ABSTRACT
Validation..................................................................... 525 13.4 Case Study: Matrix Validation of Pneumovax®23,
a 23-Valent Polysaccharide-Based Pneumococcal Vaccine ......................................................................... 527 13.4.1 Process Development........................................ 528 13.4.2 Matrix Validation Plan..................................... 530 13.4.3 Regulatory Buy-In and Study Execution........ 537 13.4.4 Conclusions ....................................................... 539
Acknowledgments................................................................. 540 References and Notes .......................................................... 541
13.1 INTRODUCTION
The goal of any process validation is to ensure process consistency and robustness so that each lot of product manufactured is of the same purity, potency, and overall quality as every other lot. The concept of process validation has been reviewed extensively in other chapters of this book, so we will limit our discussions by simply stating the definition in the 1987 FDA Guideline on General Principles of Process Validation1:
At Merck, this has meant that the process is thoroughly characterized at laboratory and pilot scale, through both a detailed understanding of individual unit operations and the interactions between the unit operations in their final sequence. The formal process validation exercise is then performed at full scale under predetermined process parameter ranges, with the objective of demonstrating that the process and the product meet predetermined quality attributes. The validation study at full scale usually involves at least three full-scale lots.
