Nitrosamine Risk Assessments in Oligonucleotides

EMA, FDA and other regulatory agencies expect that all pharmaceutical products be assessed for the potential presence of N-nitrosoamine (nitrosamine) impurities. This white paper addresses general considerations for nitrosamine risk assessments of oligonucleotide products. The authors propose a general risk assessment platform which should facilitate safe, consistent development of new treatments and alignment with regulators. The European Pharma Oligonucleotide Consortium (EPOC)1 is a collaboration among multiple pharma companies with the aim of sharing chemistry, manufacturing, and controls (CMC) knowledge as well as strategies to enable harmonization of oligonucleotide development and commercialization. \nThe objective of the consortium is to publish science-based recommendations for the development of oligonucleotide therapeutics in a series of technical and regulatory white papers, drawing on its collective subject matter expertise and complementing that in the literature and guidelines. This public body of prior knowledge endeavours to serve as a reference for industry practice and help establish development principles for oligonucleotides. The consortium aims at being proactive and inclusive, and it anticipates initiating wider discussion on oligonucleotide CMC practice and policy, thus expediting access to these potentially life changing medicines.