Animal Use in Carcinogenicity Studies Supporting Approved New Drug Applications in the U.S., 2015-2019

Published: 4 October 2022| Version 2 | DOI: 10.17632/m7mkp7j92w.2
Joseph Manuppello, Eryn Slankster-Schmierer


Data supports "Animal Use and Opportunities for Reduction in Carcinogenicity Studies Supporting Approved New Drug Applications in the U.S., 2015-2019" in Regulatory Toxicology and Pharmacology (in revision). Includes: number of animals used in long- and- short term carcinogenicity and pivotal chronic toxicity studies as summarized by FDA in its publicly available reviews of New Drug Applications separated by control and dose groups in main carcinogenicity, toxicokinetics and other satellite studies; justifications for waiving carcinogenicity studies; concern for human toxicity and animal study results from current Supplemental Product Labeling; tables, figures, and supporting analysis. Changes from previous version: "Discussion" sheet renamed "Abstract & Discussion" and two tables added to support calculating the combined total reduction in the revised MS abstract; animals used in extra control groups in TK and other satellite studies have been added to the total reduction resulting from using single control groups.


Steps to reproduce

The data were acquired by manual curation of publicly available U.S. Food and Drug Administration (FDA) reviews of New Drug Applications and Structured Product Labeling. Drugs@FDA: FDA-Approved Drugs was searched from January 2015 through December 2019 for FDA reviews of approved, original NDAs for new molecular entities and the approval date, drug name, active ingredient(s), and sponsoring company were recorded in a Microsoft Office 365 Excel workbook. From the "Products on NDA…" table, we recorded the route intended for human administration and in the “Approval Date(s) and History, Letters, Labels, Reviews” table, we accessed “Reviews.” From the drug approval package, we downloaded the non-clinical (pharmacology/toxicology) or multi-discipline review identified and, for reviews including scanned documents, recognized text using Adobe Acrobat Pro 2017. When carcinogenicity studies were waived, we categorized the justifications sponsors gave. When carcinogenicity studies were completed, we recorded the dates they were initiated and whether FDA concurred with study design and conduct, as well as the substance tested and basis for setting the highest dose, the route and duration of exposure, and the sex and species of animals used. We also noted FDA's genotoxicity determination and searched for and recorded relevant information on pharmacology, hormonal perturbation, and immune modulation. For each main carcinogenicity, toxicokinetics satellite, and other satellite study completed, we recorded the number and types of controls used, the number and levels of doses administered, and the number of animals used in control and dose groups as well as for sentinels. For statistically significant, treatment-related increases in neoplasia, we recorded the sex and dose group(s) where they were found as well as the affected organs and tumor types; we also noted FDA's reasons for approving applications for new drugs causing cancer in rats or mice and relevant label text. For 26-week studies in rasH2 mice, we also recorded the percent incidence of the most frequently reported tumors in the positive control groups. We identified the pivotal rodent chronic toxicity study completed and recorded corresponding information. We also searched FDALabel: Full-Text Search of Drug Product Labeling, Section 13.1, Carcinogenesis, Mutagenesis, Impairment of Fertility and recorded any additional results of carcinogenicity studies in rats and mice; we searched Section 5, Warnings and Precautions, and recorded whether any concerns for drug-related human carcinogenicity identified were based on clinical or nonclinical evidence and if that evidence was with the drug (or new molecular entity in SPLs for combination products) or with other drugs in its pharmacologic or product class, as well as whether the drug was intended for the treatment of cancer or another indication.


Physicians Committee for Responsible Medicine


Pharmacology, Health Sciences, Life Sciences, Drugs Toxicology, Informatics Application in Medicine, Animal Biomedical Model, Computational Biology