In the synthesis of oligonucleotides, the control strategy of starting materials is essential to guarantee manufacturing process reliability and API quality. A holistic approach to control and ensure high quality of phosphoramidites will be presented.
The concept is based on a combination of tailor-made and generically validated analytical methods deriving from a detailed understanding of the starting material manufacturing process and evaluation of the specific impurity profile. Structure elucidation of starting material impurities obtained by state-of-the art high resolution LC-MS/MS is key to understand the mechanism of API impurity formation and to trigger targeted process optimization. An essential part of this control strategy approach is the setup of appropriate specifications. In addition, reliable supply chains with defined change control processes will guarantee that the established control strategy remains effective.

Subject area:
Biologics

Objectives (If applicable):
na

Target Audience (If applicable):
– Regulatory scientists
– Analytical scientists
– Quality assurance analysts
– R&D scientists and managers
– Quality control analysts
– Contract research organizations