The question of what makes injections safe has never been more complex. It includes several aspects, such as giving the right dose, keeping the drug stable and free from contamination, and avoiding injuries. Sharps injury claims cost the NHS £4.077 million during 2012–17, and an NHS report estimated that 80% of those injuries were preventable.
Needle sticks, however, are not the only common syringe injury; glass cartridges present a problem due to their fragility, and can often shatter in use or in transit. A possible solution to this issue is polymer packaging, which has seen a growth in popularity in recent years.
Meanwhile, an ageing global population and a rise in the prevalence of chronic diseases has piqued major interest in self-injection. This, in turn, is driving a boom in prefilled and safety syringes, micro-needles, and needle-free solutions, as well as the nascent world of wearable electronic self-injection devices. Biological drugs, too, are expanding their market share, requiring specialised packaging solutions and prompting a new wave of innovation.
A new standard
Glass has long been the gold standard for syringe barrels due to its effectiveness as a barrier against water and oxygen, and the ease by which it can be sterilised. Its long history as a packaging material – stretching back to the 1700s – means that it is compatible with most filling machines, presents few challenges to regulators and is widely produced, making it easy to integrate into a supply chain.
Despite its longevity, however, glass containers can cause problems. They can leach heavy metals into their contents depending on the composition of the drug, and some new biological products are also sensitive to silicone oil, which is often used as a lubricant for glass syringes to ensure a smooth and comfortable injection experience after long periods of storage.
As the market for prefilled and self-administered injectables has grown, the potential for injury or chemical reaction from glass has spurred manufacturers to look into plastic alternatives. Polypropylene and cyclic olefin polymer (COP) are two of the more widely used plastics, and a July 2017 report by market intelligence firm Fact.MR predicted that “more than 99% of global syringe sales will be accounted by plastic as raw material” in the period leading up to 2022.
The need for safety systems for self-administration is not only driving the demand for polymer, but also for safety syringes, auto-injectors and wearable injection devices. As the populations of developed countries grow older and more obese over time, the prevalence of several chronic health conditions is experiencing a corresponding jump. The International Diabetes Federation predicts there will be 38 million diabetics in the EU by 2030, and Europe is now the second-largest market for cortisone shots, commonly used to treat rheumatoid arthritis. These patients may need to take medication several times a day, which is why they’re behind the push for selfinjecting – a Research and Markets report in 2015 predicted that self-injection devices would increase their market share at a compound annual growth rate of 16.1% by 2020. In practice, self-injection products tend to be prefilled, ready-to-use syringes in sturdy plastic packaging, such as a pen injector, with a mechanism like auto-retraction to protect the user from needle stick injuries.
When asked about developing trends in prefilled syringes, Anil Kumar Busimi, the head of global product management for syringe business at Schott, told Pharmaceutical Processing: “drug stability is the primary concern, especially for sensitive biotech drugs.”
The biologic trend
Together with self-administration, biological drugs are one of the other major contributors to the expanding market for plastic prefilled syringes. These drugs could contain almost anything, from live cells and proteins, to blood components and nucleic acids; it’s very difficult to define their chemical make-up, so it’s harder to predict whether they will have a surface reaction with their containers. As well as reacting with silicone oil, many biologics are also sensitive to temperature changes and bacterial contamination. Some manufacturers are working on tweaks to the traditional syringe design to solve this. At Pharmapack 2018, for example, Gore launched a silicone oil-free plunger especially for prefilled glass syringes with biologic contents. However, this kind of solution doesn’t address the main problem with injecting biologics.
“One challenge posed by new generations of biologics is that many of them [have] large molecules and [so must] be administered in high concentrations,” a spokesperson for injective device manufacturer SHL Group explained to European Pharmaceutical Manufacturer. “The resulting formulations reach high viscosities, sometimes together with high volumes, thus creating a challenge for traditional delivery systems.
Occasionally, biologics need to be delivered in quantities as large as 50ml, and so came the advent of the ‘patch pump’: a small wearable device that sticks to the skin and administers an injection gradually over a time frame of up to 15 minutes, allowing the patient to stay mobile. The hands-free nature of the system, and the plastic housing where the needle can be concealed, means wearables are low-risk for sharps injuries. A study published by Thomas Jefferson University, however, found that “pain scores were significantly (p < 0.001) higher than baseline at the end of injection”.
The conundrum is how to account for the high viscosity and sensitivity of biologics without compromising on convenience or comfort. Patient adherence already tends to be low when needles are involved, but when a self-administered injection is consistently difficult and painful, patients are even more likely to skip their medication.
“Needle phobia is a major barrier to health,” Dr Faz Chowdhury, CEO of Nemaura, explained in May 2017 when the company launched its Memspatch, an insulin micro-needle device. “Over 50% of adults with type 2 diabetes delay starting insulin due to needle fear, and over 90% feel fear reactions every time they inject.”
– Dr Faz Chowdhury, Nemaura
Modern alternatives
Nemaura’s device is one of a crowd of new systems looking to do away with the hypodermic needle entirely. ReportsWeb forecast in March 2018 that the global market for needle-free injection systems would grow from $11.35 billion to $27.23 billion by 2023. Microneedles often come in the form of a skin patch, one side of which consists of minute needles that can break the skin and administer the medication. A user doesn’t need training to safely use them, and the drug coating can be in powder form or incorporated into the material of a dissolvable patch.
In June of last year, a study by researchers from Emory University School of Medicine and Georgia Institute of Technology revealed that a flu vaccine was just as efficient as a hypodermic needle when delivered via a micro-needle skin patch. Out of the test subjects who got the patch, more than 70% said they preferred it over a shot or a nasal spray. Animal trials also suggested that receiving a vaccine through the skin provoked a stronger immune response because, as the project’s chemical engineer Mark Prausnitz told NPR, the immune system is more accustomed to finding pathogens on the body’s surface than in the blood.
Another needle-free method is jet injection: a narrow stream of liquid that is delivered in a sharp burst to penetrate the skin. The technology was developed more than 100 years ago for mechanical uses and is still used for applications like fuel injection in cars. It has, in fact, been used on humans since the 1960s, but, historically, the technology was imprecise – a spring-powered method that forced all the liquid out at once. It resulted in a fairly large and imprecise jet that wasn’t any less painful than a needle. It wasn’t until 2012 that a team at the Massachusetts Institute of Technology (MIT) found a way to use computer-controlled magnets to regulate the jet, delivering an initial strong burst, and then tapering off to ensure precise and painless dosage.
Jet injector manufacturer PharmaJet’s latest project is a contract with WHO to deliver five million of their devices for polio vaccinations. The developing world is one of the biggest markets for needle-free systems; not only do they have the potential to increase immunisation rates by removing the fear factor, they also drastically cut down on the potential for infection through sharps injuries or the reuse of needles. In an environment where hygiene can be difficult to maintain and treatment for transmitted diseases isn’t always readily available, this makes an enormous difference to the wellbeing of patients and healthcare professionals.
Jet injections also works well for viscous biologics because the drug and injector need a lot of force to inject efficiently. Start-up Portal Instruments announced in 2017 that it had licensed MIT’s technology to develop a smart needle-free injector system that also tracks adherence. The device collects data on injection frequency, dosage and type of drug used for review by healthcare providers. The internet of things can’t force a patient to take their medication, but it can keep doctors in the loop so non-adherence is immediately apparent.
Yet, even the most up-to-date technologies can only do so much in making hypodermic needles safe. Ultimately, training users to behave responsibly is the most effective way to keep injuries to a minimum. Luckily, the industry seems to be reaching a point where injections are no longer synonymous with needles. A modern and safe injection can now mean a device that keeps its contents stable; stands up to rough handling without shattering; encourages patients to get vaccinated; removes the threat of disease transmission from contaminated needles; and persuades chronic-disease patients to stick to a drug regimen that does not increase their suffering. For the 10% of people who are needlephobic, it’s a dream come true, and for pharma, as a whole, it’s a reminder that there is nothing that can’t be improved upon.
