Perspectives on the Designation of Oligonucleotide Starting Materials
William F. Kiesman, A. McPherson, Louis J. Diorazio, Leo Van den Bergh, Peter D. Smith, John M. Northall, Alec Fettes, Tiejun Wang, Martin Mehlmann, Syed Mohammad Raza, Gary A. Held
Abstract
The designation of starting materials (SMs) for pharmaceuticals has been a topic of great interest and debate since the first ICH quality guidance was published. The increase in the number and variety of commercialized oligonucleotides (antisense oligonucleotides-ASOs, small interfering RNAs-siRNAs, etc.) in recent years has reignited dialogue on this topic because of the unique complexity of the monomeric nucleotides and other contributory materials used to manufacture oligonucleotides. The SM working group in the European Pharma Oligonucleotide Consortium (EPOC) was formed to help establish simple, risk-based criteria to guide the justification of oligonucleotide SMs. This article provides a description of the common types of SMs, classes of SM impurities, and control strategies that will be helpful to maintain manufacturing consistency.