Compressed Gas Monitoring of Microbes:

The Contamination Control Strategy in Pharmaceutical Manufacturing Environments

Abstract

Compressed gases, such as nitrogen, carbon dioxide, and oxygen, are used for a variety of applications in pharmaceutical manufacturing. These applications, such as aseptic packaging, purging, and filtration, are critical processes monitored for their efficacy. To avoid sampling compressed gases, it has been speculated by some manufacturers that the rapid decompression of a gas when exiting its container kills any microbial contamination. However, it has been shown by multiple studies that microbial survival is not impacted by the typical compression or decompression seen in pharmaceutical process gases.

Many GMP standards recommend sampling process gases for contamination before use in critical areas of manufacturing. This step, along with many others that make up a contamination control strategy, contribute to the purity and quality of the final product.

Introduction

The quality attributes of manufactured pharmaceutical products include the physical, chemical, and microbiological characteristics of the raw materials, excipients, active pharmaceutical ingredients (APIs), and final drug products. Here, absence of microbiological contamination is critical because it can dramatically impact a drug’s safety. As a result, the cleanliness of compressed gases, which often come into contact with pharmaceutical products, is also critical.

For the variety of gases used in manufacturing, their compressed state refers to how they are contained. Compressed gases are typically sampled by taking a small amount from a gas line and drawing it into a smaller space (i.e., a sampler). The decrease in volume that the gas occupies increases its pressure. Gases are decompressed when exiting whatever is containing them for use in a manufacturing line. Process gases are therefore more likely to be decompressed before coming into contact with the product.