Yannick Elias
Janssen (Cilag AG), Switzerland
Title: Achieving Quality by Design for parenterals filling with a time-pressure setup
Biography
Biography: Yannick Elias
Abstract
Particulate matter in parenteral drug products is recognized by Health Authorities as a critical quality attribute. A strong focus of fill
and finish process development is put on the appropriate selection and operation of the filling system to reduce intrinsic particle
formation, often related to shear induced drug product degradation. Rotary Piston Pumps (RPP) have been a standard selection in
Janssen for many years, as they offer a simple, compact and robust design and show a very high dosing accuracy. However, as the
drug product acts as a pump lubricant, the product is exposed to very high shear rates, which in turn can cause enhanced intrinsic
particle formation. Thus, alternative filling technologies, such as peristaltic pumps (PP) or a time-pressure (TP) system, are required
for shear-sensitive products. A TP system consists essentially of a pressurized tank and a pinch valve. Dosing accuracy is achieved by
harmonizing the vessel over pressure and the valve opening duration. To improve the overall product quality during filling of shearsensitive
products, a Quality by Design and Right the First Time approach is chosen to ensure proper equipment operation. For this,
understanding the critical process parameters, risks associated with those parameters and their impact on critical product quality
attributed is crucial. Thus, a Design of Experiment study was performed to identify and characterize the impact of six distinct process
and equipment parameters on different solutions to obtain a Design Space for optimal TP filling operation.