Replacing Animal Tests to Improve Safety for Humans

Archibald, Kathy; Coleman, Robert A.; Drake, Tamara

doi:10.1163/9789004391192_019

Cited by 4 publications

(3 citation statements)

References 51 publications

(53 reference statements)

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“…These models will be replaced by research tools that mimic human physiology and biological processes (for example, organ-on-chip models). 9,10…”

Section: Keynote Lecturesmentioning

confidence: 99%

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Naik,

Vadloori,

Poosala

et al. 2023

Altern Lab Anim

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Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.

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“…These models will be replaced by research tools that mimic human physiology and biological processes (for example, organ-on-chip models). 9,10…”

Section: Keynote Lecturesmentioning

confidence: 99%

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Naik,

Vadloori,

Poosala

et al. 2023

Altern Lab Anim

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“…All new medications must first pass legal testing on rodents (often mice or rats) and a bigger nonrodent mammal (typically a dog, pig, or monkey) before being administered to humans. This is done because unfavorable effects in either species frequently point to comparable reactions in people, and if a dose is toxic in both rodent and nonrodent species, it is probably also going to be toxic in people 13 . However, recently the FDA changed the legislation originally passed in 1938 on animal studies to state that they “no longer require drugs to be tested on animals” 14…”

Section: Introductionmentioning

confidence: 99%

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Janapati,

Junapudi

2024

Anim Models and Exp Med

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Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by hyperglycemia, a condition involving a high blood glucose level brought on by deficiencies in insulin secretion, decreased activity of insulin, or both. Prolonged effects of diabetes include cardiovascular problems, retinopathy, neuropathy, nephropathy, and vascular alterations in both macro‐ and micro‐blood vessels. In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis, identifying targets, and reviewing novel treatment options and medications. Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences. The most popular in vivo studies involves the small animal models, such as rodent models, chemically induced diabetogens like streptozotocin and alloxan, and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals. Other models include virally induced models, diet/nutrition induced diabetic animals, surgically induced models or pancreatectomy models, and non‐obese models. Large animals or non‐rodent models like porcine (pig), canine (dog), nonhuman primate, and Zebrafish models are also outlined. The in vitro models discussed are murine and human beta‐cell lines and pancreatic islets, human stem cells, and organoid cultures. The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition of α‐glucosidase activity.

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“…Predicting the safety of a new chemical entity (NCE) prior to first-in-human administration is a main aspect of preclinical testing [ 1 ]. Despite new methods of toxicological testing arising from rapid advancements of in vitro models, including three-dimensional cell cultures, microphysiological systems and computational modelling, the complexity of a living organism still prevents the full replacement of animal studies [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Pharmacobezoar Formation from Suspensions of Spray-Dried Amorphous Solid Dispersions: An MRI Study in Rats

et al. 2023

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Spray-dried amorphous solid dispersions of new chemical entities and pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were found to form solid agglomerates in the gastrointestinal tract of rodents after oral administration. These agglomerates, referring to descriptions of intra-gastrointestinal aggregated oral dosage forms termed pharmacobezoars, represent a potential risk for animal welfare. Previously, we introduced an in vitro model to assess the agglomeration potential of amorphous solid dispersions from suspensions and how it can be reduced. In this work, we investigated if the in vitro effective approach of viscosity enhancement of the vehicle used to prepare suspensions of amorphous solid dispersions could reduce the pharmacobezoar formation potential following repeated daily oral dosing to rats as well. The dose level of 2400 mg/kg/day used in the main study was determined in a dose finding study carried out in advance. In the dose finding study, MRI investigations were carried out at short time intervals to gain insights into the process of pharmacobezoar formation. Whereas MRI investigations underlined the importance of the forestomach for the formation of pharmacobezoars, viscosity enhancement of the vehicle reduced the incidence of pharmacobezoars, delayed the onset of pharmacobezoar formation and reduced the overall mass of pharmacobezoars found at necropsy.

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Replacing Animal Tests to Improve Safety for Humans

Abstract: This is an open access chapter distributed under the terms of the prevailing cc-by-nc License at the time of publication.

Cited by 4 publications

References 51 publications

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Evaluation of Pharmacobezoar Formation from Suspensions of Spray-Dried Amorphous Solid Dispersions: An MRI Study in Rats

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