08 Jan Designing Complex Medical Fluidics Systems
How do you design a fluidics system that can accurately dispense a wide variety of liquid ingredients ranging in dose-volume from fractions of a milliliter to multiple liters in an efficient way with the same pumping modality? This was the tough development challenge B. Braun Medical gave the Key Tech team in designing their APEX Compounding System.
Finding the solution to this challenge required a multidiscipline development approach that began with a solid foundation in fluidics and a framework for system design. By following the process shared in this post, Key Tech was able to design the APEX to automate the complicated process of mixing customized nutritional formulations, providing pharmacists in hospitals and compounding laboratories a simple, efficient, and precise way to meet patient needs.
Design to Address Fluidics Challenges
The Key Tech team started with a general framework for development, defining what needed to be considered for any fluidic challenge:
- Know your target – What are the dispense or flow accuracy requirements?
- Define the fluid types – What are you processing? How is it stored? At what temperatures?
- Understand the duty cycle – What is the frequency or workload?
- Where will the product be used? Are there any environmental concerns or controls? Are there size constraints for the instrument?
- Human Factors Usability – How easy does it need to be to use? Who are the users?
- Define the mix – What mixing needs to happen?
- What are the materials the fluids are in contact with?
- Map out the control, timing, and target flow rates. How do you control the flow/control the fluid?
- An instrument with a consumable transfer set – What are the important interfaces between the fluid handling set and the instrument? What mechanisms and technologies are needed to support this arrangement?
What are the Specific Fluidics Challenges for the Device?
For the APEX Compounding System, the Key Tech team needed to understand the important factors of this specific fluidic challenge. A milliliter of medication could make the difference in a patient’s health, and a mistake could cause serious harm, leaving no room for error. Key Tech worked with B. Braun to design the APEX® Compounding System with the most critical patients and their most critical needs in mind.
- The design solution needed to provide efficiencies to pharmacies. It required precision dispenses of a variety of ingredients (up to 26 different lines) from different source containers (bags, bottles, vials, syringes) in a range of volumes and fluid properties. Requirements were:
- Small volume dispenses as low as 0.2ml with +/- 10% accuracy
- Large volume dispenses as high as multiple liters, delivered at high flowrates (greater than 1L/min) with +/- 3% accuracy
- Ingredients ranging in viscosity from water-like liquids to thicker solutions like dextrose
- The solution needed to be a high throughput device to meet the high demands of a busy contract compounding site; while also meeting the needs of lower throughput hospital pharmacy users. The Key Tech product development challenge was to design a compact and easy to use compounder that could process up to ~100 compounded orders a day with minimized order fill times and integrate seamlessly into compounding center workflows.
- The transfer set had to be sterile, allow aseptic technique in the pharmacy hood, reduce operator errors during setup, and maintain accuracy and patient safety throughout an entire day of compounding with minimal calibration.
- Residual contamination of ingredients between patient orders had to be prevented, delivery sequences of incompatible ingredients had to be managed, and source ingredient purity had to be maintained throughout all dispenses.
User Observation a Key Requirement to the Design
Leveraging early user observations and collaborating on a product requirements document, Key Tech designed a user-centric device with hardware complying with IEC 60601-1 and embedded firmware complying with IEC 62304. A dual-channel peristaltic pump system, which provides the ability to dedicate small volume dispenses to a small bore “micro” pump, and large volume dispenses to a large bore “macro” pump, and allows both pumps to operate in parallel, was central to the solution. It was necessary for B. Braun to design the consumable to support parallel pump operation, protect the integrity of source solutions, and be “flushable” to address the potential for cross-contamination. Finally, the hardware, software, and consumable were all designed to work together to promote successful and efficient operation by users.
De-Risking the Compounder to Meet Accuracy Targets
With a strong framework built around the dual-channel peristaltic pump architecture, and the fluidic challenge well understood, the next endeavor in the Apex development process was to engineer the system to hit the accuracy targets on every dispense of every possible ingredient. In order to maintain dispense accuracy of a peristaltic pump system, all contributing variables to the error stackup were examined. Some were characterized to develop algorithms and compensation, while others were used to inform bounds for system operating points or alarm conditions.
Volumetric pump output was tested and characterized as a function of:
- Pump speed
- Inlet and outlet pressures
- Pump segment wear
- Fluid viscosity
- Fluid temperature
- Peristaltic rotor position
- Environment temperature
- Transfer set conditions (fluid path geometry, sterilization method, installation variability)
Analytical models and software algorithms were developed to compensate for all the factors which could be controlled by the system and behaved in a predictable way. The pump module and transfer set designs evolved in ways to minimize the potential for conditions that would add uncertainty or dispense variability.
The remaining accuracy uncertainties and dispense variabilities that could not be controlled or compensated for were examined further in a large design-of-experiment to test these conditions at their worst-case combinations. The team proved with sufficient statistical confidence that accuracy claims were being met across all of the known operating condition limits through verification testing.
Using thoughtful analysis and thorough testing, and evolving a solution that minimizes risk, the team was able to meet the multiple requirements of accuracy, speed and size. This initiative benefited from persistent and seamless teamwork throughout the development and transition to B. Braun manufacturing, including verification and validation phases.
When you have a complex challenge that needs a smart, well-executed solution, reach out to collaborate with Key Tech at TalkToUs@keytechinc.com