Evaluation and Control of Mutagenic Impurities in a Development Compound: Purge Factor Estimates vs Measured Amounts

Using the Teasdale method, purge factor estimates for six impurities identified as mutagenic alerts in the synthesis of MK-8876 are compared to actual measured amounts of these impurities determined via appropriate analytical methods. The results from this comparison illustrate the conservative nature of purge factor estimates, meaning that overprediction of mutagenic impurity purging is unlikely when using this method. Industry and regulatory acceptance of the purge factor estimation method may help minimize analytical burden in pharmaceutical development projects.