基于BCS的普通口服固体常释制剂生物等效性试验豁免的量化风险评估

Quantitative Risk Assessment of Biowaiver for Immediate-release Solid Oral Dosage Forms Based on BCS Classification

建立了口服固体常释制剂的生物等效性试验豁免的量化风险评估方法。基于生物药剂学分类系统(BCS),利用鱼骨图找到生物豁免风险的影响因素并进行综合分析,利用量化指标的风险评价方法对风险因素进行综合评分,从而为生物豁免的风险和可行性进行分级。此量化风险评估方法基于科学与风险,为制药企业及监管部门的生物豁免决策提供了简单易行的风险分析工具。

A quantitative risk assessment method of biowaiver for immediate-release solid oral dosage forms is established. Based on biopharmaceutics classification system （BCS）, fishbone analysis method is used to find the influence factors for biowaiver. Influence factors are analyzed synthetically and given different weight assignments according to their influence degree to biowaiver risk, which are multiplied by the property value to get the biowaiver risk score. Eight points are defined as high risk factors, while 4--6 points are medium risk factors, and 1--3 points are low risk factors. A model of ranking biowaiver risk and feasibility is established according to different risk factors combination. Levofloxacin, nifedipine and other 8 kinds of pharmaceutics in FDA ＂Bioequivalence Recommendations for Specific Products＂ are analyzed and ranked using this quantitative risk assessment model, the conclusions are consistent with FDA＇s recommendations. This quantitative risk assessment is based on science and risk, and provides a simple and easy risk analysis method for the biowaiver decision in pharmaceutical companies and regulators.