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.

Antimicrobial Activity of Xibornol and a Xibornol-Based Formulation Against Gram-Positive Pathogens of the Respiratory Tract.

Xibornol is known since the 70s and a xibornol-based formulation is commercialized as spray suspension for the antisepsis of the oral cavity and as adjuvant in pharyngeal infections caused by Gram-positive microorganisms. Herein, we evaluated the antimicrobial activity of xibornol and the xibornol-based formulation against common pathogens of the upper and lower respiratory tract.Our results indicate that xibornol alone and the xibornol-based formulation have strong antibacterial action against Streptococcus pneumoniae, Streptococcus pyogenes, and Staphyloccus aureus, as well as against the two emerging pathogens Actinomyces israelii and Corynebacterium ulcerans. These findings highlight the antimicrobial potential of these drugs in the topical control of pathogenic Gram-positive bacteria of the respiratory tract.

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.

Development of Methods for Recovering Endotoxins from Surfaces and from Air in Production Environment of Injectable Drugs.

The aim of this work is to develop and validate methods for quantifying endotoxins on surfaces and in the air of the manufacturing environment of injectable drugs, in order to use them to evaluate the quality of the process and the risk for the products processed therein. The method for recovering endotoxins from surfaces is a direct method that provides sampling surfaces by swabbing and extraction of endotoxins from the swabs with an appropriate diluent, while the method for airborne endotoxins provides an air-active sampling on a glass fiber filter and endotoxins extraction with an appropriate diluent.LAY ABSTRACT: Bacterial endotoxins are present in the environments devoted to the manufacturing of injectable drugs and could be a real risk for the quality and the safety of such drugs. So the quality control laboratories should have analytical methods to recover bacterial endotoxins from environmental samples. The aim of this publication is to show how we succeeded in developing and validating methods to quantify bacterial endotoxins on surfaces and in the air.