Clinical Testing System Demands Precision Blow Molding
Reagent packs blow molded by Novapak to high dimensional specifications for Ortho-Clinical Diagnostics Inc. The basic designs are shown here in white HDPE.
Blow-molded containers often have relatively wide tolerances. But normal dimensional variability isn’t acceptable for many healthcare product packages, especially for the small reagent packs for Ortho-Clinical Diagnostics’ clinical testing system.
The dual-chamber blow-molded packs contain MicroTip reagents or diluents that help the Vitros 5,1 FS chemistry system determine the concentration of more than 20 substances, or analytes, in tiny samples of body fluids. This new MicroTip technology complements the patented Vitros MicroSlide technology, allowing the system to run more than 80 assays.
As these reagent packs moved from design to production, Ortho-Clinical Diagnostics and blow molder Novapak Corp. (Eatontown, NJ) worked closely to achieve the required tolerances. They also collaborated to establish manufacturing procedures that met or exceeded Ortho-Clinical Diagnostics’ strict interpretation of GMPs. Ortho-Clinical Diagnostics adheres strictly to FDA manufacturing guidelines and requires the same of its component and assembly suppliers. This includes tight calibration and control of production equipment, ensuring repeatable results.
Thirty-six dual packs, with capacities up to 60 ml (~2 oz), fit in a carousel on the Vitros 5,1 FS. The system selects the proper reagent for a given test by scanning bar coded labels on the packs during carousel rotation. It then removes the cap from the pack to aspirate a predetermined amount of reagent, recapping the bottle to maintain reagent stability and reduce reagent-to-reagent contamination. The system dispenses the reagent into a disposable cuvette, a small, square vessel that holds test solutions or analytes. A small amount of the body fluid is added, and if required, a second reagent is added. After an incubation period, the system measures the concentration of the analyte.
The system can accommodate as many as 160 samples on board at one time, and as many as 125 reagent cartridges or packs. The Vitros 5,1 FS embodies high-precision electromechanical, chemical, and software elements to accomplish tests for everything from alcohol and drugs to proteins and lipids. It allows for small amounts of sample and reagents to be precisely aspirated and dispensed. The system’s patented Intellicheck technology ensures the right amount of fluid is aspirated and dispensed every time.
“We considered a number of candidate designs for the reagent containers,” says Scott Schwallie, senior product development engineer, Ortho-Clinical Diagnostics. “Virtually every assay requires two reagents, dictating the dual-pack configuration. The candidate designs were ranked against the pack requirements using a weighting prioritization matrix. The blow-molded dual-reagent pack scored the highest in meeting our design and functional requirements.”
The gray colorant helps protect light-sensitive reagents.
There are three basic dual-pack configurations. All feature full threads for caps designed for mechanical capping and decapping. One configuration is a cylindrical bottle paired with a hollow wedge shape. A conical bottom to the cylinder enables extraction of the maximum amount of the reagent, which can be quite valuable. The hollow wedge shape contains the greatest volume of all the packs and is intended for reagents that are used more frequently.
The second configuration unites a conventional cylindrical bottle shape with a cylinder-plus-conical bottom form. The final pair is composed of a straight cylindrical bottle with a low-volume, arrow-shaped bottle. The latter is intended for reagents that are used less frequently. These last two designs incorporate a vane that enforces loading of the packs in the carousel in the correct orientation.
Two high-density polyethylene (HDPE) formulations are used, one with a white colorant, the other with a dark, light-controlling colorant to help protect light-sensitive reagents. As with many resins used in medical production, both the white and the dark HDPE molding compounds contain no release agents or additives capable of leaching into the test solutions.
“In evaluating the carousel-slot tolerances specified by our mechanical design team and knowing typical blow molding tolerances with the bottle dimensions I would need to hold, [I knew] there would be some significant challenges,” says Schwallie.
The dual design offers the greatest production efficiency, permits the use of a single bar coded label, and provides system users with an easily handled, easily loaded package. When the design was finalized, Schwallie called on Andy Elder, Novapak technical manager.
“The path to production was as intense as anything I’ve experienced,” says Elder, who has been involved in bottle production for more than 35 years. “We measured, made changes and adjustments, and measured again. This cycle went on for quite a while, but the result is a product meeting Ortho-Clinical Diagnostics’ capability requirements of Cpk Å½ 1.67 (index of process capability) on Critical to Quality dimensions.”
Encountered most often in such high-performance manufacturing methodologies as Six Sigma and statistical process control (SPC), Cpk is a value calculated on the statistical spread of product variation and is one of the most reliable indexes or expressions of production consistency. A Cpk Å½ 1.67 means that 999,767 out of 1,000,000 parts fall within Ortho-Clinical Diagnostics’ acceptable limits—and in blow molding, these are very tight limits. Novapak has consistently demonstrated they have met or exceeded these capability requirements for the Vitros 5,1 FS reagent packs.
Design of experiments (DOE) is a standard methodology used in Ortho-Clinical Diagnostics’ design process. Schwallie explains, “A DOE, which uses a structured experimental approach, provides the most efficient method for determining the relationship between process factors and part features and/or attributes.”
For example, a DOE project allows the multiple effects of each factor and the often complex interactions among factors to be studied in one experiment. Schwallie adds, “With what was learned from the DOE, we were able to set a process window wide enough to meet critical quality parameters while still ensuring our predetermined capability requirements could be met.”
He continues: “We worked with Novapak to map each step of the manufacturing process, from the resin hopper to the parison extruder to the blow molding stage. We identified the inputs for all process steps and weighted each—extrusion speed, metering temperatures, mold open and close times, and more. These were all measured against the packs’ Critical to Quality features (CTQs), identifying the most critical process inputs.” These inputs were included in the DOE design as factors and evaluated against the pack CTQs and attributes.
Schwallie says, “This structured DOE approach and collaborative effort between Novapak and Ortho-Clinical Diagnostics allowed for a robust manufacturing process, ensuring a high-quality product for use on the Vitros 5,1 FS Chemistry System.”