Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
Division of Modified Release Products, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
AAPS J. 2016 Nov;18(6):1406-1417. doi: 10.1208/s12248-016-9974-2. Epub 2016 Sep 20.
This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.
本文介绍了开发固体口服改良释放（MR）药物产品的科学和监管考虑因素。它包括基于质量源于设计（QbD）原则的以患者为中心的开发原理。MR 产品的产品和工艺理解包括对关键物料属性（CMA）、关键工艺参数（CPP）的识别和基于风险的评估，以及它们对影响临床性能的关键质量属性（CQA）的影响。强调了使用各种生物药剂学工具将 CQA 与可预测和可重现的临床性能联系起来，以造福患者。产品和工艺的理解导致了更全面的控制策略，可以通过整个货架期和药物产品的生命周期来维持产品质量。总体目标是开发能够持续满足临床目标的 MR 产品，同时通过降低 CQA 失效的概率和提高其可检测性来降低对患者的风险。
