title: Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.
abstract: The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: E L
authors.initials: EL
authors.lastname: Andrade
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: A F
authors.initials: AF
authors.lastname: Bento
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: J
authors.initials: J
authors.lastname: Cavalli
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: S K
authors.initials: SK
authors.lastname: Oliveira
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: R C
authors.initials: RC
authors.lastname: Schwanke
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: J M
authors.initials: JM
authors.lastname: Siqueira
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: C S
authors.initials: CS
authors.lastname: Freitas
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: R
authors.initials: R
authors.lastname: Marcon
authors.affiliation: Centro de Inovação e Ensaios Pré-clínicos, Florianópolis, SC, Brasil.
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000592:standards*; D017321:Clinical Trials, Phase I as Topic; D004353:Drug Evaluation, Preclinical / Q000592:standards*; D015507:Drugs, Investigational / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007753:Laboratories / Q000592:standards*; D009152:Mutagenicity Tests; D010601:Pharmacology, Clinical / Q000592:standards
chemical_list: D015507:Drugs, Investigational