| On June 27th, 2022, the FDA announced the availability of a draft guidance for industry entitled Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics. This guidance provides recommendations to assist industry in the development of oligonucleotide therapeutics under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) and 21 CFR parts 312 and 314. Oligonucleotide therapeutics are an emerging therapeutic modality that include a wide variety of synthetically modified RNA or RNA/DNA hybrids specifically designed to bind to a target RNA sequence to alter RNA and/or protein expression. Increasing numbers of oligonucleotide therapeutic drugs are currently in development. Oligonucleotide therapeutics have unique characteristics compared to small molecule or biological products (e.g., chemistry, structure, sites of action, pharmacokinetic disposition, pharmacodynamics). While oligonucleotide therapeutics generally are cleared rapidly from systemic circulation, these drugs typically have longer tissue and pharmacodynamic half-lives. Therefore, several factors should be considered in determining which studies are needed to characterize the clinical pharmacology of these products. This guidance represents the FDA's recommendations regarding clinical pharmacology considerations during the development of oligonucleotide therapeutics, including: (1) characterizing the potential for QTc interval prolongation, (2) performing immunogenicity risk assessment, (3) characterizing the impact of hepatic and renal impairment, and (4) assessing the potential for drug-drug interactions. This guidance provides recommendations on when to conduct these assessments and what types of assessments are suitable. The recommendations in this guidance currently apply only to oligonucleotide therapeutics that use an RNA-centric mechanism of action. This guidance is based on the knowledge gained in the development of oligonucleotide therapeutics submitted to the Agency in new drug applications (NDAs) as of the date of this guidance. As the development of oligonucleotide therapeutics evolves, sponsors should contact appropriate review Divisions for questions related to the topics in this guidance. The "Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics" guidance is available at: https://go.usa.gov/xJ7YR. Please refer to the draft guidance for more details. FDA is publishing this draft guidance to collect additional public comments. You may submit your comments regarding the draft guidance to the docket (Docket No. FDA-2022-D-0235) available at https://www.regulations.gov up to 90 days following publication in the FEDERAL REGISTER. This draft guidance, when finalized, will represent the current thinking of the FDA on this topic. It does not establish any rights for any person and is not binding on FDA or the public. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count. |
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