ABSTRACT
Process Train ...................................................... 74 4.3 Examples of Scale-Down Models ................................. 75
4.3.1 Chromatography ................................................. 75 4.3.2 Protein Modification Reactions.......................... 85 4.3.3 Precipitation........................................................ 91 4.3.4 Microfiltration..................................................... 97 4.3.5 Ultrafiltration ................................................... 101 4.3.6 Centrifugation................................................... 105
4.3.7 Viral Inactivation ............................................. 108 4.3.8 Virus Removal Filtration ................................. 111
4.4 Evaluation of Suitability of Scale-Down Systems as Models of Full-Scale Operation............................. 117
4.5 Application of Scale-Down Systems........................... 121 4.5.1 Clinical Development Phase-Process
Validation .......................................................... 122 4.5.2 Commercial Processes ...................................... 129
4.6 Summary...................................................................... 131 Acknowledgments................................................................. 132 References............................................................................. 132
4.1 INTRODUCTION
The U.S. Food and Drug Administration (FDA) defines process validation as “establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined quality attributes” [1]. Regulatory agencies have published general guidelines to aid in developing validation strategies [2,3]. A complete process validation package is a major component of any regulatory filing. The process validation package consists of systematic documentation of protocols, reports, and results from well-planned studies. A key to successful process validation studies is ensuring strong scientific rationale in their design and interpretation while maintaining cGMP (current Good Manufacturing Practice) compliance.
