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The K/M formula was presented in the FDA LAL-Test guideline (1987) as a
way to calculate the endotoxin limit as shown below:
K(tolerance limit)
Endotoxin Limit (EL) =
M (maximum dose/kg/hour)
EXAMPLE
To calculate the endotoxin limit (EL) of a parenteral drug with a dosage (M) of
1.40 mL per kg per hour.
K 5 EU/kg 350 EU
EL (Endotoxin Limit) = = or
M M dosage
Product: A (injection)
Maximum Dose/kg (M): 1.40 mL/kg
K 5 EU/kg
EL (Endotoxin Limit) = = = 3.57 EU/mL
M 1.40 mL/kg
Or
K 350 EU
EL (Endotoxin Limit) = = = 3.57 EU/mL
M 98.0 mL
The MVC is used to determine the lowest concentration of sample that can be
tested while still being able to detect the required endotoxin limit. It is used
when the EL is listed in units, other than mL.
(λ )(M) λ
MVC = or MVC = EL
K
• Example 1
Product: A (injection)
Potency: 20 mg/mL
Maximum Dose/kg (M): 30 mg/kg
Lysate sensitivity (λ ): 0.0625 EU/mL
• Example 2
Product: B (injection)
Endotoxin Limit: 0.20 EU/mg
Lysate sensitivity (λ ): 0.05 EU/mL
(λ ) 0.05 EU/mL
MVC = = = 0.25 mg/mL
EL 0.20 EU/mg
Maximum Valid Dilution (MVD)
Two methods of calculating the MVD can be used (all examples given are for
a non-intrathecal parenteral drug and appropriate values have been utilised).
Method 1
units/mL and for drugs administered on a volume-per-kilogram basis, the potency is equal to
1.0 mL/mL.
(EL)(product potency)
MVD =
λ
Method 1 Examples
Product: A (Injection)
Potency: 20 mg/mL
Lysate Sensitivity (λ ): 0.0625 EU/mL
Endotoxin limit: 0.17 EU/mg
This method is used when no official endotoxin limit provided. It has two
steps.
(λ )(M) λ
MVC = or MVC = EL
K
Product potency
MVD =
MVC
Method 2 Examples
Product: A (injectable)
Potency: 20 mg/ml
Maximum Dose/kg (M): 30 mg/kg
Lysate sensitivity (λ ): 0.0625 EU/ml
Step 1
Step 2
Step 2