By John Erdner, Product Manager – Aseptic Fill-Finish, SP Scientific, Warminster, PA, USA
Regulatory agencies prefer injectable products to be terminally sterilized. For some products, such as biological drugs, terminal sterilization is not possible because it will adversely affect the product. In these cases, the product must be aseptically filled in a class 100 or iso-5 environment. The vials must be washed, to remove particles, and then depyrogenated before filling.
Historically, if products were terminally sterilized, it was common practice to discharge vials from the washer directly to the filling room. However, the ISPE Baseline Guide volume 3: Sterile Product Manufacturing Facilities1, published in April 2018, recommends that all vials be depyrogenated, even if the product is terminally sterilized.
Depyrogenation, as the name implies, is the process to remove pyrogens, including bacterial endotoxins from vial surfaces. There are several different ways to depyrogenate vials. One of the most common and effective is using dry heat. Exposure of the vials to temperatures above 250°C destroys the pyrogens. Most depyrogenation processes are designed to achieve at least a log three, and preferably, a log six reduction of endotoxin.
The two most common methods for depyrogenation are batch ovens and depyrogenation tunnels, but there are different risk levels associated with these two processes. The risks involved with installing a depyrogenation tunnel come primarily from the management of airflows within the tunnel. The risks associated with batch oven depyrogenation involve the manual manipulation of vials and the dwell time between depyrogenation and filling. This paper discusses these risks and the opportunities for mitigation.