MA Guideline published in 2014[1] and PDA TR49[2] clarify some cleaning validation aspects for therapeutic macromolecules. But they don’t bring a clear position on acceptance criteria  definition.

Based on scientific rational arguments, biotechnological Process is considered as a “self cleaned” process because many purification steps are performed to remove process impurities as well as degradation products generated by the cleaning process. According to this principle, ICH Q7[3], defining GMP requirements for cleaning validation for API, states that no validation is  requested for the early steps of the process if the effectiveness of purification is demonstrated.

However, no identification of degradation products following cleaning is generally performed to confirm that these specific impurities are removed during the downstream process. In these conditions, it is not possible to definitively conclude on the level of acceptable limit in residues on the surface of manufacturing equipment after cleaning.

Reasonable justifications must be provided if different acceptance criteria are applied for equipment used for the upstream and downstream phases of the manufacturing process and establish the clearance of degradation impurities in the drug substance.

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