Crystallization Monitoring of Active Pharmaceutical Ingredient By Raman Spectroscopy
07th October 2020 | 10.00 am EST | John-David McElderry, Scientist at Biogen and Maryann Cuellar, Life Science Product Manager at Kaiser Optical Systems, Inc. |BOOK FREE SEAT
Crystallization of active pharmaceutical ingredients (API) as a process of purification, final crystal form selection, and/or particle size control is an important step in pharmaceutical manufacturing processes. Some crystallizations exhibit high degrees of complexity, making process development optimization and control challenging. In this study, Raman spectroscopy was utilized to monitor in real-time the polymorph form transition (Polymorphic form change: A → B → C) of an API in development at Biogen. Using polymorph reference materials, a multivariate approach was developed to identify the in-situ crystalline form of the API during the crystallization. The process started by dissolving API in dichloromethane in a jacketed lab reactor. A distillation was then performed to reduce the water content. Then a constant-volume distillation was implemented removing dichloromethane while iso-propanol was added (Polymorphic form nucleation of A). After all the dichloromethane was removed, seeds of the target form (C) were added and the mixture was held overnight. The real-time identification approach was capable of detecting the final form change (A → B → C or A → C).
Presented by John-David McElderry, Scientist at Biogen
John-David McElderry graduated from University of Michigan with his PhD in 2012 and has been an analytical scientist and PAT expert in the Pharma/Biotech industry for seven years. He started his career at Vertex Pharmaceuticals creating PAT applications for the first continuous DP manufacturing rig and helped develop the first real-time release strategy in the industry. He is currently at Biogen where he has developed PAT-based control strategies for continuous flow chemistry of small-molecule drugs and continuous synthesis of oligonucleotide drugs. He is interested in enabling real-time control of quality attributes in pharmaceutical manufacturing through the application of smart sensors and machine learning.
Followed by an Industry Perspective Presented by Maryann Cuellar, Life Science Product Manager at Kaiser Optical Systems, Inc.
Maryann Cuellar is the Life Science Product Manager at Kaiser Optical Systems, Inc. She has been providing application support for pharmaceutical implementation of Raman spectroscopy for 15 years at Kaiser with recent years devoted to advancing bioprocess applications of Raman. She holds a Master of Science Degree in Analytical Chemistry with a research focus in chemometrics and process analytical technology.
Sponsored by Kaiser Optical Systems, Inc
Kaiser Raman Bioprocessing Solutions
Kaiser Optical Systems, Inc. has been at the leading edge of in situ PAT in upstream bioprocessing for over 10 years. Kaiser Raman technology is robust, scaleable, and transferable. During process development, Raman enables adoption of QbD principles to define manufacturing design spaces, optimize process conditions, and demonstrate process robustness and quality. In production, improvements to product quality and yield have been demonstrated by employing Raman-based control strategies. In recent years, Kaiser Raman successes in upstream bioprocessing have expanded into downstream and cell / gene therapy applications.