Aseptic manufacturing of regenerative medicine products using isolator technology

Abstract

Aseptic processing or manufacturing is a method of manufacture in which microorganisms are excluded from the production environment and thereby prevented from entering the product. It has been recognized for decades, and humans working in aseptic environments were the only signifi cant source of contamination and therefore posed the greatest risk to both successful production of heat-labile products and to the patient. Over the last two decades, there has been a technological evolution in aseptic processing which has greatly increased patient safety by dramatically reducing the risk of microbial contamination in aseptic processing. The improvements that have occurred in aseptic processing arise from two principal technological features. The fi rst of these is the use of isolator technology and the second is the introduction of effective machine automation and robotics. Isolators have reduced contamination risk by effectively separating the human technician from the aseptic environment. Because isolators are an unmanned environment, which is much smaller in volume than a conventional manned clean room, they can be decontaminated in a manner that effectively eliminates microbial contamination of all kinds. The isolator after sporicidal decontamination is effectively a microorganism-free environment. The capabilities of the isolator have been further enhanced by the application of robots and other forms of automation. An important recent innovation is the introduction of robotics that could be built into isolator systems and decontaminated in place. These specialized robots along with machine automation have further reduced contamination risk and at the same time eliminated the possibility of technician error. The modern isolator system is very well suited to meeting the cell culture requirements necessary for the production of cytotherapeutics, and as a result cell culture isolators are proving to be the best option for the production of many regenerative medicine products.