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

• Published in: Journal of pharmaceutical sciences 2019-03, Vol.108 (3), p.1130-1138
• Main Authors: Hanslip, Simon, Desai, Kashappa Goud, Palmer, Mark, Kemp, Ian, Bell, Stephen, Schofield, Paul, Varma, Prashant, Roche, Frank, Colandene, James D., Nesta, Douglas P.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - chemistry; Chemistry, Pharmaceutical; Computer Simulation; Drug Packaging - instrumentation; Drug Packaging - methods; high-concentration mAb formulation; Hydrodynamics; meniscus instability; Models, Chemical; needle clogging; needle priming; Needles; process capability (Ppk); product drying; syringe filling; Syringes
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2018.10.031

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.