SBIR Phase II: A complete bioprocess for medicinal plant opioids

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop a manufacturing platform for opioid medicines. Opioids enable physicians to provide compassionate care to patients suffering from acute or chronic disease and trauma. The need for opioid analgesics is even more salient for surgeons anticipating the post-operative recovery of their patients and planning for end-of-life care. However, opioids are highly addictive medicines, a property that has been exploited for commercial gain by certain players in the pharmaceutical industry. The impact of this project will be to deliver a technology that transforms the existing supply chain for opioids by removing the need to grow opium poppy as a drug crop. Instead of sourcing poppy materials from poppy-growing countries, this new technology will allow for complete production of opioids in a secure industrial facility located in the United States where federal agencies can provide oversight and regulation. Additionally, investment in this technology will enable the development of many more existing and experimental medicines derived from plants, including greatly improved opioids with improved efficacy and safety, and cardiovascular and chemotherapeutic therapies that will extend and enhance human lives. This SBIR Phase II project will develop a bioprocess for opioid active pharmaceutical ingredients (APIs). To date, the only commercially-competitive method for manufacturing opioids and related alkaloids is to extract these molecules from plants. However, Baker's yeast was recently engineered to biosynthesize opioids, which is a technological advance that could enable opioid production by fermentation. However, many technical hurdles remain in developing a reliable and cost-effective, commercially-viable production system based on existing strains. The objective of this Phase II project is to provide a complete demonstration and pilot-scale operation of an API bioprocess that is ready for industrial scale up. The research employs four approaches: 1) Further development of the engineered yeast strains, 2) scale up of fermentation from laboratory scale to pilot scale, 3) optimization of downstream recovery and purification, and 4) evaluation of the resulting products to establish their validity as drop-in-replacements for existing opioid APIs. The outcome will be a process validated at pilot scale and ready for technology transfer to a secure industrial facility that will make and sell into the opioids API market. This research will replace opium poppies with a modern bioprocess that resembles established, standardized pharmaceutical industry methods for antibiotic and biologic APIs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.