Syringe Filling of a High-Concentration mAb Formulation: Experimental, Theoretical, and Computational Evaluation of Filling Process Parameters That Influence the Propensity for Filling Needle Clogging.

This article summarizes experimental, theoretical, and computational assessments performed to understand the effect of filling and suck-back cycle factors on fluid behaviors that increase the propensity for filling needle clogging. Product drying under ambient conditions decreased considerably when the liquid front was altered from a droplet or meniscus at the needle tip to a point approximately 5 mm inside the needle. Minimizing the variation in size of product droplet formed after the fill cycle is critical to achieve a uniform meniscus height after the suck-back cycle. Several factors were found to contribute to droplet size variability, including filling and suck-back pump speed, suck-back volume, and product temperature. Filling trials and the computational fluid dynamics simulations showed that product meniscus stability during the suck-back cycle can be improved by reducing the suck-back flow rate. The computational fluid dynamics simulations also showed that a decrease in contact angle had the greatest effect in reducing meniscus stability. As the number of filling line stoppages increases, the product buildup at the needle increases. The interaction between stoppages and the number of dispenses between stoppages was established to minimize product buildup at the filling needle. Improved suck-back control was shown to improve process capability of large-scale batches.

Syringe Filling of High-Concentration mAb Formulation: Slow Suck-Back Pump Speed Prevented Filling Needle Clogging.

Partial and complete clogging of filling needles occurred during syringe filling of a high-concentration mAb formulation. This caused nonvertical liquid flow, which eventually led to the termination of filling. Overcoming this phenomenon was essential to ensure minimal fill weight variation, product waste, and manufacturing downtime. The liquid behavior inside the filling needle was studied using glass and stainless steel needles and demonstrated that effective suck-back control was critical for preventing needle clogging. A key finding of our work is that the suck-back pump speed was a critical factor to achieve an effective suck back. More specifically, a slow suck-back pump speed (<10 rpm; liquid flow rate, <5 mL/min) was essential to improve suck-back control inside the conventional stainless steel filling needles. In contrast, higher suck-back pump speeds (>10 rpm; liquid flow rate, >5 mL/min) resulted in downward product migration within the filling needle leading to formation of a liquid plug at the needle tip, which was prone to rapid drying. Slowing the suck-back pump speed in conjunction with modifying the suck-back volume was effective at consistently withdrawing product into the stainless steel filling needles and prevented needle clogging.