4^th European Biopharma Congress

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.