Medical devices can be active or static. Static devices are the simplest, having few or no moving parts. Stents, for example, hold arteries open by virtue of their shape. Active devices are more complex. Some active medical devices operate through the application of human movement or by the effect of gravity. A syringe is powered by the force applied by the patient or medical technician, while an IV drip is powered by gravity. Other devices can be activated by a patient’s natural body movements, such as walking or breathing. These devices are categorized as passive. The term “active medical devices” refers to devices that require an artificial power source, such as a battery or other electrical supply. Such appliances generally perform more complex functions than static or passive devices. Implements in this category range from blood oxygen level sensors to advanced heart-lung machines that can take over a patient’s cardiopulmonary functions during surgery.
Active implantable medical devices are powered devices that are inserted into a patient’s body, through either a natural orifice or by surgical means, and are intended to remain in the patient’s body after the procedure. Such devices are usually battery powered, and the power supply can either be contained in the instrument or be connected to wires that protrude from the patient’s body. Early cardiac pacemakers, for example, were powered (and operated) by an external unit that could be worn by the patient. The first fully implantable devices were powered by plutonium, but most modern versions use internal lithium batteries that can last up to fifteen years.
Due to their internal use, the complexity of their function, and their relatively small size, active implantable medical devices are among the most difficult to manufacture. Medical devices that come into contact with patients have to meet high standards, and those that have long-term contact—such as implantable devices—must conform to the highest standards of all. Their creation, therefore, requires extensive expertise in both the design and manufacturing stages as well as facilities and machines with the capabilities to produce components that meet stringent parameters. Proven Process has the expertise, personnel, equipment, and the facilities needed to create the highest-quality active implantable medical devices.
Examples of Active Implantable Medical Devices
An example of an active implantable medical device is the internal, long-term blood pressure sensor (shown at right). Proven Process was the first company to develop such a device. This tubular appliance was designed to monitor blood pressure via an electrical resistance strain-gauge sensor. One of the biggest challenges with such a device is measuring the flow of blood without significantly constricting or altering the hemodynamics. Computational fluid dynamics analysis was used to model the flow of blood, while finite element analysis identified the optimal locations for depositing strain gauges on the outside surface of the diaphragm.
Another example is the implantable ventricular assist device (shown at left), a vascular pump that helps weakened heart muscles provide sufficient blood flow. Proven Process sought to improve on existing ventricular assist devices. We created a motor that simultaneously rotates and translates a piston, allowing it to facilitate blood flow while maintaining lubrication. The piston worked in conjunction with two artificial heart valves to allow blood movement in only one direction. 3D modeling, finite element analysis, and control system simulation were used to prototype the device rapidly and efficiently.
Standards and Regulations
The manufacture of medical devices is covered by ISO 13485:2016. These standards also apply to active implantable medical devices. But because of the internal nature of the devices and their long-term lifecycle, additional standards also apply. These include:
- ISO 14708-1:2014 - General requirements for safety, marking, and for information to be provided by the manufacturer
- ISO 14708-2:2012 - Cardiac pacemakers
- ISO 14708-3:2017 - Implantable neurostimulators
- ISO 14708-4:2008 - Implantable infusion pumps
- ISO 14708-5:2010 - Circulatory support devices
- ISO 14708-6:2010 - Particular requirements for active implantable medical devices intended to treat tachyarrhythmia (including implantable defibrillators)
- ISO 14708-7:2013 - Particular requirements for cochlear implant systems
- ISO 14117:2012 - Electromagnetic compatibility test protocols for implantable cardiac pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization devices
- EC 62304:2006 - Medical device software
For devices to be used in the United States, additional regulations must be followed. Most of these are administered by the Food and Drug Administration (FDA). The FDA ensures that active implantable medical devices conform to appropriate standards prior to being brought to market through its Center for Devices and Radiological Health. Some products—including implantable devices that wirelessly communicate with external appliances—also fall under the purview of the Federal Communications Commission. The EU stipulates its regulations in MDR 2017/745, adopted in 2017.
Design and Manufacture
The design and manufacture of active implantable medical devices require special considerations beyond those associated with other medical implements. The operating parameters of such devices must be specified to precise tolerances to prevent unintended harm to the patient. An example of such a parameter would be the temperature of the device. Although the device may function quite well in a wide range of temperatures, standards require the device to operate no more than 2℃ above normal body temperature (37℃). With the exception of those parts intended to convey an electrical charge to the body, the exterior must be electrically neutral. The external surface of the active implantable device must also be free from any sharp edges or corners that can cause irritation or inflammation.
Due to the extended lifecycle of active implantable medical devices and the fact that they are in direct contact with patients for years, the materials used in their manufacture must be chosen carefully for their biocompatibility. In particular, the toxicity of the material must be below levels that would affect patients even after the long-term contact required by the appliance. The materials must also be durable enough to last for the intended period and stable enough to provide reliable functionality throughout the device’s lifecycle.
The sensitive nature of active implantable medical devices means special care must be taken in the design of their packaging to prevent damage during shipping and storage. Environmental factors such as temperature, humidity, and barometric pressure can affect the devices, and packaging must protect against such harm. Vibration during transportation may need to be dampened, and devices must be cushioned against forces encountered during shipping. Packaging will also need to indicate the proper environment for storage of the implantable devices prior to use.
Even after being surgically implanted, these medical devices must be protected against damage from external forces. In addition to the everyday physical stresses on the device, extreme events must also be considered. Because active implantable medical devices are powered by an electrical current, external shocks can interfere with their operation or damage the device. Because some internal devices are life sustaining, failure must be avoided. These electrical shocks can be unintentional or intentional. A defibrillator, for example, generally delivers between 200 and 1000 volts. If the internal device is attached to the heart— as is the case with ventricular assist devices and pacemakers—it will lie directly in the path of the current created by the external defibrillator. When possible, the internal device must be insulated to shield it during such an event.
The FDA also requires active implantable medical devices to demonstrate electromagnetic compatibility. Manufacturers need to show that their devices work as required even when they encounter interference in the form of electromagnetic energy, such as radio waves or a strong magnetic field. Most devices will encounter non-ionizing radiation that has energy levels below that of natural light, so this type of energy is the primary concern. Ionizing radiation, such as x-rays and gamma rays, will be less commonly encountered by patients in high doses. The device also must not significantly interfere with other devices due to its own emissions. In cases where the device is incompatible with certain types of electromagnetic energy and such incompatibility cannot be eliminated, this must be clearly noted in the specifications and made clear in the documentation provided to medical professionals and users of the device. In particular, patients with implantable pacemakers who work in close proximity to strong electrical fields—such as a medical technician working with MRIs—will need to be informed of the limits of their device.
A final consideration in the design and manufacture of active implantable medical devices is related to the internal power supply. Despite continuing advances in battery technology, lithium batteries do have a limited lifespan, and their depletion will cause the failure of the device. Unlike an external power supply, which can be quickly switched, the replacement of the power supply in an active implantable medical device requires surgery. This involves coordinating several factors, including the availability of the surgical team, the patient’s schedule, and the procurement of either a new power supply or a new device. It is imperative, therefore, that the implanted device provide a system to notify the patient and physician well in advance of the battery’s depletion.
Active implantable medical devices are among the most complicated to manufacture. Their design must take into account multiple factors that do not affect other devices and, therefore, requires a highly specialized and experienced team. Because of their extended lifecycle and prolonged contact with patients, they are subject to the most stringent standards and regulations. As a pioneer in this field, Proven Process has the expertise, the experience, and the facilities necessary to create high-quality active implantable medical devices.