February 15, 2009 (Vol. 29, No. 4)
Providing Solutions in a Single-Use Biomanufacturing Environment
New drug development is focused largely on biopharmaceuticals rather than chemicals, which means the resultant drugs tend to be injectable liquids instead of solids. Furthermore, the new drugs are typically designed for specific populations, hence batch sizes are smaller.
Alongside these two trends are ongoing pressures to increase efficiency, reduce costs, and minimize risks, including cross-contamination between batches. Additionally, there is a need for reduction in the time involved in validation procedures (e.g., in paperwork and man hours). Taken together, these factors point toward peristaltic pumps with single-use tubing or tubing sets as representing the future for biopharmaceutical fill/finish lines.
Traditionally, fill/finish lines have used piston pumps, but in today’s biopharmaceutical production environment piston pumps suffer from a number of drawbacks. One of these is that they contain numerous contact parts that must be dismantled, cleaned, and sterilized between batches of different product. As batches become smaller, there is a need to shorten changeover times. Even if duplicate pumps are purchased to achieve faster changeovers, each pump still needs to be stripped, cleaned, and sterilized, with a small risk of cross-contamination between batches always an issue.
In contrast, the only component of a peristaltic pump that comes into contact with the product is the tubing. If the tubing is a single-use item that is supplied pre-sterilized, the need for cleaning and sterilization is eliminated, as is the risk of cross-contamination.
Extending validation periods in aseptic and sterile processes by providing single-use tubing sets and predictable pump-service intervals is an important aspect of product development at Flexicon. Part of Watson-Marlow Pumps Group, Flexicon offers single-use tubing sets, each of which is supplied complete with a validation package.
The DAFPA (disposable aseptic fluid path) sets are supplied double-bagged and gamma-irradiated ready for use. Various single-use tubing-set configurations are available. These include the required pharmaceutical-grade silicone tubing for the pump and, depending on the application, a sterile filter, aseptic quick-connect fittings, prefillable product bag, and filling nozzle.
Production managers switching from piston pumps to peristaltic pumps are often surprised at the highly accurate, pulsation-free flow that modern peristaltic pumps achieve. In addition, sophisticated electronic control of the pump motor enables the flow rate to be ramped up, maximized, and ramped down again, thereby reducing aeration and foaming so that short cycle times can be maintained. It is not unusual for peristaltic pumps to be used on filling systems processing up to 150 bottles per minute.
Flexicon’s pumps are normally fitted with a pumphead having two sets of six rollers, with the two sets of rollers offset from each other. Product is drawn through two parallel tubes and, after exiting the pumphead, the flows are combined via a Y-connector so that the pulsation from the two sets of rollers is combined. The resultant smooth flow is comparable with that achieved using piston pumps down to microfill levels.
With appropriately sized tubing, peristaltic pumps can deliver volumes down to 0.5 mL at an industry-standard accuracy of +/-0.5%; smaller volumes can be delivered with an accuracy of +/-1%. Typical high-speed filling machines use in-process checkweighing to monitor the filling accuracy and, if necessary, the output from this can be used in a closed-loop pump-control system.
Changing the Pump Speed
Varying the pump speed is one way to change the flow rate, but peristaltic pumps can also operate with different sized tubing. This can be beneficial in applications where a facility produces a range of substantially different batches. Although it is an extreme example, a single peristaltic pump can fill volumes between 0.1 mL and 250 mL simply by changing the tubing size.
Some of today’s biopharmaceutical products such as live vaccines and organisms are sensitive to shear and high pressure. Once again, peristaltic pumps offer advantages over piston pumps. In microfilling applications, for example, peristaltic pumps are calibrated to provide a maximum of 1.3 bar pressure. The smooth flow past the pumphead rollers means that the liquid is not subjected to shear in the same way as it would be when passing through the valves and small orifices of a piston pump.
Single-use technology is becoming popular in the production of injectable liquid biopharmaceuticals. While it would be impractical to have a single-use (piston) pump, peristaltic pumps offer a significant advantage in that the only contact part is the tubing. And single-use tubing sets are both practical and cost-effective.
Peristaltic technology, therefore, offers reliable, cost-effective pumping that fits with the single-use production philosophy without compromising the required pumping characteristics.