Shieu Wendy, Stauch Oliver B, Maa Yuh-Fun
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA.
Pharmaceutical Processing and Technology Development, Genentech, a member of the Roche Group, South San Francisco, CA
PDA J Pharm Sci Technol. 2015 May-Jun;69(3):417-26. doi: 10.5731/pdajpst.2015.01055.
Syringe filling of high-concentration/viscosity monoclonal antibody formulations is a complex process that is not fully understood. This study, which builds on a previous investigation that used a bench-top syringe filling unit to examine formulation drying at the filling nozzle tip and subsequent nozzle clogging, further explores the impact of formulation-nozzle material interactions on formulation drying and nozzle clogging. Syringe-filling nozzles made of glass, stainless steel, or plastic (polypropylene, silicone, and Teflon®), which represent a full range of materials with hydrophilic and hydrophobic properties as quantified by contact angle measurements, were used to fill liquids of different viscosity, including a high-concentration monoclonal antibody formulation. Compared with hydrophilic nozzles, hydrophobic nozzles offered two unique features that discouraged formulation drying and nozzle clogging: (1) the liquid formulation is more likely to be withdrawn into the hydrophobic nozzle under the same suck-back conditions, and (2) the residual liquid film left on the nozzle wall when using high suck-back settings settles to form a liquid plug away from the hydrophobic nozzle tip. Making the tip of the nozzle hydrophobic (silicone-coating on glass and Teflon-coating stainless steel) could achieve the same suck-back performance as plastic nozzles. This study demonstrated that using hydrophobic nozzles are most effective in reducing the risk of nozzle clogging by drying of high-concentration monoclonal antibody formulation during extended nozzle idle time in a large-scale filling facility and environment.
Syringe filling is a well-established manufacturing process and has been implemented by numerous contract manufacturing organizations and biopharmaceutical companies. However, its technical details and associated critical process parameters are rarely published. Information on high-concentration/viscosity formulation filling is particularly lacking. This study is the continuation of a previous investigation with a focus on understanding the impact of nozzle material on the suck-back function of liquid formulations. The findings identified the most critical parameter-nozzle material hydrophobicity-in alleviating formulation drying at the nozzle tip and eventually limiting the occurrence of nozzle clogging during the filling process. The outcomes of this study will benefit scientists and engineers who develop pre-filled syringe products by providing a better understanding of high-concentration formulation filling principles and challenges.
高浓度/高粘度单克隆抗体制剂的注射器灌装是一个尚未被完全理解的复杂过程。本研究基于之前的一项调查展开，该调查使用台式注射器灌装装置来研究灌装喷嘴尖端的制剂干燥及随后的喷嘴堵塞情况，进一步探究了制剂与喷嘴材料相互作用对制剂干燥和喷嘴堵塞的影响。使用玻璃、不锈钢或塑料（聚丙烯、硅胶和特氟龙®）制成的注射器灌装喷嘴来灌装不同粘度的液体，包括一种高浓度单克隆抗体制剂，这些喷嘴代表了通过接触角测量量化的具有亲水性和疏水性的全系列材料。与亲水性喷嘴相比，疏水性喷嘴具有两个独特的特性，可抑制制剂干燥和喷嘴堵塞：（1）在相同的回吸条件下，液体制剂更有可能被吸回疏水性喷嘴；（2）在使用高回吸设置时，留在喷嘴壁上的残留液膜会沉淀形成一个远离疏水性喷嘴尖端的液塞。使喷嘴尖端具有疏水性（玻璃上涂硅胶和不锈钢上涂特氟龙）可实现与塑料喷嘴相同的回吸性能。本研究表明，在大规模灌装设施和环境中，在喷嘴长时间闲置期间，使用疏水性喷嘴最有效地降低了高浓度单克隆抗体制剂干燥导致喷嘴堵塞的风险。
注射器灌装是一种成熟的制造工艺，已被众多合同制造组织和生物制药公司采用。然而，其技术细节和相关关键工艺参数很少公布。尤其缺乏关于高浓度/高粘度制剂灌装的信息。本研究是之前一项调查的延续，重点是了解喷嘴材料对液体制剂回吸功能的影响。研究结果确定了最关键的参数——喷嘴材料的疏水性，它可减轻喷嘴尖端的制剂干燥，并最终限制灌装过程中喷嘴堵塞的发生。本研究的结果将有助于开发预填充注射器产品的科学家和工程师更好地理解高浓度制剂灌装的原理和挑战。
