Maximum allowable carryover

Equipment is cleaned after a production batch. The maximum allowable carryover (MAC) of materials from one production batch to the next batch is given by the formula... 

The purpose is to validate the cleaning procedure and ensure that residues of previous product are removed in accordance with the maximum allowable carryover limit calculated, as well as other tests, i.e., visual inspection, pH, conductivity, and TOC. 

Acceptance criteria the active ingredient in the hnal rinse is not detected, equal to, or less than the maximum allowable carryover limit determined. 

Notes TOC = total organic carbon MAC = maximum allowable carryover. 

Finally, the maximum allowable carryover (MACO) can be calculated from the relationship... 

In simple terms, the limit or maximum allowable carryover of aproduct into the next product can be quantitatively established by the following relationship ... 

After the limits are calculated for all products that are to be processed and all equipment used, the limits are compared. The smallest limit calculated for a product using all of the calculations becomes the acceptance limit for the cleaning verification for that product. If product B, the lot to be manufactured next, is unknown at the time of manufacture of Product A, the worse case should be assumed in the calculation. For example, if the smallest lot that has ever been manufactured in the facility is 5000 dosage units, or alternatively 1 kg, those values should be used in the equation to generate a maximum allowable carryover of product A. To reiterate some of the initial points, the rationale for which equation is utilized should be documented, and the limits that are established should be practical, achievable, and verifiable based on the most deleterious residue. 

Residue/contamination limits can be determined in various ways although this can be the most challenging part of the validation. As outlined in PDA Technical Report No. 29, Points to Consider for Cleaning Validation,some commonly used approaches are to base the maximum allowable carryover (MAC) on... 

To assess acceptance criteria for cleaning validation, limits for the maximum allowable carryover of product residues must be calculated, based on the pharmacological or toxicological properties of the substances studied and their permitted daily exposure (see Sect. 26.7.2). A risk assessment may be useful to support choices and decisions. 

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