INTRODUCTION

The scope of this chapter includes any material intended for use in the manufacture of nonsterile, sterile, and low bioburden products that is subject to a test for bioburden as defined in Microbiological Chapters—Glossary 〈1117.1〉; this includes, but is not limited to, in-process samples (e.g., sample stages upstream and before final bioburden reduction in the case of sterile products), drug substances, components, raw materials, excipients, and water. The scope of this chapter does not include application of a test per Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use 〈1111〉. When faced with a decision regarding the quantification of microorganisms (bioburden) or performing a microbial enumeration test purposed for the examination of nonsterile products, refer to the decision tree, Figure 1, in the Appendix. Bioburden includes aerobic, facultative anaerobic, aerotolerant, and anaerobic microorganisms. In most cases, bioburden comprises mesophilic aerobic microorganisms, which can be adequately enumerated by a total aerobic microbial count as described in Bioburden Test 〈1119.1〉. In other cases, however, a different type of bioburden may be anticipated. This would require either modification of the method described in 〈1119.1〉—including, but not limited to, selecting an appropriate choice of nutrient culture medium—or the use of an alternative, suitably validated method. This chapter provides guidance for these modifications in those circumstances.