Selecting the Right Motion Solution for Biologic Delivery Devices
By definition, biologics are drugs made of proteins and/or derivatives that modulate the immune system, down-regulate the inflammatory response or support tumor-specific defense. A typical drug is manufactured through chemical synthesis, which means that it is made by combining specific chemical ingredients in an ordered process. Conversely, a biologic is made from a living organism, is manufactured in a living system (such as a microorganism) using biotechnology and works by changing the way the human immune system responds.
Biologic drugs, which include antibodies, interleukins, and vaccines, are used for treatment of numerous diseases and conditions and are the most advanced therapies available. Biologics have revolutionized cancer treatments, delayed or reversed the course of immune related conditions, changed the lives of people with rare diseases and have offered hope for many patients who previously had no effective treatment options for their condition.
Biologics are more complex and have much higher molecular weight than traditional, smallmolecule chemical drugs and thus are very viscous. This complexity increases the costs, challenges and risks of development and manufacturing. The injection profile is critical for the proper delivery of the drug, so the delivery mechanism plays a key role. The delivery mechanism is operated by a motion solution, making it the driving factor in the device development.
Before exploring the motion solutions for injection devices, it’s pertinent to cover how and where drugs are injected. Let’s start with the 3 methods used to deliver a drug into a patient’s body (Figure 2):
|•||Intravenous - Intravenous (abbreviated as IV therapy) is a medical technique that delivers the medication directly into a patient’s vein. There are limitations with this delivery method, as higher viscosity biologic drugs are a challenge.|
|•||Subcutaneous - Subcutaneous tissue lies between the fat layer just under the skin and over the top of the muscles. It has few blood vessels, so drugs injected here are intended for slow, sustained rates of absorption. It is absorbed more slowly than intramuscular injections.|
|•||Intramuscular - Intramuscular injections are preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption of the drug.|
Based on the above methods, there are three main types of devices used to inject the drug (Figures 3 and 4).
|•||Disposable: As the name suggests, this is a one-time use device. It is designed for a specific drug application. The delivery time of a drug can be in the range of a few seconds to a few days, requiring a cost-optimized solution. Mechanical injectors and disposable patch pumps are a few examples. Patch pumps are worn directly on the body and have a reservoir, pumping mechanism and infusion set inside a small case.|
|•||Limited use: A motorized solution can be used to allow multiple biologic drug cartridges over the course of a therapy. This offers the advantage of having separate drug and pump units with the drug unit being disposable and the pump unit being reusable.|
|•||Reusable pump: These devices are more robust, rugged, and long lasting. They are designed to handle various viscosity drugs as a platform, which offers a broader range of therapies.|
TECHNICAL REQUIREMENTS FOR THE MOTION SOLUTION OF THE INJECTION DEVICES
Table 1. Key performance parameters for different biologic drug devices
Reusable biologic pumps are highly demanding in terms of their motion solution. These types of devices require high axial force output up to and exceeding 100 N. This linear force is needed because of the higher viscosity biologics; when supporting various biologics as a platform, the pump must be able to deliver the highest viscosity drug while still accurately delivering the lower viscosity ranges. As these devices are portable, their size and weight are critical parameters. A premium biologic device motion solution typically ranges from 10 mm to 12 mm outside diameter.
Apart from force and size, a reusable pump must be robust and reliable. Product warranties can be in the range of 2 to 5 years, demanding the motion solution be properly sized to deliver the same accuracy from day one to the end of life of the pump. For the motion solution, the designer confirms a confidence factor of >90% to ensure achieving the required life.
Additional factors in the motion solution selection are feedback, repeatability, and storage conditions. An encoder will confirm the motion solution has provided the needed drug delivery, ensuring the therapy is successful. It will also ensure every delivery increment is met each time. The biologics can have different requirements for storage, with some needing cold storage. This reflects back to the motor and gearhead capability to withstand lower temperatures and humidity over periods of time.
Overall brushless DC motors or coreless brush DC motors (with precious metal commutators) are best suited for these types of devices. A spur gearhead or a custom-designed gearhead provides a great torque / force density within the smallest size available.
Limited-use biologic devices are a new trend seen in the pharmaceutical industry. Unlike a long-term device, a limited-use biologic device provides flexibility for performance and life against the pump price. These devices are generally designed with a single biologic drug or limited drug offerings; hence the force and size requirements for motion solutions can be different versus reusable devices.
A motion solution that can meet a force range of 50N to 80N is typically sufficient. These devices are battery-driven, so efficiency plays a key role in the design of the pump. Coreless brush DC motors with precious metal commutators are well suited to meet these higher battery life requirements, providing high power density and reliability. A spur compound gearbox or custom gearhead provide optimum solutions for limited-use biologic applications.
Disposable biologic devices are single-use applications. With advanced research and development in drug device technologies, a proper match in motor technologies is essential. These devices are tied to a specific drug, so an optimized motion solution is key for these high-volume devices.
Many motion solutions can provide a good fit for this application. Some of the most suited motor technologies are can stack stepper and brush DC, though alternate actuator technologies can be solutions. Can stack or brush DC offer a mature technology which provides advantages over some non-conventional actuators which require complex drive electronics for operation.
The duty cycle for such application is limited and ranges from a few seconds to a few hours only. Based on the application requirements, a reliable cost-optimized motion solution serves these devices well.
CURRENT CHALLENGES IN BIOLOGIC DRUG DELIVERY SYSTEMS
In the modern era, new and innovative drug formulations are peaking. In comparison to IV drug delivery, biologics use subcutaneous or intramuscular deliveries. Recently developed biologics are complex drugs whose molecular weight can reach upward in the range of 150,000 Da (Daltons). This molecular weight of biologic drugs is quite high in comparison to some of the synthesized drugs molecular weight (in the range of few thousands Da). This leads to the larger viscosity of biologic drugs, which ultimately poses a challenge for the design of the drug delivery device.
Table 2. Technology and key performance parameters for motion solutions for different biologic drug devices
Like biologic drugs, biologic delivery devices are comparatively new to the market and are continuously improving. There are certain challenges in today’s scenario for biologic drug devices:
|•||Ability to handle larger viscosity drugs|
|•||Delivery of a large volume of a drug|
|•||More accurate deliveries|
|•||Cost-optimized solution for larger population reach|
Some of these challenges can be supported and resolved by motion solutions, which are illustrated in Table 2:
|•||Higher power densities of brushless and brushed motors, along with higher reduction ratio gearheads to handle larger viscous drugs (> 50 Cp)|
|•||Power density helps to accommodate larger drug volumes in a smaller size (10 mL to 50 mL)|
|•||Absolute encoder technology can help precisely monitor drug delivery (resolution 3 - 5 um)|
|•||Reliable motors and gearheads provide long life for safe home-based therapies|
MOTION SOLUTIONS FOR BIOLOGICS DRUG DELIVERY DEVICES
As mentioned, the motion solution for the delivery mechanism is the crucial part of the device design. Various options for motor and gearhead technologies are available to the design engineer, making the initial selection somewhat daunting. To help with this task, we will detail the key performance parameters and review how the different technologies address those parameters.
Torque / Power – all technologies offer the ability to produce torque, but their internal design provides for different output capabilities. BLDC slotted designs provide higher output torque than BLDC slotless, based on the higher amount of copper and magnets in the motor. When considering stepper motors, hybrids provide the highest torque.
Speed – the drug will dictate the duration and flow for the therapy, so the device speed will be set. Higher speed requirements can be met by brushless DC and disc magnet stepper motors, medium speed requirements met by brush DC, and lower speed requirements met by steppers. The addition of a gearbox to increase the output torque must be considered, as this increases the speed requirements on the motor by the corresponding ratio.
Efficiency – as these devices run on battery, efficiency is critical to keep the battery size as low as possible. Brush DC coreless and brushless DC slotless are the best choices for efficiency because of their rotor design.
Reliability – the device will have a specific life requirement based on the number of therapies to be delivered to the patient. The key technology factors affecting the motor life are the commutation and bearing systems. Brush DC motors have a mechanical commutation, meaning that the motor life is dictated by brush wear. Brushless DC and stepper motors have electrical commutation, which provides longer motor life potential. Bearings are an additional factor for motor life, with ball bearings providing longer life than sleeve bearings. Motor technologies offer both bearing versions, with some providing them as standard and others requiring customization.
Weight – these devices are portable, so weight of the motion solution is an important factor for the comfort of the patient. Brush DC coreless motors offer the best option for weight.
Cost – each technology has a cost profile based on its design. The device and accompanying therapy will mandate a cost profile for market acceptance, so understanding the cost drivers for each technology is critical.
Table 3. Comparison of key performance parameters for different motion technologies
This table shows a comparison of the various motor technologies, showcasing their strengths in different parameters. These guidelines provide a reference for a design engineer looking to create a new drug delivery device. Connecting with a motion solution supplier is the key first step when initiating the device development.
More biologics are being developed, with many on the way to market. To enable the best drug delivery device, it is prudent to have co-development between the device developer and the motion supplier. Specific challenges will be encountered for each device based on the biologic therapy requirements, so engaging early with a motion supplier provides a path to utilize the appropriate motor technology coupled with the right accessories for the optimum solution.