How much do animal models play a role in drug development?
Published by Vijay K Singh and Thomas M Seed on September 3, 2021, in Expert Opinion on Drug Discovery and deals with the necessity of animal models for modern drug research in the direction of animal strains, animal models, requirements, and pathways for developing new drugs.
The use of experimental animal models in drug development aids in the understanding of disease and/or related conditions' origins, pathophysiological features, mechanisms, drug target identification, properties, toxicity and safety, pharmacokinetics, and efficacy evaluation, as well as the development of therapies. Despite the success of the Human Genome Project and other molecular biology approaches in drug discovery, the success rate of drug regulatory approval remains low.
Traditional animal models can be used to validate the safety, efficacy, clinical prediction, and non-clinical "proof of concept" of specific drug molecules during the drug development process, however clinical prediction is not always accurate. As a result, while performing clinical trials, the limitations of data obtained from preclinical animal model studies must be understood and taken into account.
Standard, commonly used animal models:
* Experimental animals: mice, rats, rabbits, guinea pigs, dogs, pigs, sheep, non-human primates.
* Inbred testing: provide consistency of potential targets, including molecules, cells, organs, and animals.
* Distant strain testing: broad analysis of drug effects.
* Ultimate goal: assess and quantify the safety and efficacy of drugs, as well as to comprehend the basic biological processes behind pharmacological action.
Other animal models for drug development and research
* Mutant animal models: for seeking preventive and/or therapeutic options for patients.
* Chimeric animal models: for basic biology and pharmacological research, with numerous genomically different physiological systems.
* Parabiosis animal models: surgically linked animals that share a single physiological system for drug discovery, research, and development.
Genetically engineered animal models
Humanized mouse models are typical genetic animal models that produce more accurate reflections of comparable human disease states through xenografts (obtained from one species and transplanted into another) for testing preclinical drug safety and efficacy.
* Unique genomes: studying the nature of specific human genes or related diseases.
* Gene knockout: to investigate gene function and develop new therapeutics and techniques.
* Inserted microbial genes: to study their role in the disease treatment process.
* Inserted reporter genes: to study the expression of the identified genes.
Animal model requirements for chemical, biological, radiological and nuclear (CBRN) drug development.
Animal Rule Information | FDA
* The goal is to anticipate human safety and toxicity, as well as drug dosage, based on the findings of animal studies.
* Chemical, biological, radiological, and nuclear (CBRN) medications are the focus of this research.
* Conditions that apply: Due to ethical concerns, human volunteers are not permitted to participate.
The FDA approves the acquisition of data for studies from animal models on the following four premises.
* The pathophysiology, toxicological mechanism, and mechanism of drug prevention or treatment are clear.
* Validated in more than one animal species to predict its response in humans, and when validated in only one animal, the animal model must be recognized as being able to predict human response.
* The pharmacodynamic study endpoint indicator should be related to clinical benefit, as reflected in both improved survival or reduced morbidity.
* The effective dose in humans can be inferred based on pharmacokinetic and pharmacodynamic related data from animal studies.
Pathways to the discovery of new drugs
* Phenotype-based drug development (PBDD): now re-substituted as a drug discovery platform, this approach relies more on animal models and TBDD for drug identification and discovery results, followed by secondary screening.
* Target-based drug development (TBDD): specifying specific molecular targets for drug action, which is often used in the development of indications for most drugs.