Clinical Development Division, Celltrion, Inc, Incheon, Republic of Korea.
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.
J Biopharm Stat. 2020 May 3;30(3):521-536. doi: 10.1080/10543406.2020.1726372. Epub 2020 Feb 23.
As indicated in a recent published draft guidance on comparative analytical assessment, the United States (US) Food and Drug Administration (FDA) seems to suggest the use of quality range (QR) method for analytical similarity evaluation. It is a concern that the use of QR method for analytical similarity evaluation could potentially approve biological products which are not deemed biosimilar to the reference biological products. In this article, the limitations and potential risk for the use of the QR method for analytical similarity evaluation are discussed. Alternatively, two modified versions of the QR method, which are referred to as effect size (ES) mQR and plausibility interval (PI) mQR methods are suggested. The performance and statistical properties of the mQR methods are evaluated via extensive clinical trial simulation under various scenarios. The results indicate that the modified versions of the QR method not only overcome the limitations of the QR method for analytical similarity evaluation, but also can potentially help in detecting reference product changes during manufacturing process.
如最近发布的关于比较分析评估的指导草案所示，美国食品和药物管理局（FDA）似乎建议使用质量范围（QR）方法进行分析相似性评估。令人担忧的是，使用 QR 方法进行分析相似性评估可能会批准被认为与参比生物制品不相似的生物制品。本文讨论了使用 QR 方法进行分析相似性评估的局限性和潜在风险。另外，还提出了 QR 方法的两种改进版本，即效应大小（ES）mQR 和似然区间（PI）mQR 方法。通过在各种情况下进行广泛的临床试验模拟，评估了 mQR 方法的性能和统计特性。结果表明，QR 方法的改进版本不仅克服了 QR 方法在分析相似性评估中的局限性，而且还有助于检测制造过程中参比产品的变化。
