Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
J Pharm Sci. 2019 Sep;108(9):2824-2837. doi: 10.1016/j.xphs.2019.04.030. Epub 2019 May 3.
This article summarizes historic developments, recent expert opinions, and (currently) unresolved challenges concerning the Biopharmaceutics Classification System (BCS)-based Biowaiver. An overview of approval statistics and application potential, case examples addressing the discriminatory power of the procedure, as well as an outlook on possible refinements in the future are provided and critically discussed. Over the last decade, regulatory guidance documents have been harmonized, for example, following scientific consent on allowing biowaivers for BCS class III drugs, making over 50% of orally administered drugs on the World Health Organization Essential Medicines List eligible for an abbreviated approval. Biowaiver monographs that present a complete risk-benefit evaluation for individual drugs have been issued by the International Pharmaceutical Federation for more than 25% of those drugs with the long-range aim of covering all essential drugs. Unresolved issues that have emerged from reported examples of false-negative and false-positive outcomes in the literature demand further adjustments to the regulatory requirements. Possible solutions for resolving these issues are the use of modeling and simulation and refined biorelevant in vitro tests that are better able to discriminate between dosage forms with unequal performance in vivo, potentially allowing biowaivers for selected BCS II drugs.
本文总结了基于生物药剂分类系统（BCS）的生物豁免的历史发展、近期专家意见和（当前）尚未解决的挑战。提供并批判性地讨论了批准统计数据和应用潜力的概述、解决该程序区分能力的案例示例，以及对未来可能进行的改进的展望。在过去的十年中，监管指导文件已经得到了协调，例如，在科学上同意允许 BCS 分类 III 类药物的生物豁免后，世界卫生组织基本药物清单中超过 50%的口服药物有资格获得简化批准。国际制药联合会已经为超过 25%的具有长期目标的药物发布了生物豁免专论，为个别药物提供了完整的风险效益评估。文献中报告的假阴性和假阳性结果出现了一些未解决的问题，这要求对监管要求进行进一步调整。解决这些问题的可能方法是使用建模和模拟以及更能区分体内性能不等的剂型的改良生物相关体外试验，这可能允许对选定的 BCS II 类药物进行生物豁免。
