Managing Aseptic Interventions

This article outlines a comprehensive approach for organizing a firm’s aseptic operations, including planning for routine and nonroutine interventions, establishing effective process simulations, and determining which vials to incubate. erforming an aseptic process almost always requires operators to manipulate sterile or sterilized products and components. These activities are universally considered to offer the greatest potential for introducing microbial contamination (1–4). That potential has been recognized by the US Food and Drug Administration inspectors and has led to some substantial concerns raised in warning letters issued in 2000 (5–6). The measures taken to respond to these concerns by the companies involved have implications for other firms performing aseptic processing. The PDA held a conference call in November 2001 with representatives of the Office of Compliance at FDA’s Center for Drug Evaluation and Research (CDER) to address relevant issues and establish some ground rules for the industry to follow. Participants in that conversation were Joseph Famulare and Richard Friedman of FDA, and Edmund Fry, Russell Madsen, and the author, who represented PDA. The essence of that conversation was subsequently reported in the PDA newsletter (7). This article outlines a comprehensive approach for organizing a firm’s aseptic operations consistent with the results of that discussion and aligned with recently defined regulatory expectations. The approach was initially developed in the spring of 2000 to suit the specific needs of a major manufacturer of aseptic products and subsequently was refined through application in a variety of settings at other firms.