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Cleaning Validation MACO Calculator (Maximum Allowable Carryover)

Maximum allowable carryover (MACO) is the largest amount of a previous product residue that can end up in the next product without risk. This calculator applies the classic 0.001 dose and 10 ppm criteria and, if you have it, an ADE or PDE, then turns the lowest limit into a swab limit your QC lab can test.

Your numbers

Previous product: smallest therapeutic daily dose

Lowest normal daily dose of the product you are cleaning away.

Next product: smallest batch size

Smallest batch size of the next product made on the shared train.

Next product: largest daily dose

Maximum daily dose of the next product, in the same dose basis.

Safety factor

ADE or PDE of previous product (0 if not used)

mg/day

Health based limit from a toxicologist. Leave at 0 to ignore the ADE criterion.

Shared equipment surface area

cm2

Swab area

cm2

Commonly 5 cm x 5 cm.

Swab extraction volume

Swab recovery factor

80 %

From your recovery study. Many sites require at least 70 to 80 percent.

Your results

Lowest MACO (limiting)

2,000

mg allowed to carry over, the lowest of the applicable criteria.

Limit per swab

mg of residue allowed on one swab area.

Next batch size in mg

200,000,000

MACO by 0.001 dose criterion

4,000

mg of previous product allowed in the next batch.

MACO by 10 ppm criterion

2,000

10 ppm means 10 mg per kg of next batch.

MACO by ADE criterion

ADE x next batch (in mg) / next max daily dose. Zero when not used.

Surface limit

0.04

mg per cm2 of shared equipment.

Target conc. in extract (recovery adjusted)

ug per mL the lab should be able to quantify at the limit.

Screening calculation. Acceptance limits for your products must be approved in your cleaning validation protocol and, for health based limits, supported by a documented toxicological assessment (ISPE, EMA and PIC/S guidance). The 0.001 dose and 10 ppm criteria are historical; EU GMP Chapter 3 and 5 and the EMA guideline expect health based exposure limits.

Save results:

Lowest MACO vs next batch size

Sweeps Next product: smallest batch size from 20 to 1000, holding your other inputs fixed.

Worst case product matrix from ERP data

An optional outline for building a changeover and worst case product matrix from your product and routing master data.

Optional. The tool and every export work without this. No spam.

How to use the calculator

Enter the previous product's smallest daily dose, the next product's smallest batch size and largest daily dose, then the shared equipment surface area. Add an ADE or PDE if toxicology has set one. Enter your swab area, extraction volume and the recovery factor from your recovery study. Read the primary results: the lowest MACO, the limit per swab and the concentration the analytical method must be able to detect. Change batch size to see the sensitivity on the chart.

Use the worst case product pair, not an average one
Keep dose units identical for both products
Use the smallest next batch and the largest next daily dose
Use total shared surface area of the equipment train

The formulas

Dose criterion: MACO = (lowest daily dose of previous product x smallest next batch size) / (safety factor x largest daily dose of next product). The 10 ppm criterion: MACO = 10 mg per kg x next batch in kg. Health based: MACO = ADE x next batch in mg / largest daily dose of next product in mg. The limiting MACO is the lowest value. Surface limit is MACO divided by shared surface area, and the swab limit multiplies by swab area. The extract concentration adjusts the swab limit for recovery.

Worked example

Previous dose 10 mg, next batch 200 kg (200,000,000 mg), next maximum dose 500 mg, safety factor 1000. The dose criterion gives 10 x 200,000,000 / (1000 x 500) = 4,000 mg. The 10 ppm criterion gives 2,000 mg. The lowest, 2,000 mg, over 50,000 cm2 is 0.04 mg per cm2, so a 25 cm2 swab may carry 1.0 mg. With 80 percent recovery and 10 mL extract the target concentration is 80 ug per mL. Such high limits show why modern practice favours ADE based limits.

Common mistakes

Frequent errors are mixing mg and g, using the previous product's batch size instead of the next, ignoring detergent residues, and forgetting that visibly clean is a separate criterion. Equipment-specific limits should account for the surface area of the smallest shared train when only part of it is used. In ERP master data, link equipment trains and product campaigns so planners cannot schedule an unvalidated product changeover.

Frequently Asked Questions

What is the 10 ppm criterion?

It limits carryover so that no more than 10 parts per million of the previous product, 10 mg per kg, appears in the next product. It is a general limit that does not depend on pharmacology, so it is applied together with a dose or health based limit.

Is MACO still acceptable under current EU rules?

The EMA guideline on shared facilities expects health based exposure limits (PDE or ADE) based on toxicology. The 0.001 dose and 10 ppm criteria can still appear as additional limits, but are no longer enough alone as the primary justification.

How do I pick the worst case product?

Rank candidates by lowest ADE or lowest dose, lowest solubility, hardest to clean and highest potency. Validate the product that is the worst on those factors and justify bracketing the rest in a documented matrix.

Why does recovery matter?

Swabbing never picks up all residue. A recovery of 80 percent means the swab result understates the true residue, so the analytical result is divided by recovery or the limit is lowered. Low or variable recovery weakens the method.

If you need MACO worst case products identified from your ERP product and routing data, Netray can help build that analysis privately. The calculator itself needs nothing from us.

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