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
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.
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What approach shall be adopted in case of MACO value is less than LOQ?
ReplyDeleteConcentrate samples of rinsing water by evaporation in 5, 10, 20 ... times to achieve a measurable value
Deletethen, use LOQ as limit, and justification is the limitation of instrument used
DeleteHow i can do cleaning validation for Topical formulations, Is there any procedures?
ReplyDeleteMBS stands for minimum batch size of the subsequent product if i am not wrong
ReplyDeleteyes, MBS in here means batch size for following product, following product means product which will be produced in that equipment after cleaning procedure has been performed in that equipment
DeleteMBS Means Maximum Batch Size
DeleteMBS stands for Minimum Batch Size
ReplyDeletethe problem in this approche i mean application of toxicological data is critical because we dont have a real toxic dose date of APIs human vody
ReplyDeleteHow to calculate MACO for drug substance.
ReplyDeleteTThanks andregards, A. Prabhakar
hi,
ReplyDeleteregarding B.Size, 400kg is considered but this comprises both API & excipients,to my knowledge we need to consider 500mg X NO. Of tablets, then it gives the whole API quantity in the minimum b.size.
what do you say, replay is awaited.
What a safety factor practically mean and why it is needed to use in formulas.Elaborate safety factor in general sense for better understanding.
ReplyDeleteSir all your blogs are beneficial. Concise and easy to understand. Could you please launch a certificate course on cleaning validation studies?
ReplyDeleteAverage Adult weight is taken as 70kg. Is there any article from regulatory agencies for the average weight consoderations.
ReplyDeleteWhat is the case if we dont know what our next product is. It will be common in pilot plant or clinical trail manufacturing facilities. How can we handle MACO calculations if we dont know the Minimum batch size of next product.
ReplyDelete