The goal of validation of a fermentation process is to provide documented evidence that the production process performs as intended. The product from a validated fermentation process should have pre-determined characteristics which indicate the process is performing consistently. Changes in the fermentation process for production of recombinant human interleukin-1 receptor antagonist while in clinical trials included growth medium and extended time after induction. The goals of the development and scale-up activities were to develop a reproducible, scalable process yielding high quality material and to introduce the new process to the manufacturing facility in a timely fashion. In the course of development and scale-up, further modifications were required to maintain reproducibility and product quality. The start-up batches from both the pilot-scale and the production facility provided the data sets for validating the process, establishing the limits for operating variables and the control limits for performance parameters.