ABSTRACT
Sterile drug products are manufactured in facilities where airborne particles are controlled. Although a sterile manufacturing environment consists of rooms that are designed, maintained, and controlled to minimize the introduction and retention of airborne particles and microbial excursions, opportunistic contaminations are unavoidable. Therefore, it is essential to establish an environmental monitoring (EM) program to assess the cleanliness of the manufacturing areas and to ensure a state of environmental control. In fact, establishment of an EM program is required by both regulatory guidance and law (Food and Drug Administration [FDA] 2004c; 21 CFR 211). The FDA 2004 Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing-Current Good Manufacturing Practice and the Code of Federal Regulations governing the manufacture of pharmaceutical products clearly state the need to establish and follow procedures to prevent microbiological contamination of sterile drug products. Rooms where sterile products are manufactured are termed cleanrooms. Each of these rooms has a class designation and associated action limit for the maximum acceptable microbiological level. For example, in Class 100 (ISO 5) cleanrooms and isolation systems, it is expected that the normal microbial recovery is zero. The performance of the cleanrooms is monitored and corrective steps are taken if an unacceptable microbial level is identified. To this end, an EM program should specify sampling frequency and location, types of samples, and culture media. Before specifying these, alert and action limits should be defined. Data from real-time monitoring are compared to these limits so as to detect any microbial excursion that might put the product at risk. This chapter discusses statistical methods for trending environmental data from cleanrooms and setting alert and action limits.
