Oliva Alexis, Echezarreta Magdalena, Santana-Mayor Álvaro, Conde-Díaz Adrían, Goncalves Joao, Chow Shein-Chung, Llabrés Matías
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, Avda. Fco. Sánchez, s/n, 38200 Santa Cruz de Tenerife, Spain.
Servicio de Apoyo a la Investigación (SEGAI), Universidad de La Laguna, Avda. Fco. Sánchez, s/n, 38206 Santa Cruz de Tenerife, Spain.
Pharmaceutics. 2024 Nov 26;16(12):1520. doi: 10.3390/pharmaceutics16121520.
The manufacture of biologics is a complex, controlled, and reproducible process that results in a product that meets specifications. This should be based on data from batches used to demonstrate manufacturing consistency. Ten batches of originator product (Avastin) were analyzed over a 10-year period.
The β-expectation tolerance intervals and the process capability analysis were proposed to establish the specification limits for determining the acceptance criteria of the final product from the manufacturing process. Protein concentration and dimer content were utilized as CQAs. The analytical similarity between three biosimilars authorized in Spain since 2021 (Vegzelma, Alymsys, and Oyavas) and the originator product were evaluated for both CQAs using two methods: the quality range (QR) method, based on one sample per batch, and the QRML one, which takes into account the inter- and intra-batch variability of the originator product.
The results indicate that the two main sources of variation are under control; even the level of variability observed is close to the capability of the analytical method. The manufacturing process, therefore, continues under statistical control. Similarity is demonstrated for the bevacizumab concentration regardless of the approach used, whereas similarity is demonstrated for the dimer content for only one of the biosimilar products.
The proposed methodologies allow for the analysis of the consistency of the manufacturing process and the variability from batch to batch.
生物制品的生产是一个复杂、可控且可重复的过程，其结果是得到符合规格的产品。这应基于用于证明生产一致性的批次数据。在10年期间对10批原研产品（阿瓦斯汀）进行了分析。
提出了β-期望公差区间和过程能力分析，以建立用于确定生产过程最终产品验收标准的规格限度。蛋白质浓度和二聚体含量被用作关键质量属性（CQAs）。使用两种方法对自2021年以来在西班牙获批的三种生物类似药（Vegzelma、Alymsys和Oyavas）与原研产品在两种CQAs方面的分析相似性进行了评估：质量范围（QR）法，基于每批一个样品；以及QRML法，该方法考虑了原研产品的批间和批内变异性。
结果表明，两个主要变异来源处于受控状态；即使观察到的变异水平接近分析方法的能力。因此，生产过程仍处于统计控制之下。无论使用何种方法，贝伐单抗浓度的相似性都得到了证明，而对于二聚体含量，只有一种生物类似药产品表现出相似性。
所提出的方法能够分析生产过程的一致性以及批次间的变异性。
