Aseptic Processing Qualification and Monitoring

Aseptic Processing Qualification and Monitoring

What is an aseptic processing simulation or media fill?

An aseptic processing simulation is used to determine the capability of a manufacturing process to be performed without the introduction of microbial contamination. This is of great importance for certain products that do not undergo a terminal sterilization process.

Why perform an aseptic process simulation using media fill?

Aseptic process simulations are performed with a microbiological growth media as an imitation product fill to evaluate the use and management of critical equipment and operator technique, and to demonstrate that environmental controls are sufficient to manufacture a drug or therapy by aseptic processing methods within fundamental regulatory requirements.

Aseptic process simulations are typically part of the qualification of a new manufacturing line, and semi-annual aseptic process simulations are also a regulatory expectation.

How is a validation of aseptic processing using media fill performed?

Soybean Casein Digest Medium (SCDM), a bacterial and fungal growth promoting media also known as Tryptic Soy Broth (TSB), is used to simulate the manufacture of the cell or gene therapy or pharmaceutical drug product. The broth/liquid media is used for filling the same container and closure systems. The containers with the broth media are then incubated at the prescribed incubation temperature(s) and visually inspected periodically for signs of bacterial or fungal growth.

A bacteriostasis/fungistasis test is also typically performed to ensure that visual growth can be detected, particularly for small volumes of dispensed liquid, and that no inhibitory substances contributed to the test media through the manufacturing process.

What is the USP <1116> testing standard as it relates to aseptic processing monitoring and qualification?

USP<1116> Microbiological Control and Monitoring of Aseptic Processing Environments, provides guidance on measures to monitor and control aseptic processing environments. The standard also includes the ongoing use of aseptic processing simulations or media fill studies, to be used periodically as techniques to evaluate aseptic conditions.