[Paper Review] Analyzing Vaccine Manufacturing Supply Chain Disruptions for Pandemic Preparedness using Discrete-Event Simulation

Robin Kelchtermans, Valentijn Stienen+3 more|arXiv (Cornell University)|Feb 9, 2026

Supply Chain Resilience and Risk Management0 citations

TL;DR

The paper develops a discrete-event simulation that integrates production, QA/QC, and raw materials to quantify disruptions in vaccine manufacturing and evaluate resilience investments, demonstrated on an mRNA case study.

ABSTRACT

The COVID-19 pandemic exposed critical vulnerabilities in vaccine supply chains, highlighting the need for robust manufacturing for rapid pandemic response to support CEPI's 100 Days Mission. We develop a discrete-event simulation model to analyze supply chain disruptions and enables policymakers and vaccine manufacturers to quantify disruptions and assess mitigation strategies. Unlike prior studies examining components in isolation, our approach integrates production processes, quality assurance and control (QA/QC) activities, and raw material procurement to capture system-wide dynamics. A detailed mRNA case study analyzes disruption scenarios for a facility targeting 50 million doses: facility shutdowns, workforce reductions, raw material shortages, infrastructure failures, extended procurement lead times, and increased QA/QC capacity. Three main insights emerge. First, QA/QC personnel are the primary bottleneck, with utilization reaching 84.5% under normal conditions while machine utilization remains below 33%. Doubling QA/QC capacity increases annual output by 79.1%, offering greater returns than equipment investments. Second, raw material disruptions are highly detrimental, with extended lead times reducing three-year output by 19.6% and causing stockouts during 51.8% of production time. Third, the model shows differential resilience: acute disruptions (workforce shortages, shutdowns, power outages) allow recovery within 6 to 9 weeks, whereas chronic disruptions (supply delays) cause prolonged performance degradation.

Motivation & Objective

• Identify system-wide bottlenecks in vaccine manufacturing under normal and disrupted conditions.
• Quantify how disruption scenarios affect production performance and pandemic response capabilities.
• Evaluate mitigation strategies and resilience investments for improving vaccine supply chain robustness.

Proposed method

• Develop a modular discrete-event simulation model in Julia that integrates production processes, QA/QC activities, and raw material procurement.
• Incorporate stochastic lead times, processing times, inventory management, and resource contention for QA/QC and materials.
• Enable dynamic scenario generation and parallel replications to assess multiple disruption scenarios.
• Validate the model via unit tests, expert face validation, and sensitivity analyses.
• Provide a decision-support framework to compare mitigation strategies and their impact on KPIs.

Experimental results

Research questions

• RQ1 How do raw material procurement disruptions and QA/QC workforce constraints interact to affect vaccine manufacturing performance during pandemic response?
• RQ2 What mitigation strategies most effectively improve resilience given QA/QC bottlenecks and material lead-time variability?

Key findings

• QA/QC personnel are the primary bottleneck, with utilization at 84.5% under normal conditions while machine utilization remains below 33%.
• Doubling QA/QC capacity increases annual output by 79.1%.
• Raw material disruptions are highly detrimental, with extended lead times reducing three-year output by 19.6% and causing stockouts during 51.8% of production time.
• Acute disruptions (e.g., workforce shortages, shutdowns, power outages) lead to recovery within 6–9 weeks, whereas chronic disruptions (supply delays) cause prolonged performance degradation.