Toward a two-tier process-development paradigm: prototype versus commercial biomanufacturing

Abstract

Speed is often positioned as a key element in the development of any novel therapeutic. After all, reducing development timelines can have a beneficial impact in managing investment cycles (crucial for small biotech), facilitate the introduction of translational medicine (bench to bedside and back to bench) and extend market exclusivity awarded by intellectual property rights. Yet speed is precisely a largely absent attribute in the development of virtually any new drug, and we could argue that biopharmaceuticals, because of the intrinsic complexities associated with their production, are perhaps the worst positioned amongst most drug classes. As an optimistic estimate, the road for a lead biopharmaceutical candidate to reach first-in-human clinical trials could take between 1.5 and 2 years of, sometimes perilous, travel involving a considerable out-ofpocket investment at a very high risk. High risk because an immense majority of products in development will fail (sometimes catastrophically) at some point during their development. Below I discuss how past development and manufacturing challenges during the onset of biopharmaceuticals have conditioned the evolution of manufacturing praxis and the perception of risk in the industry. I would also like to discuss how a two-tier manufacturing paradigm, addressing separately early prototype versus commercial requirements, could change dramatically how biopharmaceutical development is approached today, perhaps opening the door to new treatments for medical conditions that today are still largely out-of-reach for protein-based therapeutics, such as infectious diseases.