easy. The employees are familiar with the user interface and do not have to readjust or learn anything new, but can apply what they know 1:1,” says Andreas Gräber, summing up.

The manual robot panel and the smart ENGEL CC300 control unit access one and the same database. Another benefi t is that both systems coordinate their motion sequences with each other. This reduces the handling time in some applications. 500 MILLION DOSING UNITS A YEAR As an expert for innovative medication delivery systems and packaging solutions, Aptar pursues a two-supplier strategy in-house. Of the total of 85 injection moulding machines with clamping forces of 35 to 250 tonnes, ENGEL machines account for more than 60 percent. Some 850 employees produce more than 500 dosing units annually at both locations. With several global good manufacturing practice (GMP) production sites, Aptar Pharma ensures both a reliable supply chain and local support for its customers. The division of the company focuses on injection moulding technology. “We buy in other processing technologies strategically,” explains Ralf Fichtner: “The answer to the question as to what we do in-house, and what we don’t, is driven by the complexity of the parts to be produced.” of the parts to be produced.” After all, the company name, Aptar, is derived from the Latin word aptare. And that means to adapt, which refl ects the company’s philosophy the company’s philosophy in practice.

The injection moulding machines and automation are encapsulated in cleanroom-compatible production cells in compliance with ISO 7 requirements.

The applicator (right top) and spray pin (right bottom) are produced on the two new ENGEL e-victory injection moulding machines. The dosing systems consist of eight parts all told, seven of which are made of polymer materials.

Medical diagnostic equipment & biotech applications

ALBIS offers the medical industry an unparalleled choice of standard, technical and high-performance polymers from renowned producers. This offering is complemented by customized polymer compound solutions tailored to customer’s needs and made by ALBIS’ sister company, MOCOM.

Our products comply with the requirements of the VDI 2017 Medical Grade Plastics Directive. We support numerous projects in the medical sector, pharmaceutical packaging and diagnostic equipment and biotechnology, putting technical and regulatory requirements at the heart of our work, so that we can define the most appropriate material for each application. Our regional experts draw on in-depth knowledge of the medical and pharmaceutical industry to provide you with a powerful service offering that integrates technical support, product safety and risk management. Contact us to learn more about our solutions and assortment of medical polymers and compounds: healthcare@albis.com

albis.com

CHOOSING THE RIGHT PARTNER FOR YOUR NEXT MEDICAL DEVICE.

Learn more at

www.lubrizol.com/Health/Medical

9911 Brecksville Road Cleveland, OH 44141-3201 USA

TILMANN PETERSON, HEAD OF BUSINESS DEVELOPMENT MEDTECH & CORPORATE PLANNING, AMSILK, SHARES HOW TO OPTIMISE INTERACTIONS BETWEEN THE HUMAN BODY AND IMPLANTS.

Spider insider

Over the last decade, we have seen a lot of improvements and developments made within the implants industry, whether it be in the quality of silicone or the improved texture of implant surface. The mission for the next decade is to optimise the interactions between the implants and the human body, reducing the risk of rejection, infection and capsular formation.

AMSilk is a biotechnology company developing a range of vegan silk biopolymers that can be applied in various medical devices. The overall aim is to enhance the bio compatibility of medical devices. The properties of such coated implants include anti-adhesion and increased hydrophilicity. This results in reduced infl ammation and capsular formation, less invasive stress and better handling during surgical procedure.

One problem with implants is in some cases the body can identify it as a foreign object and cause the immune system to respond and reject it. If the body attacks the implant, it can result in serious complications such as pain, infection or capsular formation, all of which can require further surgery.

Spider silk coatings have the potential to prevent infection-caused infl ammation and to reduce post-operative issues caused by implants, minimising the risk of further medical intervention. Together with its biocompatibility and biodegradability properties, biofabricated spider silk has the potential to be part of a strategy to reduce complications of implant applications.

As well as reducing the risk of implants being rejected, spider silk coatings can prevent infections by forming a surface on which bacteria cannot grow. Engineered spider silk coatings work by creating a ‘bioshield’, a non-stick surface which has an anti-adhesive eff ect on bacteria so that it does not adhere to the implant shielding it from bacteria and thus infection. This unique silk technology is safe and bioharmonic for the human body, and is also non-immunogenic, non-infl ammatory and non-toxic.

Biofabricated coatings have the potential to become a powerful tool in the fi ght against antimicrobial resistance (AMR). AMR is a major concern, with medical procedures such as surgery becoming extremely diffi cult, or even impossible, due to an increase in resistant infections. AMR has the potential to aff ect people at any stage of life with resistance to even one antibiotic causing serious problems. Many medical advances are dependent on the ability to fi ght infections using antibiotics.

Current pharmaceutical coatings available on the market can have high antibacterial eff ects however, this can create an environment that’s diffi cult to control. Non-active ingredients, such as AMSilk’s, promote a positive acceptance of implants and limit negative body reactions in a controlled way.

The unique biofabrication process reprogrammes microbes enabling them to produce silk proteins. The microbes are grown in large-scale stainlesssteel vessels, fed with natural and renewable raw materials such as sugar. Upon a trigger, they start to produce the silk proteins. The biofabricated silk polymers are vegan, completely biodegradable and produced only with renewable resources, and thus are truly environmentally friendly making a contribution to a future zero-waste society. In the near future, we will need new directions concerning the fi ght against infections, which have to be far beyond the simple use of antibiotics. In this respect, coatings made of silk proteins are an important step towards a new generation of biocompatible surfaces and bioharmonic solutions to better patient outcomes after surgery.

The multiple benefi ts of silk polymers can be adapted to the needs of various market segments, enhanced skin comfort whilst also improving bacteriostatic and hygienic properties. These individually developed solutions will enable the medical sector to address industry challenges in the best possible way.

ALAN HUTCHINSON, PRINCIPAL SCIENTIST AT BROUGHTON, DISCUSSES THE CHALLENGES AND TRENDS WITH EXTRACTABLES AND LEACHABLES.

Up for the challenge

Extractables and Leachables (E&L) testing aims to reduce the safety risk to end-users of products such as pharmaceutical medicines or Electronic Nicotine Delivery Systems (ENDS), from the container closure system of the product.

E&L testing in the ENDS community is a recent requirement, with new regulations introduced as part of US Premarket Tobacco Product Application (PMTA) guidance. In contrast, in the pharmaceutical industry, E&L testing has been part of the required safety evaluation of products for a while. As pharmaceutical requirements are more developed, the materials used for these products are more consistent and understood. For the ENDS industry, the hope is that the use of grades of materials like those used in the pharmaceutical industry will become more prevalent over time.

CHALLENGES One of the major challenges with performing leachables studies is the common requirement to meet lower detection limits, which challenges both the instrument vendors and the laboratory scientists. Highly skilled and experienced analysts are required to develop instrument methods and sample preparation techniques to meet these low analytical evaluation thresholds, and state-of-the-art mass spectrometry instruments and software are needed to detect these low levels and process the data. The formulation of the product can contribute to this issue of sensitivity in so-called dirty matrices such as e-liquids, as their natural fl avours and biological samples can make it increasingly problematic to detect lower levels in a forest of peaks due to formulation interference.

Another challenge is a historical lack of clarity regarding the guidelines for designing and performing E&L testing. This has been a slow process and alignment of approaches would be valuable.

TRENDS The greater emphasis on performing risk assessments as a fi rst step of the E&L process is a main trend. This helps focus the studies and determine where eff ort is best placed to quickly and effi ciently de-risk any concerns from the container closure system. To perform a valuable risk assessment, the knowledge and information, as well as the expertise of the Subject Matter Experts (SMEs) performing the risk assessment that inputs into a Failure Mode and Eff ects Analysis (FMEA) style process, is essential.

This helps to focus eff ort and can reduce testing if previous data can be used to bridge to past studies. E&L studies are expensive and timeconsuming, and using previous relevant data will reduce costs and accelerate E&L projects.

The use of high-resolution accurate mass instruments for the analysis of E&L samples is becoming more widespread with E&L projects, helping to identify leachables and reduce the number of unknown compounds reported. Accurate mass instruments can help target leachables in complicated matrices, which can reduce the sensitivity burden by removing interferences from the formulation.

THE FUTURE In the future, it would be helpful to see the further alignment of processes and methods for performing E&L projects, and this would benefi t spectral libraries for identifying leachables. The development of response factor libraries for determining uncertainty factors would help in determining improved analytical evaluation thresholds for methods.

We are starting to see the use of automation for the sample preparation methods required for sample clean-up and enrichment. More use of automation can only help with the consistency of data and reduce the time taken.

The improvement of knowledge around E&L processes and materials, and the standardisation of materials used for products, will mean that E&L assessments become a more desk-based activity. For pharmaceuticals, we are already seeing this with common industry-grade materials being used; within companies, the same materials are being used across product ranges. ENDS products will likely follow this path and in the future, cleaner, bettergrade plastics and rubbers will also become common across that industry.