Calculating MAC in Cleaning Validation

For shared equipment, the key question in cleaning validation is: how much residue can be carried over from one product to the next at most? This value is called MAC (Maximum Allowable Carryover) or MACO and is the basis for all acceptance criteria.

Health-based limits (HBEL)

With EMA's guideline on health-based exposure limits for shared facilities, limits are expected to be derived from PDE (Permitted Daily Exposure) values based on toxicological data. The basic calculation is:

MACO = (PDE_{previous product} × MBS) / TDD_{next product}

• PDE: permitted daily exposure for the active substance of the previous product (mg/day)
• MBS: minimum batch size of the next product (mg or units)
• TDD: maximum daily dose of the next product (in the same unit)

The classic "1/1000 of the dose" and "10 ppm" criteria can still be used as an additional safety check, but they are no longer accepted as a justification on their own.

Converting to a surface limit

The calculated MACO is divided by the shared product-contact surface area to give a limit per unit area; multiplying this by the swab area gives the acceptance criterion per sample. Results from recovery studies must be reflected in this criterion.

Swab or rinse?

Swab sampling allows samples to be taken directly from the hardest-to-clean (worst-case) locations. Rinse sampling represents large, closed or hard-to-reach surfaces. In most cases, using both methods together with a justified sampling plan is the most robust approach.

Points to watch in the sampling plan

• Worst-case locations defined on a risk basis and documented with photographs
• A separate recovery study for each surface material
• Verification of dirty hold and clean hold times
• Assessment of detergent residues and microbiological limits as well