4/13/22, 8:07 AM NOEL and MACO Calculations in Cleaning Validation : Pharmaceutical Guidelines

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NOEL and MACO Calculations in Cleaning Validation

Calculations of NOEL and MACO, those are important factors in cleaning validation of pharmaceutical equipments.

NOEL is “No Observed Effect Level” of any pharmaceutical drug. It is determined

to calculate the MACO (Maximum Allowable Carry Over) in
cleaning validation. NOEL
is the amount of drug in mg that does not have any effect on the human health.

NOEL is calculated by using Lethal Dose 50 (LD50) of the

drug. Lethal Dose 50 is the amount of drug that kills the 50% population of the
animals
used in the test.

NOEL = (LD50 x 70kg)/2000

Where,
LD50 – Lethal Dose
70kg – Average adult weight
2000 – Constant
For Example: If any drug has LD50 331 mg/kg, then its NOEL will
be calculated as below.
NOEL = 331x70/2000
= 23170/2000
= 11.58 mg

Related: Cleaning Validation in Pharmaceuticals

Now this value of NOEL is used to calculate the MACO (Maximum Allowable
Carry Over)
MACO = (NOEL x MBS)/ (SF x TDD)

Where,
MBS – Maximum Batch Size
SF – Safety Factor (1000 for oral drugs)
TDD – Total Daily Dose of Next Product

For Example: If Total Daily Dose of the next product is 500 mg and batch size is 400 kg then MACO can be calculated as below.
MACO = (11.58 mg x 400000000 mg)/(1000 x 500 mg)  -------- 400 kg = 400000000 mg
= 4632000000/500000
= 9264 mg
= 9.264 gm

Related: Cleaning Validation Sample Protocol

It shows that the drug with 331 mg/kg LD50 should not be
carried over more than 9.264 gm in next batch having 500 mg daily dose and 400
kg batch
size. This criterion is used to calculate the cleaning validation
limits.

Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read
pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.

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