Biopharmaceutics Group, Global Clinical Management, Integrated Product Development Organization (IPDO), Dr. Reddy's Laboratories Ltd, Bachupally, Medchal Malkajgiri District, Hyderabad-500 090, Telangana, Hyderabad, India.
AAPS J. 2023 Jul 27;25(5):77. doi: 10.1208/s12248-023-00837-y.
Quality risk assessment following ICH Q9 principles is an important activity to ensure optimal clinical efficacy and safety of a drug product. Typically, risk assessment is focused on product performance wherein critical material attributes, formulation variables, and process parameters are evaluated from a manufacturing perspective. Extending ICH Q9 principles to biopharmaceutics risk assessment to identify factors that can impact in vivo performance is an upcoming area. This is evident by recent regulatory trends wherein a new term critical bioavailability attributes (CBA) has been coined to identify such factors. Although significant work has been performed for biopharmaceutics risk assessment for new molecules, there is a need for harmonized biopharmaceutics risk assessment workflow for generic submissions. In this manuscript, we attempted to provide a framework for performing biopharmaceutics risk assessment for generic regulatory submissions. A detailed workflow for performing biopharmaceutics risk assessment includes identification of initial CBA (iCBA), their confirmatory evaluation followed by definition of the control strategy. Tools for biopharmaceutics risk assessment, i.e., bio-discriminatory dissolution method and physiologically based biopharmaceutics modeling (PBBM) were discussed from a practical perspective. Furthermore, a case study for CBA evaluation using PBBM modeling for an extended-release product for regulatory submission has been described using the proposed workflow. Finally, future directions of integrating CBA evaluation, biopharmaceutics risk assessment to the FDA Knowledge Aided Structured Assessment (KASA) initiative, the necessity of risk assessment templates, and knowledge sharing between industry and academia are discussed. Overall, the work described in this manuscript can facilitate and provide guidance for biopharmaceutics risk assessment for generic submissions.
ICH Q9 原则下的质量风险评估是确保药物产品最佳临床疗效和安全性的重要活动。通常，风险评估侧重于产品性能，从制造角度评估关键物料属性、配方变量和工艺参数。将 ICH Q9 原则扩展到生物药剂学风险评估，以确定可能影响体内性能的因素，是一个即将到来的领域。最近的监管趋势证明了这一点，其中引入了一个新术语“关键生物利用度属性（CBA）”来识别这些因素。尽管已经为新分子的生物药剂学风险评估进行了大量工作，但需要为仿制药提交制定协调一致的生物药剂学风险评估工作流程。在本文中，我们试图为仿制药监管提交提供执行生物药剂学风险评估的框架。执行生物药剂学风险评估的详细工作流程包括识别初始 CBA（iCBA），对其进行确认性评估，然后定义控制策略。从实际角度讨论了生物药剂学风险评估工具，即生物区分性溶出度方法和基于生理的生物药剂学建模（PBBM）。此外，还使用提出的工作流程描述了使用 PBBM 建模对仿制药监管提交的缓释产品进行 CBA 评估的案例研究。最后，讨论了将 CBA 评估、生物药剂学风险评估纳入 FDA 知识辅助结构化评估（KASA）倡议、风险评估模板的必要性以及行业和学术界之间知识共享的未来方向。总体而言，本文描述的工作可以促进和为仿制药提交的生物药剂学风险评估提供指导。
