Medical-Grade Compressed Gas Power for Innovative Drug Delivery Devices
After decades of limited options to power drug delivery devices, the next generation has arrived. Medical-grade compressed gas cylinders represent the next innovation in drug delivery device power sources. Picocyl’s technology and application expertise offers broad injection platform capability and flexibility, matched with minimized downstream one-time and ongoing costs of platform variants.
TABLE OF CONTENTS
Define a broad volume-viscosity platform around a single cylinder size
Ease of gas and pressure selection in the same cylinder to match with specific drug volumes, viscosities, and human factors (i.e. platform variants)
Laser-marked traceability, assembly error-proofing, and bowl feeding enabled by cylinder form factor
Low one-time development costs for platform variants
Low one-time industrialization costs for assembly of platform variants
Ease of production assembly changeover between platform variants
The single-use autoinjector has been focused on spring power since its inception in the 1970s. Compression springs have offered a simple and inexpensive energy storage option. The power density is high, meaning the energy can be released very quickly. However, the energy density is very low; in other words, the more work required, the larger the spring. It is also difficult to control the energy release once it is activated and moreover some potential energy is converted to kinetic energy by the spring mass, which can pose challenges such as loud noises on activation and glass syringe breakage at the end of the motion.
The continued trend toward patient-use devices leads to a projected 18.1% CAGR through 2027 for the autoinjector market1. As the number of drugs, especially biologics and biosimilars, and patient dosing regimens expands with autoinjectors, it creates the opportunity for next-generation innovation in drug delivery power sources, and Picocyl is at the forefront of the innovation. In the past, industrial gas cylinders were the only option, and these had leak, size, and activation issues. Picocyl, a medical device components design and manufacturing company, has solved these problems, producing gas cylinders with the quality, reliability, and application engineering expertise necessary for medical applications. This combination of capabilities has resulted in many applications to date, including ophthalmic surgery, autoinjectors, specialty oral doses, and other parenteral drug delivery applications.
Compressed Gas Provides Broad Platform Capability
Reusability is the core of any drug delivery device platform. The ability to reuse device design, test data, human factors studies, and manufacturing assets across a range of drug formulations with varying properties reduces program time, cost, and risk. Commonality across platform variants, and flexibility to drug-specific requirements, is the balance to be achieved. A well-designed and proven platform reduces development and manufacturing costs, while providing predictable human factors and patient tolerability outcomes.
Ideally, a platform’s functionality provides a maximum range of drug volume and viscosity capability, minimum cost and time to customize for each application, and a minimum effort to manage autoinjector variants once in commercial production. Picocyl allows a platform to achieve all these objectives.
Compressed gas cylinders of a fixed size can be manufactured at different pressures, customized to injection force requirements. In the visual representation shown (Figure 1), a cylinder used in an autoinjector system designed for cylinders up to 276 bar delivers the same force as springs that are physically much larger, while requiring a much smaller footprint.
While the cylinder itself may be safely pressurized to 276 bar – or more – this pressure is isolated to the cylinder only, and the remaining autoinjector will not be subjected to such pressure. Instead, upon activation the gas first expands into a designed “dead space” before applying pressure to a plunger. The device will be subjected to a fraction of the cylinder pressure determined by the “dead space” design, and only for the seconds to minutes of delivery time that is engineered for the application.
Additional flexibility is achieved by tailoring the gas type to the application. Autoinjectors, in practice, can be used across a wide temperature range from refrigerated storage temperatures to high temperatures in automobiles, baggage, or on-person. As such, pure gases such as argon or nitrogen are appropriate as the gas pressure varies as a function of the absolute temperature. On the other hand, the vapor pressure of liquified gases such as HFC 134 vary significantly. As an example, from 0-40°C, the pressure of argon will increase by 15%, while for HFC 134, the pressure will increase by 150%.
Liquified gases, however, are well suited to applications where a relatively constant pressure is desired over a long stroke and the temperatures do not vary widely. This includes applications such as OBIs and surgical devices where the temperature is regulated by body temperature or the environmental controls of an operating room. In these applications, liquified gases such as liquified carbon dioxide provide higher expansion volumes at high pressures than the pure gases.
High pressure gas cylinders can be filled with naturally occurring gases such as argon and carbon dioxide that are environmentally friendly compared with fluorinated gases.
Improve Human Factors
The same flexibility offered by compressed gasses in generating pressure can also extend to human factors such as noise, vibration, and time. Upon activation, gas is released, fills the dead space, and then the dead space and then moves the plunger. The associated noise and vibration during this process is limited to the piercing of the cylinder and the movement of the plunger, both of which are insignificant compared to spring uncoiling.
Compressed gas cylinders also offer customization of delivery time to accommodate patient tolerability and drug absorption, adjusting to application factors such a temperature, volume, viscosity, body location, and subcutaneous vs. intramuscular injection. As shown in Figure 2, varying the cylinder pressure in these 4 volume-viscosity scenarios provides a broad range of injection times, including longer times that may be better suited to an OBI than an autoinjector, that offer customization to patient needs.
Design for the Maximum Expected Cylinder Pressure to Provide Maximum Platform Flexibility
An ideal platform provides a maximum range of drug volume and viscosity capability, minimum cost and time to customize for each application, and a minimum effort to manage autoinjector variants once in commercial production. Building upon the first need (maximum range of drug volume and viscosity), the data modeled in Figure 3 projects the dose volume that can be delivered for viscosities of 10 cP and 100 cP, at a minimum of 2 seconds and a maximum of 20 seconds. The intention here is not to suggest the volumes are suitable for a specific drug or within the patient tolerability range, but to demonstrate the very broad operating window for a compressed gas-powered autoinjector platform with the same form factor.
The isolated pressure within the cylinder, and not applied to the device until activation, also offers benefits compared to springs, including lower stress on the assembled device, no plastic creep within the device subsystems, and no energy loss due to stress relaxation in the spring resulting from long shelf-life storage under high compression.
Single Size Power Source to Reduce Manufacturing Cost and Complexity
The benefits to a platform with flexibility in volume and viscosity is not limited to the drug and the patient, but also to unit manufacturing cost. New or modified autoinjector components must consider the following downstream impacts to cost and risk:
- Component tooling build, validation, and ongoing maintenance
- Component manufacturing set-up complexity and inventory management
- Assembly process equipment build cost, validation, and ongoing maintenance
- Assembly process manufacturing set-up (i.e. changeover complexity) and inventory management
The use of a platform with a single variable (gas pressure in the selected cylinder size) provides capability across a broad range of drug volumes and viscosities which results in a less complex and lower cost supply chain, at both the component level and the assembly level. Further, there are assembly process benefits to a common size cylinder installed via a simple bowl feed to a “pick and place” robotic operation, as compared to a platform with multiple spring options and the associated complexity of feeding and assembly to compress and retain the spring during subsequent assembly operations.
In addition to bowl feeding to an assembly station, the compact gas cylinder form factor also supports bulk packaging to minimize shipping and storage costs. The laser marking features on gas cylinders also provide traceability and assembly error-proofing.
Picocyl enables the future of drug delivery and other special applications through innovative device design and gas-powered solutions for the medical and pharmaceutical markets. Every product, application and solution we deliver is built from the ground up in our USA-based, state-of-the-art, cleanroom manufacturing facilities (ISO Class 8). A pioneer in developing unique energy sources for drug delivery, the Company’s flagship Pico-Cylinders have become the industry standard for single use, gas-powered devices.