Pharmaceutical toxicology: Designing studies to reduce animal use, while maximizing human translation

https://doi.org/10.1016/j.yrtph.2013.03.001Get rights and content
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Highlights

  • Strategies to reduce animal use and improve efficiency in drug development.

  • Including in vitro methods, safety pharmacology, biological development and DART.

  • Common practical challenges and expert opinion on how to solve them is provided.

  • In summing up the authors provide a global three step strategy to accelerate progress.

Abstract

Evaluation of the safety of new chemicals and pharmaceuticals requires the combination of information from various sources (e.g. in vitro, in silico and in vivo) to provide an assessment of risk to human health and the environment. The authors have identified opportunities to maximize the predictivity of this information to humans while reducing animal use in four key areas; (i) accelerating the uptake of in vitro methods; (ii) incorporating the latest science into safety pharmacology assessments; (iii) optimizing rodent study design in biological development and (iv) consolidating approaches in developmental and reproductive toxicology. Through providing a forum for open discussion of novel proposals, reviewing current research and obtaining expert opinion in each of the four areas, the authors have developed recommendations on good practice and future strategy.

Abbreviations

3Rs
replacement, refinement and reduction of animals in research
ACSA
Agricultural Chemicals Safety Assessment
ADA
anti-drug antibody
CNS
central nervous system
DBS
dried blood spot
DART
developmental and reproductive toxicity
DRF
dose range finding
ECG
electrocardiograph
EFD
embryofetal development
EPA
environmental protection agency
ePPND
enhanced peri-postnatal toxicity study
GLP
Good Laboratory Practice
hERG
human Ether-a-Go-go Related Gene
ICATM
International Cooperation on Alternative Test Methods
ICH
International Conference for Harmonisation
ILSI-HESI
International Life Sciences Institute Health and Environmental Sciences Institute
IND
investigational new drug
JET
jacketed external telemetry
LLNA
Local Lymph Node Assay
mAb
monoclonal antibody
NHP
non-human primate
NRC
National Research Council
OECD
Organisation for Economic Co-operation and Development
PD
pharmacodynamic
PK
pharmacokinetic
PPND
peri-postnatal toxicity study
TK
toxicokinetic

Keywords

Safety
Toxicology
3Rs
In vitro methods
Safety pharmacology
Rodents
Biologicals
New chemical entities
Developmental
Reproductive

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