Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects.

Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo-fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings.

Comparing rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on systemic dose and developmental effects.

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (C) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and C exposures. For 13.

Micro-CT imaging: Developing criteria for examining fetal skeletons in regulatory developmental toxicology studies - A workshop report.

During the past two decades the use and refinements of imaging modalities have markedly increased making it possible to image embryos and fetuses used in pivotal nonclinical studies submitted to regulatory agencies. Implementing these technologies into the Good Laboratory Practice environment requires rigorous testing, validation, and documentation to ensure the reproducibility of data. A workshop on current practices and regulatory requirements was held with the goal of defining minimal criteria for the proper implementation of these technologies and subsequent submission to regulatory agencies.

Value of juvenile animal studies.

The Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute has undertaken a project to address the impact of juvenile animal studies on pediatric drug development. A workshop, sponsored and organized by the Health and Environmental Sciences Institute Developmental and Reproductive Toxicity Technical Committee, was held on May 5-6, 2010, in Washington, DC, to discuss the outcome of a global survey and the value of juvenile animal studies in the development of drugs intended for use in pediatric patients. During this workshop, summary data from the 2009-2010 survey were presented, and breakout sessions were used to discuss specific case studies to try to assess the impact of juvenile animal studies performed to support specific pediatric drug development.

Juvenile animal toxicity study designs to support pediatric drug development.

The objective of juvenile animal toxicity studies of pharmaceuticals is to obtain safety data, including information on the potential for adverse effects on postnatal growth and development. Studies in juvenile animals may assist in identifying postnatal developmental toxicities or other adverse effects that are not adequately assessed in the routine toxicity evaluations and that cannot be safely or adequately measured in pediatric clinical trials. Unlike the traditional reproductive and developmental toxicology studies that have been discussed in the accompanying reports, the design requirements for toxicity studies in juvenile animals are not explicitly defined in regulatory guidance.

The nonclinical fertility study design for pharmaceuticals.

Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document, "Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility." Studies that assess a candidate drug's effect on fertility are generally conducted in rats. The evolution of, and ultimate harmonization of, fertility study designs are reviewed, and specific elements of an acceptable design, as well as the recommendations for presentation of data, are described in detail.

Embryo-fetal developmental toxicity study design for pharmaceuticals.

Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the International Conference on Harmonization (ICH) S5(R2) document (available at http://www.ich.org).

Terminology of developmental abnormalities in common laboratory mammals (version 2).

This update (Version 2) of the Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 1) incorporates improvements and enhancements to both content and organization of the terminology to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops. The terminology remains organized into tables under the broad categories of external, visceral, and skeletal observations, following the manner in which data are typically collected and recorded in developmental toxicity studies.

Terminology of developmental abnormalities in common laboratory mammals (version 2).

This update (version 2) of the Terminology of developmental abnormalities in common laboratory mammals (version 1) by Wise et al. [Wise LD, Beck SL, Beltrame D, Beyer BK, Chahoud I, Clark RL, Clark R, Druga AM, Fueston MH, Guittin P, Henwood SM, Kimmel CA, Lindstrom P, Palmer AK, Petrere JA, Solomon HM, Yasuda M, York RG. Terminology of developmental abnormalities in common laboratory mammals (version 1).

Terminology of developmental abnormalities in common laboratory mammals (Version 2).

This update (Version 2) of the Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 1) by Wise et al. (1997) incorporates improvements and enhancements to both content and organization of the terminology, to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops.