NOEL and MACO Calculations in Cleaning Validation : Pharmaceutical Guidelines

# 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
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

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

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.

1. What approach shall be adopted in case of MACO value is less than LOQ?

2. How i can do cleaning validation for Topical formulations, Is there any procedures?

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