API Innovation Center works to reshore generic drug production

While the United States has the capacity to make the country’s most critical drugs, much of it is sitting idle, according to the API Innovation Center (APIIC). In 2025, more than $500 billion was committed by pharmaceutical companies to domestic drug manufacturing investment. However, the U.S. should repurpose existing FDA-approved sites which could add nearly 30 billion doses, while getting up to speed in a fraction of the time needed to build new facilities, APIIC contends.

Last month, APIIC announced it developed and refined a new synthetic manufacturing approach capable of supporting large-scale production of metoprolol succinate, the active pharmaceutical ingredient (API) used in the widely prescribed beta-blocker metoprolol.

The drug is a cornerstone therapy for hypertension and other cardiovascular conditions. It ranked as the sixth most prescribed drug in the U.S. in 2023 and remains the most prescribed systemic beta-blocker, according to APIIC. Yet, multiple metoprolol injection products appear on the drug shortage list maintained by the American Society of Health-System Pharmacists, underscoring ongoing vulnerabilities in the supply of widely used generic medicines.

For APIIC, the metoprolol project represents more than a manufacturing milestone for a single drug. It also illustrates the organization’s broader strategy to rebuild domestic capacity for critical generic medicines by combining new manufacturing technologies with underutilized U.S. production infrastructure. Significant pharmaceutical production capacity already exists in the country, much of it sitting idle and available to help strengthen domestic supply chains, according to APIIC.

Idle US capacity

APIIC’s work to expand domestic production aligns with a broader industry push to improve the nation’s pharmaceutical supply chain resilience.

According to Charlie Lyon, vice president of manufacturing, procurement, and logistics at APIIC, that offshoring trend has affected multiple layers of the pharmaceutical supply chain.

“It’s been roughly a 30-year trend,” Lyon said. “This shift offshore applies not only to finished drug products, but also to APIs and the key starting materials that go into making them.”

At the same time, a large portion of the country’s existing pharmaceutical infrastructure remains underutilized. According to APIIC, roughly 25% of U.S. generic manufacturing sites they surveyed are operating at or below 50% utilization due to the long-term offshoring trend.

That unused capacity represents a significant opportunity to expand domestic production without the need to build entirely new facilities. APIIC estimates that existing infrastructure could produce roughly 30 billion additional doses of medicines domestically.

“Our end-to-end solution is to develop the API and then move that into finished drug products through our ecosystem of manufacturing partners,” Lyon said. “Those finished drug manufacturers already have available capacity. The infrastructure is there, and we intend to start filling it.”

Assessing the repercussions of offshoring

While the presence of underutilized manufacturing capacity suggests an opportunity to rapidly expand domestic production, the reasons that capacity exists in the first place are largely economic. Over the past three decades, much of the production of generic pharmaceuticals has shifted overseas to countries such as China and India as manufacturers pursued lower costs and higher margins.

A recent analysis by U.S. Pharmacopeia (USP) found that generic drugs come primarily from India, while the U.S. produces only 12% of the APIs for medicines going to patients in this country. Similarly, a study from Washington University found that 83 of the top 100 generic drugs taken by Americans have no domestic source of key ingredients. The COVID-19 pandemic highlighted the fragility of this globalized supply chain and the risks associated with relying heavily on a limited number of international suppliers.

“If there is a geopolitical disruption, a trade issue, or a quality event overseas, U.S. patients can feel the impact very quickly,” Lyon said. “From our perspective, national security and public health are tightly linked. If we cannot reliably produce critical generic medicines domestically, we are exposed.”

In 2024, APIIC was awarded $14 million by the U.S. Health and Human Services (HHS) Administration for Strategic Preparedness and Response’s (ASPR) Center for Industrial Base Management and Supply Chain (IBMSC) to lead the development and domestic production of three critical APIs used in the treatment of asthma, hypertension, and anxiety disorders.APIIC is focusing on low-margin generics with highly concentrated global supply chains. The organization prioritizes APIs identified by the ASPR as critical to national health security.

“Our pipeline is aligned with APIs that ASPR has identified as critical to national health security, particularly essential generics where supply disruptions would have an immediate impact on patient care,” Lyon said. “These include medicines used in hospital settings, oncology, and other life-sustaining therapeutic areas.”

In late 2024, APIIC awarded a contract to Missouri-based Sentio BioSciences to advance the development and domestic production of two pharmaceutical molecules that have historically faced shortages: propofol, which is used during general anesthesia for medical procedures, and a local anesthetic bupivacaine which currently has no U.S. API source.

Advanced manufacturing, new synthetic routes

A key component of APIIC’s strategy to strengthen domestic pharmaceutical production is modernizing how APIs are manufactured through advanced technologies.

One example is the organization’s development of a new synthetic manufacturing approach for large-scale production of metoprolol succinate API, which applies continuous-flow chemistry integrated with next-generation separation technologies designed to mirror large-scale manufacturing conditions.

“Traditionally, both APIs and key starting materials have been produced in batch processes. Developing new synthetic routes using continuous processes represents a significant shift,” said Lyon.

Continuous manufacturing can improve efficiency, reduce waste, and enhance process control — advantages that are particularly important when attempting to compete with lower-cost overseas production.

“If we can produce APIs and key starting materials more efficiently and with less variability, we improve both cost competitiveness and reliability,” Lyon said.

APIIC demonstrated this approach through its work on metoprolol succinate. In one critical upstream step, the team achieved rapid formation of metoprolol base in minutes using advanced processing methods rather than the hours typically required in traditional batch manufacturing.

The organization has applied similar approaches to other medicines as well. In 2022, APIIC worked to reestablish domestic production of lomustine, a chemotherapy drug used to treat aggressive brain cancers. At the time, there was no U.S.-based source of the drug’s active pharmaceutical ingredient.

Using advanced drug manufacturing techniques — including continuous-flow processing — the organization helped establish a new domestic pathway for lomustine API production, demonstrating how modern manufacturing technologies could help restore U.S. production of critical generic medicines.

By combining modern manufacturing technologies with underutilized infrastructure, APIIC hopes to accelerate the reshoring of critical generic medicines while strengthening the long-term resilience of the U.S. pharmaceutical supply chain.Time is of the essence in addressing these challenges, according to House Select Committee on China Chairman John Moolenaar (R-Mich.), who held a congressional hearing last week regarding the supply chain challenges facing this country.

“If China restricted API exports tomorrow in the same way it has restricted rare earth exports, then American hospitals and pharmacies would begin running short on essential medicines,” Moolenaar warned.