Pre-Sterilized, Single-Use Filling Systems for Liquid Pharmaceuticals

Written by Eric Isberg, Bosch Packaging Technology

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The rolling diaphragm pump is comprised of a stainless steel pump with a diaphragm. A headpiece and diaphragm make the liquid chamber. Dosing occurs by actuating a piston that is attached to the diaphragm. It is similar to piston dosing, except the diaphragm keeps the product from contact with the piston and other internal components. The only stainless steel part in contact with the product is the headpiece (see Figure 2 below).

Constructing this system from plastic requires the use of o-rings or a lubricant-or both-to separate the moving piston from the body. Unlike the piston pump, however, these surfaces are separated from the fluid path by the diaphragm, so contamination of product stream is not an issue. The tolerances for each part are not as critical as with piston pumps because dose accuracy is related to accurate piston stroke while maintaining consistent dimensions in the fluid chamber.

Time pressure systems are designed to dispense using a pressurized product supply and timed valve openings (see Figure 3 below). A portion of the product path from the product supply manifold to the filling nozzles is made of elastomeric tubing. This tubing is used in association with an automatic tubing pinch mechanism to create the valve. The use of disposable tubing seems to make the system a good candidate for a single-use system.

However, these systems often use a small surge tank for product supply, and this tank must be pressurized to 10-psig (or more) for the system to function. Replacing this tank with a bag would require pressurization beyond its normal design pressure. There is currently no good solution for pressurization of a surge bag system for use with time pressure filling.

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Other Technical Hurdles Exist

Ensuring a single-use system dispenses at high speed while being durable enough for commercial use requires rigorous testing. No dosing system is appropriate for commercial use without proof of accuracy and precision throughout its operating lifetime. The maximum intended run duration for commercial systems can last as long as a week or more and involve 500,000 to 1 million dosing cycles per station. This is well beyond the design specification of existing single-use dosing systems.

A limitation to all current single-use pre-sterilized dosing systems is the plastic filling needle. The current plastic needles are not designed for commercial filling operations. Most are too wide to penetrate small containers and/or are too short to perform bottom-up filling. Bottom-up filling, where the filling needle penetrates the container and is drawn out during dosing, is common with high-speed filling to reduce product splash and foaming. The plastic needles are not shaped to fit correctly within needle holders on common commercial filling systems. Custom fixtures are required to use them on existing machines.

High-speed filling requires needles be made with tight tolerances, particularly the needle diameter, as this influences dosing accuracy and precision. Because high-speed needles travel during and after dispensing, needle drip between doses must be eliminated. Precise needle opening size and opening shape is also required. Substituting plastic needles with ones made from stainless steel can solve most of these issues, but is too expensive for single-use assemblies.

Summary

There are tremendous advantages to single-use, pre-sterilized dosing systems for commercial filling operations. Increased processing efficiency through the elimination of preparative steps like CIP and SIP, reduction of validation efforts including elimination of cleaning validation, containment of toxic products and matching existing single-use upstream processes are all compelling arguments for these systems for product filling operations. However, significant technical achievements must be realized before a system can be scaled for high-speed filling operations.

Eric Isberg is the product manager, liquid pharmaceuticals for Bosch Packaging Technology, 8700 Wyoming Avenue North, Brooklyn Park, MN 55445, 763-493-6143, www.boschpackaging.com.

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