The creation of AllStar®

Published on: 30^th November 2020

An insulin pen injector for developing markets.

In this article, first delivered as a paper at the 2019 PDA conference in Gothenburg, Rob Veasey describes how Sanofi and DCA developed the AllStar reusable pen injector, a device aimed at the needs of patients in developing markets.

Diabetes in India

The importance of developing countries within the global economy is well known and much documented. The so-called BRICS countries (Brazil, Russia, India, China and South Africa) cover 40% of the world’s population and currently account for approximately 30% world’s GDP¹. India alone is the world’s sixth-largest economy, with annual GDP growth of around 7.5%. By 2030, domestic consumption in India is predicted to develop to $6 trillion, making its consumer market the third-largest in the world. With a rapidly growing middle class, changing lifestyle and diets, the population of India has sadly become a global hotspot for type 2 diabetes. For reasons that are perhaps not yet fully understood, Indians appear to develop diabetes at a younger age and at lower body weights than many other populations². Over 70 million Indians are currently affected by the disease and a study by the American Diabetes Association predicts that India will see the greatest increase in people diagnosed with diabetes by 2030³.

A number of factors make the Indian pharmaceutical market different to many others. Driven by intense bio-similar competition, margins are significantly lower than in North America and Europe. Healthcare costs are generally paid directly by patients as an out-of-pocket expense, meaning that drugs are often purchased in small quantities and due to tight margins, volume growth in the insulin market in India has been driven primarily by reusable, rather than the disposable pens. As a means of keeping costs down, most global manufacturers have traditionally opted to offer their previous generations of products in India. Whilst this approach may achieve cost savings, it does not address the strong desire in India and other developing markets to achieve parity with the west in terms of access to high-quality healthcare. In recognition of this dichotomy, Sanofi made a decision in 2009 to create a cost-efficient, state-of-art, locally manufactured insulin pen, aimed specifically at the needs of the growing diabetes patient population in India. They wanted this new reusable pen injector to disrupt the market and to become the patient’s primary choice. With this objective in mind, Sanofi commissioned DCA to develop a new reusable pen injector that would be suitable for manufacture in India at an extremely competitive cost. This pen had to offer superior features and performance to the main competitor pens on the market in India at the time: Novo Nordisk’s NovoPen 3, Eli Lilly´s HumaPen Ergo and Wockhardt’s Pen Royale.

Features that provide value

When setting out to design a new product that has to be better and yet cheaper to manufacture than its predecessors, it is essential to gain a thorough understanding of the features and performance parameters that will be valued by customers. This is a basic principle of value engineering.

In the case of the AllStar development project, we were fortunate to have comprehensive knowledge of the pen injector market in India and elsewhere from the outset. We knew the pens that were available in India well, since most of them had been on the market for a long time. We also knew from market research that diabetes patients in India, in common with other markets, value features that go well beyond the requirements of ISO11608; the set of standards that govern essential performance of needle-based injection systems. Diabetes is a complex condition that requires regular monitoring and intervention by both patients and their doctors. People living with diabetes want devices that fit in with their lifestyle, function well when needed and can be forgotten about when they are not. This desire for better performance is what had driven the development of a newer generation of pen injectors, such as Novo Nordisk’s NovoPen 4, launched in 2005 and Sanofi’s ClikStar pen launched in Europe in 2009. Neither of these devices were available in India in 2009.

When assessing pen injector features that patients value, we can group these parameters within six broad categories:

Dose selection – how easy users find it to select a dose
Dose delivery – how easy and comfortable it is to inject doses from the pen
Ease of resetting and refilling - the simplicity of cartridge exchange
Dose capability – the maximum dose and dial resolution
Handling and portability – the size and weight of the pen
Robustness – the reliability and resilience of the pen injector

The importance attached to each parameter varies by patient. For example, those needing to deliver large doses will be very concerned about the maximum dosage that can be delivered in a single injection. Alternatively, patients who only ever take their medicine at home probably will not worry significantly about portability. Some of the parameters are objective, measurable things like the force required to deliver an injection. Others are more subjective, such as the feeling of reassurance that comes from a precisely engineered dialling mechanism.

To help to visualise some of the shortcomings of the range of pen injectors that were marketed in India in 2009, their features and performance can be mapped against the categories described above on a spider diagram. By evaluating the parameters, in turn, a score can be assigned to the pens in each category (refer to Figure 1a). Whilst there is some subjectivity in this exercise, in most cases, the scores can be derived from measured data. Given that a theoretically ‘perfect pen’ would fill the entire spider diagram, this exercise shows that none of the devices available in India at the time were particularly good. This is perhaps not surprising, since most of these pens were more than ten years old at the time and had already been superseded in other markets around the world.

Figure 1a – spider diagram illustrating performance characteristics of pen injectors available in India in 2009

When the spider diagram is developed to include parameters of newer generation pens such as NovoPen 4 and ClikStar, it can be seen that these devices offer clear advantages over the older pens in most categories, particularly in the maximum dose size, ease of dose selection, dose delivery and cartridge exchange performance (refer to Figure 1b). This is because the newer pens have more efficient drive mechanisms which make dial extension shorter and injection force lower, as well as improved cartridge release and reset mechanisms

How cost is ‘designed iN‘

Perhaps unsurprisingly though, the performance improvements of the newer pens comes with a significant cost premium. To understand this better, one needs to look briefly at how cost is embodied within products. The total manufacturing cost of a product is dependent on a range of factors, often broken down into direct and indirect costs. Direct costs include bought-in raw materials and the labour costs or consumables directly associated with the manufacture of each component. Indirect costs are associated generally with overheads such as maintenance costs, Quality Assurance and management and factory infrastructure. When making design choices, these costs are effectively ‘locked in’ to the new product and most of them are largely defined at the conceptual stage of development. In new product development, designers typically concern themselves mainly with direct costs, since these are easier to measure and control. However, in the development of AllStar, we tried to look broader, considering the total cost of ownership for the new device.

Returning to the pen injectors discussed above, a good comparison of relative manufacturing costs can be made by examining the components of each. The total number of parts in a product strongly influences both direct and indirect costs, because as well as defining the material and labour content, it also dictates the requirement for factory floor space and Quality Assurance costs. At this simplistic level, it is immediately evident that the newer generation pens contain many more components than the pens that were marketed in India, averages of around 30 compared with 20 or less (refer to Figure 2).

Figure 2 – a comparison of components contained with pen injectors

When looking deeper at how the parts are produced, it can also be seen that the newer generation pens comprise many more components that are expensive to manufacture than their predecessors. For example, the newer pens contain more machined and cast metal parts, each of which costs many times more than an equivalent plastic component to manufacture. They also contain more painted parts, more springs and more mouldings that require complex tooling actions. On average, the newer pens contain almost double the number of these ‘expensive parts’ when compared to the previous generation of devices. When all of these factors are accounted for, it becomes evident that the manufacturing cost of the newer pens is likely to be many times greater than most of the pens marketed in India. This understanding raised a key question for the AllStar development team; how does one achieve more for less?

To keep labour and shipping costs low, a local manufacturing partner was identified and engaged at an early stage of development, but the challenge of developing a competitive new pen that could be produced in India at a fair price still threw up a range of questions. For example, design challenges in which the improvement of one aspect would conventionally require a trade-off against another, such as:

How do you maximise the device feature set with fewer parts?
Is it possible to deliver best in class robustness without metal components?
Can complex component interactions be achieved with simple moulding tools?
How do you achieve a reliable and precise assembly process in a very cost-sensitive environment?

These questions drove us to generate a totally novel design for the AllStar pen, in which all aspects of the development targeted best-in-class performance at a very low cost.

What makes the AllStar design special?

To understand the innovations that make the AllStar pen injector design so cost-effective, one needs to examine the design of its mechanism in some detail. AllStar contains a mechanically efficient drive mechanism that achieves low injection force with very few components. This mechanism also allows provides a very short dial extension, meaning that the device remains comfortable to inject, even with a large maximum dose capability. This is achieved with a clever twin-thread drive mechanism, which contains only two components; a piston rod and a drive sleeve (refer to Figure 3).

Figure 4 – drive mechanism components of NovoPen 4

A second innovation can be found in the cartridge exchange and resetting mechanism. AllStar contains a unique clutch system, which uses a single spring component to control the pen in three operating modes: dialling, dose delivery and resetting. This design saves many components in comparison with equivalent systems and facilitates a robust last dose lock-out system that eliminates the need for structural metal parts.

These two innovations, amongst others, facilitate a reduced component count with fewer metal parts, meaning that AllStar has only three simple pressed metal components. In contrast, ClikStar has six metal parts and NovoPen 4 has eleven, many of which are machined or cast. Yet despite this, AllStar has similar reliability and robustness to these two pens. Interestingly, the inclusion of metal parts within a product often creates the impression of robustness, but this can be misleading. In a high-volume product such as a pen injector, the presence of metal components is often a good indication of where the development team has encountered challenges with a design. Injection moulding, even with high-performance polymer grades, is nearly always a much more cost effective manufacturing solution than machining or casting metal parts in high-volume.

To help reduce indirect costs in the manufacture of AllStar, the components were designed to enable uncomplicated moulding tool constructions. All parts are designed to facilitate simple open-shut moulding tools with a maximum of two slides (sometimes called side actions). Unusually for a pen injector with many threaded components, there is not a single tool with a rotating core pin or a need for robot de-moulding. This design strategy helped to keep investment costs low, but also makes the tools more robust. There is less to go wrong, so maintenance costs are lower.

When developing a new drug delivery device, at DCA we always seek to prototype the assembly process. This approach facilitates rapid, first-hand understanding of problems with any process steps and allows our design teams to develop and transfer robust specifications for assembly equipment during industrialisation. In the case of AllStar however, we went much further than this. We developed and manufactured most of the assembly equipment in-house, working closely with the device manufacturer to install, commission and qualify it. This approach kept our team interactions simple, allowing rapid and efficient iteration of the device design alongside the equipment needed to produce it. Our philosophy in developing the assembly process was to seek to minimise complexity, but where this was unavoidable to focus it in one place in which suitable controls could be deployed. Manual pick and place operations are used to load the device components onto precision nests. These nests are then fed sequentially into an electronically controlled assembly machine, which automates and monitors all complex and critical assembly steps ensuring that every pen meets specification.

AllStar’s competitiveness

AllStar has a feature set that places it amongst the very best manual pen injectors. It matches ClikStar in providing a large maximum dose volume (80U) and yet equals NovoPen 4, with the shortest dial extension per unit of dose selected. AllStar has a large, magnified dose display with all non-selected dose values concealed by the mechanism. When a dose is delivered the injection force is low and consistent and there are no rotating parts that a user can catch their finger on. Cartridge exchange is straightforward because the mechanism resets automatically when a replacement cartridge is fitted. Beyond this, AllStar is extremely small and lightweight, yet also robust and precise.

In terms of its manufacturing complexity, AllStar comprises just 19 components. This is less than two-thirds of the number of parts contained in either ClikStar or NovoPen4. It also has very few complex or expensive parts, just three printed components and three pressed metal springs (refer to Figure 5). This means AllStar is an order of magnitude less costly to manufacture than most pen injectors with similar performance.

Figure 5 – components contained within NovoPen 4, ClikStar and AllStar pen injectors

Since launch in India in 2012, AllStar has received very positive feedback from both patients and healthcare professionals and there have been few customer complaints. Importantly, the pen meets the requirements and constraints of developing markets without compromising performance or quality. AllStar is now offered by Sanofi across a wide-range of markets.

References

¹The Mixed Fortunes of the BRICS Countries, in 5 Facts, Time, 1st September 2017

²The Elevated Susceptibility to Diabetes in India: An Evolutionary Perspective, PMC, 7th July 2016

³Global Prevalence of Diabetes. Diabetes Care. American Diabetes Association, 26th January 2004. Web. 22nd April 2014.