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."
Currently, the device is available for 20-mm neck vials and for small production runs such as for research and development,
preclinical, and early-phase development stages. The company is working on a 13-mm version as well.
Figure 2. (ALL FIGURES ARE COURTESY OF W.L. GORE & ASSOCIATES.)
Toward full automation
One of the most vulnerable stages in the efforts to reduce the risk of contamination is the loading and unloading of the freeze-dryer
trays of the lyophilizer. Eliminating the human factor from production provides an extra level of safety in terms of sterility
assurance levels, less risk of encountering problems during processing, and faster cycle times.
"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."