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CONNECTED, NEEDLE-FREE DRUG DELIVERY

Citation: Taylor B, “Connected, Needle-Free Drug Delivery: Improve Outcomes with a Next Generation Device”. ONdrugDelivery Magazine, Issue 86 (May 2018), pp 14-18.

The healthcare industry is seeing an ever growing trend towards patients self-administering their therapies at home. Barbara Taylor discusses this trend and how Portal is making a bold step towards this goal with its novel needle-free injection device.

INTRODUCTION

When examining today’s healthcare market, some clear trends become apparent:

“According to a survey conducted in 2012, 20% of RA sufferers report that they would not consider using a medication that required self-injection…”

  • People are living longer, as such more people are living with chronic diseases (149 million Americans in 2015).1
  • There have been tremendous advancements in treatments available for chronic diseases, especially with monoclonal antibodies (mAbs). However, despite their therapeutic value, compliance is as low as 50% (Figure 1).2
  • This has put a toll on healthcare systems worldwide and requires rethinking how patients are treated and the overall population approach to healthcare.

One result of these trends is a push to move treatment to the home setting by empowering patients to take control of their health and treatments, with less direct supervision. With this in mind, the challenge for the pharmaceutical and drug delivery industry is to think beyond just the pill (or the injection) itself and to design the therapy to fit into patients’ lives with minimum possible disruption. Treatment decisions should take into consideration a patient’s lifestyle, anxieties, obstacles to taking the medication and necessary support, as well as what happens before and after the treatment administration. Patients should be provided with the tools and support needed to be better empowered to take control of their health.

Figure 1: Despite the therapeutic value of modern medicine, adherence is low (50%), which puts a heavy burden on healthcare systems.1-3

With an understanding of the needs for home treatments, Portal is developing a needle-free drug delivery platform technology to transform the administration of medicines and improve the patient experience for chronic diseases (Figure 2). Portal’s needle-free injector enables the administration of biologic drugs without the anxiety induced by needles. The Portal platform is also cloud-connected and provides reminders and real-time tracking of injections to improve adherence and communication between the patient and care teams – all with the aim to improve therapeutic outcomes.

UNDERSTANDING THE PATIENT EXPERIENCE

Many patients exhibit anxiety when it comes to the subject of needles. It is important to understand that this needle anxiety goes beyond physical pain; some patients dislike the stigma associated with needle usage, whilst others are afraid of not being able to properly self-administer injections. This fear of needles can interfere with administration and ultimately patient compliance. There are other circumstances that discourage patients from bringing needle-based devices into their homes, one example being parents with young children, who may fear that children will hurt themselves should they stumble across or decide to play with the device. According to a survey conducted in 2012, 20% of RA sufferers report that they would not consider using a medication that required self-injection.4

Figure 2: Portal Instruments’ needle-free, digitally controlled injector, represents the next generation of needle-free drug delivery platforms.

Alternative devices, utilising needle-free technology, could bypass such fear. Portal Instruments has developed one such device, a needle-free injector based in jet-injector technology. Uniquely, Portal’s next-generation needle-free injector uses a computer-controlled linear actuator to pressurise the medication and inject it in a very fine liquid stream, roughly equivalent in diameter to a strand of hair. The entire injection takes place in less than half a second. The algorithms in the device’s software enable the injections to be specifically tuned, both in terms of injection depth within tissue and precisely controlling the release of medication during the injection process – fast at first and then slow.

THE HISTORIC NEEDLE-FREE PROBLEM

Needle-free drug delivery devices are nothing new, examples have been around since the 1960s, but their widespread adoption has been hampered because, to date, such devices have been unable to overcome key issues, including:

  • Being able to deliver only a limited volume of medication.5
  • A limited ability to control injection depth.5,6
  • Loud and painful during injection.6

The reason prior attempts at designing needle-free injectors have struggled is that they have been limited by relying largely on either mechanical or gas-based approaches to generate the high pressures required to expel the fluid at sufficient speed to pierce the skin and thus achieve a successful subcutaneous injection. Stored energy systems, such as a high-powered spring or compressed gas cartridges (e.g. air, CO2, N2), work by generating a sudden burst of energy (and often an accompanying loud bang) when that spring releases or the CO2 cartridge explodes, driving the injection with the necessary force and pressure.

A key problem with this historic approach is that the stored energy is the same fixed amount for every patient, despite differences in skin types and patient profiles, resulting in an injection depth that is difficult to regulate. Stored energy systems lack the ability to control the injection (i.e. the fluid stream) in real time, meaning that once the mechanism of action is activated, there is no possibility of further modifications to the injection. Portal refers to this as an “open-loop system”. This issue becomes very significant when attempting to deliver larger volumes, 1 mL for example, often needed for viscous biologics, to the subcutaneous space in a needle-free fashion.

“Algorithms in the device’s software enable the injections to be specifically tuned, both in terms of injection depth within tissue and precisely controlling the release of medication during the injection process – fast at first and then slow…”

An additional problem is that, just as this energy is released quickly, it dissipates quickly – meaning only a limited volume of medication can be delivered at a time. With the spring-based approach, the spring is used to generate the necessary energy to force the fluid out of an orifice at high speed (>150 m/s). Since the spring has an energy profile that decays over the course of the injection, the fluid velocity will also decay over time. A similar decaying velocity profile is also characteristic for gas-based injectors. Thus, the highest velocity of fluid expulsion occurs at the onset of the injection, followed by a decrease to smaller and smaller velocities. When considering a 1 mL injection of a viscous biologic, this profile may be insufficient to achieve a successful subcutaneous injection. Furthermore, for every doubling of dosage volume, a fourfold increase in power is required, resulting in more force (and therefore theoretically more discomfort) on the patient.

Figure 3: Comparison of standard needle gauges with the Portal device’s liquid jet.

PORTAL’S SOLUTION

To solve these problems, Portal Instruments, is developing a needle-free injector with a computer-controlled motor and with an internal feedback control system, similar to a car’s cruise control. This “closed-loop” control system senses pressure and adjusts the jet speed to appropriately deliver the drug.

The Portal needle-free jet-injector platform consists of an electromagnetic actuator controlled by a computer that generates a jet of liquid with a diameter of 100 μm, about a quarter of a 27 gauge hypodermic needle, approximately the diameter of a human hair (Figure 3). It is this jet of liquid, which contains the drug of interest, that pierces the skin to reach the desired subcutaneous space, without the intervention of any physical component to puncture the skin (Figure 4).

Figure 4: Comparison of injection by a standard autoinjector and Portal’s jet-injection device.

The actuator enables precise control of the speed of the pressurised jet of liquid, thus resulting in accurate targeting of the desired subcutaneous space with the exact amount of drug needed. In contrast to historic devices, the velocity profile of Portal’s device is much more controlled, with an initial fast penetration phase followed by a consistent, slower delivery phase (Figure 5). The high adaptability of the system further allows the jet-injection device to accommodate the delivery of low to very high viscosities and drug concentrations without any changes to the device. The design of the device currently supports the subcutaneous administration of up to 1 mL of drug preparation in less than a second.

“Portal’s unique technology allows full control of the jet via a computer-controlled feedback mechanism, thus decreasing sensation when compared with needle and syringe,” said Patrick Anquetil, CEO of Portal Instruments.

Figure 5: The velocity curve of the Portal injection over time: a fast penetration with a controlled, slower delivery phase, consistent across a range of viscosities.

Furthermore, the jet-injection device is relatively quiet, fast and the software automatically adapts injection parameters to suit not only the viscosity, but also the temperature of the medication. The pain of traditional needle-free injectors has also been addressed; studies have shown that patients perceive less pain using, and demonstrate an overall preference for, Portal’s needle-free injector compared with needle-based injections (Figure 6).8

Figure 6: Subject preference for the Portal Handheld Device versus 27G needle and syringe.

The other advantage with Portal’s innovative injector is that Portal has developed a primary container that is compatible with standard pharmaceutical fill/finish lines. This reduces any additional capital expenditure for manufacturing on the pharmaceutical line. And the patient receives their medication dose pre-packaged in the cartridge, ready to be used; there is no need for the patient to have to transfer medication from a syringe to the injector.

Portal’s development process is based on a design, build, test and iterate model throughout which Portal places a heavy emphasis on patient input and expertise of healthcare providers. Portal has run rigorous human factors studies including contextual inquiries, formative and other heuristic evaluations. In-depth interviews with patient groups revealed challenges and needs and provided valuable insight about how the design of the device could affect the experience of their prescribed therapy and overall adoption of their treatment as an integrated part of their lifestyles.

DIGITAL TOOLS FOR IMPROVED EXPERIENCES & OUTCOMES

Digital tools and accompanying services are another way to build a positive patient experience and enable the patient to take control of their health and medication. When properly designed around the patient, such tools can assist with educating a patient as to the proper usage of their device, reminding them to take their medication at the correct times and logging treatments and symptoms – all important aspects of managing a chronic disease.

Figure 7: Portal’s digital ecosystem, designed around the patient with the goal to improve outcomes.

In a similar vein, Portal is looking to ensure their digital tools can assist communication with physicians by providing injection and symptom data (Figure 7). With clear, accurate data recorded over time, physicians can review patients’ therapeutic results and make more informed decisions about further treatment.

Additionally, when digital tools are integrated with the drug delivery device, information can be gathered in near real-time. At the aggregate level, this data can lead to identification of trends with regard to adherence obstacles, patient behaviours and possibly correlated lifestyle data. This data can, in turn, be used to enhance the patient experience with the goal of improving adherence and therapeutic outcomes.

If trends continue, nearly 50% of the population will have a chronic disease by 2030.1 However, with novel therapeutics, patient-centred treatments which take the patient’s lifestyle into account and digital tools to aid in treatment support and decision making, progress is being made towards a healthcare system in which patients are empowered to take control of their health and therapy.

PARTNERSHIPS

Portal is looking to develop strong partnerships with all major biologics players seeking to gain an edge by offering their therapeutics fully integrated with a digital, patient-centred delivery system.

REFERENCES

  1. “Growing Crisis of Chronic Disease in the US”. Fact sheet, Partnership to Fight Chronic Disease.
  2. “Why You Need to Take Your Medications as Prescribed or Instructed”. US FDA. www.fda.gov/Drugs/ResourcesForYou/SpecialFeatures/ucm485545.htm (Accessed May 2018)
  3. Viswanathan M, “Interventions to Improve Adherence to Selfadministered Medications for Chronic Diseases in the United States, A Systematic Review”. Ann Intern Med, Dec 2012, Vol 157(11), pp 785–795.
  4. “Preliminary Findings From Rheumatoid Arthritis Patient Survey Reveal Strong Interest in Needle- Free Self-Injection”. News Release, Zogenix, Nov 2012.
  5. Taberner A, Hogan NC, Hunter IW, “Needle-free jet injection using realtime controlled linear Lorentz-force actuators”. Med Eng Phys, Jan 2012, Vol 34(9), pp 1228–1235.
  6. Ravi AD et al, “Needle free injection technology: A complete insight”. Int J Pharm Investig, Oct-Dec 2015, Vol 5(4), pp 192–199.
  7. Stachowiak JC et al, “Dynamic control of needle-free jet injection”. J Control Release, Apr 2009, Vol 135(2), pp 104–112.
  8. Kojic N et al, “An Innovative Needlefree Injection System: Comparison to 1 ml Standard Subcutaneous Injection”. AAPS PharmSciTech, Nov 2017, Vol 18(8), pp 2965–2970.

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