University of Maryland School of Pharmacy, Baltimore, Maryland 21201, USA.
AAPS J. 2012 Sep;14(3):627-38. doi: 10.1208/s12248-012-9376-z. Epub 2012 Jun 9.
This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro-in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C (max) acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).
本总结研讨会报告重点介绍了 2011 年 10 月研讨会的演示文稿和总体主题。讨论的重点是在口服药物产品开发中应用生物药剂学的最佳实践以及不断发展的生物等效性方法。最佳实践利用生物药剂学数据以及其他药物、配方和患者/疾病数据，以确定在开发成功产品方面存在的药物开发挑战。还讨论了质量源于设计和产品可开发性范式。开发工具包括早期开发策略，用于确定关键吸收因素和口服吸收模型。一个持续的主题是希望通过质量目标产品概况以及根本原因和风险分析，全面系统地评估产品失败的风险。然而，还需要减少时间和资源。有几个演示文稿讨论了在开发中和开发后应用生物药剂学分类系统 (BCS) 和体内-体外相关性，以及讨论了资源节约和最佳科学实践。研讨会还重点关注了不断发展的生物等效性方法，强调了高变异产品 (HVDP) 以及特殊的缓释产品。在美国，针对 HVDP 的两种生物等效性方法是参比缩放平均生物等效性方法和两阶段分组序贯设计。在加拿大，适应性序贯设计方法也是可以接受的。在欧盟，针对 HVDP 有两种方法，一种是两阶段设计，另一种是扩大 C（max）接受限度的方法。对于某些特殊的缓释产品，FDA 现在要求部分曲线下面积。讨论了这些指标的原理和局限性（例如，唑吡坦和哌甲酯）。一个共同的主题是科学和监管界开发、验证和协调更新的生物等效性方法（例如，基于 BCS 的豁免和 HVDP 试验设计）的好处。
