On-Demand Peptide Therapeutics for Multi-Year Space Exploration: Analysis of Clinical and Operational Relevance and Recombinant Production Feasibility

Introduction : Future crewed expeditions beyond Earth will be measured in years rather than weeks, necessitating a transition away from Earth-dependent pharmacies. Conventional medications degrade more rapidly in space due to radiation and storage constraints. Launching large quantities of temperature-controlled biologics requires impractical mission architecture and hardware. To enable self-sufficient medical capabilities for multi-year missions to deep space, this study assessed the operational and clinical relevance (OCR) and recombinant production feasibility (RPF) of on-demand peptide therapeutics in space using prokaryotic expression systems, particularly B. subtilis . Methods Building on Blum’s astropharmacy database and using available databases, we compiled a list of 27 peptide-based medications relevant to multi-year spaceflight and ranked them using 10 OCR and RPF criteria, each scored from zero to two points, yielding a maximum possible score of 20. OCR criteria included regulatory status, shelf stability, storage requirements, NASA Human Research RoadMap risk/impact score, and processing/purification requirements. RPF criteria included amino acid chain length, prior transgenic production history, available functional assays, dose requirements, and post-translational modifications for functional activity. Medication inclusion required clinical relevance to space-specific risks and peptide-based composition. Exclusion criteria included any two of the following: shelf stability at room temperature exceeding 36 months; spinal/intrathecal route of administration; no previous prokaryotic recombinant production; and/or absence of regulatory approval or recent clinical trial in the last 10 years. Scores were normalized to highlight higher-priority medications for on-demand production in space. Results Teriparatide is most likely to benefit from on-demand production in space during multi-year space missions with an overall score of 17/20. Abaloparatide and amylin were close seconds with scores of 16/20. Third place was occupied by six medications including angiotensin II, daptomycin, GLP-1 agonists, G-CSF, GM-CSF, and salmon calcitonin, with scores of 14/20. Discussion This study presents a structured framework for prioritizing and down-selecting pharmaceuticals for space-based production during multi-year missions. By integrating clinical and operational relevance, and on-demand manufacturing readiness, this study can guide future research towards on-demand production of peptide-based medications that offer the greatest health benefits while meeting manageable production and operational constraints.