药物压力测试中的质量平衡:原理与实际应用综述。

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Stacey Marden, John M Campbell, Neal Adams, Ronan Coelho, Chris Foti, Juçara Ribeiro Franca, Steven Hostyn, Zongyun Huang, Mariah Ultramari, Todd Zelesky, Steven W Baertschi
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引用次数: 0

摘要

对药物物质和药物产品进行压力测试(也称强制降解)是药物开发过程中的一个重要环节,可深入了解药物物质和药物产品的降解途径。这些信息用于支持稳定性指示方法 (SIM) 的开发,该方法能够检测在生产、长期储存、分销和使用过程中可能观察到的药物相关降解产物。评估受压样品的质量平衡是开发 SIM 的一个关键方面,也是监管部门的期望。然而,不同制药公司测量、计算和解释质量平衡的方法可能各不相同。这种差异也给卫生部门审查质量平衡评估带来了困难,可能导致药物申请审批的延误。作者收集了 10 家制药公司的意见,对评估和解释质量平衡结果的科学方法和技术细节进行了实用性审查。书中介绍了质量平衡的关键概念,演示了各种质量平衡计算方法,并通过实际案例研究提出了如何调查质量平衡不良结果的建议。在此,我们就小分子药物物质和药物产品在制药强制降解过程中的质量平衡这一主题提供了单一来源的参考资料,以支持监管呈件,目的是促进制药科学家和卫生当局之间的共同理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mass Balance in Pharmaceutical Stress Testing: A Review of Principles and Practical Applications.

Mass Balance in Pharmaceutical Stress Testing: A Review of Principles and Practical Applications.

Stress testing (also known as forced degradation) of pharmaceutical drug substances and products is a critical part of the drug development process, providing insight into the degradation pathways of drug substances and drug products. This information is used to support the development of stability-indicating methods (SIMs) capable of detecting pharmaceutically relevant degradation products that might potentially be observed during manufacturing, long-term storage, distribution, and use. Assessing mass balance of stressed samples is a key aspect of developing SIMs and is a regulatory expectation. However, the approaches to measure, calculate, and interpret mass balance can vary among different pharmaceutical companies. Such disparities also pose difficulties for health authorities when reviewing mass balance assessments, which may result in the potential delay of drug application approvals. The authors have gathered input from 10 pharma companies to map out a practical review of science-based approaches and technical details to assess and interpret mass balance results. Key concepts of mass balance are introduced, various mass balance calculations are demonstrated, and recommendations on how to investigate poor mass balance results are presented using real-world case studies. Herein we provide a single source reference on the topic of mass balance in pharmaceutical forced degradation for small molecule drug substances and drug products in support of regulatory submissions with the goal of facilitating a shared understanding among pharmaceutical scientists and health authorities.

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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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