Quality aspects to be considered in oligonucleotide manufacturing

Oligonucleotides have long been a tool of molecular biology and used in medical agent applications as early as 1978. Synthetic oligonucleotides can be produced via commercially available automated synthesizers following the same basic process consisting of synthesis, removal of the protecting groups, purification, desalting, and lyophilisation. Given that there are a multitude of modifications that can be incorporated into these synthetic oligonucleotides, the real challenge is to develop suitable protocols and methods that ensure necessary quality and yield of the end product. In this article, we take a closer look at the quality aspects to be considered during the manufacturing of these synthetic oligonucleotides. Specifically, we discuss the concept that the quality of product is a reflection of the entire production process and therefore the quality of starting materials must also be considered in the discussion. Key to the analysis of oligonucleotide quality is the availability of suitable detection methods for impurities, whether they originate from the process or the raw materials used in the process. Overall, analytically accessible specifications and recorded process documents should be in place in order to ensure the reproducibility of the production process and equivalence of the material being produced over time.