Injector pens and autoinjection devices are emerging that meet higher standards of quality, accuracy, and ease of use. Testing equipment is being developed to keep up with this trend.
For U.S. diabetic patients requiring insulin, the use of the traditional vial and syringe is still predominant, though such syringes are beginning to lose favor. Physicians are concerned that these syringes make it difficult to obtain a high dosing accuracy while patients also find them cumbersome to use.
There is a transition away from syringe vials towards prefilled syringes and pen-injector devices. Because of this shift, quality control initiatives must evolve to meet emerging market needs. Such evolution calls for rigorous product testing to ensure safety, dose accuracy, and ergonomic functionality.
Keeping Up with Key Trends
Quality control strategies must address important trends associated with prefilled injectors including increased customization, decreased time to market, and reduced cost per unit.
Standardized platforms have been developed to meet the need of high-volume applications such as insulin injections for diabetes and hydrocortisone for emergency treatment of allergic reactions like insect stings. The ability to leverage a single injection device design across multiple high-volume markets lowers costs and shortens time to market. Standardized designs can also be used to reduce time to market in low-volume clinical trials.
Many of the high-volume applications such as insulin injectors are disposable devices. By some estimates, over a billion insulin cartridges are filled each year, with about half dedicated to use in disposable devices and the remainder deployed in reusable devices. With growing interest in the convenience associated with disposable devices, demand for reusable injectors to replace vials stems primarily from emerging markets. Reusable injectors also provide an effective delivery mechanism for frequently injected therapies that use prefilled syringes, such as those prescribed for the treatment of multiple sclerosis (MS).
As the range of injectable pharmaceutical therapies continues to increase, so does the need for injection devices capable of delivering new formulations to treat conditions as diverse as MS, cardiovascular diseases, and Alzheimer's disease. An emerging trend is the design of custom injector platforms to support the administration of a variety of doses and application-specific criteria such as needles with varying sizes.
Fixed-dose platforms differ from those applied to the development of insulin pens and other variable dose injectors, which must be capable of accurately delivering a range of units in a package that is simple for the patient to interpret and operate. These requirements translate to product testing protocols that must be addressed during manufacture. Areas in which manufacturers are establishing quality initiatives are component-level material properties, pen-gearing mechanisms, and tactile feedback.
The International Organization for Standardization (ISO) established the 11608-1 standard to specify performance requirements and to prescribe testing requirements for essential aspects of pen injection devices. The standard provides guidance on preconditioning and testing conditions, including temperature, humidity, and dose accuracy requirements.
As pens move from manual gearing to spring-driven designs, it is necessary to understand both the mechanical and human engineering factors concerned including actuator force measurement. Studies have demonstrated patient preference for lower injection forces.
Testing Out the Injector Pens
Zwick/Roell (Ulm, Germany), which makes materials- and component-testing equipment, has developed products designed to measure specific characteristics of injector devices including actuation force and accuracy. The company's test device for automated testing of injection pens is based on its zwicki-Line Z0.5 TN tabletop testing machine with additional torsion drive, allowing the various operations of the pen to be tested using a single device. In this way, the dosage setting, release force, stroke, and the dose dispensed are measured in one continuous process. The test device can be combined with a robotic specimen feed system and the test methods using either axis or both axes can be combined as required.
Autoinjectors are subject to stringent quality control measures. As an alternative to manual quality control, Zwick offers a product for automatic determination of the relevant test parameters. Previously, parameters such as the firing time and duration of expulsion could only be measured manually. The company has developed a platform for automated determination of actuation force, firing time, expulsion time, ejected volume, and extended needle length.
The zwicki-Line materials testing machine applications are specifically tailored to high throughput requirements in quality assurance. Zwick testXpert II measurement and control software combines with multiple control modes and a vast array of fixturing and tooling to deliver the capabilities required in product development as well. The smallest version of the zwicki-Line testing system, with a maximum force of up to 500 N, is also suitable for multistage tests on autoinjectors or pen systems. Key features include a device for tests including safety functions and activation forces, together with sensors for measuring the delivery time for the liquid and the extended needle. Parameters such as firing time, expulsion time and the length of the extended needle are determined via dual lasers.
Evaluation of all the data obtained is performed time-synchronously via the testXpert II testing software. For precise measurement of the active ingredient delivered, signals from external devices such as scales can be incorporated directly into the testXpert II software. In addition, a microphone for detection of activation noise and a camera for time-synchronous visual recording of the test may also be processed directly in the testXpert II software as external data channels.
Ever-increasing demands are placed on software used in the medical and pharmaceutical industries to document the traceability of completed actions. The requirements set forth in FDA 21 CFR Part 11 are addressed by the expanded traceability option available for Zwick's testXpert II testing software.
The electronic records function permits complete, tamper-proof documentation of all actions and modifications performed in the testXpertII software. The user defines the degree of actions to be logged and justified according to exact specifications, which can originate from a QM manual or external requirements. In a specific case, this could involve recording every change in a parameter relevant to testing, such as the test speed, in its entirety in an audit trail. The capture of electronic signatures permits the assumption of responsibility to be documented and simultaneously supports a reduction in the use of paper, as physical signatures can be replaced with digital signatures by means of entering user login information in the testXpertII software.
As injector devices continue to replace traditional vials and syringes, quality control and associated testing processes will play a crucial role in their manufacture.
Erik Berndt is the industry manager medical/pharmaceutical at Zwick GmbH & Co KG.