Oligonucleotide and Nucleic Acid Synthesis

Eliminate Development and Manufacturing Challenges

Oligonucleotide synthesis is the chemical process by which nucleotides are specifically linked to form a desired sequence product. The repetitive cyclic nature of the synthesis used in producing these biopolymers requires careful control of reaction variables, as well as step-wise reagent identification and verification, control of Critical Process Parameters (CPPs), measurement and trending of sequential reactions, impurity and by-product mitigation, quantitative analysis of endpoints and evidence that the desired sequence is attained. Critical insights are needed quickly to monitor and take control of processes in order to reduce cycle time, avoid batch failure, make the most of costly materials and create processes that can be reproduced at manufacturing scale. For these reasons, PAT methodologies, like real-time spectroscopic analysis, are useful to support the development and production of these important biomolecules.

In this presentation, Tyler Gable discusses the complex nature of oligonucleotide synthesis, the challenges for scientists and engineers, as well as the current techniques used to achieve analytical requirements; principally the process requirements for speed of measurement complemented with analytical needs for selectivity and sensitivity. Additional topics discuss the use of non-UV spectroscopy and automated sampling that blend the strengths of speed, selectivity and sensitivity to gain actionable insights for optimization and control at both development and manufacturing scales.

In-situ spectroscopy provides scientists and engineers the benefits of real-time material identification and verification as well as quantitative analysis without the delay or burdens of sampling and analytical backlog while also reducing the risk of human error and batch failures and facilitating automated skid control with process feedback and supporting evidence for sequence verification.

Tyler Gable