Die mikrobielle Kontrollstrategie in der biopharmazeutischen „Low-Bioburden“-Wirkstoffproduktion
Übersichten
Key Words mikrobielle Kontrollstrategie | microbial control strategy | keimreduziert | low bioburden | Biopharmazeutika | biopharmaceuticals
Abstract
Microbial Control Strategy in the Biopharmaceutical Low Bioburden Drug Substance Production
Microorganisms are essential for our wellbeing, but may also cause serious illness if they appear at the wrong time and place. Primarily depending on the dosage form, drug products have legally binding limits specifying their bioburden. The bioburden of the drug product in turn dictates whether the processes for manufacturing have to be run non-sterile, low bioburden or sterile (aseptic). Biopharmaceuticals, like monoclonal antibodies or other proteins for parenteral applications, have a mixed process regime. The drug substance is typically produced in a low bioburden regime, then formulated and sterile filtered in order to yield a sterile drug product.
Low bioburden processes for drug substance production are legally in an intermediate position between aseptic and non-sterile regulatory requirements, and there is a lack of dedicated clear legal guidance. This article covers the EU and US regulatory landscape for low bioburden processes and outlines the required microbial control strategy.
Korrespondenz:
DI Birgit Krenn, VTU Engineering, Parkring 18, 8074 Raaba-Grambach, Österreich; e-mail: birgit.krenn@vtu.com
Zusammenfassung
So wichtig Mikroorganismen für unsere Gesundheit sind, so pathologisch können ihre Effekte sein, wenn sie sich zur falschen Zeit am falschen Ort befinden. Arzneimittel haben daher, abhängig von der Darreichungsform, strikte Grenzwerte für mikrobiologische Kontamination. Diese spiegelt sich in einer nicht sterilen, Low-Bioburden- (keimreduziert) oder sterilen (aseptischen) Prozessführung zur Herstellung der Wirkstoffe und Arzneimittel wider. Biopharmazeutika, wie
