Preclinical pdf

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However, there is growing challenge against the use of animals in research by animal rights activists. The ethics of animal testing is currently becoming a world-wide controversy. Many non- governmental organizations and rights activist exist in different countries, fighting against ill- treatment of animals whether for research purposes or as delicacies on family dining tables. They see no justification in the use of animals in research despite its contribution to quality of life of the human race.

Counter organizations like the Americans for Medical Progress AMP feels that the benefits of use of animals in researches has lead to the betterment and longevity of the human race.

The pro- animal groups claim that millions of animals are experimented on and killed annually; for food, clothing and entertainment. In reality most of the animals used for experiments are reared or bred in the laboratory for that purpose.

They spare no thought on the impact the absolute restriction of the use of animals for research would have on the scientific progress of the human race. This is presently a tall order in preclinical research trials. Many countries; especially where animal right issues are prominent have adopted this principle.

Replacement:- This advocates use of alternative methods instead of animals testing procedures, provided same scientific aim is achievable. This principle is otherwise requesting for total replacement of animals in the preclinical trials of drug discovery process.

The current introduction of automation and computational biotechnology in the drug discovery process may hopefully offer a window of opportunity in this direction.

Reduction:- this principle advocates the application of methods that employ less number of animals in an experiment while achieving the same or more level of information if more number of animals were used.

It therefore encourages less number of animals for comparable level of information or use of same number of animals for more level of information. Refinement: - This preaches the principle that methods adopted should be such that pain, suffering and distress is minimized for the animals that are still in use in the preclinical research process. It encourages animal welfare and care. These principles are still being contested by the extreme animal rights protectionists.

The guidelines differ from one country to the other but the underlying principles are the same. Though the choice of a specie for trial is made to be as close to the human as possible, there exists, differences which has to be taken into consideration when evaluating the findings from the study. The documentation of the result of the pre-clinical study, according to the Pharmaceutical product development Inc, , should provide information about the pharmaceutical composition of the drug, its safety, formulation and manufacture process.

Further required information is the route of administration to the human subjects, packaging and handling guidelines; including storage, among other factors. These studies are carried out in animal species in which the following among others are evaluated: - 1. Acute Toxicity Effect in a single large dose. Sub-acute toxicity; involving multiple doses. Chronic toxicity in case of prolonged usage. Reproductive Toxicity of possible effect on Reproduction function.

Genetic toxicity for possibility of mutagenicity and; 6. Carcinogenicity Acute Toxicity Effect in a single large dose This study involves the use of two animal species, of which one should be a non-rodent specie. Acute toxicity study may involve the administration of a single dose or more over a period of up to twenty four hours. The goal is to determine the toxic dose levels and observe indications of toxicity on the study animals. Animals should be observed for fourteen days.

Post-administration mortality if any and morbidity clinical signs and Symptoms are recorded. Other factors documented are time of onset of any reaction, duration and reversibility. The histopathological changes are also recorded. Sub-acute toxicity involving multiple doses This study involves a minimum of fourteen days daily drug administration of three or more doses in at least two animal species.

The effects of this prolonged multiple doses are evaluated and recorded for use as a pre-requisite for the human clinical trial. Similar findings as in the acute single dose study are documented. Chronic toxicity in case of long term application Certain medications for some disease conditions last for up to one week or more.

Such drugs may also be used in the treatment of chronic diseases. Such drugs require animal studies of three to six months and up to one year or more for any chronic diseases to demonstrate its safety. The specific duration should determine the length of the trial of the new drug.

Here also, at least two animal species are required. Allotted effects are noted and documented. Reproductive Toxicity Reproductive toxicity study is a requirement for any new drug compound before administration to any female of child bearing age. The studies are used to determine any effect of active ingredients on the reproductive system.

This study may be divided into three segments: Segment I reproductive toxicity study documents effects of the drug on fertility. Multigenerational effects and teratology are also studied. Any effects on the chromosomes or the DNA strands may be a precursor for gene mutation. Salmonella typhimurium is usually used in assays to detect mutation. Carcinogenicity Studies Testing for carcinogenicity usually applies to drugs for treatment of chronic disease conditions.

The duration of this test is about 18 — 24 months. The surviving animals are killed and studied at specified weeks during the period of the study.

Data collected are animal deaths, tumour incidence, type and site of tumour appearance if any and pre-neoplastic tissue changes etc. A successful pre-clinical trial provides extensive information for perfection of the drug development and subsequent trial in human beings. It is a pre-requisite for investigational new drug application. However, preclinical drug trial has mainly relied on animal species for testing prior to application on humans. This is greatly being challenged and hampered by the animal right activists who are advocating for total ban on the use of animals for research and experimentation.

Though efforts are ongoing to find alternatives to animal testing of drugs prior to clinical trial, the use of animals may still go on for some time to come.

The target product profile as a planning tool in drug discovery research. Pharmatech, 67 — Ultrasound Medical Biology, 5 10 : High throughput screening; update on practices and successes. J Biol Sreen, 11, J Pharmacology, 6 , Guided Genetic interaction Networks. PLoS One; 5 11 : e Nat Rev Drug Discov. The basics of pre-clinical drug development for neurodegenerative disease indications. Comprehensive genomic characterization, defines human glioblastoma genes and core pathways.

Nature; Google Scholar. Accessed June 15, Retrieved June 15, Modelling cancer patient populations in mice: Complex genetic and environmental factors. Drug Discov Today Dis Models ; doi S, Widdie, D. R, et al. Drug discovery. Pre-clinical Imaging.