Juvenile animal testing in drug development – Is it useful?

Baldrick, Paul

doi:10.1016/j.yrtph.2010.03.009

Cited by 41 publications

(51 citation statements)

References 27 publications

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“…[50][51][52][53] Recent reviews in the pharmaceutical area have indicated that from a total of 241 juvenile toxicity studies, 84% were conducted in rats, 14% in dogs, and the remaining 2% in other species. 51,53 In 15% of programs reviewed, existing adult preclinical and clinical data had already been considered sufficient to support pediatric drug trials. The majority of the juvenile toxicity studies showed findings comparable to that in adults.…”

Section: Juvenile Animal Modelsmentioning

confidence: 99%

An integrated approach to the safety assessment of food additives in early life

Constable

Mahadevan

Pressman³

et al. 2017

Toxicology Research and Application

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During the development of international standards by the Codex Alimentarius Commission, infant foods and their constituent ingredients are subject to rigorous risk analysis and are strictly regulated by many authorities. Various jurisdictions have approved only a limited number of additives specifically with regard to infant foods to fulfill specific technical requirements of quality. As part of the approval process, a rigorous safety assessment is essential to confirm that the use of additives does not pose any health risk for the consumer. An acceptable daily intake (ADI) may be derived from the toxicological databases. However, the ADI may not be applicable to infants because of the possible developmental sensitivities and potentially high exposure scenarios, leading to possible lower margins of safety than would often be determined for adult populations. There is interest in defining better food safety assessment approaches for pre-weaned infants aged less than 12-16 weeks. To confirm safe use in infants, we reviewed the suitability of the existing safety databases of six additives with historical uses in infant nutrition products. To determine further toxicity testing strategies, it is necessary to understand whether the chemical used in the additives is identical to endogenous physiological metabolites and/or whether immature organs of infants are targets of toxicity. Combined with an in-depth review of the existing relevant toxicological and nutritional studies, this integrated approach will facilitate decision-making. We propose a decision tree as a tool within this approach to help guide appropriate data requirements and identify data gaps. In cases of reasonable uncertainty, studies of targeted juvenile should be considered to investigate the safe use levels in food products.

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Section: Juvenile Animal Modelsmentioning

confidence: 99%

An integrated approach to the safety assessment of food additives in early life

Constable

Mahadevan

Pressman³

et al. 2017

Toxicology Research and Application

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“…Apart from animal welfare and ethics concerns, the reason behind the lack of a strict requirement for studies in juvenile animals might be that results are difficult to extrapolate and, in some cases, have been found to be of little relevance to humans (Anderson et al, 2009). However, the interest in juvenile animal models in drug development is increasing (Baldrick, 2010). ICH is currently working (as of June 2015) on a new guideline S11, "Nonclinical Safety Testing in Support of Development of Pediatric Medicines," to provide guidance, for example, on the design of studies in juvenile animals.…”

Section: Exposure Of Pharmaceuticals To the Developingmentioning

confidence: 99%

Cracking the Egg: Potential of the Developing Chicken as a Model System for Nonclinical Safety Studies of Pharmaceuticals

Bjørnstad

Austdal

Roald

et al. 2015

J Pharmacol Exp Ther

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The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and in newborns a significant safety concern. Recent initiatives of the Food and Drug Administration and European Medicines Agency have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies, as governed by several guidelines summarized in the multidisciplinary International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, respiratory, and central nervous system. The chicken embryo and fetus have features that make the chicken a convenient animal model for nonclinical safety studies in which effects on all of these organ systems can be tested. The developing chicken is inexpensive, accessible, and nutritionally self-sufficient with a short incubation time and is ideal for drug-screening purposes. Other high-throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals regarding the respiratory organ system and certain aspects of central nervous system development (Caenorhabditis elegans, zebrafish).This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.

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“…In addition to these general toxicology studies, specialized repeat-dose toxicity studies are also required and include rodent carcinogenicity, reproductive toxicology, and juvenile toxicity studies [3,[7][8][9][10][11][12][13].…”

Section: Principles Of Repeat Toxicology Studies In Drug Developmentmentioning

confidence: 99%