How to Evaluate If Microorganisms Isolated From Sterile Drug Production Environments Monitoring Are Undesirable.

This study addresses the identification of undesirable microorganisms (MOs) recovered during the environmental monitoring in manufacture of sterile medicinal products. We developed a methodology evaluation based on a decision tree; then, such approach was applied to hypothetical scenarios of uncommon MOs isolation in sterile drugs production settings. The scenarios were formulated on the basis of our field experience, in terms of both MOs selection and types of sampling site. The MOs were chosen in order to include emerging pathogens and MOs responsible for drug recall, and several sampling sites were considered for their detection (air, surfaces, and personnel). The classification of the unusual MOs revealed that most of them were undesirable, because they represented the loss of environmental control or a potential impact on the quality of the product. In some cases, the uncommon MOs were not considered as undesirable. Therefore, our results demonstrated the importance of a methodology, also in terms of recovery rate of unusual MOs and of the threshold probability for the unacceptability (e.g., 1% or 5%). The proposed methodology allowed an easy and documented evaluation for the undesirable MOs isolated from the environment of the analyzed settings for sterile drugs production.

Objectionable microorganisms in pharmaceutical production: Validation of a decision tree.

The release of quality, safe, and effective non-sterile drugs needs to exclude the presence of objectionable microorganisms, which include microorganisms potentially involved in product degradation, or considered as poor hygiene indicator during manufacturing, or causing adverse effect on patient's health. In this paper, a method allowing objective and verifiable evaluations has been investigated through the development of a suitable decision tree with a template for data collection. The decision tree has been used to establish which microorganisms were objectionables, using several hypothetical scenarios in which 24 different biological agents, both harmless microorganisms and opportunistic pathogens, were combined with 9 different products, representing each type of administration route for non-sterile drugs. The results showed that the use of aforementioned approach makes the microorganisms evaluation easy and verifiable and highlighted that even the microbes initially considered harmless could be objectionable.