Use of pilot plant facilities to aid validation programs

According to the FDA guidelines (1), pilot plant facilities may be used to generate material to support process validation studies. The guidelines also state that process modifications are an inevitable part of process development and scale-up. However, if such modifications are made, there is a need to demonstrate that the products from both the old and new processes are comparable (2). Both of these guidelines were combined and applied during a recent development of a product at Genentech. In order to implement the process modifications and demonstrate product comparability, the pilot plant facilities were used for these production runs. As the process had changed and the product was being prepared for BLA submission, in process samples from the new manufacturing process were also required to support the process validation studies. By using pilot plant facilities to implement the process modifications, test product comparability, and produce material for process validation, we were able to minimize the impact of such work on the large-scale manufacturing facility.