ABSTRACT
One objective of conducting process validations for a biopharmaceutical manufacturing process is to demonstrate that the process will reproducibly provide a product of a specified purity and quality to a satisfactory degree of assurance. Process variability may arise as a consequence of variability in either controlled or uncontrolled process parameters in product expression and downstream separations. Variability in expression arises from the biological complexity of the cell or bacterial culture and the inability to completely control product synthesis by the production host and is thus inherent to the manufacturing process. Further, variation in other process variables, including raw materials, measurement of control parameters or process states, and environmental effects, may result in additional process variability. Although complete assurance that every batch of product produced by such a complex manufacturing process is not currently possible, it is possible to prospectively evaluate the impact of the expected variation changes in key process parameters using a study specifically designed for this purpose. Sometimes called a robustness or ruggedness study, such a test is intended to demonstrate that a process will not fail to produce product of sufficient purity and quality when multiple variables thought to influence the process performance are varied over ranges that are likely to be encountered in the manufacturing process.
