Risk assessment and mitigation in aseptic processing
INTRODUCTION Sterile products are frequently administered to patients through the dermal layer to attain rapid therapeutic response and accurate dosing. Delivery in this manner intentionally circumvents the body’s protective mechanisms, and mandates that the product be largely free of infectious microorganisms and endotoxin. These concerns are heightened when the drug is delivered to patients whose health is already compromised as is common in clinical settings. Awareness of the patient has prompted regulatory preference for the use of terminal sterilization (1,2). While the use of lethal processes on finished formulations in their final container is favored because of their lethality, material considerations have limited their application such that an estimated 85% of all sterile products are manufactured by aseptic processing that are less abusive of essential material and container properties.a
Aseptic processing customarily use a variety of sterilization procedures for the individual components of the formulated product, container, and product contact parts, enabling the sterilizing process to be chosen for preservation of the key quality attributes of the materials. The core aseptic process assembles the sterilized items into the final dosage form in an environment specifically designed for that purpose. Because product containers are closed after the individual sterilization processes are carried out, the potential for contamination ingress is ever present during aseptic processing. In the belief that knowledge of the conditions under which the aseptic process is carried out would be valuable in determining the acceptability of the resulting product, environmental monitoring has historically been considered essential. Microbial sampling of air and surfaces as well as personnel gloves and gown within the aseptic environment were instituted as a means of environmental monitoring, which ultimately evolved into a program thought to provide critical information regarding sterility assurance. When monitoring was first instituted, the environmental conditions and gowning systems were markedly less capable than those presently in use. As a consequence, performance expectations and demonstrated performance were understood to be nonabsolute. Nevertheless, it was certainly understood that improvement in contamination control performance was both desirable and attainable. The gradual refinements in aseptic processing technology and performance expectations took place over a period of some 50 years.