Page 72 - Pharmaceutical Solution for Pharma Analysis

Application No.J99"
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Table 2 Calculation by Option 1: Maximum Permitted Common Concentration Limits of Elemental Impurities Across
Drug Product Components for Products with Daily Intake of Not More Than 10 Grams
Max. Permitted Concentration
Assuming a 10 g Max. Daily Max. Intake from Each
Component (μg)
Intake of Formulation (μg/g)
Max. Daily Intake
Component of Each PDE (μg) Max. Daily Intake (g) of Each
Substance Component × Max. Permitted
Substance (g) PDE/10 g
Concentration (μg/g) of Each
Component
Pb As Pb As Pb As
Drug substance 0.2 5 15 0.5 1.5 0.1 0.3
MCC 1.1 5 15 0.5 1.5 0.55 1.65
Lactose 0.45 5 15 0.5 1.5 0.225 0.68
Calcium phosphate 0.35 5 15 0.5 1.5 0.175 0.53
Crospovidone 0.265 5 15 0.5 1.5 0.133 0.4
Magnesium stearate 0.035 5 15 0.5 1.5 0.018 0.05
HPMC 0.06 5 15 0.5 1.5 0.03 0.09
Titanium oxide 0.025 5 15 0.5 1.5 0.013 0.04
Iron oxide 0.015 5 15 0.5 1.5 0.008 0.02
Max. Daily Intake (Total) 2.5 1.25 3.75
PDE (μg/day) 5.0 15

Table 3 Calculation by Option 2a: Maximum Permitted Common Concentration Limits Across Drug Product Component
Materials for a Product with a Specified Daily Intake (Assuming That Concentration Remains Constant)
Max. Permitted Concentration Max. Intake from Each
(μg/g) Component (μg)
Max. Daily Intake Max. Daily Intake (g) of Each
Component of Each PDE (μg) PDE/Max. Daily Intake of Component × Max. Permitted
Substance
Substance (g) Actual Drug (e.g. 2.5 g) Concentration (μg/g) of Each
Component
Pb As Pb As Pb As
Drug substance 0.2 5 15 2 6 0.4 1.2
MCC 1.1 5 15 2 6 2.20 6.6
Lactose 0.45 5 15 2 6 0.9 2.7
Calcium phosphate 0.35 5 15 2 6 0.7 2.1
Crospovidone 0.265 5 15 2 6 0.53 1.59
Magnesium stearate 0.035 5 15 2 6 0.07 0.21
HPMC 0.06 5 15 2 6 0.12 0.36
Titanium oxide 0.025 5 15 2 6 0.05 0.15
Iron oxide 0.015 5 15 2 6 0.03 0.09
Max. Daily Intake (Total) 2.5 5.0 15
PDE (μg/day) 5.0 15

Table 4 Calculation by Option 2b: Maximum Permitted Common Concentration Limits Across Drug Product Component Materials
for a Product with a Specified Daily Intake (Arbitrary Setting of Maximum Concentration Possible from Actual Value)
Max. Daily
Intake of Arbitrary Setting of Max.
Component Each PDE (μg) Measured Concentration Concentration Possible Max. Daily Intake of Each
Substance Value (μg) Componen (μg)
Substance from Actual Value (μg/g)
(g)
Pb As Pd Ni Pb As Pd Ni Pb As Pd Ni Pb As Pd Ni
Drug substance 0.2 5 15 100 200 ** 0.5 20 50 ** 5 500 200 ** 1 100 40
MCC 1.1 5 15 100 200 0.1 0.1 * ** 0.5 5 * ** 0.55 5.5 * **
Lactose 0.45 5 15 100 200 0.1 0.1 * ** 0.5 5 * ** 0.225 2.3 * **
Calcium phosphate 0.35 5 15 100 200 1 1 * 5 5 5 * 200 1.75 1.8 * 70
Crospovidone 0.265 5 15 100 200 0.1 0.1 * ** 0.5 5 * ** 0.132 1.3 * **
Magnesium stearate 0.035 5 15 100 200 0.5 0.5 * 0.5 5 10 * 50 0.175 0.4 * 1.75
HPMC 0.06 5 15 100 200 0.1 0.1 * ** 2.5 5 * ** 0.15 0.3 * **
Titanium oxide 0.025 5 15 100 200 20 1 * ** 40 20 * ** 1 0.5 * **
Iron oxide 0.015 5 15 100 200 10 10 * 50 20 100 * 200 0.3 1.5 * 3
Max. Daily Intake (Total) 2.5 4.3 14.5 100 115
PDE (μg/day) 5 15 100 200
*: Since it has been determined that there is no possibility of Pd being present, a quantitative result is not obtained.
**: Below the detection limit