title: [Current concept for the microbiological safety of cell-based medicinal products].
abstract: 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.
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland. bakteriologische-sicherheit@pei.de.
authors.forename: Utta
authors.initials: U
authors.lastname: Schurig
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: Jan-Oliver
authors.initials: JO
authors.lastname: Karo
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: U
authors.initials: U
authors.lastname: Sicker
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: E
authors.initials: E
authors.lastname: Spindler-Raffel
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: L
authors.initials: L
authors.lastname: Häckel
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: I
authors.initials: I
authors.lastname: Spreitzer
authors.affiliation: Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
authors.forename: I
authors.initials: I
authors.lastname: Bekeredjian-Ding
mesh_terms: D057205:Automation, Laboratory; D001688:Biological Products / Q000009:adverse effects* / Q000592:standards*; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects* / Q000592:standards*; D004203:Disinfection / Q000592:standards*; D004340:Drug Contamination / Q000517:prevention & control*; D005060:Europe; D006801:Humans; D008828:Microbiological Techniques / Q000592:standards*; D009174:Mycoplasma / Q000302:isolation & purification / Q000472:pathogenicity; D061214:Patient Safety / Q000592:standards*
chemical_list: D001688:Biological Products
keywords: Automated culturing systems; Cell-based medicinal products; Microbiological safety; Mycoplasmas; Rapid microbiological methods