Merck expanded its HPAPI and ADC manufacturing plant located in Verona near Madison, Wisconsin, US. Credit: Merck via PR Newswire.
The expanded facility will enable large-scale production of more potent compounds for potential cancer treatment. Credit: PRNewsfoto/MilliporeSigma.
Merck has launched new ChetoSensar™ technology for alleviating the solubility challenges of ADCs. Credit: Merck via PR Newswire.

US pharmaceutical company Merck expanded its high-potent active pharmaceutical ingredient (HPAPI) and antibody-drug conjugate (ADC) production capabilities and capacity with a new contract drug manufacturing organisation (CDMO) facility in Verona near Madison, Wisconsin, US.

Developed with an estimated investment of $69m (€59m), the new facility was opened in June 2022. The expansion facilitated the large-scale production of increasingly potent compounds for potential cancer treatment, creating 50 full-time new jobs.

The expansion has doubled the company’s HPAI production capacity, positioning it as one of the biggest single-digit nanogram occupational exposure limit (OEL) CDMO providers in the world. HPAPIs are assessed using a potency scale, where the most powerful ones have measurements below ten nanograms per cubic metre. Handling HPAPIs with single-digit nanogram potency requires extremely specialised procedures, as indicated by the OEL designation.

Merck’s ADC manufacturing facility expansion

Merck added a new 6,500m² (70,000ft²) commercial building dedicated to the HPAPI manufacturing facilities in its established Madison campus.

The new structure features one of the largest single-digit nanogram containment production facilities for the manufacturing of HPAPIs. It handles nanogram-single-digit OEL materials, allowing for a continuous flow of ADCs production.

The Madison facility is the first commercial plant in the US dedicated to the development of ADC and handles highly active materials.

The new building expands the company’s ADC manufacturing capabilities together with the existing campus in St Louis, Missouri, which specialises in ADC bio-conjugation, APIs, excipient, and adjuvants manufacturing.

The expansion doubled the Madison facility’s HPAPI kilo lab capacity, allowing the company to accelerate the manufacturing of HPAPIs, ADC linker and payloads, as well as complex APIs.

The company launched ChetoSensar™ technology to address the solubility challenges of ADCs in October 2021. It improves ADC solubility, offering hope to ADCs that had previously been terminated.

The new DOLCORE™ platform significantly reduces the time required for ADC development and manufacturing, accelerating the time to market for a new Dolostatin-based ADC payload by up to a year.

ADC details

ADCs are a new group of medications designed as a targeted therapy for cancer treatment, developed by linking a cytotoxic anticancer drug payload to a highly specific antibody via a biodegradable linker.

The biochemical reaction between the antibody and targeting antigen absorbs the ADC into the cancer cells where the cytotoxic drug is released to destroy the cancer cells.

The production of ADCs is complex and requires a strict containment infrastructure. Its structural exceptionality requires experience in various technologies for small and large molecules, as well as analytical capability.

There are currently 13 different ADCs in the world that hold approval, with the ADC market projected to hit $15bn by 2030.

Details of Merck’s ADC manufacturing facility in Madison

Merck’s existing manufacturing facility in Madison handles HPAPIs, APIs, linkers, cytotoxic materials, payloads, and secondary metabolites.

The facility has a wide range of manufacturing spaces and machinery. It not only has the requisite versatility for the multi-step synthesis of complex and HPAPIs but it can support the development and production of complex small molecules from pre-clinical to commercial scale.

Pilot and production-scale facilities and equipment are certified for handling Safebridge® Cat IV materials and can support HPAPI manufacturing. Most of the kilo labs are also Safebridge Cat IV qualified.

Some of the safety features of the facility include differential room pressure designed for containment, airlocks, HEPA-filtered single-pass air and contaminants capturing with safe-change filters.

The company has two sites in Madison for process development with process scale-up laboratories.

The Madison facility’s experience in linker and payload technology manufacturing combines with the St Louis’ clinical and commercial ADC facilities to provide comprehensive supply chain solutions.

The solutions include the company’s end-to-end BioReliance® capabilities for process development and cGMP monoclonal antibodies manufacturing for clinical supplies.

Marketing commentary on Merck

Merck is a global pharmaceutical company that delivers vast expertise in both clinical and commercial manufacturing. Furthermore, it has more than 35 years of experience in the production and manufacture of small molecules, biologics, and ADC technologies.

In December 2022, Merck collaborated with US-based biotech company Kelun-Biotech to develop seven experimental preclinical ADCs for the treatment of cancer.

Merck holds the exclusive global licence to research, develop, manufacture and commercialise multiple experimental preclinical ADC drugs, as well as exclusive options to secure further licences to ADC candidates while Kelun-Biotech retains the right to research, develop, manufacture and commercialise certain licensed and option ADCs for Mainland China, Hong Kong and Macau, as per the agreement.

The company holds global rights to the Merck brand except in the US and Canada, where it is known as Merck & Co. Outside of these countries, it is known as MSD.