The purpose of the cleaning validation is to verify that the cleaning procedures of a plant and of an equipment ensure that it does not occur a contamination. Cleaning validation is part of Annex 15 of the European GMP.
Contaminations can be of this type:
Cleaning validation should not be confused with cleaning verification. Cleaning verification is an on-time check in order to continue the production in the absence of a cleaning validation. Cleaning verification is carried out by means of a swab analysis which certifies the cleanliness of the equipment at that particular time. In the long term, cleaning verification leads to an increase in costs and time (swabs and analysis are needed at the end of each production run).
The first aspect to be considered is that cleaning validation must consider the equipment and its processes as a whole.
The protocol must contain the following information
DETECTION AND ANALYSIS
There is no specific number of batches after which testing should be carried out, we speak of an “adequate number”, generally 3 is considered acceptable.
Microbiological analysis requires 5 days incubation to obtain full results. Preliminary results can also be obtained after 2 or 3 days, but these must then be confirmed and depend on the microorganisms present (the various types have different culture media that require different preparation and incubation phases).
Chemical analysis (HPLC – High Performance Liquid Chromatography) provides results within a day, but these results then have to be re-processed.
The results of the verifications have to be inserted in a report. If the results are compliant all is well, in the case of non-compliant results an analysis is carried out.
The non-compliance is analysed and a corrective action is started.
When everything is in compliance, it is declared that the procedure ensures proper cleaning and the production can begin.
Replacement of equipment parts or detergents
If you replace a part of the equipment in like-for-like modality, the cleaning validation is still valid, but you have to do the initial cleaning verification (because it comes from the factory) and a microbiological verification.
If I add a new part in the equipment, the cleaning validation has to be done again. The validation must be done on the new component and the results added to those of the rest of the equipment (a recalculation is performed with a general re-evaluation of the validation status and it is checked that the new element does not cause the global result to exceed the expected limit).
Change of processed products or detergents used for cleaning
If I change the products processed by the equipment or the detergents used for washing, I have to update the matrix and if the product I insert is less dangerous than the one I replace, then the cleaning remains valid. Otherwise, I have to do the cleaning validation again.
Example: I have to produce a new drug, I do production, sampling and analysis. While I am waiting for the results, I carry out a cleaning verification in order to proceed with the production of other batches. If these other batches are of products already verified in the cleaning, I do not have to do anything after their normal production and subsequent washing.
Note carefully: sometimes the same machinery may have different washing procedures depending on the productions carried out. Some productions may need acidic washing detergents and others may need basic detergents, so there will be different procedures and all of them will need to be properly checked.