Making Drug Delivery Devices

LAUREN ZETTS, GLOBAL HEAD OF MARKETING FOR HEALTHCARE AT COVESTRO, DELVES INTO THE DIFFERENT DEVICES THE COMPANY HAS DEVELOPED AND HOW THEY’RE CHANGING THE WAY WE DEAL WITH DRUG DELIVERY.

ome delivery

Drug Delivery demonstrator, which utilizes Makrolon polycarbonate and Bayblend PC+ABS.

Drug delivery is constantly changing – and the materials to support new applications must continue to evolve as well. Meeting current and future needs requires innovative materials to overcome age-old familiar hurdles and Covestro experts are leading the way. Continuous innovation in the pharmaceutical industry requires novel drug delivery devices. These new devices can off er solutions to address ease-of-use, sustainability, and safety concerns for both patients and healthcare providers across a variety of treatments including fl exibility to use at-home or on-the-go. As a result, devices such as inhalers, pens or autoinjectors have seen strong growth over a number of years. Advances in this space require innovative materials to ensure reliable administration of pharmaceuticals. Covestro’s medical portfolio of Makrolon polycarbonates (PC), Bayblend PC+ABS blend and Makroblend PC+ polyester grade plastics provide reliability and quality for use in drug delivery devices. One device comes from Pirouette Medical with their single-use, portable auto-injector device for the safe dosing of epinephrine and other medications. With this disklike design, it considers the patient anxiety and unwanted attention that a traditional pen-like autoinjector can cause. A number of components in this device utilize Makrolon 2458 for the biocompatibility and durability supporting an innovative device introduction to the market.

ADDRESSING TRENDS IN THE INDUSTRY Device makers are addressing key mega trends and incorporating digital features into new devices. Connectivity in devices supports patient adherence to dosing and frequency all while allowing patients to administer in the convenience of their homes or on-the-go. Connectivity is also impacting this segment with smart pill dispensing. A concept developed in collaboration with Shenkar College of Engineer, Design and Art was created for enhanced safety and well-being of patients that depend on the regular use of medication. This smart pill dispenser concept intends to improve ease of use – off ering reminders and notifi cation when refi lls are needed for both the convenience of patients and caregivers.

KEEPING IT SUSTAINABLE Simply having a connected device is no longer enough. Consumers are increasingly demanding more sustainable solutions as well. Circular economy and sustainability are now considered by pharmaceutical and device companies in the design of new devices. In order to support this, Covestro has introduced a proof-of-concept drug delivery device. This device demonstrates by using polycarbonates in each piece, the possibility for simplifi ed sorting and recycling after disposal of bio-contaminated pieces is available. Each material used can play a specifi c and signifi cant role in creating a high-functioning and sustainable solution that can reduce medical waste and enhance patient comfort. For further emphasis on sustainability, the expanding CQ portfolio of low carbon footprint materials now includes Makrolon RE polycarbonate, Bayblend RE PC+ABS and Apec RE high temperature PC for healthcare can also be used to support companies’ sustainability targets. These products off er a drop-in solution that utlize raw material from mass-balanced bio-waste and residues.

FURTHER DEVELOPMENTS IN DRUG DELIVERY DEVICES Safety will always be a top priority in the healthcare industry. Needle-free injectors are one step to improve safety and prevent needle-stick injuries while ease-of-use and patient acceptance are also touted as benefi ts compared to traditional needle injections. Needle-free injectors fi nd applications in vaccines and other treatments. One example of a needle-free injector is the PharmaJet’s Needle-free Injection System (NFIS) that provides a more eff ective way of administering drug and biologics and are preferred by patients, caregivers and healthcare workers. The PharmaJet systems require a polycarbonate material to meet the specifi cations of the syringe and vial adapter while standing up to gamma radiation and ethylene oxide sterilization. Covestro was able to support PharmaJet’s material needs, despite supply chain issues that aff ected many medical suppliers. NFIS is the world’s fi rst plasmid-based DNA vaccine which received Emergency Use Authorization for Covid-19 in India. Materials matter. What a device is made of matters. And now, more than ever, materials are improving drug delivery.

radiation and ethylene oxide sterilization. Covestro was able to support PharmaJet’s material needs, despite supply chain issues that Polycarbonate syringe Polycarbonate syringe from PharmaJet. from PharmaJet.

ROBERTO VALENTI, HEAD OF MATERIALS DEVELOPMENT, BORMIOLI PHARMA, HIGHLIGHTS EVIDENCE THAT EXTRACTABLES IN SUSTAINABLE PLASTIC PACKAGING IS AS SAFE AS CONVENTIONAL PACKAGING.

The is in the packaging

In 2021, global carbon emissions reached 36.4 billion tonnes of CO2 globally, the highest figure in human history. Moreover, according to the Global Footprint Network, humanity is “using up nature 1.75 times faster than our planet’s bio-capacity can regenerate”.

In the last couple of years, enhanced interest in more responsible packaging solutions has already resulted in an increase in sales. Bormioli Pharma registered a 20% increase in sales of sustainable plastic products in 2021, compared to 2020, with expectations for a further 14% increase in 2022.

A further push is needed to ensure a quicker transition, allowing the achievement of results in line with the emission reduction agreements.

Bormioli Pharma, a global pharmaceutical packaging manufacturer, has committed to a wide range of actions.

Firstly, it has been investing in the development of pharma-grade packaging solutions that feature a more responsible approach towards the environment. The company has introduced a new range, EcoPositive, that characterizes such solutions.

This new offer relies on more than 15 years of research into more responsible packaging solutions for the pharma industry, gathering the wide sustainable offer of the company. These products have been split consistently with 3 different sustainability strategies: regeneration of raw materials, renewable sources and manufacturing with infinitely reusable materials.

To further support the massive adoption of such solutions by the pharma industry, the company has chosen to expose a prejudice still standing in the industry with scientific evidence: the safety of sustainable primary packaging in plastics, in terms of extractables.

For this reason, Bormioli Pharma has commissioned a third-party, certified analysis to provide evidence about the safety of these packaging solutions, starting from rPET bottles. The analysis has been run by a specialized laboratory, Lab Analysis, and then validated by an institute, Tecnopolo Mario Veronesi, to investigate the level of extractables in sustainable packaging solutions, comparing them with a risk index, to determine whether there is a safe amount that may be present in pharmaceutical formulations.

The analysis consisted of a chemical analysis with the bottles being tested with 5 different solvents, such as water solutions with different pH (2.5 and 9.0), alcoholic solutions with ethanol and isopropanol, and methanol to investigate the presence of nitrosamines. After the chemical analysis had run, a subsequent toxicological assessment of the solvents had been undertaken to analyze the inertness of the containers.

The outcome showed unprecedented results: not only did the analysis make evident that these solutions can meet the industry’s most stringent requirements in terms of quality and safety, but it also revealed that these values are up to 150 times lower than the hazard index, calculated by the ISO regulation on biocompatibility. Indeed, in some specific cases, sustainable primary packaging has proved to be even more performant and safer than conventional plastic primary packaging.

This test, commissioned by Bormioli Pharma on a voluntary basis, sheds light on a topic that has been so far rarely taken into consideration by the pharma regulation – and hopes that this analysis could serve as a first step to define a dedicated regulatory framework for low impact, more responsible packaging solutions, and further supporting an ecological transition to take place in the pharma industry.

BOB TILLING, VP GLOBAL SALES AT KALLIK, UNDERSTANDS THE INCREASE IN COMPLIANCE PRESSURES FACING MEDICAL DEVICE FIRMS SINCE 2021, AND ASSESSES THE TECHNOLOGIES THAT WILL HELP EASE THE PAIN OF COSTLY COMPLIANCE PROJECTS.

Put a

LABEL on it

During the rush for MDR compliance, the sheer scale of the compliance eff ort for medical device manufacturers doing business in the European market was a major eye-opener for many business leaders. Asset siloes were uncovered, disparate systems identifi ed, and labels and artwork painstakingly updated – often manually, at extensive cost. Plenty of companies operating in the medical device market are doing a great job of using technology to handle assets such as labels and artwork that require management at both the global and national levels in response to regional rules and market requirements. But this often only extends just to simple content management instead of providing full editing, version control and re-issuing that is often required in bulk to streamline compliance projects. With more regulations being the order of the day, medical device manufacturers need to consider the bigger picture. It is clear there is more to be done for many fi rms in terms of addressing full digital maturity.

MDR SHOULD BE SEEN AS A WAKE-UP CALL – NOT A ONE-OFF CHALLENGE One Kallik client, a leading multinational medical device manufacturer, internally updated over 90,000 labels in just six months to achieve full MDR compliance – a monumental task that simply would not have been possible to achieve at scale without leveraging technology. Yet many fi rms are still a long way from complying with the full extent of MDR rules such as updated product Instructions for Use (IFUs) – and the regulatory pace of change is not set to stop there. Here’s how the medical device regulatory landscape could evolve over the coming months and years – and how fi rms can prepare early to avoid costly, disruptive compliance burdens:

EXEMPT TODAY, REGULATED TOMORROW: THE COMPLIANCE SCOPE IS WIDENING Regulators in the EU, individual member states and further afi eld are all continually refi ning the requirements and scope of their regulations for the medical device market – both reactively in response to product defi ciencies, or proactively to tighten quality and traceability.

WIDER AND WIDENING STILL… The scope for devices that fall under MDR for requirements such as Unique Device Identifi er labels has risen signifi cantly, expanding from roughly 2.6 million devices to fi ve million. Colored contact lenses, dermal fi llers, medical software – even AI solutions – now fall under the regulations, leaving manufacturers scrambling to comply with unfamiliar rules. These fi rms dealing in products previously exempt or outside the scope of older legislation now run the risk of an uncomfortable, short notice demand for compliance. Once regulators begin to fl ex their muscles and crack down on non-compliance where they identify risks, there could be signifi cant pain on both a fi nancial and reputational level.

TECHNOLOGY WILL BE CRITICAL TO MEET THE GROWING COMPLIANCE BURDEN Regardless of how the regulatory pipeline shapes up, one lesson to be learned from the struggles witnessed during the MDR compliance push remains clear – manual solutions will be a non-starter for successive rules and regulations. Will organizations be able to manually identify, edit and re-issue labels, artwork and packaging aff ected by new regulations? Certainly not without investing excessive time, capacity and fi nances. Adopting an end-to-end digital solution such as Veraciti will be critical to provide eff ortless mass asset adjustments in response to emerging regional or national regulatory shifts. If medical device organizations act now, they will reap the long-term rewards – all while benefi ting from continuous operational effi ciencies and powerful new artwork and label management capabilities.

that simply would not have been possible to achieve at scale without leveraging technology. Yet many fi rms are still a long way from complying with the full extent of MDR rules such as updated

PETER CLODD-BROWN, CO-FOUNDER AND TECHNICAL INNOVATOR AT MERYL FABRICS, EXPLAINS THE TECHNOLOGY BEHIND ACHIEVING A FULLY SUSTAINABLE AND COMFORTABLE MEDICAL AND CARE WORKWEAR.

CUT FROM A DIFFERENT CL TH

Manufactured using a hi-tech smart fabric with a full circular economy, zero shedding and virus, bacteria and odor technology, the Meryl Nurses Tunic off ers an environmentally friendly workwear solution for the healthcare industry. The soft-touch Nurses Tunic is made from a fabric which provides comfort, quality, durability and protection, and with infi nite recyclability, all of which lessens the environmental impact of the garment’s functionality and care.

MANUFACTURING THE GARMENT

The manufacturing process aims to minimize the impact of the garment on the environment, reducing the use of water and eliminating microfi ber pollution, off ering a more sustainable option for those requiring and sourcing PPE. The garment can play a major role in stopping the spread of acquired infections and transmission of viruses by preventing crosscontamination, while also lessening the reliance on the use of single-use PPE non-recyclable plastic items for certain tasks. Sustainability is a signifi cant aspect; through advanced hydrogen technology, starting from the highest quality molecular structure of the yarn, we have delivered a highperformance fabric which does not release microplastics, is manufactured with no water consumption or use of chemicals, and is 100% recyclable.

THE CHOICE OF MATERIAL

The yarn used to create the uniforms is made by a process using a silver ion, widely recognized as having antimicrobial properties, and this technology provides antiviral protection. Bringing these together gives permanent protection against the likes of MMR and even Covid-19 – no matter how many washes they are put through. The fabric’s construction means that dirt, viruses and bacteria can simply be washed away as they stay on the surface rather than penetrating the material. For performance, the fabric of the tunic is made using a twist and weave process which off ers a cotton-like soft touch, while ensuring the garment does not absorb dirt or stains into the fabric, therefore preventing odors from developing. Meryl Fabrics have virtually eradicated all production waste at the manufacturing stage, which can be as high as 22%, by returning, weaving, and cutting waste for reuse in new yarns. All coloring and treatments are applied to the fi laments at the spinning stage of the yarn, removing the need for chemicals and solvents that are normally used in the fi nishing process.

THE SUSTAINABLE PROS

The circular economic implications constitute a signifi cant step forward in recycling; taking both pre- and post-consumer product back to reuse in new fi bers allows for a full circular economy – we return the waste to its original base polymer, producing new yarn with a straightforward process and using it for new manufacturing. This environmentally friendly fabric maintains its quality with all the performance, together with an exceptional touch. Furthermore, the company has a hugely reduced transport throughout the manufacturing process, signifi cantly lowering the product’s carbon footprint from its creation to the end of its life, when it can be fully recycled and made into another sustainable development. The medical and care uniforms produced are the perfect example of the circular economy, as Meryl Fabrics makes and then recycles the workwear all within a closed-loop supply chain. Technological advances in the manufacturing of the material are making items greener and this can continue throughout their lifecycle by making them easier to clean and care for, demonstrating that is possible to become more sustainable without sacrifi cing comfort and durability.

Peter Broom, Meryl Fabrics – winner of the Med-Tech Innovation Awards 2022 Sustainability Award, sponsored by Medical Plastics News.

Innovation makesthe

WIDGO ROUND

SRUTHI CHIRRA, ASSOCIATE CONSULTANT, POLYMERS & SPECIALTY CHEMICALS AT CHEMBIZR, DISCUSSES MATERIAL AND DESIGN INNOVATIONS FOR WEARABLE INJECTION DEVICES.

The advances in Wearable Injection Devices (WID) technology are key attempts conforming to concerns of patient comfort and patient treatment adherence. Chronic diseases, such as Oncology, Parkinson’s, and Congestive heart diseases, require regular injections and maximum patient comfort and a WID can add great value to the patient’s life. There are numerous device options currently available for pharmaceutical companies, with at least 25 current brands of WIDs. The competition by device developers is to construct or optimize a design that is all low-cost, lightweight, and simple-to-use, while also fulfi lling the primary objective to administer highly viscous and large dosage biologic drugs. Despite the clear advantage and specifi c use-case, the adoption of WIDs by drug developers has been quite cautious until now. This is majorly in view of the possible risks and delays in clinical approvals and consequently, only a few projects with WID combination products are in progress and just two or three have been approved in the past fi ve years. But the scenario is picking-up pace as newer developments are forcing the pharma companies to rethink the aspects of risk vs value-addition to their product.

DESIGNING THE DEVICE

To tailor the needs of specifi c therapies, device developers are driving innovations in various device concepts: be it pumping mechanisms, drug fi lling, primary packaging, or user interface/ data connectivity.

The major directional advancement is observed in three aspects.

The fi rst is the development of robust high volume WIDs in the range of 3.5 - 10 ml, with a few even up to 50 ml dosage considerations. None of the presently approved devices is designed for volumes greater than 3ml. Various therapy segments requiring a large volume injection can benefi t from the advantages of WIDs. Correspondingly, a few high-volume WID design projects are underway and expected to reach the market in the coming decade. The requirement for high-strength and precision dosing for such systems drives the need for high-performance polymers. And in this sense, we see a couple of devices developed using medical-grade PC, which are currently in the clinical trial stages. Next in line is the development of small-sized designs that aid in device discretion, resulting in high acceptance amongst patients. To bring this into eff ect, innovations are taking place both in the design and material sphere. Various brands are incorporating built-in custom drug containers that aid the small-sized design, by fi tting perfectly into the device layout. And one interesting material-wise innovation is the development of an experimental semi-reusable WID using PEEK. It is claimed that the use of PEEK presents a cost-eff ective way for mass production of lightweight, interactive device designs all while keeping the device size low. The third driving trend is to reduce the overall cost of the devices which makes them more accessible to the end consumer. This is certainly the target for all device developers as extensive research is put forth for cost reduction. One such example is the use of a non-mechanical pumping system, osmosis, for pushing out the drug. It will signifi cantly reduce the device fabrication cost, by eliminating the need for electromechanical components. In a similar case, LCP material manufacturers have claimed that the material signifi cantly lowers the processing costs compared to PC. This leads to a reduction of the overall cost, enabling higher reproducibility of these devices.

NEW AGE DEMAND

The potential for WIDs is well recognized in the medical and pharmaceutical industries. The eff orts to enhance its accessibility are steadily yet surely growing. The pandemic has brought a considerable need to reduce the dependency on medical infrastructure. There is a heightened consideration for patient comfort. Pharmaceutical companies need to eff ectively weigh the risk factors and valueaddition for the patients to comply with the new age demand.

accessibility are steadily the dependency on medical risk factors and value-

FEDERICO BARUFFI, CUSTOMER TECHNICAL DEVELOPMENT ENGINEER AT SOLVAY, EXPLAINS HOW PEEK MATERIALS ARE SHAPING THE FUTURE OF MEDICAL DEVICES.

PEEK Performance

The medical and healthcare market has been growing signifi cantly in the last decades. New products and innovations are being generated almost on a daily basis, and to satisfy the new demands, the selection of appropriate materials have become more and more crucial to deliver desired performances. Requirements such as high mechanical properties, enhanced biocompatibility, resistance to repeated sterilization and chemical resistance to disinfectants. All of these are often combined with complex part design, special color requirements and high aesthetics. Within this space, plastic materials became very popular and started replacing metal in many applications. However, only a few plastics are eligible for applications that require higher performance than those delivered by commodity materials such as PP, PVC, PE, etc. PolyEtherEtherKetone (PEEK) is one of these high-performance plastics that is suitable for use in the medical and healthcare sector.

KETASPIRE PEEK KetaSpire polyetheretherketone is widely considered one of the highest performing, semi-crystalline thermoplastics available on the market today. Its chemistry off ers a combination of exceptional properties that allow KetaSpire PEEK to withstand the harshest conditions and eff ectively replace metal in some of the most severe end-use environments such as those employed in the medical sector during sterilization and disinfection procedures.

Solvay off ers KetaSpire PEEK in multiple versions, which include unreinforced, glass-reinforced, carbon-reinforced and lubricated grades. The versatility of the material makes it suitable for multiple processing techniques such as extrusion, injection molding and coating. Most grades are also biocompatible and can be therefore put in direct contact with bodily fl uids for less than 24 hours. It is compatible with a variety of sterilization methods, including EtO sterilization, gamma irradiation, hydrogen peroxide and steam sterilization. In particular, 1000+ steam sterilization cycles can be applied to components made of KetaSpire PEEK without any signifi cant alteration in performance.

Chemical resistance, high mechanical strength, fatigue resistance, low moisture absorption, high purity and resistance to hydrolysis make KetaSpire PEEK a front-line option for a variety of applications within the healthcare market.

Reusable instrument for Spinal Surgery: Titanium rod bender made with KetaSpire PEEK.

Typical healthcare applications of KetaSpire PEEK are:

• Reusable medical devices: in this domain, KetaSpire PEEK is mainly used as a metal replacement alternative to stainless steel. By taking advantage of its extreme resistance to steam sterilization (1000+ autoclaving cycles), high mechanical resistance and design fl exibility,

KetaSpire PEEK can be used to manufacture surgical tools being signifi cantly lighter than their metallic counterparts. Moreover, harsh disinfectants such as bleach, IPA 70% and many others are not posing any issues to KetaSpire PEEK. Examples are external fi xation devices, orthopedic surgical tools, microtubes and microneedle patches used for drug delivery.

• Surgical robots: surgical robots are becoming more and more common and are nowadays utilized by several hospital facilities. It is an industry trend based on the advantages of surgical robots such as reduced post-surgery pain, fewer and smaller scars, increased accuracy, shorter hospitalizations and lower risk of infections. KetaSpire PEEK proves very valuable for this type of applications: multiple components of surgical robots are required to resist repeated sterilization by autoclaving, high mechanical loads and high speed rotations.

• Single use biopharma equipment: Single-use biopharma technologies continue to replace reusable ones. This is a strong industry trend observed in the latest decades, and this is driven by an increasing need of cost reduction, elimination of cross-contamination risks and enhanced production flexibility, which single-use productions can help achieve with lower effort and cost. In this scenario, KetaSpire

PEEK can greatly contribute to the manufacturers’ strategic objectives.

With its compatibility with gamma sterilization, extremely low leaching in biopharma chemicals, high purity and USP Class VI compliance,

KetaSpire PEEK is successfully being used in many different single use biopharma components such as connectors, flow-meters, sensor housing and in all those parts where mechanical loads are significant such as in clamping parts.

Another important market for PEEK materials is that of implantable plastic components. In this field, having a plastic implant carries multiple advantages vs metals, such as increased biocompatibility, lower weight and radio transparency. For these reasons, the industry started moving towards these solutions almost a decade ago with the overall aim of easing the life of patients carrying implantable devices. This, combined with the organic growth of this market and the ever-coming innovations, made this sector a significant outlet market for PEEK materials.

ZENIVA PEEK As an implantable solution, Solvay offers Zeniva PEEK. Zeniva PEEK is a high-performance specialty polymer with high strength and advanced stiffness that offers extreme toughness and reliability for use in structural, load-bearing implantable medical devices.

Solvay manufactures Zeniva PEEK in a facility registered to the ISO 13485 quality standard and in compliance with relevant current Good Manufacturing Practices (cGMP) and ensures that it meets ASTM F2026-17 requirements as a PEEK polymer for surgical implant applications. Zeniva PEEK is compatible with a full range of sterilization methods including steam, ethylene oxide gas, vaporized hydrogen peroxide and high-energy gamma radiation. Moreover, it is capable of resisting prolonged contact Single-use flow meter made with KetaSpire PEEK.

with bodily fluids without any performance alteration.

As material for implantable devices, Zeniva PEEK provides several advantages over metals and other plastics. This material is easily molded or machined in complex shapes maintaining tight tolerances. It is also radiolucent and MRI compatible, allowing surgeons and their equipment to see through parts made of this material without any obstructions of the image, leading to easier procedures and enhanced effectiveness of surgery being performed. On top of this, its lower density vs metals allows to manufacture lighter implants that can prove for the patient to bear.

All of these properties make Zeniva PEEK ideal for applications such as dental implants, knee implants, trauma plates and spinal cages.

Knee Implant made with Zeniva PEEK.