RT Journal Article
SR Electronic
T1 A Holistic Approach for Fill volume Variability Evaluation and Control with Statistical Tool
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2023.012867
DO 10.5731/pdajpst.2023.012867
A1 Chen, Quanmin
A1 She, Qingqing
A1 Jin, Zhaowei
A1 Hei, Mingyang
A1 Sun, Chunmeng
A1 Tu, Jiasheng
A1 Guo, Jeremy
YR 2024
UL http://journal.pda.org/content/early/2024/08/29/pdajpst.2023.012867.abstract
AB Vial and syringe filling by peristaltic pump has been widely implemented by contract manufacturing organizations and biopharmaceutical companies. Fill volume is commonly considered as critical quality attribute related in aseptic filling process and the variation needs to be well controlled to guarantee the safety, efficacy and consistency of drug products. However, the criteria for justifying the filling variation and underlying mechanisms that affect the variability are not fully revealed quantitatively in the literatures. This study selected filling accuracy, filling process capability and filling precision as three criteria for evaluating the filling process performance with four statistical indexes: Relative Error Mean, Critical Control Limit (Cpk ≥ 1.33), Relative Standard Deviation and Relative Moving Range Mean. The impact of liquid properties, pump tubing sizes and pump settings on above indexes were investigated using a bench-top system with a peristatic pump and a high-precision balance. The results showed that the viscosity, target fill volume, pump tubing size, pump speed, acceleration/deceleration rate and suck-back had statistical significance on the fill volume variability. Definitive Screening Design was further applied to clarify and visualize the priorities and interaction impact of above factors on fill volume variability. Stepwise approach for fill volume variability optimization and control based on predictive models was established and verified for drug product solution with viscosity between 1-23 cp and target fill volume between 0.2-2.0 mL.