Kimanani E, Stypinski D, Curtis G, Stiles M, Heessels P, Logan S, Nelson K, St Germain E, Boswell G
MDS Pharma Services, Lincoln, Nebraska, USA.
J Clin Pharmacol. 2000 Oct;40(10):1102-8.
The new FDA Guidance for Industry BA and BE Studies for Orally Administered Drug Products--General Considerations and Average, Population, and Individual Approaches to Establishing Bioequivalence imply significant changes in the areas of enrollment, cost, ethics, time, entry, validation applications (EVAs), and statistical and pharmacokinetic methods. The changes from three-period to two-period design for food effect studies, the elimination of most steady state studies, and the analyses of only the active moiety or ingredient are welcome. However, if the current guidances are adopted, additional time will be needed for participants, and more participants will be needed, resulting in higher costs to drug developers. The PK parameters needed to assess BE and the need for replicate designs for drugs with long t1/2 are still unclear. Finally, the advantages of the aggregate property of the FDA metric versus the disaggregate criteria are challenged, and four bioequivalence criteria are proposed.
美国食品药品监督管理局（FDA）发布的关于口服药品生物利用度和生物等效性研究的新行业指南——一般考虑因素以及建立生物等效性的总体、群体和个体方法，意味着在受试者招募、成本、伦理、时间、进入方式、验证性申请（EVA）以及统计和药代动力学方法等领域将发生重大变化。食物影响研究从三期设计改为两期设计、取消大多数稳态研究以及仅对活性部分或成分进行分析，这些变化是值得欢迎的。然而，如果采用当前的指南，受试者将需要更多时间，并且需要更多的受试者，这将导致药物研发成本增加。评估生物等效性所需的药代动力学参数以及长半衰期药物重复设计的必要性仍不明确。最后，FDA指标的总体属性相对于分解标准的优势受到质疑，并提出了四种生物等效性标准。
