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Implementation of high-throughput quality control processes within Compound Management

Giovannoni, Jerome and Peltier, John (2011) Implementation of high-throughput quality control processes within Compound Management. European Pharmaceutical Review, 16 (4). pp. 49-52.


The constant growth of compound collections, combined with screening efforts on more challenging targets, is creating an increasing demand for quality control in order to ensure the integrity of the compound solutions being tested. This is true throughout the early drug discovery pipeline, from Hit identification to Lead nomination. Novartis has recently updated its QC capabilities by creating 2 High Throughput Quality Control (QC) laboratories, enabling a systematic QC at 3 critical stages:
1. Production of DSMO stock solutions used in High Throughput Screening (HTS)
2. Creation of dilution series for Hit-Validation
3. Production of DMSO solutions prepared in the Novartis "Compound Hubs" for the Hit-to-Lead optimization stage of projects

High-throughput LC-MS methods were developed to confirm the identity and the purity of ca. 500,000 samples/year in a highly automated fashion.
The identity of the substances is determined by mass spectrometry (MS) while the purity is measured by UV absorbance and Evaporative Light Scattering Detection (ESLD). In addition, the concentration of the Compound Hub solutions is assessed by nitrogen detection (CLND) and/or ELSD.
The large volume of analytical data is communicated directly to the relevant biology and chemistry laboratories in tabular form in order to support their immediate research work and decision making. Additionally, the same tabular data is deposited in the global Novartis data warehouse and all raw data is stored in a Waters Analytical Workflow Manager (AWM) database for review, if required.
In addition to providing project level feedback, this systematic analytical QC approach gives Compound Management (CM) snapshots of the quality of the compound collection. These snapshots at multiple stages in the process can then be compared over time. This comparison over time enables the evaluation of the collections’ evolution from compound purchase, to library replenishment, and new synthesis. It also enables a systematic evaluation of the compound management process itself.

Item Type: Article
Additional Information: archiving policies unknown
Keywords: Analytical QC; LCMS; high-throughput; compound management
Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15