Cleaning Validation

MACO Calculator & Complete Guide

Calculate Maximum Allowable Carryover using the three standard methods — dose-based, 10 ppm, and PDE/HBEL — and see which one governs your acceptance limit.

What Is MACO?

Maximum Allowable Carryover (MACO) is the maximum quantity of residue from a previously manufactured product that can be present in the next product without posing a safety risk to the patient. It is the central number in every cleaning validation acceptance criterion — everything else (swab limits, rinse limits, visual thresholds) is derived from it.

Because a single facility may share equipment across several products, MACO must be calculated for every relevant product pair, and the most restrictive value across all applicable methods is the one that governs the acceptance criterion.

Method 1 — Dose-Based (1/1000th Criterion)

Limits carryover to no more than 1/1000th of the minimum therapeutic dose of the previous product, relative to the maximum daily dose of the next product.

MACO = (0.001 × MinDose_A × BatchSize_B) / MaxDailyDose_B

Method 2 — 10 ppm Criterion

Limits residue of the previous product to no more than 10 parts per million in the next product's batch.

MACO = 10 × BatchSize_B (mg, when batch size is in kg × 1000)

Method 3 — PDE / Health-Based Exposure Limit (HBEL)

The current preferred method (per EMA and PIC/S guidance), based on a toxicological Permitted Daily Exposure assessment of Product A, particularly important for potent or highly sensitizing compounds.

MACO = (PDE_A × BatchSize_B) / MaxDailyDose_B

Once MACO is known, it is converted to a practical swab limit or rinse limit based on the sampled surface area or rinse volume:

Swab limit (µg/swab) = (MACO / Total shared surface area) × Swabbed area Rinse limit (µg/mL) = MACO / Rinse solvent volume

Interactive MACO Calculator

Enter data for Product A (previous product, being cleaned off) and Product B (next product, manufactured after cleaning).

Product A — Previous Product

Minimum Therapeutic Dose (mg)

Used for dose-based method

PDE (µg/day)

From toxicological assessment

Product B — Next Product

Batch Size (kg)

Maximum Daily Dose (mg)

Equipment / Sampling

Total Shared Surface Area (cm²)

Swabbed Area (cm²)

Typically a 5×5 cm template

Dose-Based MACO (1/1000th criterion) —

10 ppm Criterion MACO —

PDE-Based MACO —

Governing (Most Restrictive) MACO

—mg

—

Swab Limit —

How to Read the Result

Situation	What It Means
PDE method governs	Toxicologically-driven limit — expected and preferred outcome for potent/low-dose actives
Dose-based method governs	Common for conventional, non-potent small molecules with a defined therapeutic dose
10 ppm method governs	Often a fallback ceiling; if it's the tightest, double-check PDE data is available and current

This tool is for engineering/educational estimation only. Final acceptance criteria must be established through a formally approved cleaning validation protocol, using a PDE/HBEL derived by a qualified toxicologist per current EMA and PIC/S expectations.