5.5.1 The following approaches shall be considered for setting acceptance criteria and analytical method limitation.
5.5.1.1 Visual criteria:
Equipments shall be visually cleaned and no traces of previous product residue should appear on equipment surface.
5.5.1.2 Dose criteria:
Not more than 1/1000th dose of the previous product in Maximum Daily Dose (MDD) of next product.
5.5.1.3 10 ppm criteria:
Not more than 10 ppm of any product will appear in another product.
5.5.2 When existing commercial products in the processing line is less and individual product cleaning validation is possible then cleaning validation is carried out individually and limit so obtained for individual product shall be considered for the individual cleaning validation.
5.5.3 In case of worst case approach, a marker product is selected based on worst case senerio form the existing commercial products in the processing line and the limit so obtained shall be considered for the cleaning validation.
5.5.4 The limit is obtained based on the dose criteria/ l0 ppm criteria from the matrix and the product is identified based on the solubility, Therapeutic dose and Toxicity. More than one product may be selected as worst case.
5.5.5 The following points shall be considered for cleaning validation matrix and also in case of product containing more than one API (active Pharmaceuticals ingredient)
5.5.5.1 Solubility
5.5.5.2 Strength
5.5.5.3 Toxicity
5.5.5.4 Maximum Daily Dose (MDD)
5.5.5.5 Batch size
5.5.5.6 Total surface area of equipments
5.5.5.7 Product list
5.5.5.8 Lower composition among the ingredients (Active and Color).
5.5.6 Matrix shall be prepared for the existing commercial products in the module/line and the limit so obtained shall be considered for the cleaning validation.
5.5.7 When a new product (Exhibit and Commercial) is included, check for the change in marker product status and the limit. If any change is observed in the acceptable limit and marker product, then the below cases apply.
Case-I:
If there is no change in acceptable limit and the marker product, then existing cleaning methods are valid. Hence there is no need of cleaning validation.
Case-II:
If there is a change in acceptable limit and no change in the marker product, then check for the LOQ details and the previous cleaning validation results. If the previous marker product results are failing with new limit, then the existing cleaning methods shall be reestablished and once again cleaning validation shall be repeated.
Case-III:
If there is no change in acceptable limit and there is a change in marker product, then cleaning validation shall be performed for the new marker product.
Case-IV:
If there is change in acceptable limit and change in marker product, then cleaning validation shall be performed for the new marker product.
Case-V:
When new marker Product is identified from the matrix then validation to be performed for new marker product and existing marker product.
5.5.8 When a new equipment (Exhibit and Commercial) is included, check for the change in marker product status and the limit due to change of surface area. If any change is observed in the acceptable limit and marker product, then the below cases apply.
Case-I:
If the new equipment installed is a replacement of existing equipment with same operating principle but small equipment capacity then the total surface area is considered same resulting no change in acceptable limit, then existing cleaning methods are valid. Hence there is no need of cleaning validation.
Case-II:
If the new equipment installed is a replacement of existing equipment with same operating principle but larger equipment capacity but if the increase of surface area is within the range of 3% additional surface area then the total surface area is considered same resulting no change in acceptable limit, then existing cleaning methods are valid. Hence there is no need of cleaning validation
Case-III:
If the equipment installed is a new equipment with same or different operating principle but larger equipment capacity and the increase of surface area is not within the range of 3% additional surface area then the total surface area will changed, resulting change in acceptable limit, In such case check for the LOQ details and the previous cleaning validation results. If the previous marker product results are failing with new limit, then the existing cleaning methods shall be reestablished and once again cleaning validation shall be repeated.
5.5.9 When a cleaning validation is performed for a single module is needs separation of modules due to use of different technique in new formulation. Eg if cleaning validation is performed for dry granulation and compression & coating together and when a new formulation is introduced with wet granulation, compression and coating. Then due to introduction of new formulation the cleaning validation module needs separation. Then matrix shall be prepared for dry granulation, wet granulation and compression differently. In such case, the below cases apply.
Case-I:
If the new product used wet granulation technique then the existing product validation for dry granulation compression and coating shall be considered for dry granulation and no separate cleaning validation is required for dry granulation. The same shall be concluded in cleaning validation matrix.