Global Product Quality, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD, 20878, USA.
Global Regulatory Affairs CMC, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
J Pharm Sci. 2024 Apr;113(4):837-855. doi: 10.1016/j.xphs.2024.01.006. Epub 2024 Jan 25.
To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.
为确保药品的质量、安全性和疗效，有必要制定并执行适当的生产工艺和产品控制策略。传统上，产品控制策略侧重于测试已知的质量属性，并设定源自临床前和临床研究中给药水平的限度，同时进行相关的统计分析以考虑变异性。然而，并非所有质量属性都会对患者产生影响，而那些有可能影响安全性和疗效的属性，在以患者为中心的剂量水平下可能并不显著。因此，实现以患者为中心就是要了解患者的相关性，这是指质量属性在潜在暴露范围内对安全性和疗效可能产生的影响程度。因此，以患者为中心的质量标准（PCQS）是一套与患者相关的属性及其相关的可接受范围，药物产品应在预期的患者暴露范围内符合这些属性和范围。本文描述了历史观点，并详细介绍了在各种药物产品模式下创建和利用 PCQS 的方法。
