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

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

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

Evaluation of the virucidal effect by contact with water-insoluble substances: the case of Xibornol

The virucidal activity of xibornol has been known since the 70s, but its determination is primarily based on few clinical data. Experimental quantitative estimation in vitro is limited by the absence of appropriate test neither the European nor the American Pharmacopoeia; however some recent standards, concerning antiseptics, could be utilized for this purpose. The tests were carried out by following the European Standard EN 14476, which foresees contact test between viruses and 3 different concentrations of xibornol, in two experimental conditions and viral titer estimation by cell culture method. The tested viruses were chosen among those ones most closely responsible of upper respiratory tract infections: Human Adenovirus, Human Rhinovirus and Human Corona virus. For the commercial concentration (3%), the results show a common trend for all the viruses with an estimated titer that reached values below 1 log DCP50/ml after each condition contact test. The reduction was greater in clean conditions with average value of 3 logs, compared to the test in dirty conditions (2 log). The data confirm the virucidal action of xibornol and show, for the first time, a quantitative variation in disinfection efficiency depending on contamination scenario