2月15日周三，FDA发布了题为“二氟泼尼酯指南草案”（Draft Guidance on Difluprednate）的生物等效性修订版指南草案。在修订文件中，FDA声明“提供生物等效性研究的设计的具体指导，以支持二氟泼尼酯乳剂的简化新药申请（Abbreviated new drug applications，ANDAs）”。
背景
2008年，FDA批准了Durezol（二氟泼尼酯眼用乳液）的新药申请（New drug Application， NDA）。Durezol是一种“局部皮质类固醇，用于治疗与眼外科手术相关的炎症和疼痛以及治疗内源性前葡萄膜炎”。2016年1月，FDA发布了关于此药仿制药的最初版BE指南草案。
All 3 exhibit batches should be at least 1/10 the size of the commercial batch and the manufacturing process used for the 3 exhibit batches should be reflective of the process used for the commercial batch.
The manufacturing process for the exhibit batches should be reflective of the manufacturing process to be utilized for commercial batches.
I体外试验
测量参数有变化
Parameters to measure: Globule size distribution, viscosity profile as a function of applied shear, pH, zeta potential, osmolality, surface tension and drug distribution in different phases of the formulation.
Parameters to measure: Globule size distribution, viscosity profile as a function of applied shear, pH, zeta potential, osmolality, and surface tension. Sponsors should also submit information on the drug distribution in different phases within the formulation.
II体内试验
测量分析物有明显变化
Analytes to measure (in appropriate biological fluid): Difluprednate in aqueous humor
Analytes to measure (in appropriate biological fluid): Difluprednate and its active metabolite, 6α, 9-difluoroprednisolone 17-butyrate (DFB), in aqueous humor
II体内试验
生物等效性的判断有明显变化
Bioequivalence based on (90% CI): Difluprednate
Bioequivalence based on (90% CI): Difluprednate
Please submit DFB metabolite data as supportive evidence of therapeutic outcome. However,the DFB metabolite data will be subject to the CI approach for BE demonstration if you demonstrate that the difluprednate parent drug levels are too low to allow reliable analytical measurement.
参考资料：FDA Responds to Citizen Petition & Publishes Revised BE Recommendations for Difluprednate, THE WEINBERG GROUP, 2017-02-21.
