The preparation (cleaning, washing, etc.) of containers and packaging materials is normally performed in
a “clean” room (Grades C or D). After these operations, the containers and materials used for drugs sterilized
by filtration (and not further subjected to terminal sterilization in their final containers) must be
depyrogenated and sterilized before being introduced in the aseptic rooms by the use of double-ended
sterilizers or any other validated method. The depyrogenation step can be done using pyrogen-free water for
injection (WFI) for the last rinse prior sterilization or by performing the depyrogenation and sterilization in
one operation using a dry heat oven. Filling of these products normally takes place in a Grade A with a Grade
B background.
For products submitted to terminal sterilization, it is not mandatory to use containers and packaging materials
that are sterile but those that are in direct contact with the product should be free of pyrogen. This is usually
achieved by using pyrogen-free WFI for the last rinse of these materials unless they are subsequently
depyrogenated by another method (e.g., dry heat oven).
In addition, the initial bioburden of these materials should meet pre-established limits (that are based on
sound science) and the risk of contamination during their introduction in the filling areas should be kept to a
minimum.
