Formulation Sciences, MedImmune LLC, One MedImmune Way, Gaithersburg, Maryland 20878.
Formulation Sciences, MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK.
J Pharm Sci. 2017 Aug;106(8):1971-1977. doi: 10.1016/j.xphs.2017.04.039. Epub 2017 Apr 26.
Selecting optimal formulation conditions for monoclonal antibodies for first time in human clinical trials is challenging due to short timelines and reliance on predictive assays to ensure product quality and adequate long-term stability. Accelerated stability studies are considered to be the gold standard for excipient screening, but they are relatively low throughput and time consuming. High throughput screening (HTS) techniques allow for large amounts of data to be collected quickly and easily, and can be used to screen solution conditions for early formulation development. The utility of using accelerated stability compared to HTS techniques (differential scanning light scattering and differential scanning fluorescence) for early formulation screening was evaluated along with the impact of excipients of various types on aggregation of monoclonal antibodies from multiple IgG subtypes. The excipient rank order using quantitative HTS measures was found to correlate with accelerated stability aggregation rate ranking for only 33% (by differential scanning fluorescence) to 42% (by differential scanning light scattering) of the antibodies tested, due to the high intrinsic stability and minimal impact of excipients on aggregation rates and HTS data. Also explored was a case study of employing a platform formulation instead of broader formulation screening for early formulation development.
由于时间紧迫且依赖预测性检测来确保产品质量和足够的长期稳定性，因此在首次人体临床试验中为单克隆抗体选择最佳制剂条件具有挑战性。加速稳定性研究被认为是赋形剂筛选的金标准，但它们的通量相对较低且耗时。高通量筛选 (HTS) 技术可快速轻松地收集大量数据，并可用于筛选早期制剂开发的溶液条件。评估了使用加速稳定性与 HTS 技术（差示扫描光散射和差示扫描荧光）进行早期配方筛选的效果，以及各种类型的赋形剂对来自多种 IgG 亚型的单克隆抗体聚集的影响。使用定量 HTS 测量的赋形剂等级顺序仅与 33%（差示扫描荧光）至 42%（差示扫描光散射）的测试抗体的加速稳定性聚集率等级相关，这是由于赋形剂对聚集率和 HTS 数据的影响很小，以及抗体本身的固有稳定性很高。还研究了一个案例研究，即使用平台配方代替更广泛的配方筛选来进行早期配方开发。
