Designing Implantable Drug-Delivery Systems for Safety, Operational Complexity, and Compatibility with Diagnostic and Treatment Procedures

This article addresses how implantable devices can be de - signed to modulate drug infusion safely and precisely, even minimizing disruption for concurrent treatment and diagnostics, while optimizing drug delivery. Other challenges impacting safe, tolerable or painless operation of implantable devices will also be addressed along with potential design and engineering solutions that can help make diagnostics, treatment, and drug delivery compatible for the safety, comfort and convenience of medical professionals and their patients.

Fig. 1 – Proper testing of implantable pumps includes environmental testing as well as measuring the impact of fluctuating temperatures.

Implantable pumps for drug delivery can significantly improve quality of life for patients requiring a steady dose of medication while they live their lives, and the advancement of this technology represents significant progress in health care. At the same time, new risks are assumed that must be minimized or eliminated through extremely robust device design, testing, and validation/verification.

Compatibility with Diagnostic and Therapeutic Procedures

Patients who benefit from implantable drug delivery systems are usually receiving concurrent medical attention for underlying conditions. Whether the drugs being delivered are analgesic/narcotics, insulin, chemotherapy, antispasmodics, or something else, patients may need diagnostic testing and treatment while the device is in place. Ideally, pumps are designed to operate reliably throughout these procedures. One example of a diagnostic procedure that can interfere with drug delivery is magnetic resonance imaging (MRI). MRI systems emit significant electromagnetic energy that can impact a pump’s performance. Radiation therapy and other sources of electromagnetic interference (EMI), such as power stations and laser procedures, can also affect pump operation.

A drug delivery pump can be engineered to allow infusion to continue without interruption or failure, minimizing risk, inconvenience and discomfort for the patient. One example is a pump that has a flow-activated safety valve that shuts off drug flow to the patient in the event a high flow rate occurs during an MRI procedure.

This device allows patients to have an MRI without the necessity of drug removal prior to the procedure and increases patient safety and clinical convenience by providing safe, dependable, automatic dosing of drugs directly into the intrathecal space around the spine.

Variable Dosing and Multiple Medications

Even the everyday operation of drug infusion pumps requires robust design to prevent malfunctions with potentially life-threatening consequences. Precise dosing requirements, delivery of multiple infusates, and other factors complicating the device’s optimal operation must be considered in the design and engineering phase. (See Figure 1)

Implantable infusion pumps are currently used for a variety of medical purposes. Two general classes of such pumps include “constant flow” and “programmable” pumps. Constant flow devices typically rely on a liquid/vapor equilibrium to maintain constant pressure on the contained drug, so that it flows through a capillary (flow restrictor) and maintains a constant flow rate. Such devices are used in a variety of medical applications, for example, to dispense chemotherapy at a relatively constant flow rate.

In other applications, however, some patients require adjustments in dosage or bolus infusions—for example, when receiving treatment for chronic back pain and/or spasticity as seen in multiple sclerosis. Constant flow pumps are inadequate under such circumstances, so a programmable pump is used instead to achieve proper flow rates over the range of preferred rates.

An example of a design that facilitates individualized adjustments is a pump with a refillable drug reservoir that is maintained at constant pressure vapor. The reservoir communicates with a medication metering assembly consisting of a fixed volume accumulator positioned between a pair of valves. The valves alternately open and close to admit medication from the reservoir into the accumulator and to dispense a precise volume spike to an outlet catheter. The unit is externally programmed. The device is capable of delivering easily and precisely dosed medication from any one or any combination of two or more reservoirs without complex pumping and flow control mechanisms and has the capability of mixing and/or diluting medications. Other infusion pumps are designed to dispense medication from multiple reservoirs in accordance with different specified flow rates, allowing for variant dosing to meet specific circumstances, such as time of day, activity level, etc.

When One Is Not Enough

Multiple medications are often put into implantable pumps to treat certain conditions. The use of multiple medications in a single drug reservoir presents difficult clinical and medical device challenges. The mixture of drugs may present drug stability issues and a complex dosing challenge given the varying concentration and administration rates for each drug.

More than one drug in the reservoir of the implantable infusion device substantially increases patient dosing difficulties. Here’s why: the clinician not only must program the device to perform a series of steps in order to deliver one drug to the patient, but also take into consideration the possible side-effects of changing one drug’s dosage amount on other drugs also contained within the same reservoir. Therefore, the pump’s programming system must make incredibly precise adjustments for accurate, effective and safe dosing of primary and secondary drugs.

Designing a programmable implantable pump with multiple chambers or reservoirs for storing drugs, each coupled to a dedicated pumping mechanism and outlet catheter provides an effective solution. This way, the device does not permit the mixing and/or dilution of medication. Separate pumping mechanisms affect device reliability and manufacturing efficiencies, while also increasing the complexity of an already highly sensitive process. (See Figure 2)

Conclusion

Fig. 2 – Long term implantable constant flow pumps like the ones shown are critical in delivering appropriate dosages of medications.

Benefits of implanted drug pumps go beyond patient convenience and quality of life. These devices can be programmed to deliver drugs in dosage amounts, frequencies and intervals that would be impractical for professional administration. For example, a drug infusion pump can deliver medication in doses as small as 0.1ml/hour, too small for an intravenous drip. It can be programmed to inject medication every minute, with or without repeated boluses within the patient’s control, or to provide dosages that vary with the time of day. The ability of implanted pumps to deliver medicine to specific parts of the body can reduce the amount of medication needed for therapeutic effect, and can also reduce drug side effects as a result.

Risks include programming and mechanical malfunctions that can cause over-infusion or under-infusion. These events can lead to patient overdose, reduction in pain relief or therapeutic improvement, and/or unintended withdrawal from the drug. The pumps must be designed to be scrupulously accurate and reliable, and patients need education to recognize signs of malfunction.

Technology driving advancements in medical device design will continue affording improved treatment options, and implantable drug delivery systems are no exception. Increasingly complicated requirements are being met with new engineering solutions that increase accuracy, effectiveness and versatility of these devices, while reducing risks.

This article was written by Kenneth A. Fine, President and Co-Founder, Proven Process Medical Devices, Mansfield, MA. For more information, Click Here .