Filling of High-Concentration Monoclonal Antibody Formulations into Pre-Filled Syringes: Filling Parameter Investigation and Optimization

Abstract

Syringe filling can be considered 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. The information on high-concentration/viscosity formulation filling is particularly lacking. The purpose of this study is three-fold: (1) to reveal design details of a bench-top syringe filling unit; (2) to identify and optimize critical process parameters; (3) to apply the learning to practical filling operation. The outcomes of this study will benefit scientists and engineers who develop pre-filled syringe products by providing a better understanding of HC formulation filling principles and challenges.

Utility of High Resolution 2D NMR Fingerprinting in Assessing Viscosity of Therapeutic Monoclonal Antibodies

“…The development of high-concentration mAbs can pose significant challenges to product development pertaining to stability, manufacturability, and processing. High-concentration mAb formulation in a prefilled syringe are well documented; however increased injection force for syringes with high fluid viscosity along withformulation stability is particularly challenging ( 6 ).…”

Development of delivery device technology to deal with the challenges of highly viscous mAb formulations at high concentration

“…A recent study using mAb formulated at 180 mg/mL investigated the key parameters for successful filling of the mAb into a prefilled syringe (Shieu et al, 2014). The key parameters investigated were solution viscosity, concentration, and surface tension.…”

Stress Factors in Protein Drug Product Manufacturing and Their Impact on Product Quality

“…Additionally, for high protein concentration formulations, the suck-back (pump-reversal) on peristaltic pumps must be carefully controlled to avoid droplet formation on the end of the filling needle, which is prone to rapid drying and clogging of the filling needles during the process. 65,66 The time-pressure filling system is another technology that has gained increasing popularity in the pharmaceutical industry. One of the benefits of this system is reduced product contact parts and the absence of surface-to-surface contact (grinding) during the filling process.…”