Sterility Assessment of Reclosable Ophtioles with Unpreserved Autologous Serum during Single-Day Use

Abstract

Background According to the European Pharmacopoeia, multidose containers for eye drops must either contain antimicrobial agents, preservatives, or be fitted with filters or non-return valves to prevent microbial contamination after opening. Vials for single-day use do not have filters or non-return valves. The aim of this study is to demonstrate the safety of reclosable vials (ophtioles) containing unpreserved autologous serum eye drops (ASEDs) by evaluating their sterility during single-day use.

Material and Methods Two types of reclosable ophtioles were evaluated, one with a screw cap (Meise System, Heinz Meise GmbH, Schalksmühle, Germany) and the other one with a plug cap (COL System, BIOMED DEVICE S. R. L., Modena, Italy). Drop application over 12 hours was simulated in the laboratory following the manufacturerʼs instructions. For the Meise System, drops were applied at 2-hour intervals, while for the COL System, drops were applied at 1-hour intervals. Each application involved inoculating a chocolate-agar PolyViteX plate (PolyViteX, bioMérieux SA, Marcy-lʼÉtoile, France) with two drops spaced apart on the same plate and then incubating the plate. After 24 hours, a final inoculation was performed to check for sterility, and the plates were scored after 24 and 48 hours of incubation.

Results In the Meise System test series, 12 vials were tested, providing 192 measurements over 12 hours with a 2-hour application interval. With the COL System, 16 vials were tested, resulting in 448 measurements with a 1-hour application interval over 12 hours. Neither the Meise nor the COL System showed contamination of any application after 24 hours of incubation. After 48 hours of incubation, two vials of the Meise System showed a contamination in one measurement, but subsequent applications were sterile again. In the COL System, nine measurements in seven vials were positive. In three of these vials, the last application at 24 hours showed contamination after 48 hours of incubation, where no further drops were applied.

Conclusion The study confirms the sterility of ASEDs in two reclosable types of ophtiole systems during single-day use in laboratory-simulated conditions within 12 hours of application and 24 hours of incubation time. This is consistent with our several years of clinical experience of the absence of ocular infections caused by the use of ASEDs in the described ophtioles.

Zusammenfassung

Hintergrund Gemäß der europäischen Pharmakopöe müssen Mehrfachdosisbehälter für Augentropfen antimikrobielle Wirkstoffe oder Konservierungsmittel enthalten, respektive mit Filtern oder Rückschlagventilen ausgestattet sein, um eine mikrobielle Kontamination nach dem Öffnen zu verhindern. Ophtiolen für den eintägigen Gebrauch haben keine Filter oder Rückschlagventile. Ziel dieser Studie ist es, die Sicherheit wiederverschließbarer Ophtiolen mit nicht konservierten autologen Serumaugentropfen (ASED) zu demonstrieren, indem ihre Sterilität während der eintägigen Anwendung analysiert wird.

Material und Methoden Es wurden wiederverschließbaren Ophtiolen bewertet, eine mit Schraubverschluss (Meise System, Heinz Meise GmbH, Schalksmühle, Deutschland) und die andere mit Steckkappe (COL-System, BIOMED DEVICE S. R. L., Modena, Italien). Die Tropfenanwendung über 12 h wurde im Labor gemäß den Anweisungen des Herstellers simuliert. Bei jeder Anwendung wurde eine Schokoladen-Agar-PolyViteX-Platte (PolyViteX, bioMérieux SA, Marcy-lʼÉtoile, Frankreich) mit 2 voneinander getrennten Tropfen auf derselben Platte beimpft und die Platte anschließend inkubiert. Nach 24 h wurde eine letzte Inokulation durchgeführt, um die Sterilität zu überprüfen, und die Platten wurden nach 24 und 48 h Inkubation bewertet.

Ergebnisse Beim Meise-System wurden 12 Ophtiolen getestet, die 192 Messungen über 12 h bei einem 2-stündigen Anwendungsintervall ergaben. Beim COL-System wurden 16 Ophtiolen getestet, die zu 448 Messungen bei einem einstündigen Anwendungsintervall über 12 h führten. Weder das Meise- noch das COL-System zeigten nach 12 h Applikation und 24-stündiger Inkubationszeit eine Kontamination. Nach 48 h Inkubation zeigten 2 Ophtiolen des Meise-Systems jeweils eine Messung mit Kontamination, wobei nachfolgende Anwendungen wieder steril waren. Im COL-System waren 9 Messungen in 7 Ophtiolen positiv. In 3 dieser Ophtiolen zeigte die letzte Anwendung nach 24 h eine Kontamination nach 48 h Inkubationszeit.

Schlussfolgerungen Die Studie bestätigt die Sterilität von ASED in 2 wiederverschließbaren Arten von Ophtiolen bei 1-tägiger Anwendung unter im Labor simulierten Bedingungen innerhalb von 12 h Anwendung und nach 24 h Inkubationszeit. Dies steht im Einklang mit unserer mehrjährigen klinischen Erfahrung, dass bei den beschriebenen Ophtiolen keine okulären Infektionen auftreten, die durch die Anwendung von ASED verursacht werden.

Keywords

autologous serum eye drops - reclosable ophtiole - cornea - dry eye - sterility - eye drops

Schlüsselwörter

autologe Serumaugentropfen - wiederverschließbare Ophtiole - Hornhaut - trockenes Auge - Sterilität - Augentropfen

Publication History

Received: 27 October 2024

Accepted: 04 December 2024

Article published online:
16 April 2025

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