Harmonisation of Sterility Assessment for Autologous Serum Eyedrops in Switzerland

PURPOSE: Autologous serum eye drops (ASED) are classified as non-standardisable medicine by Swissmedic. Future approval is dependent on whether manufacturing meets the requirements of the European Pharmacopoeia (Ph. Eur.). Currently there is an effort to harmonise the manufacturing process for ASED in Switzerland, in order to facilitate approval. This includes standardisation of sterility assessment. This study evaluates the relevant sterility testing methods as described in the Ph. Eur. and includes the verification of possible antimicrobial activity of serum and the suitability test of the selected membrane filtration method for serum concentrations of 100%, 50% and 20%.

METHODS: For sterility testing of medicinal products, Ph. Eur. specifies membrane filtration (MF) and direct inoculation (DI). Alternative methods such as automated blood culture (ABC) systems may be considered. The methods were systematically evaluated for a Switzerland-wide standard for assessing the sterility of ASED. MF was subjected to a suitability test according to Ph. Eur.

RESULTS: Although inexpensive and fast, ABC, widely used internationally for sterility assessment of ASED, had to be rejected, as none of the laboratories with a Swissmedic licence for sterility testing of finished medicinal products offer an ABC system. In addition, as an alternative method according to Ph. Eur. it would have required complex and expensive validation of the method with proof of accuracy, specificity, limit of detection, robustness, suitability and equivalence to the pharmacopoeia method. As part of the suitability assessment of the DI, serum was found to inhibit the growth of Pseudomonas aeruginosa. DI requires appropriate neutralisation of the antimicrobial activity of the serum prior to sterility testing, which is not possible and therefore DI was not considered suitable. The most expensive and time-consuming method, MF, was selected. Suitability tests were performed in triplicate for Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium sporogenes, Candida albicans and Aspergillus brasiliensis. MF was deemed suitable for the detection of bacterial and fungal strains, with antimicrobial activity of the product eliminated under the test conditions.