ABSTRACT
The most common approach for the manufacture of oligonucleotides includes isolation of the active pharmaceutical ingredient (API) via lyophilization to provide a solid product, which is then dissolved to provide an aqueous formulation. It is well known from the development and manufacture of large molecules ("biologics") that API production does not always require isolation of solid API before drug product formulation, and this article provides technical considerations for the analogous use of oligonucleotide API in solution. The primary factor considered is solution stability, and additional factors such as viscosity, concentration, end-to-end manufacturing, microbiological control, packaging, and storage are also discussed. The technical considerations discussed in this article will aid the careful evaluation of the relative advantages and disadvantages of solution versus powder API for a given oligonucleotide drug substance.
Subject(s)
Chemistry, Pharmaceutical/trends , Freeze Drying , Oligonucleotides/therapeutic use , Humans , Oligonucleotides/chemistry , Solutions/chemistryABSTRACT
A consortium of seven pharma companies has been formed with the aim of sharing knowledge on and harmonizing approaches to oligonucleotide development. This letter aims to raise awareness of this new group and to set expectations for future publications.
