As part of a more than $70 billion commitment to domestic capital and R&D spending over the next several years, biopharmaceutical company Merck is investing in both biologics and small molecule manufacturing sites and capabilities in the United States.

“The investments that we’re making are focused on the areas of growth in the business,” says Dave Maraldo, executive vice president and president of the Merck Manufacturing Division, with the goal of ensuring the “modalities, technologies, and customer needs required to deliver future supply are aligned with where the portfolio is headed.”

Merck’s manufacturing operations are headquartered in Rahway, New Jersey, with production facilities for human health products at five locations in the U.S. and Puerto Rico. The company also owns or has an interest in manufacturing plants or other properties in Africa, Asia, and Europe, creating an integrated global network of both internal and external sites designed to provide resilience and agility.

“We’ve always had this principle — manufacture closest to where the patients that we serve live,” according to Maraldo, who is responsible for the company’s worldwide human health manufacturing and supply operations across a global network of sites for pharmaceuticals, vaccines, and biologics.

Maraldo, who has been with the company for 27 years serving in a series of leadership roles, took the helm of the Merck Manufacturing Division in May 2026 having led its global biologics operations from 2022 to 2025.

While the broader pharmaceutical industry appears to be making a fundamental shift toward biologics and away from small molecules, Maraldo describes Merck’s investment approach as a “follow the science” mindset.

“That’s actually what drives a lot of what we go after,” he said. “Opportunistically, it’s hard to say if that balance will shift. It depends on where the science heads.”

Biologics and small molecules

Industrywide there’s been a lot more recent discovery around biologics relative to small molecules, Maraldo noted. Still, he pointed out that Merck’s recently announced U.S. infrastructure investments are focused on both modalities.

“If you look at the investments that we publicly disclosed between Virginia and Delaware, we have one in small molecules and one in biologics — we have equal confidence in the growing capability of both,” Maraldo said. “If I go back and I look at the molecules that are making it through clinical trials, not only for our organization but around the industry, it still feels like a pretty balanced split between the two — between small molecules and biologics.”

In October 2025, Merck broke ground on a $3 billion manufacturing center of excellence in Virginia. The new facility will expand its Elkton site, where the company has operated for 85 years, including both active pharmaceutical ingredients (APIs) and drug product investment supporting small molecules.

“It’s small molecule end-to-end,” Maraldo said, from “API all the way through drug product and ultimately moving it into our packaging site into North Carolina.”

In April 2025, Merck started construction of a new $1 billion biologics center of excellence in Wilmington, Delaware. The site is planned as a launch and commercial production center for next-generation biologics — including antibody-drug conjugates — and will become the future U.S. manufacturing home for the company’s blockbuster cancer therapy Keytruda.

Wilmington is envisioned as an “all-comers” facility, according to Maraldo. “We should be able to do trispecific [antibodies], bispecific monoclonals, antibody-drug conjugates, from drug substance all the way through primary containers and primary packaging,” he said.

“We have cell culture across all of our large molecule products,” Maraldo added. “It’s a technology we want, and we want to develop internally, and we want to have the ability to commercialize and then ultimately manufacture.”

The potential of macrocyclic peptides

Biologics are a “heavy focus” for Merck which is actively developing macrocyclic peptides, intermediate-sized molecules that combine the precision of biologics with the oral delivery advantages of small molecules, according to Maraldo.

“Macrocyclic peptides are very heavy focused antibody-drug conjugates for us,” he said. “Those aren’t technologies that we’ve typically operated within. So, [we’re] reconfiguring the manufacturing network and making sure that not only the assets and the infrastructure meet those future needs, but the capabilities of the individuals that are ultimately going to be responsible for producing these products are lined up.”

While macrocyclic peptides offer a unique combination of potency, selectivity, and drug-like properties, their structural complexity has historically made them difficult and costly to manufacture using traditional peptide synthesis techniques, according to David Thaisrivongs, executive director and head of biocatalysis at Merck.

Thaisrivongs told Pharma Manufacturing that new manufacturing approaches are emerging that aim to improve efficiency, scalability, and sustainability, while expanding access to this promising class of therapeutics.

“Solid-phase peptide synthesis, the traditional chemical workhorse for peptide manufacture, is powerful at making peptides but it has a lot of scalability challenges both at Merck and in the field,” Thaisrivongs said.

Rather than relying solely on traditional solid-phase peptide synthesis, Merck researchers in a recent Science paper presented a new enzyme-driven manufacturing process for enlicitide decanoate, an investigational oral macrocyclic peptide designed to lower LDL cholesterol, in which they were able to reduce the production steps by more than half.

“The paper itself represents an accumulation of hundreds of innovations across lots of areas of chemistry, biology, and engineering,” Thaisrivongs noted. “If I were to highlight the two primary levers that we brought to bear to improve the manufacturing efficiency, they are the route of synthesis and the purification of the peptide itself.”

Ultimately, Merck contends that macrocyclic peptides have the potential to enable the treatment of diseases that have long evaded traditional small molecule approaches and help improve access to medicines typically administered via injection or intravenously.