Chapter 2 - Aseptic Process Validation: Aseptic Process Simulation Design

Abstract

One of the reasons aseptic processes are difficult to validate is that it involves trying to prove something has not happened. Aseptic process simulations, also referred to as media fills, are studies conducted on the aseptic filling process, which is simulated to the actual production procedure where the product is replaced with growth media. The growth media is selected to act as closely to the product properties as is practically possible, while supporting and indicating relatively low levels of microbial contamination. This chapter focuses primarily on the principles and methods of aseptic processing liquid fills, but also briefly looks at nonliquid fills, such as powder and ointment filling and lyophilized products. To be effective, the design of aseptic process validation must use a risk-based holistic approach. Many of the procedures and process steps can be qualified or validated using standard validation methods, including those for sanitization, equipment function, sterilization, filtration, container-closure integrity, inspection, labeling, and transport. The approach to validating the aseptic process may include: product, equipment, and component sterilization; personnel training and certification; equipment and facility sanitization programs, equipment and facility operation; environmental controls; personnel, material, and equipment flows; and overall process design. Each control strategy and system that affects the quality of the process and product should be evaluated and tested during the validation approach.