Catalog of Regulatory Science Tools to Help Assess New Medical Devices
This regulatory science tool provides a design for a blood reservoir that can be easily integrated into the in vitro hemolysis testing of many medical devices. The three-piece reservoir consists of a 3D-printed base, a plastic clamp set, and a hemocompatible blood bag. This simple, reusable, and cost-effective design was successfully used in the hemolysis assessment of FDA benchmark nozzles and prototype rotary blood pumps, and it may be useful as an integral component to any in vitro blood circulation loop.
Bench-top in vitro hemolysis testing is a fundamental tool used during the design and regulatory safety evaluation of blood-contacting medical devices. While a number of experimental mechanical hemolysis test protocols have been published, for example ASTM F1841-19e1, descriptions of the test loop reservoir often remain ambiguous. Despite being a critical fixture within the test circuit, there was previously no readily available blood reservoir that ensures thorough mixing and complete air evacuation—two major factors which can affect results.
A full description of the reservoir design and manufacturing details is described in the instructions below. More details about the design are described in A Reusable, Compliant, Small Volume Blood Reservoir for In Vitro Hemolysis Testing - Olia - 2017 - Artificial Organs - Wiley Online Library.
The regulatory science tool, the small volume blood reservoir, is intended to be used as a key flow loop component for in vitro dynamic hemolysis testing such as the testing described in ASTM F1841-19e1 for evaluating the blood damage potential of medical devices.
This tool was successfully used as part of different flow loops in the hemolysis assessment of FDA benchmark nozzles and rotary blood pumps by the following laboratories:
- U.S. Food and Drug Administration
- University of Pittsburgh
- Rochester Institute of Technology
- Cleveland Clinic
The reusable, compliant, small volume blood reservoir was optimized to effectively help eliminate issues pertaining to inadequate mixing, air bubble entrainment, inlet collapse, and test sensitivity during in vitro dynamic hemolysis testing of medical devices. The use of this reservoir during hemolysis testing led to improved test reproducibility and blood mixing. Details about the quality of the hemolysis test data collected while using the blood reservoir can be found in FDA Benchmark Medical Device Flow Models for CFD Validation and Multilaboratory Study of Flow-Induced Hemolysis Using the FDA Benchmark Nozzle Model.
Since the blood reservoir is only a single component within a typical in vitro hemolysis test set-up, the validity of the entire flow loop in evaluation of blood-contacting medical devices is beyond the scope of this tool.
A full description of the reservoir design and manufacturing details are in the instructions below. A SolidWorks (.STL) file is also included to aid in 3D printing the reservoir base. More details about the design are available online: A Reusable, Compliant, Small Volume Blood Reservoir for In Vitro Hemolysis Testing - Olia - 2017 - Artificial Organs - Wiley Online Library.
In addition to citing relevant publications please reference the use of this tool using DOI: 10.5281/zenodo.7558811.
For more information:
Design and manufacturing instructions
1. ½″-Port reusable base
The rigid base was designed in SolidWorks (Dassault Systemes, Velizy, France) with two barb fittings to accept ½″ ID tubing, a flow separator between the inlet and outlet ports, and a 0.10″ external circumferential lip (Fig. 2A). The flow separator was shelled to remove excess material while maintaining a minimum thickness of 3/64″. All corners and edges were smoothed on the model before manufacturing. Fabrication was accomplished with a stereolithography additive (SLA) printer (Viper SLA System, 3D Systems, Valencia, CA, USA) using the Somos Watershed XC11122 (DSM, Elgin, IL, USA) photopolymer resin. Following light sanding to remove the printer-generated structural supports, a liquid coat of the same photopolymer resin was brushed onto the blood-contacting surfaces before a 30-min UV cure and a final isopropanol rinse.
2. Disposable blood bag
A medical-grade, three-port, 500-mL compliant polyvinyl chloride (PVC) blood bag (Qosina, Edgewood, NY, USA) was diagonally heat-sealed and trimmed along the bottom to remove the existing orifices. An optional Luer fitting (Qosina, USA) was fixated into the apex with cyanoacrylate glue before fitting the bag over the base.
3. Clamp set
The clamp set consisted of two plastic halves designed to secure the compliant bag against the rigid base (Fig. 2B). Milled from rigid polyvinyl chloride (PVC) stock, the clamps have a 0.10″ wide groove to accept the reservoir lip and two throughput holes for assembly using 10–32 machine bolts and wing nuts.
The single-piece design of the 3D-printed, optically clear, reusable base, devoid of seams or adhesives, reduced the possibility of cracking and contamination. Sufficient wall thicknesses and fillets ensured rigidity and fluid washout of the reservoir base, while lowering printing time and resin cost. With similar material properties as clinically used ABS plastic, the Watershed XC11122 resin meets ISO 10993 standard specifications for cytotoxicity, sensitization, and irritation, along with USP Class VI standards. As the SLA printing process leaves an inherently porous exterior, the integrated liquid resin finish reduced surface roughness to an Ra < 0.3 µm (Contour GT-KI, Bruker AXS, Madison, WI, USA), avoiding concerns of delamination and wear associated with topical sealants. Compressing the PVC bag between the circumferential lip and clamp created a labyrinth face seal and a leakproof assembly (Fig. 2C). Stain-resistant and easy to clean, the rigid bases have been washed and sanitized with degreasers, enzymatic detergents, 70% ethanol, and 10% bleach without issue before reuse with a new blood bag.