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Biomedical subjects

I Schiller

Publications and source records attributed to I Schiller.

26 records · Page 2Linked to original sources
PubMed1981

[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.

Bacteria↗
PubMed1981

[Microbiological test for the determination of the maximum permissible standing time for non-sterilised ampoule solutions (author's transl)].

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.

Drug Contamination↗
PubMed1968

Microbial content of nonsterile therapeutic agents containing natural of seminatural active ingredients.

The relationship was investigated between various chemical or pharmaceutical production processes and the extent of microbial contamination, of natural origin, of the resulting products. The products contained active ingredients of vegetable, enzymatic, or animal origin. It was concluded that (i) vegetable products practically free from microbes can be produced if the proper manufacturing steps are taken; (ii) sterilization of the media used to manufacture antibiotics, etc., produces products with little contamination; and (iii) products containing extracts of animal organs require careful refrigeration and addition of preservatives to produce acceptable levels of microbial contamination.

Bacteria↗