Validation of Cleaning Processes
- As a general concept, until the validation of the cleaning procedure has been completed, the product contact equipment should be dedicated.
- In a multi-product facility, the effort of validating the cleaning of a specific piece of equipment which has been exposed to a product and the cost of permanently dedicating the equipment to a single product should be considered.
- Equipment cleaning validation may be performed concurrently with actual production steps during process development and clinical manufacturing. Validation programs should be continued through full scale commercial production.
- It is usually not considered acceptable to test-until-clean. This concept involves cleaning, sampling, and testing with repetition of this sequence until an acceptable residue limit is attained.
- Products which simulate the physicochemical properties of the substance to be removed may be considered for use instead of the substances themselves, when such substances are either toxic or hazardous.
- Raw materials sourced from different suppliers may have different physical properties and impurity profiles. When applicable such differences should be considered when designing cleaning procedures, as the materials may behave differently.
- All pertinent parameters should be checked to ensure the process as it will ultimately be run is validated. Therefore, if critical temperatures are needed to effect cleaning, then these should be verified. Any chemical agents added should be verified for type as well as quantity. Volumes of wash and rinse fluids, and velocity measurements for cleaning fluids should be measured as appropriate.
- If automated procedures are utilized (Clean-In-Place: CIP), consideration should be given to monitoring the critical control points and the parameters with appropriate sensors and alarm points to ensure the process is highly controlled.
- During a campaign (production of several batches of the same product), cleaning between batches may be reduced. The number of lots of the same product which could be manufactured before a complete/ full cleaning is done should be determined.
Validation of cleaning processes should be based on a worst-case scenario including:
challenge of the cleaning process to show that the challenge soil can be recovered in sufficient quantity or demonstrate log removal to ensure that the cleaning process is indeed removing the soil to the required level, and
the use of reduced cleaning parameters such as overloading of contaminants, over drying of equipment surfaces, minimal concentration of cleaning agents, and/or minimum contact time of detergents.
- At least three (3) consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated. Equipment which is similar in design and function may be grouped and a worst case established for validation