Hi, I’m work in a Manufacturing companies, cephalosporin powder injection.
Now, write a SOP to cleaning validation.
the Detergents used Sodium lauryl sulfate (SLS)
the matter is Cephalosporin powder injection production,
I wanna to question that: the LD50 of SLS Intravenous products?
Or How to Calculation MACO the SLS?
thanks ands best regard!
You can calculate the MACO as per APIC’s “Guidance on aspects of cleaning validation in active pharmaceutical ingredient plants”, dated December 2000. As per this guide,
MACO = NOEL (of SLS) * maximum BS (of next product) / (safety factor) * Daily dose (of next product)
Here, NOEL = LD50 * 70 kg (adult average weight) / 2000 (empirical factor)
LD50 of SLS is 1288 mg / kg
Then, NOEL = 45.08 mg
Let us assume that batch size of next product is 10 litres and its concentration is 1%. It means 100 g of API can be used in next product. Each 1 ml of next product contains 10 mg of API. If 1 ml (of next product) is injected twice a day, then maximum daily dose of next product = 20 mg
So, MACO = (45.08 mg * 100 g) / 10000 (safety factor for injectables) * 20 mg = 22.54 mg
If the product contact surface area of the entire manufacturing line is 100 square feet, then the swab limit = 22.54 mg / 100 sft = 225µg / sft
Thanks for your help.
but this case is SLS used clean for equiment to manufacture drugs powder injection (intravenous)
because LD50 of SLS is another number. 1288mg/kg is oral product.
1288 mg/kg/oral for mice (animal studies)
This value can be used to calculate the NOEL for human beings by applying an empirical factor of 2000.
And, the risk level is decreased by applying suitable safety factor (10000 for intravenous use, 1000 for oral use and 100 for topical use)