ASHLEIGH WAKE
Intertek Pharmaceutical Services, Manchester, United Kingdom

Abstract

Analytical characterisation as well as establishing a strategic quality control program to support oligonucleotide therapeutic product development, regulatory approval and to ensure continued safety and efficacy is fundamental to the success of both individual products as well as to realise the potential this class of molecules offers as a therapeutic agents. The complexity of structure and relative infancy of this product class requires careful scientific consideration when designing such programs to ensure analytical programs meet the requirements for first class quality control.  This article discusses the design of such programs as well as providing insight into learnings around experimental design and the use of orthogonal approaches.

For many years the potential of oligonucleotides as a “new” class of therapeutic agents suited to a range of yet unmet medical need has been discussed with a considerable amount of research presented supporting this classification. Despite the quality of research, there has however been only very limited success. By the end of 2017 only 6 oligonucleotide products having ever received FDA approval and some of these have since been withdrawn.

This situation is however anticipated to soon change.  With around 120 global companies currently active in oligonucleotide research and development, the market for antisense and RNAi industry alone is predicted to be worth $4.58Bm by 2022 (1). Such optimism is built of the strength of the current pipeline, with over 140 active oligonucleotide clinical programs in various phases of development now underway. (ClinicalTrials.gov).

The reason for this change in perspective is a combination of factors including improvement in chemistries leading to more efficient production, a better understanding of the basic biology of oligonucleotides, more sophisti ...