[Low-level challenge test for the examination of the microbiological susceptibility, during the period of use, of liquid and semi-solid dosage forms in multiple-dose containers (author's transl)].

In the case of preserved liquid and semi-solid pharmaceutical preparations in multiple-dose containers, the adequacy of protection against microbial contamination is examined by means of a strict microbiological preservation test (Table 1). On account of a reduction in the amount of preservative added, either for medical (allergies) or technological (solubility etc.) reasons, or on account of a decrease in the antimicrobial efficacy during storage due to degradation or adsorption of the preservative or incompatibility with other excipients, the requirements of the preservation test may in some cases no longer be fulfilled during use. In such cases, a so-called low level multi challenge test is used to examine whether, after first opening the package, microbial growth can be prevented, in spite of renewed slight contamination during the period of use. To this purpose, samples are contaminated with very small quantities of various test organisms and stored at room temperature during the entire testing period (twice the theoretical period of use). The count of organisms is determined after certain intervals of time and the samples contaminated anew (Table 2). If at some time during the entire testing period, the number of organisms determined before a fresh inoculation exceeds the sum of the microbial counts from all inoculations carried out beforehand, one can no longer preclude the possibility of microbial, proliferation during the normal period of use and thereby detriment to the dosage form or danger to the patient. In such cases, the maximal permissible period of use should be limited or the size of the package reduced accordingly. If very poor results are obtained for the test, a change in composition of the dosage from must be envisaged in certain cases.