Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying-the Road to Manufacturing Scale.
Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying-the Road to Manufacturing Scale.
复制标题
DOI：
10.5731/pdajpst.2015.01003
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Maa, Yuh-Fun
中科院分区：
文献类型：
--
作者：
Gikanga, Benson;Turok, Robert;Maa, Yuh-Fun
未标记：喷雾干燥单克隆抗体（mAb）粉末可以提供比冻干蛋糕更通用的应用，包括制备用于皮下给药的高浓度制剂。然而，关于这一主题的已发表的研究通常很少。本研究评估了中试规模喷雾干燥机与实验室规模干燥机对多种单克隆抗体进行喷雾干燥的效果，考虑了扩大规模、对单克隆抗体稳定性的影响以及高浓度制备的可行性。在相似的条件下，两种干燥机生产的粉末具有相似的特性——例如含水量、颗粒大小和形态，以及mAb稳定性——尽管中试规模装置的输出速度快了4倍。所有含有精氨酸盐或精氨酸盐和海藻糖组合的配方都能以较高的粉末收集效率（约95%）进行喷雾干燥，但在含有高海藻糖含量的配方中，由于粉末粘附在干燥室内，收率受到不利影响。喷雾干燥生产的产量由干燥机的大小决定，在最佳的液体进料速率下运行。喷雾干燥的粉末可以重组成高粘度液体，>300 cP，大大超出了超滤过程所能达到的。考虑到单克隆抗体浓度为250 mg/mL时制剂的等压性，海藻糖与单克隆抗体的摩尔比需要降至50:1。即使有这种低水平的糖保护，基于大小变化和效力数据，喷雾干燥制剂的长期稳定性仍然优于液体制剂。该研究为生物散装储存提供了一种商业上可行的喷雾干燥工艺，并为高浓度mAb制造提供了一种选择。摘要：本研究从扩大规模、对单克隆抗体稳定性的影响以及高浓度制备的可行性等方面，对中试喷雾干燥机和实验室喷雾干燥机喷雾干燥多种单克隆抗体（mAb）的效果进行了评价。数据表明，与常规超滤工艺相比，喷雾干粉重组制备高浓度单抗制剂对溶液粘度没有工艺限制。该研究提供了一种商业上可行的喷雾干燥工艺，用于生物散装储存和高浓度单抗皮下给药。这项研究的结果将为开发高浓度单抗产品的科学家和工程师提供一种可行的制造替代方案。
UNLABELLED: Spray-dried monoclonal antibody (mAb) powders may offer applications more versatile than the freeze-dried cake, including preparing high-concentration formulations for subcutaneous administration. Published studies on this topic, however, are generally scarce. This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple mAbs in consideration of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. Under similar conditions, both dryers produced powders of similar properties-for example, water content, particle size and morphology, and mAb stability profile-despite a 4-fold faster output by the pilot-scale unit. All formulations containing arginine salt or a combination of arginine salt and trehalose were able to be spray-dried with high powder collection efficiency (>95%), but yield was adversely affected in formulations with high trehalose content due to powder sticking to the drying chamber. Spray-drying production output was dictated by the size of the dryer operated at an optimal liquid feed rate. Spray-dried powders could be reconstituted to high-viscosity liquids, >300 cP, substantially beyond what an ultrafiltration process can achieve. The molar ratio of trehalose to mAb needed to be reduced to 50:1 in consideration of isotonicity of the formulation with mAb concentration at 250 mg/mL. Even with this low level of sugar protection, long-term stability of spray-dried formulations remained superior to their liquid counterparts based on size variant and potency data. This study offers a commercially viable spray-drying process for biological bulk storage and an option for high-concentration mAb manufacturing.LAY ABSTRACT: This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple monoclonal antibodies (mAbs) from the perspective of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. The data demonstrated that there is no process limitation in solution viscosity when high-concentration mAb formulations are prepared from spray-dried powder reconstitution compared with concentration via the conventional ultrafiltration process. This study offers a commercially viable spray-drying process for biological bulk storage and a high-concentration mAb manufacturing option for subcutaneous administration. The outcomes of this study will benefit scientists and engineers who develop high-concentration mAb products by providing a viable manufacturing alternative.