Normally only cleaning procedures for product contact surfaces of the equipment need to be validated. Consideration should be given to non-contact parts into which product may migrate. For example, seals, flanges, mixing shaft, fans of ovens, heating elements etc. Cleaning procedures for product changeover in the case of marketed products should be fully validated.
Generally, in the case of batch-to-batch production, it is not necessary to clean after each batch. However, cleaning intervals and methods should be determined.
Several questions should be addressed when evaluating the cleaning process. For example:
- At what point does a piece of equipment or system become clean?
- What does visually clean mean?
- Does the equipment need to be scrubbed by hand?
- What is accomplished by hand scrubbing rather than just a solvent wash?
- How variable are manual cleaning processes from batch to batch and product to product?
- What is the most appropriate solvent or detergent?
- Are different cleaning processes required for different products in contact with a piece of equipment?
- How many times need a cleaning process be applied to ensure adequate cleaning of each piece of equipment?
Cleaning procedures for products and processes which are very similar, do not need to be individually validated. It is considered acceptable to select a representative range of similar products and processes concerned and to justify a validation programme which addresses the critical issues relating to the selected products and processes. A single validation study under consideration of the “worst case” can then be carried out which takes account of the relevant criteria. This practice is termed “Bracketing”.
At least three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.
Raw materials sourced from different suppliers may have different physical properties and impurity profiles. Such differences should be considered when designing cleaning procedures, as the materials may behave differently.
Control of change to validated cleaning procedures is required. Revalidation should be considered under the following circumstances:
- Re-validation in cases of changes to equipment, products or processes.
- Periodic Re-validation at defined intervals.
Manual methods should be reassessed at more frequent intervals than clean-in-place (CIP) systems.
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. For the system or equipment with a validated cleaning process, this practice of “test until clean” should not be required. The practice of “test until clean” is not considered to replace the need to validate cleaning procedures.