[Microbiological test for the determination of the maximum permissible standing time for non-sterilised ampoule...

As opposed to most large volume parenterals (LVP), which on account of their composition provide good nutrient media for microbial growth, it can be expected that many ampoule solutions have an antimicrobial activity of their own, due to the high activity of their drug substances. It is therefore questionable as to whether the requirements laid down by the American Food and Drug Administration (FDA) for LVP, demanding a maximum time limit of 8 hours for the manufacture, filling and sterilisation, can simply be extrapolated to apply to small volume parenterals. A method is now described whereby the behaviour of various micro-organisms can be studied in non-sterilised ampoule solutions. The tests carried out show that only a negligible fraction of the ampoule solutions permit proliferation of contaminating organisms. On the contrary, the majority of the preparations examined had an inhibitory or even microbicidal effect. On the basis of the findings, it is proposed to make a generally valid classification of ampoule solutions into 5 different risk classes. While it is essential to adopt the rigorous FDA restrictions for the entire manufacturing period in the case of those preparations most susceptible to microbial proliferation, the standing times, i.e. the period of time between the manufacture of the solution and the subsequent antimicrobial treatment of the ampoules, can be prolonged without risk for the other groups. This maximum standing time, laid down specifically for each product, in many cases enables the manufacturer to produce larger batches or to improve exploitation of production capacity, yet at the same time maintain security for the product and the user.