Cleaning procedures should normally be validated, focusing on the steps where contamination or carry-over poses most risk to API quality (validation may be unnecessary early in the process where later purification removes residues). Validation should reflect actual equipment use; where several products share equipment and cleaning, a representative product can be chosen based on solubility, difficulty of cleaning and residue limits derived from potency, toxicity and stability. The protocol should describe the equipment, procedures, materials, acceptable cleaning levels, parameters monitored and controlled, analytical methods and the sample types and how they are taken and labelled. Sampling should use swabbing, rinsing or alternatives such as direct extraction to detect soluble and insoluble residues quantitatively, recognising that swabs may be impractical for hoses, pipes, small-port vessels and intricate equipment. Validated methods sensitive enough for the set residue level should be used, with recovery established and limits practical, verifiable and based on the most harmful residue, for example from the lowest known pharmacological, toxicological or physiological effect. Microbiological and endotoxin contamination should be addressed where relevant, such as non-sterile APIs used for sterile products. After validation, cleaning should be monitored at suitable intervals by analytical testing and, where feasible, visual inspection.
The graph holds this control, the 0 it maps to, and the evidence behind each claim, over MCP and REST.