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Aktuelles Konzept zur mikrobiologischen Sicherheit von zellbasierten Arzneimitteln

Current concept for the microbiological safety of cell-based medicinal products

  • Leitthema
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Die Gewährleistung der mikrobiologischen Sicherheit bei Arzneimitteln für neuartige Therapien stellt nach wie vor für die Hersteller eine große Herausforderung dar. Besonders bei zellbasierten Arzneimitteln bestehen grundsätzliche Probleme, zu denen die Sterilität der Ausgangsmaterialien, die kurze Haltbarkeit der Endprodukte und die Wahl geeigneter mikrobiologischer Kontrollmethoden gehören. Im Unterschied zu den klassischen Arzneimitteln müssen bei neuartigen Therapeutika sehr viel mehr mögliche Risiken bewertet und zum erwarteten Nutzen ins Verhältnis gesetzt werden. Je nach Ausgangsmaterial ist auch das Vorkommen von Mikroorganismen mit speziellen Nährstoffansprüchen zu berücksichtigen. Diese können mit konventionellen Testmethoden nicht nachgewiesen werden, sind beim Empfänger des Präparates aber oft vermehrungsfähig. Dies sind in erster Linie Mykoplasmen, für die spezifische Tests vorgeschrieben sind. Aber auch Mykobakterien und weitere mögliche Kontaminanten müssen, je nach Herkunft und Verarbeitungsschritten des biologischen Materials, in Betracht gezogen und durch entsprechende Kontrollen ausgeschlossen werden. Neben der Verkürzung der Dauer bis zu einem zuverlässigen Ergebnis vor der Anwendung eines Präparates, können alternative mikrobiologische Methoden (z. B. NAT, Durchflusszytometrie) dazu dienen, solche konventionell nicht erfassbaren Mikroorganismen nachzuweisen.

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.

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Danksagungen

Die Autoren bedanken sich insbesondere bei R. Beshir, J. Brachert, A. Schneider, B. Becker, B. Löschner für den technischen Support.

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Authors and Affiliations

  1. Fachgebiet Bakteriologische Sicherheit, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51–59, 63225, Langen, Deutschland

    Utta Schurig, Jan-Oliver Karo, U. Sicker, E. Spindler-Raffel, L. Häckel, I. Spreitzer & I. Bekeredjian-Ding

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  1. Utta Schurig
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  2. Jan-Oliver Karo
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  3. U. Sicker
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  4. E. Spindler-Raffel
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  5. L. Häckel
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  6. I. Spreitzer
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  7. I. Bekeredjian-Ding
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Correspondence to Utta Schurig.

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U. Schurig, J. O. Karo, U. Sickert, E-Spindler-Raffel, L. Häckel, I. Spreitzer, I. Bekeredjian-Ding geben an, dass kein Interessenkonflikt besteht.

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Schurig, U., Karo, JO., Sicker, U. et al. Aktuelles Konzept zur mikrobiologischen Sicherheit von zellbasierten Arzneimitteln. Bundesgesundheitsbl. 58, 1225–1232 (2015). https://doi.org/10.1007/s00103-015-2237-z

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  • DOI: https://doi.org/10.1007/s00103-015-2237-z

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