There are no direct specifications for the inspection within the framework of microbiological monitoring, but it is expected to be carried out based on the identified risks. This involves evaluating the sources of contamination in terms of their potential impact.
EU Guidelines for Good Manufacturing Practice (GMP) for Medicinal Products for Human and Veterinary Use define:
- Part 1, Chapter 3: Premises and Equipment, 3.11 “Drains should be of adequate size, and have trapped gullies. Open channels should be avoided where possible, but if necessary, they should be shallow to facilitate cleaning and disinfection.”
- Part II: Basic Requirements for Active Substances used as Starting Materials, Section 4.24 “Drains should be of adequate size and should be provided with an air break or a suitable device to prevent back-siphonage, when appropriate.”
The GMP for sewage and refuse state that sewage, trash, and other refuse in and from the building and immediate premises must be disposed of in a safe and sanitary manner. Companies should have written procedures to ensure that sewage and refuse are properly removed and disposed of. Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture.
In other areas air breaks should be fitted between the machine or sink and the drains. Floor drains in lower grade clean rooms should be fitted with traps or water seals to prevent backflow. Checking the drains may be useful to verify the effectiveness of the disinfection process. In the outer area (on the room side on the floor above the closures), this could be considered as a potential “worst case” by sampling the surface. In this case, frequency and limit values depend on the risk of the processed dosage form and thus the cleanroom class (monitoring programme).
An inspection inside the drainage system can certainly be carried out with the aim of checking the effectiveness of the disinfection step. This also raises the question of the limit value that would have to be set for this. If the drain construction is not suitable due to design or damage (closability, backflow, ventilation, disinfectability), this should be corrected if possible. Open drains should be avoided per se. Otherwise, this risk point would have to be considered in the monitoring, accordingly. Floor areas are in any case rather rarely the subject of monitoring due to their indirect potential influence. The risk assessment for determining the monitoring programme should take this into account. Examination of the inner sides of (closed) drains is normally not necessary. However, it can be helpful for root cause investigation in the context of investigations of out of specification results on batches or in the case of deviating/abnormal monitoring results.