Sterile injectable drug production is experiencing unprecedented growth in both Europe and the USA. The surge is driven by multiple factors, including increased demand for biologics, vaccines, and other high-value therapies; stricter regulatory requirements; supply chain vulnerabilities exposed by global disruptions; and a shift toward reshoring pharmaceutical manufacturing. As the need for injectable medications rises across all therapeutic areas, pharmaceutical companies and Contract Development and Manufacturing Organizations (CDMOs) are facing new challenges and opportunities.

Regulatory changes influencing the production of sterile injectables

Strengthened Sterility Standards: Evolving regulatory frameworks in the US and EU are raising the bar for sterile manufacturing. The EMA's revised Annex 1 (effective August 2023) explicitly encourages the adoption of new technologies to improve sterility assurance and reduce contamination risks.

Regulatory authorities now require stricter adherence to aseptic processing protocols, incentivizing manufacturers to invest in advanced systems such as isolators, restricted access barrier systems (RABS), and even robotic filling lines.

These measures minimize human intervention in sterile areas, in line with the regulatory authorities' priority: ensuring product safety and quality. The FDA has also prioritized modernizing manufacturing guidelines, for example through programs promoting advanced manufacturing technologies, to improve drug quality and prevent shortages. In practice, this means that manufacturers of sterile injectable products must design facilities and processes that meet more stringent Good Manufacturing Practice (GMP) requirements (e.g., rigorous environmental monitoring and automated sterility checks), in accordance with FDA and EMA updates.

Current compliance investments, such as upgrading legacy cleanrooms with barrier systems and improving contamination control, are considered essential to meet evolving regulatory expectations and avoid compliance pitfalls.

Regulatory incentives and harmonization: Beyond enforcing stricter standards, regulators are also fostering innovation and capacity building. The FDA has launched initiatives and published the guidance document for the Advanced Manufacturing Technologies Designation Program (AMT) in December 2024. The FDA encourages the early adoption of advanced manufacturing technologies by the pharmaceutical industry (1), which can improve the reliability and robustness of the manufacturing process and benefit patients by enhancing product quality and reducing drug development time, or increasing or maintaining the supply of drugs that are life-supporting, critical to providing health care, or subject to shortages.

At the same time, agencies are collaborating internationally to harmonize requirements. For example, the PIC/S and the WHO have adopted the EMA's Annex 1 principles, which helps streamline global operations. In the United States, policy discussions emphasize the need for a sustainable market for sterile injectables, suggesting long-term contracts and infrastructure subsidies to ensure manufacturers can maintain their investments in quality.

Companies that proactively modernize their filling lines, use automation, and enhance their quality systems are better positioned to meet these growing demands and secure approval for new injectable products. In the face of drug shortages, regulatory authorities are closely monitoring quality issues, making sterility and supply reliability a top priority.

Supply chain evolution and security strategies

Disruptions and dependence: The global sterile drug supply chain has been stress-tested in recent years, revealing critical vulnerabilities. The COVID-19 pandemic and geopolitical shocks (such as the war in Ukraine) have highlighted the overreliance on overseas manufacturing of essential medicines.

In some categories, an estimated 70-80% of global capacity (for active ingredients and injectable drug components) is concentrated in India, China, and other Asian countries (2)

This globalization of production has put the United States and Europe in a difficult situation when export restrictions, factory closures, or logistical bottlenecks hit. Drug shortages are a striking illustration: in 2023, 61% of drug shortages in the United States involved sterile injectables (3), and many of these were generic hospital medicines whose supply chains relied on a few foreign sources. These disruptions have highlighted that any single failure-whether a quality defect at a single supplier or a pandemic-related lockdown-can lead to global shortages. As a result, manufacturers and health authorities are rethinking how to ensure the continuity of supply of injectable medicines.

Diversification and stockpiling: To mitigate risks, companies are adopting multi-pronged supply chain strategies. One is to diversify supply, qualifying multiple suppliers of active pharmaceutical ingredients where possible. Another strategy is to build buffer stocks or strategic stockpiles of essential injectable medicines. Although just-in-time practices predominated before the pandemic, there is growing recognition that maintaining safety stocks of essential injectable medicines can cushion short-term disruptions.

The United States and the EU are evaluating frameworks to require greater supply chain resilience; for example, the EU has considered requiring drug manufacturers to maintain an emergency stockpile of essential medicines (4)....