The maximum calibration range for the load cells is set for 20 kg so they would not be overloaded by a full 20-L bag. Each "production bag" has a minimum load of at least 30 g material, unless the product is being taken for a sample where the accuracy is not so critical. Bags as small as 50 mL have been tried in the system; the problem with these bags is that when they hang on the load cells, they are too light and cannot be properly stabilized. The measurement problem was compounded by the fact that the lines to which the bags are attached cause movement that affects the mass reading on the load cells, leading to inaccuracies. Therefore, it was necessary to use hanging load cells to make these measurements. With larger-sized bags, tubing holders can be used to stabilize the lines, preventing signal drift on the load cells.
As with any new process there are always a number of challenges. In this case they are associated with dispensing and weighing accuracy, mixing and scalability.
Hanging load cells were selected because the system is so dependent on accurate measurement and control. Overcoming the dispensing and weighing accuracy challenges were critical to the project's success. As a result, the selected load cells had the following features:
- Ability to withstand high lateral forces caused by the "pulling" of the tubing connecting the bags to the process and bracketing assembly and the pulsations associated with the peristaltic pumps;
- Required accuracy of 0.02% of cells;
- Readings unaffected by thermal or vibratory interference;
- Moveable load points to compensate for "shifting" of the bag on the strain gauge, not only as a result of changes in the bag profile, but also the "rocking" assembly used for mixing after weighing.
After some research, the selected weighing solution was a cantilevered weigh cell manufactured by BLH (http://cimail15.blh.com/process-weighing/). The KIS 3 Load cell is unique in that its "double" cantilevered design as shown in Figure 2 locates the load force application point directly above the strain gauges. This provides the following:
- Side-load force sensitivity is virtually eliminated, negating the effect of the tubes and rocking motion of the mixer;
- Moment stresses upon the gauges are zero, compensating for any slippage of the bag along the axis of the strain gauge, eliminating the need for stay rods and other expensive mechanical supports, while allowing for the motions to promote mixing of product down the line after weighing;
- The cantilever design balances the bending force to the center of the beam, reducing the bending stress at the mounting base by 50%;
- Shear stresses remain constant for higher repeatability;
- Calibration tolerance limit is ± 0.03%.g it up
Liquid ingredient addition (whereby the liquid has similar fluid characteristics to water) is volume added based on mass, with known specific gravity and starting and resulting concentrations. Weigh cells are a suitable measurement technology for this application as the multiple, changing masses of the ingredient additions require an in-line, multi-channel weighing instrument with panel readout.
These load cells are converted from strain gauge transducer signals to weight information using a G4 multi-channel weighing instrument. As a result, the measurement signal represents the only true applied force, thus making it possible to achieve the measurement accuracies required for this installation.
As this process migrates to larger scale production, it will be necessary move to larger bags which, due to their weight, will have to be supported with a more rigid floor-mounted structure. Fortunately, the BLH weighing system, forming a key part of the process and control system, can also be scaled to this configuration.
Accurate sensing and control is a critical part of the development of new biopharmaceuticals, not only to maximize return on investment through the elimination of reprocessing and remanufacturing, but also providing proper measurements to meet the strict documentation requirements and cGMP constraints for approval of products undergoing clinical trials.
Opportunities arise as the industry moves from stainless steel setups with fixed probes, to flexible and disposable mixing and reaction vessels, which require high-accuracy measurement irrespective of holding vessel geometry.