SAPIR-Net: Supply Chain Analysis for Pharmaceutical Infrastructure Resilience — A Network Model for Quantifying Cascading Vulnerability in the U.S. Generic Oncology Drug Supply Chain (Phase 1): White Paper

The United States lacks a quantitative framework for assessing geopolitical concentration risk in the upstream supply chains of essential generic oncology drugs. This paper presents SAPIR-Net (Supply Chain Analysis for Pharmaceutical Infrastructure Resilience — Network Model), a three-layer directed graph model that maps the flow of chemical precursors from geopolitical source nations through intermediate commodity nodes to three essential cancer therapies: cisplatin, carboplatin, and methotrexate. Monte Carlo simulation (N = 10,000 iterations per scenario) reveals a sharp divergence in vulnerability profiles. Under a cascading upstream shock scenario, methotrexate faces a 100% probability of severe shortage (>30% capacity loss), with a mean capacity reduction of 59%. Cisplatin and carboplatin remain below the severe shortage threshold under the same scenario, with mean capacity losses of approximately 17%. Under systemic logistics disruption, all three drugs face a 21% probability of severe shortage. The model's baseline geopolitical disruption scenario produces a predicted capacity loss of 2.95% for platinum-based drugs, falling within the 95% confidence interval of the observed real-world impact of the 2023 cisplatin and carboplatin shortage (2.7% average reduction; 95% CI: −4.4% to −0.9%), as documented in Reibel et al. (JNCI, 2025). These findings indicate that oncology drug supply chain risk is commodity-specific and requires differentiated policy responses. Methotrexate requires upstream chemical diversification away from Chinese intermediate suppliers. The platinum-based agents require logistics corridor redundancy and domestic manufacturing investment.