Open AccessTechnical Considerations for Use of Oligonucleotide Solution API
Author(s) -
Jale Müslehiddinoğlu,
Robert Simler,
Malcolm L. Hill,
Claudia Mueller,
John Amery,
Leigh Dixon,
Anna Watson,
Kirsten Storch,
Cinzia Gazziola,
Frank Gielen,
Stefan Lange,
Jeremy D. Prail,
Doug P. Nesta
Publication year - 2020
Publication title -
nucleic acid therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.255
H-Index - 67
eISSN - 2159-3345
pISSN - 2159-3337
DOI - 10.1089/nat.2020.0846
Subject(s) - active ingredient , oligonucleotide , biochemical engineering , process engineering , drug packaging , computer science , chemistry , engineering , pharmacology , medicine , dna , biochemistry , radiology
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.