ABSTRACT
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 deŒnition in the 1987 FDA “Guidance for Industry, Process Validation: General Principles and Practices”1:
16.1 Introduction .................................................................................................. 441 16.2 Worst-Case Challenges .................................................................................442 16.3 Family and Matrix Approaches to Process Validation .................................442 16.4 Case Study: Matrix Validation of Pneumovax 23, a 23-Valent
Polysaccharide-Based Pneumococcal Vaccine.............................................444 16.4.1 Process Development ........................................................................444 16.4.2 Matrix Validation Plan .....................................................................446 16.4.3 Regulatory Buy-In and Study Execution .......................................... 450 16.4.4 Conclusions ....................................................................................... 452
Acknowledgment ................................................................................................... 452 References and Notes ............................................................................................. 453
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 Œnal 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.
