Analysis of the change in molecular complexity of reaction products in process development activities at AstraZeneca over time.

17 May 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The assessment of molecular complexity of active pharmaceutical ingredients (APIs) can help guide decisions within drug development, for example by correlation to sustainability targets, project resource requirements and predicted development and manufacturing timelines. However, such quantifications are limited by the challenge of defining complexity itself, as well as the small sample size of API molecules making longer term comparisons challenging. We have used three complementary approaches to calculate the complexity of reaction products of more than 165 000 reaction entries across our process development electronic laboratory notebooks. Importantly, this covers both intermediates, APIs, and other molecules requiring synthesis, thus attempts to provide an analysis of reaction products from all out synthetic chemistry activities. This information facilitated the investigation of changes in the mean values of different measures of molecular complexity per year between 2007-2020. We discuss the insights these quantifications reveal, and how this analysis may be of more general use in understanding the diversity of the molecules in our process development portfolio.


molecular complexity
process chemistry
data analysis

Supplementary materials

HMCA_AZ_Supporting Information
Document containing supporting information regarding cheminformatic calculations, and supporting figures providing further context to the graphs in the main body of text.


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