Dosage Form Design & Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Dosage Form Design & Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
J Pharm Sci. 2023 Jun;112(6):1586-1594. doi: 10.1016/j.xphs.2023.03.009. Epub 2023 Mar 17.
Prefilled syringes are widely used as a primary container for therapeutic proteins because they are more convenient than glass vials. The stability of biologic molecules can be affected by different syringe materials and techniques, such as silicone oil levels and coating method, amount of tungsten remaining in the glass barrel after using a tungsten pin to create the needle hole, and end of the syringe, which can be Luer locked or pre-staked with a needle. We investigated the impact of these parameters by using a monoclonal antibody to collect the antibody's stability profile and the prefilled syringes' functionality data. Silicone oil levels had no impact on aggregation levels, and particle counts were lowest for silicone oil-free syringes. Functionality performance was similar and did not change throughout all stability time points for all syringe configurations. The break-loose force for Ompi syringes was initially lower and increased over time to align with those of the other configurations, all of which remained well below 25 N. Tungsten contaminants and agitation stress from shipping studies did not impact quality attributes. This work can help guide the development of similar products in prefilled syringes to ensure selection of the primary container that provides adequate stability for the protein, as well as maintain the desired functionality features over the shelf life of the drug product.
预充注射器因其比玻璃小瓶更方便而被广泛用作治疗性蛋白的初级容器。生物分子的稳定性可能会受到不同注射器材料和技术的影响，例如硅油水平和涂层方法、使用钨针制造针孔后玻璃筒中残留的钨量、注射器的末端，末端可以是鲁尔锁定的或用针预锁定的。我们通过使用单克隆抗体来研究这些参数的影响，以收集抗体的稳定性概况和预充注射器的功能数据。硅油水平对聚集水平没有影响，无硅油注射器的颗粒计数最低。在所有稳定性时间点，所有注射器构型的功能性能相似且没有变化。Ompi 注射器的初始断开力较低，随着时间的推移而增加，以与其他构型保持一致，所有这些都远低于 25N。来自运输研究的钨污染物和搅拌应激并未影响质量属性。这项工作可以帮助指导预充注射器中类似产品的开发，以确保选择为蛋白质提供足够稳定性的初级容器，并在药物产品的保质期内保持所需的功能特性。
