Moving towards a (microbiological) environmental monitoring programme that can be used to release aseptically produced pharmaceuticals: a hypothesis, a practical programme, and some results.

We present, in detail, the (microbiological) environmental monitoring programme for cleanrooms that is in use at the RIVM. The parameters that are measured are: Total airborne particles of 0.5 micron and larger, airborne colony forming units (cfu's), cfu's on surfaces, cfu's on fingertips of gloves and settling cfu's. Most attention is paid to areas where critical handling is performed (class A areas). In these areas sampling is performed continuously during work. The areas surrounding class A areas are seen as a necessary environment to create a class A area and are called supporting areas. Changes in these supporting areas that will adversely effect the quality of the class A area, will be detected in the continuous sampling of the class A area. Sampling the supporting areas should only bring forward whether the measured parameters of these areas are consistent. The frequency of sampling, either weekly, monthly or three monthly, is based on the data obtained in previous sampling. In addition to the programme some data are presented. These data indicate that the values of the earlier mentioned parameters are not particularly dependent upon the lay-out or classification of areas, but rather on the use of the areas, and how the operators behave in them. The results support the concept of our sampling schedule, that relevant information about the production areas can be gathered with relatively little effort. Evaluating the programme, we conclude that the main missing element is a known relation between the results of environmental monitoring and contamination of products. We strongly advocate research that could result in establishing such a relation.