Diabetes is not only one of the most common chronic diseases, it is also complex and difficult to treat. Insulin is often administered between meals to keep blood sugar within target range and at mealtimes based on the number of carbohydrates to be ingested. A variety of insulin types are used to regulate blood sugar levels, including fast acting, short acting, intermediate acting, long acting, and premixed. With more than 400 million adults worldwide suffering from diabetes and 1.5 million deaths directly attributed to the disease each year, it’s no wonder so many scientists, inventors, and pharmaceutical and medical device companies are turning their attention to improving insulin delivery devices.
Insulin is introduced into the body via a wide variety of devices, including traditional syringes, injection ports, insulin pens, conventional insulin pumps, and patch pumps. This article examines the current state of insulin delivery and the technology requirements for the next generation of devices to address this chronic disease. In particular, it focuses on the insulin pump sealing technology — including seal design and material selection. These pumps will require strong seals that not only have a long life but that also provide an adequate friction rate, sufficient breakaway forces, and material biocompatibility. New complex seal designs enabled by versatile materials are allowing engineers to create insulin delivery devices that are lighter and smarter than ever.
Insulin Delivery Options
Currently, insulin delivery devices range from basic to cutting edge. Following are overviews of each type serving this patient population.
Syringes. Direct, subcutaneous insulin injection through a needle and syringe remains the most common form of delivery. Selection of needle gauge, needle length, and syringe capacity are made by the patient together with his or her healthcare provider.
Pens. Insulin pens transport insulin and allow patients to discretely administer a dose. Pens are available as disposable one-shot devices and as long-term devices with replaceable or refillable cartridges. Eli Lilly and Companion Medical recently received FDA approval of a Bluetooth-enabled insulin pen that communicates dosing information to a smartphone app.
Insulin injection aids. These aids are designed to make injecting insulin easier, for example, for children and those with needle phobias. Once a device is installed, it is used as the injection site for a three-day period.
Inhaled insulin devices. Several other delivery device types are in development, including those that allow an insulin dose to be inhaled through the mouth, going directly into the lungs where it’s absorbed and passes into the bloodstream. Dry insulin devices have yet to become widely used because of dosage issues, but “wet” devices are being developed that deliver an individualized liquid dose to the lungs via new vibrating mesh micro-pump technology.
External pumps. External insulin pumps remain relatively expensive, but many people with diabetes prefer them for their precision and, thus, their ability to provide strong control over blood glucose (measured by A1C levels). When connected to continuous glucose monitoring, these devices deliver a continuous basal dose of insulin as well as a bolus dose at mealtimes.
Implantable pumps. Research teams worldwide are developing implantable insulin pumps that measure blood glucose levels and provide a precise insulin dose. The small, lightweight pumps are surgically implanted and can deliver both a continuous basal dose of insulin and a bolus dose (through an outside controller).
An exciting development in pump technology is the ability to use pumps together with glucose sensing technology (known as an artificial pancreas), which administers insulin based on actual glucose levels as determined by the glucose sensor. Insulin delivery is halted once a preprogrammed glucose level threshold is met.
Insulin Pump Technology
Insulin pumps — especially newer devices — have several advantages over traditional injection methods. These advantages make using pumps a preferable treatment option. In addition to eliminating the need for injections at work, at the gym, in a restaurant, and so on, pumps are highly adjustable, allowing the patient to make precise changes based on exercise levels and types of food being consumed.
These delivery devices comprise an insulin cartridge, a battery-operated pump, and a computer chip that allows patients to control dosage. The current generation of insulin pumps are small enough to be worn discretely under most clothing, and newer pump models don’t require tubing. The device is placed directly on the skin, and dosage adjustments are made through a controller that can be carried in a purse or pocket (a 6 ft range is typical).
However, manufacturing the new insulin pumps requires a high degree of technical precision, especially when it comes to selecting elastomeric components — in particular, seals. Not only are there stringent regulatory requirements to consider, but also factors such as compatibility to the insulin and to the sterilization process. Other considerations include lifecycle expectancy, friction, breakaway forces, cost, and ongoing material availability. Although all of these factors are important, this article focuses on seal geometry, specifically material selection.
The seal is designed to interact seamlessly with the hardware and prevent leakage or inaccurate dosage. Geometry is an extremely important factor when selecting seals for insulin pumps. The geometry determines the degree of force, the coefficient of friction, and its hydrodynamic qualities.
The correct material choice is essential to ensuring that the seal will not degrade prematurely or fail due to an incorrectly matched application condition. An incorrect material can cause unwanted effects to contact media. For example, if the selected material is not adequate for the expected storage time before the device is used, the insulin can affect its chemical stability, making it “go bad,” losing its potency and effectiveness.
The sterilization method selected by the OEM or contact with the hardware and coatings can also cause undesired effects. It is important to select the correct material for your design because thousands of configurations of polymeric compounds are available. For insulin pumps, materials include but are not limited to liquid silicone rubber (LSR), ethylene propylene diene monomer (EPDM), and polytetrafluoroethylene (PTFE). LSRs, for example, have proven particularly suitable for transdermal drug delivery, providing small, strong polymers that are stable and long wearing. When selecting a material, consider the following factors:
- Sterilization (steam, dry heat, ethylene oxide, electron beam, and gamma radiation) — each material reacts differently to various sterilization methods, so it is essential to ensure that the material selected is compatible with the method specified.
- Availability — if polymers are discontinued or modified, OEMs may need to requalify a material, which may mean longer time to market.
- Extractability/leachability — the potential release of toxic materials must be determined to ensure that the media does not become contaminated.
- Applicable regulatory requirements — some compounds used within the seal material may require USP Class VI certification, or OEMs may want the manufacturing facilities in which the seals are made to have FDA or ISO 13485 certification.
In addition, many USP Class VI-compliant coating and surface treatment options are available to provide antimicrobial, lubricity, membrane, and other properties to seals. These coating options also affect device design and will influence how engineers think about the seal geometries that will enable lighter devices and smarter wearability. It is important to note that coatings are usually a secondary process on a seal. In addition to testing the seal, the coating must be rigorously tested to ensure that it will not negatively affect the insulin pump’s functionality.
As with the finished device, it is equally important to fully vet a proposed seal design through prototyping to ensure that it will pass regulatory scrutiny and withstand the manufacturing process. It is essential to choose a supplier with expertise in seals designed specifically for insulin pumps and with an understanding of the regulatory requirements with regard to engineering, quality control, and materials. The supplier must have adequate resources to help determine the optimal sealing solution for the pump design, including but not limited to material compatibility testing, prototyping options, non-linear finite element analysis (FEA), and lifecycle testing capabilities.
For people struggling with the complexities of insulin-dependent diabetes, the idea of more automated, less-intrusive ways to manage their disease is a welcome change. Technology partnerships hold particular promise, such as Medtronic’s announcement that it is working with IBM Watson to develop an app called Sugar.IQ, which acts as a personal assistant for people with diabetes.
Selecting the proper seal for an insulin pump application ensures the adequate design, functionality, and compliance to deliver safer and more precise dosages of insulin. Device manufacturers that take advantage of new seal technologies will drive the growth of the insulin delivery device market. Lighter, smarter devices paired with sophisticated drug-delivery systems will accelerate the pace of innovation. The increasing number of people affected with diabetes is bringing focus to the market and the resulting need to manufacture safe insulin devices with defect-free sealing technology. The goal is to ensure that patients with this chronic disease can be as active, healthy, and comfortable as possible.
This article was written by Drew Rogers, global director, healthcare & medical, Trelleborg Sealing Solutions, Fort. Wayne, IN. For more information, Click Here .