Syringe Filling of High-Concentration mAb Products Using Peristaltic Pump-Based Mechanism: Challenges and Mitigation Strategies

Abstract Syringe filling of high-concentration mAb formulation during manufacturing of large-scale drug product batches may present challenges such as product deposition onto the area of the syringe barrel where the stopper is inserted, product splashing or dripping, droplets left after the fill cycle, filling needle clogging, product build-up inside the needle during line stoppages, variation in fill weight/volume, and potential impact on product quality attributes. In this article, a summary of these issues and approaches to overcome them are summarized. Potential failure modes of the syringe filling process and appropriate in-process controls are provided. In addition to developing the filling process or resolving manufacturing issues, the pharmaceutical company developing the product and associated drug product manufacturing process may want to implement long-term strategic approaches to support the portfolio progression. Potential long-term approaches such as use of a viscosity reducing formulation development approach, improving peristaltic filling technology performance, building small-scale filling capability and establishing a streamlined filling process management cycle are also summarized. The aspects summarized in this article may be used to develop a robust filling process and control strategy for high-concentration mAb products and implement long-term strategic approaches to support the portfolio progression.