Buecheler Jakob W, Luemkemann Joerg, Gieseler Henning, Mohl Silke, Streubel Alexander
Division of Pharmaceutics, Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and.
PDA J Pharm Sci Technol. 2019 Mar-Apr;73(2):111-120. doi: 10.5731/pdajpst.2018.008870. Epub 2018 Oct 25.
Vial capping plays a critical role in the drug product manufacturing process owing to the complex interplay of several adjustable process steps. Seal quality and integrity and containment assurance are essential for parenteral pharmaceuticals, as the vial's content may be contaminated or, in the case of highly potent drugs (e.g., antibody drug conjugates), may bear a risk of contamination. The residual seal force (RSF) method can enable further insight in capping equipment settings independently of the container closure system (CCS) and their resulting seal quality.The present study investigates the accuracy of the RSF method focusing on different force settings, RSF development over time, distance between capping plates and vial neck (roller-axis), time point of flip-off button removal, and internal and external vial pressure differences (flight simulation and vials closed under vacuum).Results show that the forces used on an RSF tester should be kept low to minimize CCS deformation, and a period of stable RSF values after the initial decrease should be implemented between capping and RSF measurement to increase accuracy. Variations in the distance between the capping plates and vial neck (roller-axis) can result in incomplete crimps or visual defects of the seals. In addition, the time point of flip-off button removal as part of the sample preparation had no significant impact on RSF measurements. Finally, pressure differences between the vial interior and exterior had no significant impact on the RSF data. Vial capping plays a critical role in the drug product manufacturing process due to the complex interplay of several adjustable process steps. Seal quality, integrity, and containment are essential for parenteral pharmaceuticals, as the vial's content varies and may be contaminated, sensitive to stress, and/or highly potent (eg, antibody drug conjugates). The residual seal force (RSF) method can enable further insight in capping equipment settings independently of the container closure system and their resulting seal quality.In this study, we determined RSF values by applying different force settings of the RSF tester and investigated the influence of sample preparation on the determination of RSF. Furthermore, the capping process parameter roller-axis was evaluated by RSF and visual inspection. In addition, we investigated the influence of pressure differences of vials on the RSF as they occurred during air transport and products closed under vacuum.
由于多个可调节工艺步骤之间存在复杂的相互作用，小瓶封盖在药品生产过程中起着关键作用。对于注射用药品而言，密封质量、完整性和密封性至关重要，因为小瓶内的内容物可能会被污染，或者对于高活性药物（如抗体药物偶联物）来说，可能存在污染风险。残余密封力（RSF）方法能够独立于容器密封系统（CCS）及其产生的密封质量，进一步深入了解封盖设备的设置情况。本研究聚焦于不同的力设置、RSF随时间的变化、封盖板与小瓶颈部之间的距离（滚轮轴）、翻盖按钮移除的时间点以及小瓶内外压力差（飞行模拟和在真空下封闭的小瓶），对RSF方法的准确性进行了研究。结果表明，RSF测试仪上使用的力应保持较低水平，以尽量减少CCS变形，并且在封盖和RSF测量之间应设置一段初始下降后RSF值稳定的时间段，以提高准确性。封盖板与小瓶颈部之间的距离（滚轮轴）的变化可能导致压接不完全或密封出现视觉缺陷。此外，作为样品制备一部分的翻盖按钮移除时间点对RSF测量没有显著影响。最后，小瓶内外的压力差对RSF数据没有显著影响。由于多个可调节工艺步骤之间存在复杂的相互作用，小瓶封盖在药品生产过程中起着关键作用。对于注射用药品而言，密封质量、完整性和密封性至关重要，因为小瓶内的内容物各不相同，可能会被污染、对压力敏感和/或具有高活性（如抗体药物偶联物）。残余密封力（RSF）方法能够独立于容器密封系统及其产生的密封质量，进一步深入了解封盖设备的设置情况。在本研究中，我们通过应用RSF测试仪的不同力设置来确定RSF值，并研究了样品制备对RSF测定的影响。此外，通过RSF和目视检查对封盖工艺参数滚轮轴进行了评估。此外，我们还研究了小瓶在航空运输过程中以及在真空下封闭的产品中出现的压力差对RSF的影响。
