Regulatory Concerns for the Chemistry, Manufacturing, and Controls of Oligonucleotide Therapeutics for Use in Clinical Studies

Abstract

It is important to remember that while a new class of therapeutic agents like oligonucleotides may introduce novel concerns, the basic regulatory issues regarding the chemistry, manufacturing, and controls of drug substances and drug products must be addressed. This article focuses on information that should be included in an Investigational New Drug Application (IND), a request to use an investigational drug in clinical studies. The regulatory challenge presented with oligonucleotide therapeutics is to prove the identity of the oligonucleotide, and demonstrate its quality, purity, and strength/potency using both those characteristics that are the same as all other drugs, as well as those that are unique. Most of the discussion will concern issues that are unique to oligonucleotides, or those topics that deserve more detailed attention than would be needed for more typical small molecule drugs. Regulatory issues will need to be evaluated so that safety concerns are addressed while not imposing undue burden on the sponsors of investigational drugs.