Leveraging Development and Commercial Knowledge for Root Cause Analysis...

Full title: Leveraging Development and Commercial Knowledge for Root Cause Analysis of Commercial Near-infrared Methods Presented by Brendan Lyons, Senior Scientist, Forensics and Innovative Technologies group in Global Quality at Bristol Myers Squibb and Followed by Joseph Andrew, Innovations Engineer at Optimal Industrial Technologies Bristol Myers Squibb manufactures a high-volume drug product which is tested for release primarily by Near-infrared spectroscopy (NIR) assay and content uniformity analytical methods. Due to the large testing volume, the performance of these NIR methods has been challenged with respect to system suitability, reference method comparability, statistical control limits, and release specifications. These events trigger investigations or proactive initiatives, which require root cause analysis. The determination of root cause for these NIR based methods is very different compared to the deviations and investigations typically encountered with traditional HPLC release methods. For example, NIR method performance events are rarely associated with laboratory error. Also, the multivariate calibration models and associated diagnostic metrics are abstract mathematical concepts, which can be difficult to interpret or assign to specific risk factors. However, within the appropriate context, the additional details available from these multivariate models can be leveraged to determine root cause. Appropriate context can be adopted from historical knowledge available either from the quality by design strategy used for NIR method development or from method robustness trends during commercial operations. This talk will discuss actual examples of leveraging these knowledge sources for root cause analysis of atypical NIR method performance events.