A non-clinical and clinical IUCLID database for 530 pharmaceuticals (part I): Methodological aspects of its development

https://doi.org/10.1016/j.yrtph.2023.105416Get rights and content
Under a Creative Commons license
open access

Highlights

  • 530 new drug application dossiers from the FDA were analysed.

  • Non-clinical and clinical unstructured data were incorporated into a new fully structured IUCLID database.

  • A new ontology for the structuring of effects was created by merging human and mammalian terms.

  • The IUCLID database is provided free of charge at https://iuclid6.echa.europa.eu/us-fda-toxicity-data

  • These data support alternative non-animal methods, elucidate toxicity mechanisms, and analyze human relevance of non-clinical findings.

Abstract

A new IUCLID database is provided containing results from non-clinical animal studies and human information for 530 approved drugs. The database was developed by extracting data from pharmacological reviews of repeat-dose, carcinogenicity, developmental, and reproductive toxicity studies. In the database, observed and no-observed effects are linked to the respective effect levels, including information on severity/incidence and transiency/reversibility. It also includes some information on effects in humans, that were extracted from relevant sections of standard product labels of the approved drugs. The database is complemented with a specific ontology for reporting effects that was developed as an improved version of the Ontology Lookup Service's mammalian and human phenotype ontologies and includes different hierarchical levels. The developed ontology contains novel and unique standardized terms, including ontological terms for reproductive and endocrine effects. The database aims to facilitate correlation and concordance analyses based on the link between observed and no-observed effects and their respective effect levels. In addition, it offers a robust dataset on drug information for the pharmaceutical industry and research. The reported ontology supports the analyses of toxicological information, especially for reproductive and endocrine endpoints and can be used to encode legacy data or develop additional ontologies. The new database and ontology can be used to support the development of alternative non-animal approaches, to elucidate mechanisms of toxicity, and to analyse human relevance. The new IUCLID database is provided free of charge at https://iuclid6.echa.europa.eu/us-fda-toxicity-data.

Keywords

IUCLID database
Animal testing
Human information
Standard product label
Ontology
Effect levels
Endocrine disruption
Repeat-dose toxicity
Carcinogenicity
Reproductive toxicity
Developmental toxicity
Animal-human correlation
New approach methodologies
NAMs

Data availability

We shared the link to our data/code in the manuscript

Cited by (0)

1

These authors contributed equally to this work.