Injection pens were introduced in the 1980s as an alternate solution for delivering medication to a patient. They come in many different embodiments, for many different drugs, but the core principals are the same; they allow setting of a dose which can then be injected into a patient. The injection pen is responsible for delivering the set dose accurately without any risk of deviating above or below the allowable limits of overdose or underdose.
Dose accuracy is one of the most critical functions of any injection pen, and is tested rigorously as part of ISO 11608. This article details a few key considerations for designing injection pens to achieve consistent dose accuracy, along with sharing some of the main problems we have solved at IDC in our own developments.
Common injection pens contain a cartridge/vial which contains the medicament, the cartridges are subject to change with different manufacturers, volumes etc., but they are generally well defined in terms of dimensions and tolerances (they must be to satisfy applicable standards). The cartridges are sealed at the top by a rubber septum which is where the needle is attached, and sealed at the bottom by a rubber plunger which can be forced forwards by the injection pen’s internal mechanism to cause injection through the attached needle. The amount of plunger travel dictates the volume of fluid injected through the needle. As the plunger travel is dictated by the pen’s internal mechanism, this plunger travel is the first consideration when assigning values to dimensions of parts within the pen’s internal mechanism.
At the early stage of the internal mechanism development – i.e., a concept has been developed but not tested or designed for manufacture – there will be many parameters that need defining which directly influence plunger movement and therefore influence dose accuracy. An example of a direct influence on dose accuracy would be the pitch on a plunger-driving leadscrew (this is a common method used in driving the plunger). An example of a less direct influence would be the extension of an injection pen’s button (some buttons extend when dose setting). The amount the button extends may dictate the amount of work which the internal mechanism does on the cartridge plunger when the button is pressed, and the extension of the button will likely be limited by the ergonomic constraints of the device. This means that the ergonomics of the device may have an influence on the dose accuracy, so other parts will likely require modification to accommodate for these constraints.
Although at early design stages it may be difficult to define all the pen’s parameters, those that influence dose accuracy can be assigned values and other unknowns can be estimated to allow the pen to be prototyped early. The design can be evaluated via tolerance stack analysis, further calculations, preliminary risk analysis and prototype testing to see whether the required dose accuracy is achievable with the current mechanism and whether there are any other unforeseen issues. Some important approaches to these design elements are discussed below.
Part tolerances and tolerance stack analysis
An example of an influential tolerance in terms of dose accuracy would be the tolerance on the internal diameter of the cartridge, if the diameter is at its min/max instead of nominal, for the same amount of plunger travel, a different amount of fluid will be injected. If very tight limits on dose accuracy are required, then mechanism component manufacturing tolerances must be correctly assigned and must be achievable – it is important that tolerances are achievable to avoid inconsistent, out-of-spec parts following moulding. If the dose limits and therefore part tolerances line-up and seem achievable, then the design should be somewhat theoretically achievable.
The tolerance analysis section of the design phase is critical, because it will identify areas of risk which prototype testing will not. Prototypes should have near perfect dose accuracy, as they are generally created using nominal dimensions. Quality 3D printed SLA parts will likely be accurate within ±0.05mm; when parts are moulded, more parts will be created and inconsistencies may arise (especially if multi-cavity tools are used). A detailed tolerance analysis will give confidence that the pen is designed correctly and therefore should dose accurately.
As dose accuracy cannot be compromised, other features surrounding the internal mechanism may be require compromise instead. Take for example, a threaded dose-setting dial, the thread pitch may be dictated by the initial dose accuracy calculation, however if the thread pitch gets too small then the thread may eventually become self-locking (depends on the mechanism), this would halt usage of the pen altogether. Features like these may not instantly seem threatening when only viewed as a CAD file, therefore calculations surrounding such features will highlight any areas of increased risk which should be a focused point of prototype testing. The material selection process should also be carried out at this stage to influence calculations and material choices for prototypes.
At this stage, some of the intricacies of the mechanism are unknown, however a preliminary DFMEA should constructed which considers the backbone of the design. The DFMEA will highlight areas of risk to dose accuracy, along with other risks that the mechanism may hold. As with the further calculations described above, this is required to highlight areas of concern which may need to be focussed during the prototype testing.
Prototype testing is a critical element in designing most medical devices, and there is no exception for injection pens. Dose accuracy itself can be tested, as well as other aspects of the pen’s function which contribute towards successful use. Prototype testing may be from prototype moulded parts, machined parts, 3D printed parts, etc. and the methodology used is dependant on the accuracy of the testing required and its criticality. When testing dose accuracy, it is important to be as close to actual intended parts as possible to avoid issues down the line. Careful selection of 3D printing materials and processes is essential at this stage.
Although it seems that if the injection pen development has gotten this far, then surely dose accuracy is guaranteed? Unfortunately, there are still many other potential factors which can affect the pen mechanism when actual parts are produced, these potential issues may be systematic between doses and pens (potentially arising from environmental influence or incorrect tolerance analysis), or they may be lone errors which happen inconsistently, they may occur 1 in 5 times, or 1 in 1000 etc. (unlikely to be picked up prototype testing). Some of the problems we have recently solved at IDC are discussed below.
Creep effects on parts
Creep poses a risk when it comes to injection pens as it may be one of the last things discovered given that the first-time creep may be assessed is during aging/tests at pre-verification/verification. If interference between parts is intended, they should be designed in a way that they are not susceptible to any issues caused by creep, via careful consideration of geometry and materials. If parts are out-of-spec or tolerance stacks are not correctly conducted, accidental interference of parts may occur, if creep effects start to take place, dose accuracy could be affected down the line. Discovering issues this late can be devastating to timescales and project cost.
Post mould growth and shrinkage
It is important when selecting materials that the post-mould properties are known and accounted for, for example, parts made of nylon are more susceptible to moisture absorption after leaving the mould. These changes in dimensions may not be picked up by metrology, and therefore may cause unexplainable inaccurate doses which were not seen during prototype testing.
Efficiency of translating user input
Something which can greatly affect dose accuracy and dose consistency is the pen’s efficiency to turn user input into dose delivered. For example, if the plunger is meant to be moved a certain distance when dosing, but due to clearances between parts in the pen, the plunger actually does not extend as far as intended (some of the total work is lost to the clearances/slacks); this results in the delivered dose being less than intended. This issue could be solved by tuning parameters to account for the losses, or segmenting the plunger travel to be in exact increments, this is commonly achieved using a ratchet system. When designing the internal mechanism, understanding where losses may occur means the losses can be prepared for, and if designed correctly, areas of potential tuning will be highlighted to the toolmaker before tools are created for moulding.
Fluid losses from the cartridge
Doses from injection pens are relatively small amounts of liquid, and so every drop of fluid that comes from the needle will have an impact on the dose accuracy and should be injected into the patient, any fluid which drips from the needle unintentionally will be lost from the overall volume of the cartridge and so lost from the delivered dose. A method of reducing fluid losses is to completely eliminate any chance of dripping by ensuring there is no residual pressure on the plunger following dose delivery. In rare cases where losses cannot be fully eliminated, they should be considered when assigning parameters.
These are some of the most common factors which can affect dose accuracy. However, this list is not exhaustive by any means. Injection pen designs differ based on their requirements and with each unique design comes unique problem areas relating to dose accuracy. Hopefully this article has helped in some way to shed some light and assist in anticipating key areas for consideration in your own development projects.
If this is an area you or your team would like some support with, please feel free to reach out through our Contact page.
Tom Milnes is a Design Engineer at IDC. Since graduating from the University of Sheffield with a Master's Degree in Mechanical Engineering, he has gained solid experience developing many products and devices across a wide range of industries and sectors including drug delivery.