APIC 201405原料药厂清洁验证指南：4.0可接受标准

inter-individual variability based upon a PK (kinetic component) of 2.54 and PD of 3.2 (dynamic component)). The MF is 10 (extrapolation from a ‘generally healthy’ population to a more susceptible sick patient population). Product B is an oral product (PK = 1).

A产品NOAEL70kg人类口服剂量为100mg/天，用于计算ADE的不确定因子UFS为3（从急性剂量到亚慢性/慢性给药外推得到），UFH为8.13（根据PK（动力学组成）为2.54和PD为3.2（动力学组成）所得的内在个体变化）。MF为10（从“一般健康”人群外推至易感人群）。 产品B为口服产品（PK = 1）.

100（mg/day） ADE = 3×8.13×10×1

= 410（μg/day） Result: ADE oral is 410 μg/day

结果：口服ADE值为410μg/天

If product B is a parenteral product and the PK is 62.5 (based upon an oral bio-availability study in human after parenteral).

如果产品B是一个注射产品，PK值为62.5（基于人体注射后的口服生物利用度研究）

100（mg/day） ADE = 3×8.13×10×62.5

= 6.6（μg/day） Result: ADEparenteral is 6.6 μg/day 结果：注射ADE值为6.6μg/天

Example 2: ADE calculation 例2：ADE计算

A teratogenic product A has a LOAEL of 1 mg/kg.day human oral dose (BW is 70 kg). Uncertainty factors applied to calculate the ADE are an UFL of 3 (extrapolation from LOAEL to NOAEL), an UFH of 10 (the inter-individual variability) and a MF of 10 (severity of effect: teratogenicity). Product B is an oral product (PK = 1).

1（mg/kg day）× 7ADE = 0kg 3×10×10×1 Result: ADEoral is 231μg/day. 结果：口服ADE值为231μg/天。

= 231（μg/day）

Example 3: Acceptance criteria based on Acceptable Daily Exposure 例3：根据可接受日暴露值计算可接受标准

Product A will be cleaned out. The product has an ADE of 2 mg and the batch size is 200 kg. The next product B has a standard daily dose of 250 mg and the batch size is 50 kg. Calculate the MACO for A in B. 产品A要被清洁，其ADE值为2mg，批量为200kg。 下一产品B标准日剂量为250mg，批量为50kg。 计算A在B中的允许最大残留量。

0.002（mg）× 50 000 000 (mMACO = g) 250 (mg) Result: MACO is 0.4g (400mg).

结果：允许最大残留值为0.4g（400mg）。

= 400(mg)

Example 4: Acceptance criteria based on Therapeutic Daily Dose 例4：根据日治疗剂量计算可接受标准

Product A will be cleaned out. The product has a standard daily dose of 10 mg and the batch size is 200 kg. The next product B has a standard daily dose of 250 mg and the batch size is 50 kg. Both A and B are administrated orally and SF is set to 1000. Calculate the MACO for A in B. 产品A要被清洁，其标准日剂量为10mg，批量为200kg。 下一产品B标准日剂量为250mg，批量为50kg。 A和B都是口服摄入，安全系数SF设定为1000。 计算A在B中的最大允许残留量MACO。

10（mg）× 50 000 000 (mg) MACO = 1000 × 250 (mg) Result: MACO is 2g (2000mg).

结果：允许最大残留值为2g（2000mg）。

= 2000(mg)