Merck expands its HPAPI and ADC manufacturing capabilities, capacity

The investment will allow large-scale manufacturing of compounds that have the potential to treat cancer, it said.

Completion of the expansion project is expected by mid-2022. The company expects to add around 50 full-time jobs starting in 2021 as a result of the initiative.

The new commercial building will be one of the largest dedicated high-potent active pharmaceutical ingredient (HPAPI) manufacturing facilities specifically designed to handle single digit nanogram occupational exposure limit materials, according to Merck.

The facility will also incorporate containment areas to produce next-generation linker and payload materials for antibody-drug conjugates (ADCs), it said. 

Andrew Bulpin, head of process solutions, Merck, told BioPharma-Reporter: “We plan to incorporate process, technology and infrastructure improvements in the new facility that will significantly enhance our current capabilities.” ​

ADC supply chain  ​

The expansion in Madison will nearly double Merck's HPAPI kilolab capacity and greatly supplements its current manufacturing infrastructure for current and future customers, he said.

Merck has a wide array of facilities that contribute to the ADC supply chain, producing produce monoclonal antibodies at its Martillac, France site and make critical starting materials in its Sheboygan, Wisconsin facility that feed into its HPAPI facilities in Madison. 

It manufactures activated polyethylene glycols (PEGs) in Schaffhausen, Switzerland that get incorporated into ADC drug candidates and once all of the necessary components are available, Merck performs the downstream conjugation in St Louis.

Boosting developmental candidate output​

When asked how the enhanced site will improve efficiency in the production of ADCs, whether timelines would be reduced, Bulpin told us:

“The addition of new HPAPI capacity will enable Merck to add more developmental candidates and expedite the manufacture of HPAPI linker/payload materials required for new treatments.  ​

“In addition, we continue to enhance the containment and processing infrastructure to increase both the safety and processing efficiency of these key materials.  The new suites incorporate the latest containment infrastructure and are amenable for continuous processing, which can greatly increase the production efficiencies and throughput compared to traditional production suites.”​

ADC production is complex ​

The development and production of ADCs is complex, he continued, requiring stringent containment infrastructure and expertise in a number of different technologies. 

“New candidates with novel therapeutic pathways and increasing safety standards necessitate a continuous review and upgrade of handling practices and infrastructure.  This new production facility will bring the latest in containment technology to our existing capabilities and help ensure we can confidently produce the materials required for these novel therapeutics.”​

ADCs transcend a broad range of clients from small, virtual to large multinational, said Bulpin when asked about target customers for this expanded facility.

“We work with the entire spectrum of clients in this technology area. While we cannot disclose the customers we work with, we are involved in seven out of the nine commercial ADCs with at least one of our sites.”​

For a pharma or biotech company developing ADCs, there are clear advantages to outsourcing to a firm that offers a variety of manufacturing services. Will this new plant potentially offer the bioconjugation of antibodies and cytotoxins and fill/finish?

“ADCs typify the ‘perfect storm’ of supply chain challenges. Their inherent complexity favors companies that can offer a broad range of services necessary to their manufacture.  This is complicated even more as many of the materials have been given an accelerated regulatory approval pathway and this issue leaves little time to change suppliers during clinical development.  ​

“While this new investment primarily bolsters our linker/payload manufacturing capacity, we are evaluating other unit operations including fill/finish to better serve our clients and minimize the challenges and supply chain complexity that exists within the current network of CMOs."​

Beyond oncology ​

Does Merck see interest in ADCs fueled by the exploration of their use outside of oncology, into other areas such as inflammatory disease and for antimicrobial targets?

“We see the ADC market expanding significantly in the coming years both within oncology and also targeting indications outside oncology as well.  There are programs being evaluated for inflammatory, antimicrobial/antibacterial and other indications as well.”​

ADCs have experienced incredible growth over the last decade, and Merck is very confident that they and the wider bioconjugate technologies will continue to be a significant driver of new therapeutic development for years to come, he remarked.

“With more than 35 years of experience in this space, we have been a frontrunner in the development and manufacturing of biologics, conjugation processes and small molecules. This investment underscores our commitment to working with innovators to bring new treatments to patients quickly and more efficiently,”​ commented Bulpin.