The device isolates the material inside the vial and is applied directly after the filling step. However, instead of incorporating a lyophilization stopper, a standard stopper can be used. The only time the vial is exposed to the environment is the time between when it is filled and the when the device is applied, which can be the very next station on the fill line. "At that point, it is protected until you are in the freeze dryer," says Fred Giordano, application engineer at Gore. "When the shelves in the freeze dryer collapse, the stopper is in the final position and the material inside has never really been exposed to the environments, which depending on the freeze dryer you are using and the manufacturing facility, can give you a lot more flexibility around the plant layout and around your capabilities."

Figure 2. (ALL FIGURES ARE COURTESY OF W.L. GORE & ASSOCIATES.)

Toward full automation

"Freeze drying is a critical batch process, and it is a very slow process, usually taking days, followed by subprocesses such as cleaning, sterilization, and filter testing. Carrying trays or frames with vials brings humans in fairly close contact with the open vials that are often filled with very sensitive and very expensive product. Because these vials are open, having semi-inserted stoppers, they are exposed in the cleanroom," says Meintrup. "The process involves handling sterile solutions that are filled into sterile vials which, in turn, have to be handled in a sterile environment and processed under sterile conditions. Any human interference is a risk in and a potential source of contamination. Automation takes this risk out, and the automatic system can be enclosed in an environment such as a RABS (restricted access barrier system) or an isolator."

The automatic loading and unloading of lyophilization systems, depending on the various types and executions of freeze dryers, helps reduce risk during this step. There are a few companies that design this type of equipment and the technology is not new to the industry. Nonetheless, a fully automated system, in line with automated vial-washing lines and filling lines that have no human interference, closes the gaps in the process between the filling line and the freeze drying step. "These transitions between various steps in the process are a matter of concern," says Meintrup. "We automate not only for performance but also to reduce the risk for the operators and for the product as well as to make the whole process safer, leaner, and more comprehensive."

Improvements to automated equipment include reducing its footprint, incorporating new refrigerants, and optimizing the refrigeration system. Reducing unproductive time through, for example, fast sterilization methods such as VHP (vaporized hydrogen peroxide) will increase the overall system productivity. "It's basically about improving the product quality and reducing the total cost of ownership that are the two main drivers in this area," says Meintrup. "That is the challenge in lyophilization."