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Home Expertise Library The Power of PAT at Scale in an API Pilot Plant

The Power of PAT at Scale in an API Pilot Plant

Eyes Inside the Process – PAT for Efficient Process Development

Process Analytical Technology (PAT) is used throughout AbbVie development labs for data-rich experimentation. In this presentation, James C. Marek, Ph.D. and Eric G. Moschetta, Ph.D. of AbbVie discuss how these tools facilitate both efficient development of API processes and fundamental understanding. 

In AbbVie's API Pilot Plant, acquisition of PAT data from FTIR, Raman, FBRM, simple sensors (conductivity, pH, etc.) and mass spectrometry is invaluable to confirm scale-up under conditions of prototypical heat, mass and momentum transport. Real-time monitoring of reactions, crystallizations, distillations, washes, drying and other unit operations allows better understanding of process trajectories. The in-situ analysis afforded by PAT allows troubleshooting in a timely manner with improved chances of getting to the right answer since PAT essentially provides “eyes” inside the process. 

Several applications of PAT at scale are provided. In one project, FTIR calibration models were developed in the lab to provide a reliable method for measuring the kinetics of what appeared to be a consecutive series reaction. The study led to incorporating an autocatalytic step in the mechanism to accurately predict the kinetics. The lab calibration models were applied to the FTIR trends from the API pilot plant, yielding quantitative predictions in excellent agreement with the expected values and the trends demonstrated scalability of the reaction.

Crystallization is another key API unit operation that also benefits from online PAT monitoring. FBRM tracking of particle chord lengths is valuable as an indicator of wet milling performance, as well as, crystallization progress. FTIR is often valuable for tracking the species concentration to confirm de-supersaturation and monitor crystallization progress. Particle vision systems are expected to provide even more benefits in the future. Raman spectroscopy was used to monitor the humidified drying of an API with dihydrate and trihydrate polymorphs, while mass spectrometry is useful for indicating drying endpoints. Using PAT in a GMP Pilot Plant required overcoming some unique challenges, and these aspects are also addressed.

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James Marek

James Marek, Ph.D.

AbbVie

Born and raised in metro Chicagoland, Jim Marek earned his BSChE at the University of Illinois, UIUC. Upon graduation his next endeavors were at Purdue University, where he completed his M.S. and Ph.D. in chemical engineering and met his wife, Sandra. His Ph.D. research with Lyle Albright led to a comprehensive understanding of coke formation mechanisms in thermal pyrolysis reactors for ethylene production. Jim moved to Augusta, GA where he began his first job with du Pont at the DOE owned Savannah River Site in Aiken, SC. Jim developed processes for the Defense Waste Processing Facility (DWPF), which came on-line in 1996 to immobilize high level nuclear wastes in a borosilicate glass matrix. After 13 years, Jim joined Abbott as one of the first chemical engineers in their Chemical R&D group. Jim has continued to work in process development through the transition to AbbVie in 2013. During his 24-year stint in pharma Jim has actively contributed to more than 30 drug pipeline projects. In 2018, Jim became the engineering liaison with the newly formed Center for PAT, and he actively uses PAT in nearly all his bench and scale-up work.

Eric Moschetta

Eric G. Moschetta, Ph.D.

AbbVie

A native of Pittsburgh, PA, Eric Moschetta obtained his BSE in chemical engineering at Case Western Reserve University in Cleveland, OH, and his Ph.D. in chemical engineering at Penn State under the guidance of Rob Rioux, studying kinetics and thermodynamics of liquid-phase interactions that are fundamental to organometallic catalytic mechanisms. He then moved to Atlanta, GA, to do postdoctoral work for Chris Jones and Ryan Lively at Georgia Tech, emphasizing molecularly-structured materials for liquid-phase catalysis, CO2 capture, and separations. While at Georgia Tech, Eric was part of the Center for Selective C–H Functionalization (CCHF), an NSF-funded center for cross-functional collaboration among chemists and engineers to drive innovations in C–H functionalization chemistry. He worked closely with Huw Davies’ group at Emory University to implement hollow fiber flow reactors for heterogeneous catalytic reactions, including C–H functionalization. He joined AbbVie in 2016 and is currently a senior scientist in the Process Engineering in Process R&D. His current research interests include flow chemistry, continuous extraction, photochemistry, kinetic modeling, photochemistry and crystallization.