Sustainability and drug delivery devices

In this article, Rob Veasey, Senior Sector Manager, Medical and Scientific, at DCA Design International, explores the environmental challenges facing the drug delivery device industry, and the opportunities they bring.

We are witnessing a global boom in the use of drug delivery systems. Valued at approximately $500 billion in 2016, this market is forecast to reach nearly $900 billion by 2025 (ref 1) . Increase in demand for self-administration and home healthcare devices has helped fuel this expansion, meaning that today drug delivery devices are not only much more widespread, they have become easier to use, safer and more effective. They form an essential part of our healthcare infrastructure, enabling delivery of countless therapies that save lives and improve patient outcomes on a vast scale.

As they have been targeted at wider audiences, drug delivery systems have become more disposable. This market trend has been driven primarily by the desire to improve safety and usability. Disposable devices typically require fewer operating steps than reusable ones and because they have a finite life, they are less susceptible to wear and contamination. A good example is the evolution of Dry-Powder Inhalers (DPIs). These began in the 1970s as relatively simple re-usable devices, such as Spinhaler and Diskhaler in which users fitted replaceable capsules or blister packs containing the drug product. They are now predominantly disposable products, in which the primary pack is sealed for life.

Drug delivery devices have also evolved to become more mechanically sophisticated. For DPIs, the requirement to automatically manage drug primary packaging and the addition of safety features such as dose counters has driven this trend. A similar story is found with injection devices, where one of the latest generation spring-powered disposable insulin pen injectors has seventeen components. In contrast, when first developed in the late 80s and early 90s, disposable pen injectors typically had fewer than ten parts. As device complexity has increased, designers are also able to select from an ever-growing pallet of polymers. This has enabled improvements in performance and reliability, but the mix of materials now found in many devices adds to already significant challenges for recyclability.

As scientific evidence of the environmental challenges we face becomes clearer, the necessity to improve the impact of products we use every day has become more pressing. We all share this responsibility, but governmental bodies have taken measures to drive adoption of more sustainable practices. Under the 2015 Paris Agreement, the UN is aiming to keep global temperature rise to below 2°C above pre-industrial levels. Nationally determined contributions will lay out how each country aims to reduce emissions and adapt to the impacts of climate change. The UK’s current target is a reduction in greenhouse gas emissions of at least 80% by 2050, relative to 1990 levels (ref 2). As countries develop and publish their individual strategies, the impact of commitments will become evident. It can be expected that changes will be needed to the way that most products are manufactured, distributed, used and recycled.

The contribution of our industry to environmental damage is also beginning to receive greater attention. Within the last couple of years, reports have emerged describing the global warming effects of pressurised metered dose inhalers (pMDIs). For example, it has been estimated that the propellants used within these devices contribute a staggering 4% of the total carbon footprint of the National Health Service (NHS) in the UK (ref 3). ‘Greener’ alternatives are being developed, with at least two major players, AstraZeneca and Chiesi, recently announcing a commitment to develop pMDIs with near zero Global Warming Potential. This is one example of the steps our industry is taking, but further substantial actions will be needed and we must all start to plan for and develop more sustainable drug delivery systems.

A further concern that has recently received publicity is the dramatic increase in plastic waste entering and damaging marine environments. In response, the EU has taken action to ban an array of single-use items, put in place new targets to encourage recycling of plastic products and mandated the use of more recycled polymers (ref 4). Due to the vital role that single-use plastics perform in healthcare and the difficulties in re-using many types of medical devices, this EU legislation does not apply to the medical industry. The performance and inherent safety of polymers, coupled with their cost-effectiveness, makes them ideal for medical applications. This is unlikely to change in the short term, but in the context of increased legislation and efforts within other sectors, it seems almost certain that our reliance on single-use plastics in healthcare will start to come under greater scrutiny.

Figure 1 - Single-use plastics play a vital role in healthcare

When you set out to improve a system, it is essential to define the metrics by which the improvement will be assessed. Without this, it is impossible to know if or when progress has been made. The first step in defining sustainability targets is therefore to decide what to measure and how to compare performance. In the context of the circular model, three key parameters are important:

• The energy consumed in manufacture, distribution and use of a product
• The amount of material that is derived from renewable or recycled content
• The amount of material that can be recovered for re-use at end of life

In some instances, factors influencing the choices made in relation to these parameters may be conflicting, or they may conflict with other design requirements. It is therefore essential that we develop objective ways in which conflicts can be understood and resolved to achieve the best environmental profile for a product. This understanding is typically gained through life cycle analysis (LCA), following methods defined within the ISO14000 standards. Owing to the huge array of factors involved in manufacture and distribution of products, LCAs are complex and time consuming to compile. This makes them an impractical tool to inform design decisions in real-time and as a result, they are often used to analyse designs and production systems retrospectively.

To achieve most value from LCA, detailed analysis of existing product solutions is best used to inform the development of new ones. This identifies where the biggest opportunities for improvement exist, enabling effort to be directed where it will be most effective. This can sometimes be in unexpected places; for example in the case of a device that requires cold-chain distribution, significantly more energy may be consumed in transporting and storing the product than manufacturing it. In this instance, improving secondary packaging to increase packing density may be the most effective way to improve the environmental profile.

Whilst LCA remains the ‘gold standard’ means for assessing the environmental impact of a product, the design industry needs other tools to help assess and inform design decisions rapidly during development. Such tools do not need to be fully comprehensive, but they should allow engineers to make informed decisions about options that might impact on the environment. Some promising early options, such as Eco-Indicator 99 (ref 5) have been developed, but to remain relevant and useful it is essential that these continue to be maintained and improved. Given the increasing focus on sustainable development, it seems inevitable that new tools will become available in coming years.

If we restrict our analysis to mechanical drug delivery devices, two issues that are commonly encountered in relation to sustainable development are materials selection and product lifetime. Neither of these issues are straightforward, since environmental design decisions are never taken in a vacuum. Instead, these factors must be weighed alongside many other requirements that safety critical products such as drug delivery devices must achieve.

Most drug delivery devices are made predominantly from plastics, so careful selection of these materials is important when targeting more sustainable solutions. Following the principles of the circular economy, we can break this down into three aspects for consideration.

Renewable and recycled polymers

Devices are typically manufactured from ‘medical grade’ polymers. These can be traced back to their raw material batches and come with guarantees that the formulation will not change. Recycled polymers are not currently available with medical grade certification and so the most sustainable alternatives in the medium term are likely to be biopolymers. Derived from biological rather than petro-chemical sources, a small range of biopolymers are starting to emerge. Unfortunately, in the short-term, device developers are likely to be faced with a lack of choice for biopolymer grade variants. They also carry a price premium compared with conventional polymers and some grades need to be separated from standard recycling streams. Because of the relatively small size of the medical sector in comparison with the wider polymer market, it is unlikely that our industry will drive the development of new sustainable materials. Instead, we should seek to be fast followers of other industries such as food packaging, that use greater quantities of polymer and for whom regulations and customers are demanding rapid adoption of greener solutions.

End-of-life solutions that enable better recovery and recycling

Recycling of polymer materials contained in drug delivery devices is challenging, leading to problems in establishing the infrastructure to do this safely and effectively. Firstly, they usually contain some residual drug product and may also be contaminated with biological materials. Secondly, because each component is optimised for its particular function, they typically contain a mix of polymer types as well as materials such as glass, aluminium and rubber. Thirdly, they are often designed to be inherently difficult to disassemble to deter tampering or counterfeiting. As a result, it is difficult and expensive to reprocess devices by any means other than incineration for energy recovery. Chemical recycling, in which polymers are broken down into more basic chemicals that can be reprocessed to create new high-performance polymers may be one option, but this technology is not yet widely established. To improve the recyclability of drug delivery devices, many of these issues will need to be addressed at a design level, so must become a requirement at the outset of new development programmes.

Lower embodied-energy

Not all polymers are created equal and they have subtly different environmental profiles. Generally, more complex polymers require higher energy usage during their manufacture. For this reason, simple polyolefins such as HDPE and PP are usually considered more sustainable than alternatives such as ABS, PC or POM. Clever design and materials selection can optimise part count and the use of polymers, ensuring that more complex and highly refined materials are only used where they are absolutely necessary.

Given challenges in sourcing more sustainable materials, extending product life may be the most effective path to improving the environmental profile of drug delivery devices in the near term. The longer a device can be used, the lower the environmental impact is likely to be in terms of material usage, waste and energy expenditure when assessed over a fixed period of therapy.

In this context, it is evident that reusable drug delivery devices are likely to have better environmental profiles than disposable ones. At the beginning of this article, I outlined that recent trends have been in the other direction, so what can be done to reverse this?

Reusable devices that are easier, safer and more convenient to use

A primary concern with reusable drug delivery devices has often been usability. Patient groups regularly contain large numbers of individuals with reduced manual dexterity or vision impairments. These patients can struggle to correctly replace a primary pack, or reset the operating mechanism. To address this, we should continue to make reusable devices easier to use, for example ensuring that the mechanism resets automatically when the old primary pack is removed, or when a new one is fitted.

Reusable devices that are more appealing

In the past, there have often been no real advantages to selecting a reusable device over a disposable one. Indeed, as described above there have been some legitimate concerns in relation to usability; yet this should not be the case. With reusable devices, cost is typically offset against a usable life of years rather than days or weeks, so there is an opportunity to specify better materials to achieve improved performance and to include more automated features. One interesting development that may help to tip the balance in favour of reusable devices is the advent of connected drug delivery systems. For many applications, the cost of electronic monitoring and control functionality is currently seen as a barrier to embedding this technology within disposable devices, making reusable solutions much more attractive. Connected systems may also help to balance some usability downsides of reusable devices, for example by providing warnings against potential use errors. For some applications, it may remain impractical to offer fully reusable drug delivery devices. In these circumstances, an alternative solution may be to develop disposable products that have greater dose capacity, so that their use-life is prolonged. This approach may of course bring challenges with drug stability and device affordability, but it is a trend that is already well established in some consumer markets and we are likely to see further developments of this sort within drug delivery in the future.

The environmental challenges we face are complex, but they also bring opportunities. By good design, there is no reason why more sustainable drug delivery devices cannot also be more cost effective and better for patients. But given the relatively long development cycles required for drug delivery devices, new environmental legislation may emerge that imposes targets that some businesses find hard to achieve. We are currently witnessing this in the automotive industry, where companies that have proactively developed sustainable product ranges are now in a much stronger position than those that left it late.

In many ways our industry is well equipped to deal with environmental challenges. We are systematic in our approach, data driven and highly analytical in our methods. Drug delivery devices are not subject to the whims of fashion; their performance and effectiveness must be comprehensively demonstrated before they enter the market, meaning that we tend not to embrace short-term thinking. To effect change, we will all need to adopt a more sustainable mind-set, in which we question the environmental impact of our decisions in the same way that we currently think about patient safety and therapeutic efficacy.

• View this article (pdf) that was originally published in the September/October 2020 issue of ONdrugDELIVERY magazine.

1. Size of the global drug delivery systems market in 2016 and a forecast for 2025, Statista Research, October 2018
2. UK action following the Paris Agreement - UK Government, October 2016
3. Progress on reducing F-gas Emissions - House of Commons Environmental Audit Committee, April 2018
4. Press Release from the European Parliament, March 2019
5. Eco-indicator Manual for Designers – a damage oriented method for life cycle impact assessment, October 2000