Article contributed to PharmaLeaders by Barbara Biller, President of intelliTECH, Inc., manufacturer of custom liquid fill and finish machinery that delivers precision results for regulated liquid filling environments.
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 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 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 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 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.
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 ≤ .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 [email protected]; Visit intellitech-inc.com.