Reviving Antibiotic Innovation: A Delinked Obligations and Incentives Framework for Pharma

Abstract Antimicrobial resistance (AMR) has emerged as a transboundary, dynamic market failure that no single country or region can resolve in isolation. Resistance continuously erodes the effectiveness of existing anti-infectives, while traditional pharmaceutical business models discourage sustained private investment. Antibiotics generate comparatively low financial returns because stewardship and short treatment durations rightly limit sales volumes, resulting in net present values far below those of chronic or specialty therapies. Despite the magnitude and urgency of the threat, actionable ideas for restoring antibiotic innovation at scale remain scarce. This Commentary proposes a structured, ICH-aligned Delinked Obligations and Incentives (DOI) Framework designed to restore sustainable antibiotic innovation while preserving stewardship and equitable access. Large pharmaceutical firms would be required to bring novel antibiotics to market on a defined cycle, with flexible, outcome-based compliance pathways including internal development, acquisitions, or regulated innovation credits. Mid-size, generics, and biosimilars manufacturers would contribute proportionate levies to an ICH AMR Innovation Fund, channeling resources toward high-capacity industrial developers while sustaining early-stage academic discovery. Novelty-graded pull incentives—structured as tiered, fixed subscription payments linked proportionally to therapeutic innovation—align rewards directly with clinical value. Complementary regulatory tools such as priority-review vouchers and extended exclusivity further enhance feasibility within existing institutional frameworks. Beyond correcting market incentives, the DOI Framework aims to rebuild industrial expertise, foster collaboration, and accelerate the adoption of new discovery technologies. By leveraging established regulatory and governance structures rather than constructing new supranational institutions, it offers a pragmatic pathway to sustained antibiotic innovation within the current decade.