[Current concept for the microbiological safety of cell-based medicinal products]. / Aktuelles Konzept zur mikrobiologischen Sicherheit von zellbasierten Arzneimitteln.

Ensuring microbiological safety in advanced-therapy medicinal products is still a big challenge for manufacturers. There are fundamental problems, especially in cell-based medicinal products, regarding sterility of source materials, short shelf-life of final products, and the selection of suitable microbiological methods. Different from classical medicinal products, there is the need to evaluate a large number of possible risks and to calculate the risk-benefit balance. Depending on the source material, the presence of micro-organisms with specific growth requirements has to be considered. They cannot be detected by conventional testing methods, but may replicate after the application of the preparation in the recipient. Mycoplasmas are the primary representatives of these contaminants and specific testing procedures are required. Additionally, depending on the source and processing of the biological material, specific testing methods for mycobacteria and other contaminants should be included. Alternative microbiological methods (e.g. NAT, flow cytometry) should be applied in order to reduce the time to detection and to provide reliable results before application of a preparation, but should be also assessed for their possible use for the detection of conventionally undetectable micro-organisms.

Microbial safety of cell based medicinal products--what can we learn from cellular blood components?

Today, sterility of established parenteral drugs including biologicals, such as plasma derived products, is practically guaranteed. Bacterially contaminated products are extremely rare exceptions owing to the efficiency of the manufacturing processes in the pharmaceutical industry. In contrast, the manufacturing processes of cell based medicinal products or tissue preparations show much less defined conditions. The sterility of source materials cannot be guaranteed in many cases. As a rule, these source materials cannot be sterilised, as it holds true for the final products. Furthermore, the established methods for sterility testing are not applicable for cell preparations. Sterility of a restricted sample does not guarantee sterility of the whole preparation. Thus, small amounts of residual bacteria in the product can be overlooked and can grow up to enormous numbers during storage and shipping of cell based medicinal products. Considering these problems, there are some parallels in the warranty of microbial safety of cellular blood components. Therefore, the experiences collected in transfusion medicine in the past decade can be successfully used in the production of cell based medicinal products. Comparable to the situation regarding cellular blood components, there is a need for new principles in rapid bacteria detection.