Regardless of molecule, the goal of biopharmaceutical downstream processing is to reduce process- and product-related impurities while maintaining the highest possible process yield. However, emerging modalities such as those based on gene-edited human cells, transgenes carried by viral vectors, and proteins transferred by exosomes all are pointing out limitations in current downstream strategies, which by and large have been developed around purification of monoclonal antibodies (MAbs). This year’s nominees in the BPI Readers’ Choice downstream category highlight technologies and processing strategies that biopharmaceutical developers and manufacturing organizations are developing to address the separation and purification demands raised by innovative therapies.