Validierung eines schnellen Steriltests
Herausforderungen aus der Sicht eines Dienstleistungslabors
Originale
Key Words Rapid Microbiological Methods (RMM) | Prüfung auf Sterilität | Validierung einer Alternativmethode | Ph. Eur. 5.1.6 | USP <1223> | PDA TR No. 33
Abstract
Validation of a Rapid Sterility Test – Challenges from the Perspective of a Contract Laboratory
Microbial contamination of drugs and medicinal products, which are required to be sterile for the application to humans or animals, poses a great risk to the patients’ safety. In addition to all technical as well as operational safety measures during the production, the test for sterility is the final criterion for the batch release in most cases. For the traditional sterility test according to the pharmacopeia, an incubation time of 14 days is required to provide qualitative information on a possible macroscopically visible growth of microorganisms due to a primary contamination. Therefore, alternative rapid methods that decrease the incubation time become increasingly attractive particularly to patient-specific formulation and medicinal products having a short half-life. Moreover, after sufficient validation their use is supported by authorities (e.g. FDA, EMA).
Currently there are many microbial alternative methods on the market which are in principal suitable for proofing sterility. Adenosine triphosphate(ATP)-Bioluminescence via Charles Rivers’ Celsis® AMPiScreen technology represents one of the possible alternative methods to the compendial method. This system uses ATP, that is ubiquitously present in living organisms as well as ATP that is additionally produced by an amplification step, for the qualitative detection by a luciferin-luciferase enzyme reaction. The advantage of this adapted procedure via ATP detection is that the main principle of the method for testing according to Ph. Eur. 2.6.1 and USP <71> (membrane filtration, direct inoculation) remains unchanged. Only the visual detection system by means of the human eye is replaced by an automated detection procedure using ATP-Bioluminescence. Therefore meaningful, valid results are obtained after only 7 days of incubation.
The following article describes a general method validation of this alternative method to the compendial method according to Ph. Eur. 5.1.6, USP <1223> and PDA TR No. 33 from the perspective of a contract laboratory.
Korrespondenz:
M. Sc. Carolin Fromm, Labor L+S AG, Mangelsfeld 4, 5, 6, 97708 Bad Bocklet, Germany; e-mail: Carolin.Fromm@Labor-LS.de
Zusammenfassung
Eine mikrobielle Kontamination bei Arzneimitteln und Medizinprodukten, die zur Applikation an Mensch oder Tier steril sein müssen, stellt ein großes Risiko für die Patientensicherheit dar. Neben sämtlichen technischen und operativen Sicherheitsmaßnahmen während der Produktion ist die Prüfung auf Sterilität in den meisten Fällen das finale Kriterium für eine Chargenfreigabe. Bei der traditionellen Prüfung auf Sterilität gemäß Arzneibuch muss
