cGMP commercial .scale oligonucleotide synthesis From equipment design concept to system qualification

摘要

A fully automated flow-through synthesizer connected to a dynamic axial compression (DAC) column reactor was designed to perform commercial scale oligonucleotide synthesis. Aspects of the system design which support scale-up, tech transfer to/from other sites and alternative equipment designs are reviewed. The systems were extensively tested during manufacturing and start-up. Both the IQ (Installation Qualification) and the OQ (Operational Qualification) were modelled on the testing done by the system designer prior to delivery. The PQ (Performance Qualification) of the synthesizer was done synthesizing a "reference" oligonucleotide at full production scale for the instrument of 120 mmol. The same oligonucleotide had been previously made at Girindus on a different system at a smaller scale so a performance comparison could be made. Manufacturing science can be used to develop an understanding of a process and identify critical parameters that may affect a process. The high yield of the 13-mer oligonucleotide synthesized by the cGMP commercial scale synthesizer is an example of a controlled manufacturing process.