Single-Use Tech for Liquid Handling

By John Morin

People have been putting liquids into containers for millennia. Natural objects such as hollow gourds and animal skins started the container industry, only to be improved upon with more permanent vessels made from wood and pottery.

Perhaps the best known ancient vessel used was the Amphora. There is evidence dating back to the 15th century BC that Greeks and Romans used these containers to store and transport wine, oil, olives and other commodities. These vessels were also referred to as “ampulla” from which our modern-day ampoule derived.

Modern Filling Applications

Stainless steel has long been the material of choice in the manufacture of tanks, mixers, vessels, pipes, pumps, fittings, etc. Silicones, thermo-plastics and Teflon® components are widely accepted as the material of choice for flexible connections, but stainless steel comprises the vast majority of product contact surfaces.

A typical reusable run

Products are formulated in a stainless steel mixing/holding tank, which then runs through hard plumbing via stainless pipe and fittings to a stainless manifold which is plumbed to stainless piston pumps (arguably the most accurate and durable form of dispensing), which then transfer product through stainless piping or flexible hose and terminates with a stainless steel filling needle or nozzle. In most cases the hoses are discarded and the stainless components are cleaned and sterilized.

The constant and costly maintenance of reusable items

Modern-day products prove very challenging to comprehensively clean, from intricate machine parts and small diameters such as the ID of a filler needle or small piston pump. Purified water and detergents are employed to break down the remnants of formulation, and then detergents must be removed as well, which in many cases proves to be equally difficult. It must be determined if an effluent is base, acid or alkaline. If not base, an additional buffer treatment is required prior to disposal into the city sewer or company leach field. Stainless items are then packaged and restocked. Prior to their next run, they are rinsed again with purified water and autoclaved. Autoclave cycles are time consuming and costly to perform. After all is said and done, the turnaround time on reusable stainless items can easily take 24-48 labor-hours.

For those of you who perform these daily tasks, you know that the previous explanation excludes many of the more detailed cleaning procedures involved. In addition to the constant struggle of upkeep, plants must perform initial and periodic cleaning and sterilization validation.

The breakdown of floor space in “reusable” filling plants is strongly biased towards overhead-related processes and not revenue production. Prep, cleaning, sterilization and formulation take up vast amounts of real estate. Stainless steel mixing and holding tanks are large, expensive and often hard plumbed. We have one customer who refers to his collection of tanks as “The Stainless Forest.” This does not lend itself to the flexibility required to meet constantly shifting customer demands. Inventory taxes further sap revenue, adding to the long list of burdens associated with stainless steel components.

Enter Single-Use Technology

Single-use technologies focus on increasing production and revenues by offering items that allow quick changeover and flexible scheduling. Large expensive stainless tanks can be replaced with sterile fluid handling bags. Bags from 10L to 5,000L are common and bags as large as 20,000L have been made. Leachable and extractable issues associated with bag technology mirror the initial concerns related to disposable filters. Disposable filters from companies like Meissner, Millipore, Pall and Sartorius have become mainstream due to extensive testing for chemical compatibility. The same outcome is predicted for bags as more companies streamline their formulation and fill/finish operations. Companies such as ASI, Charter, Hyclone, Stedim and TC Tech manufacture sterile bags for formulation and filling. Additionally, companies like ATMI, Lev Tech, Wave and Xcellerex offer 3D bags and liners that have the ability to mix formulations and keep them in circulation.

Peristaltic pumps are faster and more accurate than ever and are proving to be a good alternative to piston pumps. The ability of peristaltics to dispense exacting tolerances through a fully disposable fluid path is driving their popularity. A good single-head peristaltic system can dispense 1ml @ 60 units/minute with a .07% accuracy.

With the advent of very precise and accurate single-use dispensing tips, there exists the possibility for a fully disposable fluid path, from formulation through fill/finish. Innovative companies like Amesil, Cole-Parmer, Dow Corning, Parker Mitos and Saint Gobain offer custom tube sets with proper fittings that mate to the sterile bag or aseptic port, and single-use filler needles attached at the terminal end. Many companies offer these kits multi-bagged and gamma sterilized, ready to use. Several other companies are looking closely at doing the same. Machine builders like B&S, Bosch, IMA and Inova are looking into incorporating a completely disposable fluid path onto some of their new equipment.

We can see a comprehensive single-use liquid dispensing system emerging:

1. Sterile filter formulation into a single use sterile bag or mixer (closed system)
2. Product dispense via peristaltic pump (accurate, no product contact) through custom disposable tube set and single-use filler needles
3. Fill campaign concludes, lines are disposed, and machine changeover commences
4. Machine and filling room wipe down per SOP
5. Product batch arrives in sterile bag or mixer ready for dispense
6. Installation of custom disposable tube set and single-use filling needles
7. Commence next fill campaign

Realized benefits include:

• No cleaning (components are pre-cleaned)
• No sterilization (component are gamma sterilized)
• No validation (once initially validated, components are accepted until next quarterly validation run)
• No “stainless forest” (sterile fluid bags stored on racks)
• No prep of tubing or components (components come pre-configured for specific machine/product)
• Reduced labor expense
• Reduced autoclave burden
• Reduced changeover time
• Reduced floor space dedicated to prep
• Reduced floor space dedicated to capital equipment
• Reduced floor space and expenses dedicated to inventory
• Ease of purchase (filling components are preconfigured and ready to use)
• Ease of scalability (fluid path validated from R&D through clinical)
• Scheduling flexibility (consistent availability of filling components to better cope with shifting schedules and demands)

We are at the onset of a paradigm shift in the fundamental way the industry approaches sterile liquid packaging. Although still early in its inception, single use technology is the way of the future. It is critical to consider the costs of not moving forward with these new technologies. No one thought Digital, TWA or Enron would ever disappear; imagine 20 years from now when your son or daughter asks who Pfizer, Abbott or Amgen was. Companies must aggressively pursue innovative ways of producing and packaging drugs that focus on maintaining quality and protecting the health of the public while adopting a manufacturing model that emphasizes efficiency, scheduling flexibility, lowered costs and higher throughput. It’s time to embrace the future and act boldly.

John Morin is president of Overlook Industries, Inc. He started Overlook in 1993 with the primary objective of solving dispensing problems on automated liquid filling lines.