Follow
Cleaning Validation is typically performed according to a master validation plan (Cleaning Validation Plan) that will guide the cleaning validation approach and dedicated Cleaning Validation Protocols in which all the relevant cleaning procedures, equipment, areas, analytical methods, sampling plan and acceptance limits will be reported.
Cleaning Validations are conducted by sampling the product contact surfaces with several techniques that can be contact plates, swabs and rinsing. The suitability of the sampling methods must be properly verified before their application, in order to demonstrate their capability to recover residues from product contact surfaces and for all the type of materials of which they are made of. The validation of sampling technique is usually included in the analytical method validation.
Analytical methods for Cleaning Validation can be specific or a specific, depending on their capability to specifically detect the residue (i.e. HPLC, UV/VIS, etc.) or not (i.e. TOC, conductivity, etc.). As for sampling technique, analytical methods must be verified or validated for their intended use, depending on their complexity and according to the current ICH requests. Minimum requirement for analytical methods’ verification are selectivity, sensitivity and repeatability; further parameters may be necessary depending on the type of technique and intended use (i.e. qualitative or quantitative)
The acceptance limits can be calculated by applying different approaches (i.e. maximum dose and maximum ppm), but starting from the EMA turning point in 2014, the toxicity of the active substances (PQE, ADI or HBEL) must also always be considered and the calculated limit must be compared with that obtained by applying traditional approaches. From a worst-case perspective, the most restrictive limit obtained must be applied. How selecting the worst case product.
