It is common knowledge that during the production of a freeze-dried product (mostly for parenteral administration) the solution will be filled into vials at room temperature and after loaded into the freeze dryer with shelves that are generally set near to room temperature (most commonly at 10-15°C).
Though, recent changes in parenteral drug developments have defined the need for loading pre-frozen products onto shelves that are much colder than the room temperature: some examples are protein-based drugs.
New considerations have to be addressed as condensation and even frost on the freeze dryer shelves can generate several issues.
The main effects of the frost buildup on the freeze dryer shelves are:
Insulation: the product has no direct contact with the heat from the shelves
Delay: it causes a slight slowdown in the loading
Loading fault: vials can get trapped or fall due to the ice formation
Now, what is the solution?
“Let’s bring the humidity down to 0%”.
Although this would solve the issue for the loading stage, this approach is unrealistic: human presence would be extremely uncomfortable, there would be an increase of static electricity and above all the dehumidification technology needed is not quite there.
Experimentally an Rh in the 18% to 26% range is the ideal compromise.
The best way to achieve this condition is primarily to reduce the height of the pizza door opening and establish a correct loading speed, this will depend on several aspects (vial size, filling, batch size etc).
Another helpful practice is to maintain a positive pressure of nitrogen (N2) in the chamber so that cold air (then frost) doesn’t adhere on the shelves.
There is also the possibility to install in front of the freeze dryer chamber an air curtain as showed in the picture below. This will eliminate the issue of ice formation if the specification are well designed and all parameters taken into account (room temperature, loading time, seasonal changes etc.).
Finally, if we are considering potent drug, isolator’s requirements have to take into account humidity and how to cope with that.
Do not miss out LyophilizationWorld article on Isolators.