cGMP commercial scale oligonucleotide synthesis
From equipment design concept to system qualification
A fully automated flow-throughsynthesizer connected to adynamic axial compression (DAC) column reactor wasdesigned to perform commercial scale oligonucleotidesynthesis. Aspects of the system design which support scaleup,tech transfer to/from other sites and alternative equipmentdesigns are reviewed. The systems were extensively testedduring manufacturing and start-up. Both the IQ (InstallationQualification) and the OQ (Operational Qualification) weremodelled on the testing done by the system designer prior todelivery. The PQ (Performance Qualification) of the synthesizerwas done synthesizing a “reference” oligonucleotide at fullproduction scale for the instrument of 120 mmol. The sameoligonucleotide had been previously made at Girindus on adifferent system at a smaller scale so a performancecomparison could be made. Manufacturing science can beused to develop an understanding of a process and identifycritical parameters that may affect a process. The high yield ofthe 13-mer oligonucleotide synthesized by the cGMPcommercial scale synthesizer is an example of a controlledmanufacturing process.