Photochemistry in Pharmaceutical Development: A Survey of Strategies and Approaches to Industry-wide Implementation

We present and analyze the results of a pharmaceutical industry-wide survey of the strategies and approaches that companies have for implementing photochemical reactions in discovery chemistry, process development, and commercial manufacturing. The survey questions encompass the types of photochemical reactions that pharmaceutical companies pursue and why, the types of reactors (batch and flow) used, how they are characterized for photochemistry, scale-up of photochemical reactions, and how companies prioritize resources for developing photochemical reactions, among other topics. The survey focuses on many of these topics from the perspectives of discovery chemists and process scientists to highlight similarities and differences between their approaches on the specific photochemical transformations and materials of construction used in photochemical reactors. The survey results clearly demonstrate that photochemistry is a viable synthetic strategy for producing active pharmaceutical ingredients (APIs), from discovery all the way to commercialization. While photochemistry is more prevalent for discovery and early stage process development, the survey results indicate that more companies are leveraging photochemistry in successful scale-ups in later stages of process development, often using flow chemistry, and have significant knowledge resulting from these experiences. Nevertheless, there still are gaps to adopting photochemical reactions across stages of development and companies have very limited experience discussing photochemistry with regulatory agencies. Overall, the survey results demonstrate that photochemistry offers considerable benefits for synthesizing APIs and developing API processes, such as greenness and sustainability, shortening synthetic routes, and potential for improved product quality.