At life science companies, including those that deal with reagents, buffers, biologics, cells, immunotherapy and similar products, liquid measurement and filling is often done by hand during R&D and lower initial production volumes. However, as advances are made through the development process, the rising demand for production volume and the increase in product changeovers result in significant drawbacks to this approach. With hand filling, some amount of overfilling, underfilling, or product spillage can be expected, which can be costly when handling high-value product. Manual dispensing and measuring can also lead to repetitive stress injuries for employees.

In addition, in automated filling systems, production is traditionally accomplished with equipment that must be thoroughly disassembled, washed, and sterilized between batches. The process is time-consuming, expensive, and energy intensive, and it opens the door to possible cross contamination as well as occasional control breakdowns.

To address these issues, a growing number of companies are turning to sterile, single-use, closed liquid dispensing systems and kits. These utilize disposable parts that can be quickly replaced to start the next fill cycle and expedite production changeovers. Such systems reduce the risk of cross contamination since only the single-use components are in contact with the liquids being dispensed.

This approach delivers superior, repeatable dispense accuracy after hundreds or thousands of cycles, while minimizing repetitive motion injuries. It can also be scaled up to accommodate requirements from R&D to fully automated, GMP manufacturing.

Single-Use Dispensing

Single-use liquid dispensing has become a trend because of its production flexibility, streamlined production versus cleaning the entire system, and relatively nominal cost, according to Derek Dunn, P. Eng., Senior Director, Services and Customer Experience, LuminUltra, a biological diagnostic testing company that develops tests and reagents for environmental, industrial, and diagnostic monitoring, and is a key supplier of COVID-19 clinical testing reagents for the Government of Canada.

LuminUltra sought an efficient process that minimized any potential contamination or reagent degradation. (Credit: intelliTECH)

In the case of LuminUltra, the company develops a range of testing solutions. One of these is its second-generation adenosine triphosphate (ATP) test, which measures ATP in water across diverse industries. This requires multiple liquid reagents in different volumes, dispensed into containers of various sizes.

Stephen Galpin, Packaging Supervisor, LuminUltra, explains that when an existing product line was produced in lower volumes, up to six operators were needed to dispense the liquid reagents using pipettes and to then affix caps and labels. While this was sufficient during R&D and at the initial production levels, continued growth eventually forced the company to consider increasing staffing or automating the process. The company had to decide whether they wanted to hire more people just for filling. Ultimately, they decided to automate the process and reassign the existing personnel to other more productive areas.

LuminUltra also sought an efficient process that minimized any potential contamination or reagent degradation. One of the major challenges was avoiding contamination of the reagents, given that the introduction of even small amounts of ATP from unintended sources would quickly degrade the quality of the test, says Galpin.

After searching for a market solution and reviewing multiple bids, LuminUltra selected a single-use liquid measuring and dispensing system that included a pump from a manufacturer of precision liquid filling and closure equipment.

Single-use technology minimizes the risk of contamination by utilizing sterile, disposable fluid path components from product source to dispensing nozzle. Each kit is a complete unit containing intake and discharge tubing, check valves, complete pump parts and a dispensing tip/nozzle. The disposable fluid path kits are assembled and packaged in an ISO Class 7 cleanroom and postassembly gamma irradiated to eliminate or minimize biological risk and maintain microbial control.

Production downtime is minimized, and changeovers are accelerated by eliminating the need to disassemble, clean, sterilize, and reassemble the fluid path components between batches. Changes from one reagent to another take only a few minutes and require no special tools.

The total startup time traditionally would take about 30 minutes, but automating the line reduces the start-up time to about 10 minutes, says Dunn. The equipment was customized to fit the available space as well as to accept different container sizes and configurations.

Because the volume of each reagent is different, the ability to handle containers of various sizes was important, says Dunn. The process involves multiple reagents. This might involve 5 ml of reagent for one aspect of the test, 9 ml for another, and 125 and 250 ml bottles for others.

Despite being customized, the system was easy to use out of the box, allowing LuminUltra to quickly begin dispensing liquids with the needed volume and accuracy. Dunn says he also appreciated the single-use technology, precision liquid filling equipment, and the manufacturer’s willingness to consult and provide expertise throughout the process, which he views as vital for a successful implementation. This involved optimizing the process by providing input on operator selection, training, and production flow.

The system can also be easily reconfigured to accommodate a range of fill volumes, dispense profiles, containers, and closure types. Custom-designed component parts are also available utilizing in-house design and 3D printing, as needed.

According to Dunn, that kind of flexibility facilitates line expansion in the future and would make scale-up easier when LuminUltra is ready for it.

Gentler Dispensing of Biologics

In addition to dispensing a variety of liquids, filling equipment is also increasingly being used to dispense sensitive biologics manufactured by or extracted from living sources — typically proteins, cells, nucleic acids, viruses, or vaccines.

In recent decades, protein-based therapeutics have become increasingly important to the pharmaceutical industry. These biopharmaceuticals are costly, difficult to produce, and susceptible to physical degradation when subjected to high shear forces during dispensing.

In fact, biologic products can degrade when dispensed using peristaltic pumps. These pumps contain fluids in a flexible tube, housed by a pump casing. A rotor outfitted with a system of rollers compresses the tube as it turns to create continuous fluid flow. However, the pump’s shearing force is not conducive for live cells, and its rollers can gradually damage the tubing, causing it to wear and stretch over time. The shearing force can even potentially release or shed small quantities of tubing material into the liquid as it flows.

The alternative to peristaltic pump technology is a hybrid pump design that is gentler and more reliable when dispensing biologics. Because liquids in the pump are not squeezed by rollers, there is no opportunity for cultures or delicate specimens to be harmed as it flows through the tubing. In terms of accuracy, this hybrid pump-based filling equipment delivers repeatable liquid filling accuracy ≤0.5 percent of the intended volume. In comparison, conventional pump accuracy is usually within 1–2 percent.

Whether life science companies are in basic R&D, developing the product, or rapidly scaling up through clinical studies to full scale GMP manufacturing, utilizing a modular, single-use liquid dispensing systems that can be scaled up to meet increasing production demands can be a tool to achieve greater production efficiency, flexibility, reliability, and profitability.

This article was written by Barbara Biller, President of intelliTECH, Inc., manufacturer of custom liquid fill and finish machinery. For more information, visit here .


Medical Design Briefs Magazine

This article first appeared in the July, 2021 issue of Medical Design Briefs Magazine.

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