The injectable drug-delivery device market is growing at a staggering rate, with an anticipated global market value of $37.5 billion by 2025 compared to $16.7 billion in 2016. The driving factors of this growth are the increasing geriatric population and the rising incidence rates of chronic and autoimmune diseases such as diabetes and multiple sclerosis. Allergies causing anaphylactic reactions are also increasing dramatically, particularly in industrially developed countries.
In this rapidly growing market, auto-injectors and pen injectors have become the new standard for injectable drug-delivery systems. Their popularity has soared due to their simplicity, reliability, and ability to be administered directly by the patient without the aid of a physician. These devices require intensive, highly regulated testing to ensure that they work as intended every time. As their technology continues to develop and improve, the equipment required to test them is also becoming increasingly sophisticated through advanced automated capabilities and integrated sensors.
Although autoinjectors and pen injectors serve the same purpose, they are used in different medical scenarios. An autoinjector is typically used in cases where medication is needed immediately but infrequently such as the EpiPen®. With autoinjectors, the patient actuates the needle and subsequent flow of medication solely through the application of pressure on the injection site. The pressure causes the actuation of a needle shield, which engages the needle and causes the device to inject the drug. Pen injectors, on the other hand, typically serve patients with chronic diseases who require regular doses of medication to alleviate symptoms. These devices require the patient to activate a push-button, which actuates the needle into the targeted injection site. Both of these devices function similarly from a mechanical perspective, using a calibrated spring to push the medication from the device through the needle and into the target tissue. Over time, the adoption of this technology has surpassed the use of standard hypodermic needles because of their decreased cost and increased usability.
When developing and mass producing these devices, manufacturers usually perform a combination of testing to government-regulated standards and internal quality testing to ensure efficacy of the device. Internal quality testing is often necessary because the international standards committees cannot always amend testing standards as quickly as the device technology evolves. The most widely used international standard is ISO 11608-5, which discusses the test methods and requirements for automated needle-based injection devices. Within the standard, the functionality of the device is evaluated from both an ergonomic and an operational perspective. A universal testing machine is the ideal device for measuring and capturing the following results.
Needle-Based Injection Systems: Test Requirements
Removal Force of the Safety Cap. Both styles of injection device typically include a protective cap to ensure that there are no accidental needle sticks. The force required to remove these caps must be precisely calibrated to ensure that any user, from a child to an arthritic senior, can easily remove it.
Needle Activation Force. For pen injectors, it is necessary to measure the force required to depress the button and initiate the expulsion of the medicine. Autoinjectors rely on a needle shield that sheaths the needle until the device is pressed against the target injection site. It is important to accurately measure the force required to overcome the needle shield, because it is generally designed for a specific target tissue (dermis, subcutaneous tissue, or muscle) depending on the type of medication the injector is intended to deliver. Users will naturally have different degrees of tissue thickness, so the needle shield must work in each situation without error.
Override Force. Autoinjectors and pen injectors are often single-use devices and as such must be easy to dispose of safely. This calculation measures the force required to retract the needle and lock it effectively into a safe position.
Ejection Dosage. Medication dosing can often be programmed onto the delivery device itself, ensuring that the correct dose is delivered. The dose being expelled must be measured to confirm that it aligns with the expected quantity. Manufacturers will typically evaluate both the mass and volume of the expelled medication.
Needle Length. The length of the actuated needle is critical for ensuring that the medication reaches the target tissues for all potential users. This measurement can be made by either mechanical or optical means, but it cannot interfere with the movement of the needle.
Ejection Time. The time required to completely dispel the medicine into the body is an extremely important metric for manufacturers. This is directly related to the experience of the user and can be measured in several ways. The most common methods use either synced time data with ejection mass measurements or optical solutions.
Dose Setting. Injection devices either provide fixed or variable doses. Variable dose systems require the user to manually set the dose being administered. The force or torques required for setting these values should be properly evaluated to ensure that an ergonomic solution is provided.
Audible Click Detection. These devices typically provide multiple forms of feedback for the user indicating that the needle has been actuated and the medicine injected. Audible feedback is very common and can be measured using an auditory sensor.
In the past, all of these tests have been performed individually, forcing manufacturers to buy multiple pieces of equipment and manually sort through the data in order to synchronize the results. This process increases equipment costs and operator requirements while decreasing throughput. It also slows down design evaluation and testing, potentially affecting a device’s time to market. At the moment device technology is improving at an especially rapid pace, since the original patents created for needle-based injection systems are soon to expire, and manufacturers are investing in the development of in-house autoinjector and pen injector devices. The speed and efficiency with which these devices can be developed and validated determine their competitive advantage within the pharmaceutical devices market.
Out of necessity, the testing equipment for these devices has seen similar growth and development, with many companies designing fully integrated automated testing devices requiring minimal operator interaction. Through advanced technology, they can perform all required tests on a single device, eliminating the need for sequential testing setups. This is also a more realistic test case because users can activate and use the devices in one session. The less operator input between tests, the more repeatable the results will be. The total process time is significantly reduced as additional machine setups are eliminated, and the operator can focus on value-added activities. Traditional benefits aside, a fully automated system provides the manufacturer with a higher degree of confidence in the data and, in turn, the completed product.
To consolidate the tests, a standard universal testing system needs to be retrofitted with specialized equipment such as optical micrometers, auditory sensors, and high-resolution scales. Ideally, the software would be able to read and import the data from the external devices as well. This is usually accomplished with analog and digital input signals. In the system shown in Figure 1, the machine is able to perform all of the required testing with complete synchronization of the data. This is especially helpful considering the FDA requirements that are stated in CFR 21 Part 11. All of the data is produced and tracked from one device, ensuring an easy-to-follow audit trail.
As the product portfolio of drug-delivery devices expands, the testing system needs to be adaptable to various device types, geometries, and test requirements. For example, machined inserts can be used to remove various cap geometries with ease. The modular nature of the system provides manufacturers peace of mind that as their products become more advanced, so can their testing equipment. The ability to add a torsion drive to a test system unlocks previously un tapped potential, providing a simple way to effectively quantify the torque required to set a dial dose. To reduce the time spent on data entry and the incidence of manual errors, bar code scanners can be used to input individual product and lot information.
When developing drug-delivery device systems, it is important to identify equipment that can efficiently perform all of the required product testing while intelligently capturing and evaluating the test data in accordance with FDA regulations. The test system must also be flexible and modular enough that manufacturers can change and add functionality over time. A future-proof system allows the manufacturer to remain agile, constantly testing and developing new products. As the demand for these devices continues to increase, more and more companies will begin development and production, necessitating a completely integrated system to accommodate all R&D and quality control needs. Universal testing systems will continue to further specialize, creating a multifunctional product designed to precisely meet the needs of drug-delivery device manufacturers globally.
- BIS Research, “Distribution of the injectable drug-delivery market worldwide in 2016 and 2025, by device,” 2019.
This article was written by Landon Goldfarb, Applications Engineer, Instron, Norwood, MA. For more information, click here.