Balancing Chemistry, Scale, and Safety

By TPN Editorial TeamNovember 4, 2026

SPONSORED CONTENT: As complex molecular pipelines push drug developers toward highly reactive processes, specialized infrastructure, rigorous thermodynamic profiling, and early sponsor collaboration are paramount to de-risk industrial-scale manufacturing.

As pharmaceutical pipelines incorporate increasingly complex molecular structures, the demand for non-standard, highly reactive chemistry continues to grow. However, many drug developers lack the specialized containment facilities and regulatory approvals required to safely execute high-risk reactions in-house.

Speaking during an interview at CPHI Milan, Daniel Latassa, Business Development Manager at Valsynthese, revealed that within the hazardous chemistry space, customers are tending to want to combine chemistry, scale up, and safety at the same time. “Our customers are interested in very specific technologies that we can deal with, such as nitration — which is our legacy — as well as hydrogenation, phosgenation, Grignard chemistry, and all this nasty chemistry that they cannot deal with. That’s our expertise,” he said.

Overcoming Scale-Up Challenges

Transitioning hazardous processes from benchtop R&D volumes to industrial-scale production introduces significant chemical engineering hurdles, particularly regarding thermal management, mass transfer, and reactive accumulation. “The main challenge is scale,” Latassa explained. “It’s not the same when you have scale in the laboratory at small volumes compared to when you have to transfer the process to larger volumes, like 100- to 1000-liter reactors — it changes everything. You have changes in heat transfer, mixing transfer, and effects on the accumulation of reactive species.”

To mitigate thermal runaways and process instability, rigorous thermodynamic profiling and energetic safety testing must be conducted before scaling unit operations. “As a CDMO expert in hazardous chemistry, we need to control all those parameters, which means controlling the process parameters, the energy profile, and the cooling profile,” Latassa noted. “For that, we have expert colleagues who develop the processes specifically to transfer them safely to an industrial scale.”

Strategic Value of Early Collaboration

Early technical alignment between sponsor and contract manufacturer is essential for de-risking complex manufacturing pathways and avoiding costly delays during tech transfer. “The earlier we are in contact with the customer, the better,” Latassa emphasized. “It’s rarely the first process from literature that will be suitable for industrialization. We need to speak with the customer and know details on the technical package we receive — such as whether they have specialized analytical methods or established cleaning procedures.”

In a multi-purpose manufacturing environment, raw material compatibility and equipment decontamination represent critical baseline criteria. “Since we work in a multi-purpose environment, a cleaning step is the most critical aspect,” Latassa added. “If we cannot clean the installations, we are stuck and cannot move forward. The earlier you get those details from the customer, the better, so you do not face unpleasant surprises while developing the process.”

Infrastructure and Legacy

“I would summarize our positioning in three words: heritage, infrastructure, and people,” Latassa remarked. “Heritage, because Valsynthese belongs to the Swiss Society of Explosives (SSE) Group, giving us deep knowledge of nitration technology. The second aspect is infrastructure and dedicated equipment.”

Operating within specialized containment suites allows CDMOs to safely run reactions involving toxic or highly volatile reagents. “We have dedicated equipment to perform hazardous chemistry, such as a phosgenation cabin in the R&D department where we can develop processes using phosgene as a reactive reagent,” Latassa detailed. “We also have high-pressure hydrogenation facilities with Hastelloy reactors that can go up to 250 bar, and we produce Grignard reagents via flow chemistry rather than batchwise. All these particular types of equipment are mandatory to perform hazardous chemistry.”

Future Market Trends

Looking toward the future of fine chemicals and advanced intermediates, market expectations are shifting beyond simple cost metrics toward supply security, process sustainability, and continuous manufacturing platforms. “The first key trend is supply chain resilience,” Latassa highlighted. “Most of our customers are not looking only for a low-cost process — it is really important to get a supplier which is reliable, providing quality, flexibility, and security of supply.”

Additionally, the rising complexity of small-molecule APIs and advanced intermediates is driving wider adoption of continuous flow technologies to perform energetic reactions safely. “The second aspect is the complexity of molecules and processes, which opens the door for CDMOs like Valsynthese that are experts in manipulating hazardous chemistry,” Latassa noted. “The third point is sustainability and efficiency — developing processes that deliver quality while using fewer solvents and less energy to generate less waste.”

Ultimately, accelerating time-to-market while managing process safety remains the overarching goal for early-phase biopharma sponsors. “It’s not just about making chemicals,” Latassa concluded. “The core question is: how can we transfer complex structures and complex chemistry into a reliable, scalable, and sustainable process for industrialization?”

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