Good Lab Practices (GLP) form an essential regulatory requirement for submitting a New Drug Application (NDA) to the FDA. GLP requirements are especially important about the toxicology studies that must be performed before a drug moving to clinical trials.
Guidelines issued for GLP toxicology studies FDA are non-binding. However, this doesn’t mean that the studies can be non-GLP. This is done to accommodate some specific requirements or to enable justification for a case-to-case basis. The FDA specifically put GLP requirements in place to deal with problems like insufficient documentation, inadequate planning, and similar issues.
GLP thus forms a system of management control during nonclinical research. This system ensures that the studies and data show uniformity, consistency, reliability, and reproducibility. The idea is to protect animal and human health. Generally, the goal is for toxicology study and TK analysis to ensure that the proposed drug is safe to use for human clinical trials.
While GLP study is necessary for NDA, it is also relevant for use in existing drugs. It may also be required to extend the profile of an existing drug. It is required to settle the profile for new indications, formulations, routes of administration, and other changes.
Assessing TK Study with GLP
Toxicokinetic profile of a drug provides important data, including safe drug dosage and No Observed Adverse Effects Level (NOAEL). Since safety is also a primary requirement for GLP, it works closely with the TK study.
As TK analysis progresses, data becomes available on the formulation, safe dose, and concentration of the drug. Initial or preliminary studies can be conducted using non-GLP methods. However, any study whose result will be extrapolated towards human safety must follow GLP. The generated drug profile is likely to include information on safe dosage, variation between genders, biomarkers, and other characteristics.
A TK study may be carried out in vitro or in vivo. While in vitro studies could be non-GLP, in vivo studies involving animals must follow GLP. These toxicokinetic studies measure the systemic exposure of toxicity in animals. This establishes a relationship between the administration of the dose and the time taken to reach toxic concentrations. As the process is very similar to pharmacokinetics, a part of the PK profile may be used towards toxicological findings.
The toxicology study will also look at the risk of accumulation of the drug in specific organs and tissues. In cases where these may not be measured directly, blood serum concentrations are used to get a better idea. Though it is rare, the use of more invasive methods is not ruled out in some cases.
Completing in vivo studies for TK analysis usually requires at least two mammalian species, one of which must be a non-rodent.
Non-GLP studies may be used for exploratory studies in rodents, including Dose Range Finding (DRF) and Maximum Tolerated Dose (MTD). Subsequent studies must use GLP. There is no specific plan on what route to take.
However, it is generally recommended that genotoxicity studies, dose selection, and repeated dose toxicity be performed. If required for the development, studies should also be carried out to consider other factors, including carcinogenicity, reproduction toxicity, and immunotoxicity.
