Current nonclinical testing paradigm to allow clinical entry for pharmaceutical drug candidates

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology Pub Date : 2025-03-14 DOI:10.1016/j.yrtph.2025.105809

Paul Baldrick

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Abstract

Nonclinical safety testing (pharmacology, ADME and toxicology studies) needs to occur to support First-In-Human clinical entry for pharmaceutical drug candidates. Examination of the study package from the content of Investigator Brochures (IBs) for 32 small (non-oncology) molecules used to support such entry over a 4-year period (2020–2023) showed that a mean of 38 nonclinical studies were performed per molecule with pharmacology, ADME and toxicology testing contributing 37 %, 39 % and 24 % of the studies, respectively. Examination of IBs used to support clinical entry of 15 small molecule oncology drugs gave similar values of 43 studies contributing 37 %, 42 % and 21 %, respectively. Examination of IBs for 16 biopharmaceuticals showed a mean number of 19 studies per molecule with pharmacology, ADME and toxicology testing contributing 84 %, 5 % and 11 % of the studies, respectively. Overall, for both small molecule and biopharmaceutical drug candidates, similar numbers of pharmacology studies were performed but the approximately 50 % fewer studies for biopharmaceuticals was due to considerably limited ADME and toxicology testing. Comment will be made on how the current study package could be refined (a 3Rs approach) to reduce animal use.

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来源期刊

Regulatory Toxicology and Pharmacology 医学-毒理学

CiteScore

6.70

自引率

8.80%

发文量

147

审稿时长

58 days

期刊介绍： Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 1.Factors influencing human sensitivity 2.Exposure science related to risk assessment 3.Alternative toxicological test methods 4.Frameworks for evaluation and integration of data in regulatory evaluations 5.Harmonization across regulatory agencies 6.Read-across methods and evaluations -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)