Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Munich, Germany.
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
J Pharm Pharmacol. 2018 May;70(5):675-685. doi: 10.1111/jphp.12603. Epub 2016 Jul 1.
Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product.
Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2-8, 25 and 40°C were conducted.
Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo.
Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability.
由于许多生物制品对与旋转活塞泵相关的压力敏感，蠕动泵在生物制药的灌装和完成操作中越来越多地被使用。然而，由于所使用的管材的磨损，可能也会有使用蠕动泵的单元操作会将颗粒物质脱落到最终产品中。本研究旨在阐明从蠕动泵管材脱落的颗粒物质对药物产品稳定性的潜在影响。
通过在循环条件下蠕动泵输送安慰剂来制备含有脱落硅酮颗粒的加标溶液，并对其进行了表征。两种配方抗体分别以两种现实但最坏情况的颗粒水平进行了加标，并进行了 6 个月的加速稳定性研究，在 2-8°C、25°C 和 40°C 下储存。
关于聚集体和碎片的形成，两种 mAb 均以其通常预期的速率降解，并且没有观察到加标颗粒的额外影响。然而，在浊度、亚可见和可见颗粒评估方面没有发现变化。对于一种加标颗粒的 mAb 制剂的流动成像数据表明，脱落的颗粒具有有限的胶体稳定性，这表明加标安慰剂中也出现了类似的增加。
蠕动泵管材脱落的硅酮颗粒被认为不会损害药物产品的稳定性。
