Chemical and Physical Transformation Monitoring by Raman and IR Spectroscopies in Pharmaceutical Development

During the lengthy process of pharmaceutical development, an Active Pharmaceutical Ingredient (API) or its intermediates can go through many physical and chemical changes. These changes are needed to produce the API with the correct chemical structure and physical property. Monitoring the progress of these transformations is important for the process understanding as well as serving as a tool for in-process control (IPC) to ensure the completeness of the transformation. IR and Raman Spectroscopies are sensitive to both chemical and physical changes of a compound and have evolved into useful tools in our lab for monitoring both chemical and physical transformations. They can be used to monitor the progress of the chemical reaction leading to the desired product, the slurry-to-slurry form transformation leading to the desired crystalline form, and the instability of API leading to undesired degradant. When used in-line, they can also be used to study the kinetics of a chemical reaction as well as the rate of crystalline form conversion. They have been used as an IPC for chemical reactions and a tool to monitor dehydration form conversion during API drying. We will present a wide range of examples to illustrate the versatility of these spectroscopy tools for the chemical and physical transformation monitoring.
Presented John Wasylyk, Senior Principal Scientist at Bristol-Myers Squibb

John Wasylyk, Ph.D. is a Senior Principal Scientist at Bristol-Myers Squibb Company.  He leads a vibrational spectroscopy group who are focused on developing non-invasive, sustainable methods designed to enhance productivity and generate process knowledge.  The spectroscopy-based methods have been deployed in areas ranging from early scale-up to manufacturing environments at various BMS sites.   The developed methods encompass both small molecules and biologics.  In addition, the group provides hands-on training and oversees open-access spectrometers for chemists and engineers.  John is currently the Marketing Chair for the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS), and Pharmaceutical and Biopharmaceutical Section Co-Chair for SciX 2019.
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.
Followed by Utility of Raman spectroscopy in continuous processing of liquids and solids
An important consideration in successful continuous manufacturing is integrating analytical tools into the flow. In batch reaction monitoring, on-line and at-line analyses enable Quality by Design (QbD) and ensure stable operations. Intense reaction conditions, non-traditional chemistries, high throughput and speeds, and miniaturized reactors are challenging environments for analytical tools originally developed for batch reaction monitoring. We present process Raman technologies adapted for continuous manufacturing processes in liquids and solids. Over the last 20 years, Raman spectroscopy has become an established technique for process monitoring and control, with applications in continuous manufacturing of liquids and solids.
We will show In-line Raman was successfully used to monitor continuous reactions involving corrosive intermediates and end products. In-line measurement capability and fast feedback provided by process Raman enabled remote monitoring and control of hazardous reactions and improved process robustness.
An additional consideration for pharmaceutical solids monitoring is representative sampling. Representative sampling of solids is an important consideration to ensure proper process understanding and for PAT-enabled process control. An important physical attribute which affects representative sampling is optical scattering (or turbidity). We present applications in monitoring solids manufacturing where optical scattering is harnessed using a large volume sampling probe to achieve representative sampling.
Presented by Karen Esmonde-White, Senior Marcom Specialist at Kaiser Optical Systems Inc.

Karen Esmonde-White is a Senior Marcom Specialist at Kaiser Optical Systems, Inc. She completed her Ph.D. in Biomedical Engineering at the University of Michigan in 2009 in Prof. Michael Morris’s laboratory, and has a M.Eng. in Pharmaceutical Engineering and a M.S. and B.S. in Chemistry. Karen is also an adjunct faculty researcher at the University of Michigan Medical School, where she works to develop Raman spectroscopy for new biological and clinical applications. In addition to her research, Karen is an active volunteer in the analytical chemistry community including her volunteer work for the SciX conference, Society for Applied Spectroscopy, and the Coblentz Society. She serves as an ad-hoc reviewer for spectroscopy, clinical, and biomedical optics journals, was Program Chair for the 2018 SciX Conference, and continues to serve as the Biomedical Program Co-Chair for SciX.