(368ch) Shona Marie Becwar, Ph.D.

I am a Ph.D. Chemical Engineer with materials characterization expertise and a strong understanding of drug process development and scale-up activities looking for a research/process development role in the SF Bay Area. I have 2+ years of experience as a research scientist in pharmaceutical small molecule drug development, working on processes involving catalysis, organic reactions, separations, crystallizations, and tech transfer and scale-up from laboratory to plant-scale. I have 8+ years of expertise in chemical/material syntheses, macroscopic electrochemical performance, X-ray and laser diffraction/photoelectronic spectroscopy, electron paramagnetic resonance spectroscopy, specializing in solid-state nuclear magnetic resonance spectroscopy.

Abstract and Previous Research Experience

Bristol Myers Squibb, Research Scientist, Process R&D, Chemical Process Development

As a chemical process development scientist, my research focused on the development, optimization, and scale-up of processes for small molecule drug substances, with a strong emphasis on collaboration, data-driven methodologies, and process robustness. I worked on processes involving catalysis, organic reactions, separations, and crystallizations at the laboratory and pilot-plant scale. I leveraged Design of Experiment (DoE) principles to investigate new routes for chemical processes and develop the relationships between variable manipulations and process outcomes. In terms of early process design, I used classic lab-scale and high-throughput technology to screen solvent solubility options, salts for salt-break processes, or effects of pH on purity/conversion. Additionally, I have successfully decoupled processes containing reactive crystallizations or salt-breaks from metatheses to control and de-risk processes. To optimize processes, I used DoE to create a matrix of process parameters (pH, temperature, KF, oxygen content, conversion, etc.) and correlate their manipulations on other parameters, solubility, form achieved, crystallization conditions, particle size control, etc. Particularly, integrating advanced in-situ and ex-situ data collection technology enabled me to isolate, characterize, purify, de-risk, and mass-produce substances, resulting in high-yield and robust processes crucial for drug substance manufacturing. I conducted process analyses to compare the economic, safety, and sustainability impacts of pathways and alternatives creating data-driven reasons to guide resource allocation and ensure sustainable scale-up practices. While in this role, I supported the scale-up of two large Phase 2 clinical trials by generating comprehensive technology transfer documentation and coordinating with vendors to run and troubleshoot pilot-scale operation, ensuring timely delivery of high-quality drug substances.

Examples:

• I lead a cross-functional team that recently tackled the emerging issue of quantifying and mitigating nitrosamine contents in our drug product. We discovered the solvent system and an impurity in the API step were both sources of amine formation. In the work that followed, I explored two pathways to de-risk the process. First, I designed a reprocessing technique which lowered amine formation, but the extent of amine reduction was inconsistent. Second, I redeveloped the process in a new solvent system, eliminating the risk of amine formation by the solvent system. The combined efforts of my team to identify the amine source and my work to de-risk the process produced valuable knowledge which was applicable to projects across the portfolio.
• I co-lead an industry-university collaboration with the goal of developing more effective Pd-catalyzed materials for common reactions in the pharmaceutical industry (Suzuki) and understanding the properties of the catalytic sites that result in increased reactivity and conversion. This work demonstrated that Pd-based single atom catalysts show improved activity over supported nanoparticles for Suzuki reaction, resulting in a manuscript which is currently in the process of publication.

University of California, Santa Barbara, Graduate Research, Department of Chemical Engineering

Thesis: Understanding & correlating compositions, structures, & properties of conductive networks for energy conversion & storage applications

The objective of my graduate thesis was to improve understanding and viability of alternative energy conversion and storage materials. This objective encompasses many material systems. Promising systems which I investigated include 1) boron clusters for solid-state redox, 2) conductive polymers in semi-transparent organic solar cells, 3) perovskites undergoing fluoride ion intercalation, and 4) the main system I focused on which is mesoporous N- and Fe,N-carbons for oxygen & sulfur reduction. Key characteristics exhibited by these systems include 1) that they are comprised of extended networks with non-stoichiometric compositions, 2) that they consist of complicated heterogenous distributions of ordered and disordered structural features, and 3) their atomic-level structures are important to electron transport and electrochemical activity. I found that variation in synthesis conditions and macroscopic templating agents can have tunable and reproduceable effects on the catalytic active sites formed. In addition to conventional characterization techniques such as nitrogen sorption, X-ray photoelectron spectroscopy, Raman spectroscopy, ⁵⁷Fe Mössbauer spectroscopy, X-ray diffraction, solid-state NMR spectroscopy and DFT modeling calculations provide detailed atomic-level insights about the environments and distributions of nuclei which, until now, had limited use in the study of this class of materials. Specifically, solid-state nuclear magnetic resonance (NMR) spectroscopy is sensitive to atomic environments in both ordered and disordered regions of a material and can provide significantly enhanced resolution of environments which are corroborated by DFT predictions of chemical shift values. Correlating macroscopic electrochemical reduction activities with bulk and surface characterizations provides insight about material composition on many length scales enabling systematic selection and tuning of synthesis/post-synthetic processing conditions to improve the macroscopic conductivity and electrocatalytic activities. My contributions to the field relate understandings of the local atomic environments (achieved via synthesis manipulations) and interactions with complicated macroscopic properties and performance. Specifically, allowing for more strategic synthesis and optimization strategies than have been typically employed in the past.