Scaling Single-Use Liquid Dispensing from R&D to Automated Production

Easy production scale up and changeovers are possible with accurate, reliable liquid measurement and filling systems in complete kits that eliminate the need to clean and sterilize equipment between batches

At pharmaceutical 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, increasing demand for
production volume and product changeover increase, 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, energy intensive and opens the door to
possible cross contamination as well as occasional control breakdowns.
As a solution, 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 systems2
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 liquid dispensing has become a trend because of its production flexibility,
streamlined production [versus cleaning the entire system], and relatively nominal cost,"
says 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.
In the case of LuminUltra, the company develops a range of testing solutions. One of
these is its 2nd 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.
According to Stephen Galpin, Packaging Supervisor, LuminUltra, when an existing
product line was produced in lower volumes up to six operators were needed to dispense
the liquid reagents using pipettes and affix caps and labels. While this was sufficient
during R&D and at the initial production levels, continued growth eventually forced the
company to decide between increasing staffing or automating the process.
"We were growing every year and we reached a fork in the road, so we had to decide if
we wanted to hire more people just for filling," says Galpin. "We ultimately decided to
automate and re-assign the personnel to other more productive areas."
LuminUltra also sought an efficient process that minimized any potential contamination
or reagent degradation.3
"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 an i-FILL® pump, from
Florida-based Intellitech, 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 post-assembly gamma irradiated to eliminate or minimize any
biological risk and maintain microbial control.
Production downtime is minimized and changeovers accelerated by eliminating the need
to disassemble, clean, sterilize and reassemble fluid path components between batches.
Changes from one reagent to another takes only a few minutes and requires no special
tools.
The total start-up time usually takes about 30-minutes, but starting up the automation line
"is down to about 10 minutes," says LuminUltra's Dunn.
Dunn says the equipment from Intellitech 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. "Our process involves multiple reagents. We 4
might need five-milliliters of reagent for one aspect of the test, nine-milliliters for
another, and 125 ml 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 Intellitech' s willingness to consult and provide expertise
throughout the process, which he views as vital for a successful implementation.
"It wasn't just, ‘Here's the machine. This is how you run it. Good luck, see you later.'
They helped us to optimize the process by providing input on operator selection, training,
and production flow. That was very helpful," says Dunn.
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.
"That kind of flexibility facilitates line expansion in the future. It is nice to have the
option to scale up when we are ready for it," says Dunn.
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.5
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, like the i-FILL, delivers repeatable liquid filling accuracy ≤ .5% of the
intended volume. In comparison, conventional pump accuracy is usually within 1-2%.
Whether pharmaceutical companies are in basic R&D, product development 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.
For more information, call 866.434.5548; Fax 410.876.1256; Email sales@intellitechinc.com; Visit intellitech-inc.com.

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