Harmonized 3Rs-based non-mutagenic impurity qualification study designs developed using the results of an IQ consortium survey.

Autor: Mitra MS; Genentech Inc, Safety Assessment, South San Francisco, CA, USA. Electronic address: mitram2@gene.com., Datta K; Bristol-Myers Squibb, Nonclinical Research and Development, NJ, USA., Hutchinson R; Janssen Research & Development, LLC, Spring House, PA, USA., Nicolette JJ; Abbvie, Inc., Pre-clinical Safety, North Chicago, IL, USA., Pettersen JC; Vertex Pharmaceuticals, Pre-clinical Safety Assessment Boston, MA, USA., Wegesser TC; Amgen, Translational Safety and Bioanalytical Sciences, Thousand Oaks, CA, USA., Bercu JP; Gilead Sciences, Nonclinical Safety and Pathobiology, Foster City, CA, USA.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2021 Jun; Vol. 122, pp. 104895. Date of Electronic Publication: 2021 Feb 19.
DOI: 10.1016/j.yrtph.2021.104895
Abstrakt: As per the ICH Q3A(R2) and Q3B(R2) regulatory guidelines, safety studies may be needed when an impurity in new drug substances or products is above the qualification threshold, and such qualification studies should be conducted in one nonclinical species for a duration of 14-90 days. However, the guidelines do not specify details about species selection, recommended study design, and the exact study duration that would support clinical use of a specific duration. This lack of guidance leads to ambiguity and sponsors have used various study designs to qualify impurities. In 2018, the European Medicines Agency provided a draft reflection paper encouraging the incorporation of 3Rs (Replacement, Reduction, and Refinement) principles for animal use into impurity qualification. As a response, the IQ DruSafe Impurity Working Group (WG) surveyed the IQ member companies to capture the current practices for impurity qualification, and evaluate study designs for a potential reduction in animal testing. This article summarizes the results and learnings from the survey. Additionally, the WG leveraged the survey learnings and provided harmonized study design considerations aimed towards achieving the study objectives, while supporting the 3Rs initiative in reducing the total number of animals used (up to 90%) for impurity qualification.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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