A Holistic Approach for Filling Volume Variability Evaluation and Control with Statistical Tool

Area of Science:

• Pharmaceutical Manufacturing
• Process Engineering
• Biotechnology

Background:

• Peristaltic pumps are crucial for vial and syringe filling in biopharmaceutical production.
• Controlling filling volume variation is essential for drug product safety, efficacy, and consistency.
• Quantitative understanding of factors influencing filling variability is limited.

Purpose of the Study:

• To evaluate peristaltic pump filling performance using accuracy, capability, and precision criteria.
• To investigate the impact of liquid properties and pump parameters on filling volume variability.
• To develop a predictive model for optimizing and controlling filling volume variation.

Main Methods:

• Utilized a bench-top system with a peristaltic pump and high-precision balance.
• Assessed filling performance using Relative Error Mean, Cpk ≥ 1.33, Relative Standard Deviation, and Relative Moving Range Mean.
• Employed Definitive Screening Design to analyze factor interactions and impacts.

Main Results:

• Viscosity, target volume, tubing size, pump speed, acceleration/deceleration, and suck-back significantly influenced filling variability.
• Identified key factors and their interactions affecting filling volume consistency.
• Developed and verified predictive models for process optimization.

Conclusions:

• Established a stepwise approach for optimizing and controlling peristaltic pump filling volume variability.
• Models are applicable to drug solutions with viscosities of 1-23 cP and volumes of 0.2-2.0 mL.
• Provides a quantitative framework for enhancing aseptic filling processes.