ISP has announced that it is focusing efforts at its pharmaceutical fine chemicals facility in the US to better support pharmaceutical companies working with low-temperature chemistry. Configured to accommodate kilo-scale development of synthetic routes utilizing highly efficient low-temperature chemistry, the Columbus, Ohio plant is optimized for seamless scale-up to commercial volumes of intermediates and APIs. The facility offers options to pharmaceutical companies that seek to leverage the efficiencies of low-temperature reactions, secure the highest possible yield and move quickly to large-scale production. Historically, the complexity in scaling up low-temperature chemistry has driven many process development groups to convert to less efficient, lower yielding process chemistry. ISP addresses this technology gap with a comprehensive manufacturing program dedicated to low-temperature synthesis.

According to John Flanagan, senior director, global technical and business development of pharmaceuticals, securing low-temperature synthesis technologies at both laboratory and commercial-scale should be considered a practical option for pharmaceutical companies focused on optimal production and cost efficiencies. “Low-temperature chemistry is a very efficient route to many of today’s chemistries, such as chiral synthesis and Suzuki couplings,” he said.

“Yet we continue to hear from pharmaceutical process development groups that they choose to change course in the scale-up phase because the economics are not practical at full-scale or the complexity in managing low-temperature reactions in the metric tonne range has limited the options available on an outsourcing basis. At ISP, we have a proven track record in transitioning low-temperature reactions from laboratory scale to commercial quantities. In utilizing our low-temperature capabilities, more pharmaceutical companies may use ISP to move compounds developed with low temperature reactions quickly to commercial scale, rather than convert to more costly process chemistry.”

Working with custom manufacturers to improve cost parameters

Changing dynamics within the pharmaceutical industry have prompted pharmaceutical fine chemicals producers like ISP to focus on core technology offerings and deliver higher levels of value. In 2005, ISP added a kilo laboratory suite. The 60l glass-lined Buchi AG reactor system, configured with a self-contained heating and cooling system, operates between -85°C and 200°C to mimic plant capabilities. Adding a kilo laboratory to ISP’s low-temperature portfolio has allowed the R&D and manufacturing teams to advance gram and kilogram low temperature compounds, such as boronic acids, to large-scale, robust technologies with very high yields.

According to John Flanagan, ISP’s success in fine chemical scale-up is attributed to the chemists and engineers managing the project from the development phase to commercial production. “Translating project expertise at laboratory scale to successive phases of scale-up is often critical to achieve high-yield and cost-effectiveness,” he said. “At ISP, we utilize a core team of chemists and engineers throughout the lifecycle of projects.”

Securing development and manufacturing services to maximize value

According to Mike Marotta, business development manager, it is necessary in today’s custom manufacturing market to offer all of the services and manufacturing capabilities that, together, deliver on the promise of higher value. “Offering superior process development skills and the ability to scale up production within the same manufacturing location allows ISP to meet the rapid commercialization timelines requested today,” he said. “Within the low-temperature custom manufacturing arena, ISP is ready to lead the way.”

ISP’s pharmaceutical fine chemicals facility is equipped with glass-lined and stainless steel reaction vessels that range in capacity from 100gal to 4,000gal. Continuously operated since 1980, the FDA-inspected facility is engineered to support chiral synthesis, asymmetric hydrogenations, organometallics, boron chemistry, complex couplings and other major pharmaceutical fine chemical technologies.