Preclinical development, also known as preclinical studies or nonclinical studies, is a stage of drug development that occurs prior to clinical trials (human testing) and is distinguished by the collection of critical feasibility, iterative testing, and drug safety data—typically in laboratory animals.
Preclinical studies often involve innovative medical devices, prescription drugs, and diagnostics, and their major goals are to determine a starting, safe dose for first-in-human study and to analyse any potential product toxicity.
Companies use exaggerated numbers to illustrate the risks of preclinical research, such as the one in 5,000 compounds that travel from drug discovery through preclinical development before becoming an approved prescription.
Types of preclinical research
Preclinical research may take many different shapes depending on the product. Medication testing may include pharmacodynamics (PD), pharmacokinetics (PK), ADME, and toxicology (what the medicine does to the body), among other things. Scientists may use this information to allometrically determine a safe starting dose of the medicine for use in human clinical trials. In the absence of a drug attachment, medical devices may go directly to GLP testing to assure the safety of the device and its component elements. Another step that many medical gadgets go through is biocompatibility testing to evaluate whether one or all of its components will hold up in a living model. To be submitted to regulatory agencies such as the Food and Drug Administration in the United States, the majority of preclinical research must adhere to GLPs in ICH Guidelines.
In most cases, both in vitro and in vivo investigations are performed. Drug toxicity studies look at the organs that the medicine affects as well as any long-term carcinogenic or toxic effects that cause illness.
The data gained from these studies is critical for starting safe human testing. Two species are often used in drug research animal testing. Although monkey and porcine models are used on occasion, mouse and canine models are more often used.
The species to be chosen is determined by which will best correspond with human trials. Certain models are more suited than others based on the dosage type, area of action, or hazardous metabolites owing to changes in the stomach, enzyme activity, circulatory system, or other variables. For example, since the carnivore gut is less developed than the omnivore’s and stomach emptying rates are faster, canines may not be suitable models for solid oral dosage forms. Furthermore, rats cannot be utilised as models for antibiotic drugs since the resulting change in their gut flora has serious detrimental implications. Drugs may be metabolised similarly or differently in various species based on their functional groups, affecting their efficacy and toxicity.
This basic concept is also applied in medical device research. The bulk of studies are conducted on larger animals such as dogs, pigs, and sheep, which allow testing in a human-sized model. Furthermore, some species are used because of their parallels in the physiology of a certain organ or organ system (for example, pigs for dermatological and coronary stent research, goats for breast implant investigations, and dogs for stomach and cancer research).
Importantly, before approving human trials, the FDA, EMA, and other analogous international and regional organisations often require safety testing in at least two mammalian species, including one non-rodent species.
Concerns about ethics
Animal testing in the pharmaceutical research business has decreased in recent years for both ethical and commercial reasons. However, the bulk of research will continue to employ animal testing since diverse product production requires similar anatomy and physiology.
No Detectable Impact Levels
Preclinical studies are used to establish no-observed-adverse-effect levels (NOAELs) for medicines, and these values are utilised to produce the initial phase 1 clinical trial dosage levels on a mass API per mass patient basis. A 1/100 uncertainty factor or “safety margin” is sometimes specified to allow for interspecies (1/10) and inter-individual (1/10) variability.