Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products.

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability.

Novel method for the covalent immobilization of oligonucleotides via Diels-Alder bioconjugation.

The synthesis of cyclohexadiene and maleimide derivatives and their use for the functionalization of oligonucleotides and the coating of glass surfaces is reported. A method for the covalent attachment of diene or maleimide modified oligonucleotides to the coated glass surfaces via aqueous Diels-Alder reactions is presented.

13C isotopomer analysis of glutamate by tandem mass spectrometry.

Tandem mass spectrometry allows a compound to be isolated from the rest of the sample and dissociated into smaller fragments. We show here that fragmentation of glutamate mass isotopomers yields additional mass spectral data that significantly improve the analysis of metabolic fluxes compared to full-scan mass spectrometry. In order to validate the technique, tandem and full-scan mass spectrometry were used along with (13)C NMR to analyze glutamate from rat hearts perfused with three substrate mixtures (5 mM glucose plus 5 mM [2-(13)C]acetate, 5 mM [1-(13)C]glucose plus 5 U/L insulin, and 5 mM glucose plus 1 mM [3-(13)C]pyruvate).