Pardeshi Neha, Marsiglio Dan, Padmakumar Vikashni, Bernacki Joe, Rathore Nitin
Drug Product Technologies, Amgen, Thousand Oaks, CA 91320, USA.
Drug Product Technologies, Amgen, Thousand Oaks, CA 91320, USA.
J Pharm Sci. 2023 Apr;112(4):954-962. doi: 10.1016/j.xphs.2022.11.017. Epub 2022 Nov 25.
The fill-finish process for vials and syringes, although considered standard in the biopharmaceutical industry, comes with numerous technical challenges when manufacturing high concentration products. This paper includes case studies, illustrating the operational challenges associated with the filling unit operation for three of the commonly used filling technologies for biopharmaceutical products - piston pump, time over pressure pump and peristaltic pump. First case study consists of a piston pump filling operation and evaluates impact of product related parameters such as a) protein concentration, b) product viscosity and c) surface tension. The second study encompasses peristaltic pump filling. It delves into characterization of fluid flow and pump parameters while examining failure modes such as product drying. The third case study details challenges with time-pressure filling operation. In summary, for the three filling technologies, the operational challenges encountered during bench-scale and manufacturing operations implicate drug product-nozzle interactions (drying of high-viscosity material), inadequate pump clearances (piston, again, drying + seizure) and lack of optimized control parameters as key factors contributing to filling line stoppages. In each instance, recommendations are provided to mitigate these operational challenges.
小瓶和注射器的灌装-封口工艺虽然在生物制药行业被视为标准工艺，但在生产高浓度产品时面临众多技术挑战。本文包含案例研究，阐述了生物制药产品三种常用灌装技术（活塞泵、定时压力泵和蠕动泵）在灌装单元操作中涉及的运营挑战。第一个案例研究是活塞泵灌装操作，评估了产品相关参数的影响，如a)蛋白质浓度、b)产品粘度和c)表面张力。第二个研究涵盖蠕动泵灌装。它深入研究了流体流动特性和泵参数，同时考察了诸如产品干燥等故障模式。第三个案例研究详述了定时压力灌装操作的挑战。总之，对于这三种灌装技术，在实验室规模和生产操作过程中遇到的运营挑战表明，药品与喷嘴的相互作用（高粘度物料干燥）、泵间隙不足（活塞处再次出现干燥和卡滞）以及缺乏优化的控制参数是导致灌装生产线停机的关键因素。在每种情况下，都提供了减轻这些运营挑战的建议。
