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MACO and NOEL Calculation for cleaning Validation

MACO and NOEL calculation have great importance in the pharmaceutical industries. NOEL refers to “No observed effect level” and MACO is a “Maximum allowable carry over”. NOEL is used to determine MACO during cleaning validation.

NOEL Calculation

NEOL is calculated by using LD50 and avg. Adult dose.

NEOL= LD50 x Avg. adult dose/ 2000

LD50 is a lethal dose (it may vary), consodered an adult’s avg. Weight is 70kg, and 2000 is content. For example, if an LD50 of any drug product is 250mg/kg. then NOEL calculation is

NEOL= 250×70/2000= 8.75mg.

MACO (or MAC) Calculation

Method 1:

If the MACO of previoud product in the next batch. the calculation is as follows:

In this equation, product A is previous product and product B is the next product by taking into consideration of therapeutic dosage of the drug product in which the API is used.

Method 2:

Second Method of calculation takes toxicological data into consideration. From NOEL value MACO is calculated as:

MACO and NOEL Calculation

MACO= NOELxMBS/ SFxTDD

Whereas NOEL is 8.75mg.
MBS is the Minimum batch size for the next product
SF is the Safety factor.
TDD is the largest normal daily dose for the product

For example: if the total daily dose of a product is 350mg and the batch size is 100 kg, our NOEL is 8.75 mg. then MACO can be calculated as follow:

MACO= 8.75(mg)x100000000/1000×350(mg)= 250mg or 0.25 gm.

Acceptance criteria

This is the value of allowable residue of the previous product in the next product. Since the residue of previous batch is a contamination in the next product, it is necessary to limit such carryover into the next product. The maximum limit that is permitted is called the MACO.

What NOEL and MACO prove:

By using NOEL and MACO, we can find out the quantity of a drug that can not be carried out over to the next batch. As studies above 250mg /kg LD50 should not be over 0.25gm in the next batch as per above the batch has 350mg daily dose and 100 kg batch size.

Scope of MACO in pharmaceuticals:

MACO and NOEL Calculation are widely used for determining acceptance criteria, cleaning levels, Determination of the amount of residue present, and cleaning validation protocol.

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