The development of a drug product involves the evaluation of safety and efficacy in both animals and humans. The primary goal of nonclinical studies is to assess toxic effects in target organs. Researchers then use this data to determine the initial doses for in-human studies. Although carried out at the beginning of drug development studies, the acceptable conduct of preclinical studies is vital to support later stages of clinical trials.
Human clinical trials begin with lower drug doses to assess safety and efficacy in study participants. This assessment is followed by studies with an increase in duration and size. However, clinical trials are only extended based on safety and efficacy data from previous studies. Hence, assessing toxicity is crucial for bringing safe drugs to the patient population. Besides, appropriate sample collection ensures that the biological sample is in better condition for analysis. Let us individually understand the FDA guidelines for each of these aspects of drug development.
Biological sample collection
Collecting, processing, and storing biological samples are crucial aspects of preclinical and clinical studies. Unfortunately, the complexities involved are generally underestimated. Before initiating clinical studies, researchers should address sample collection, processing, and storage issues. The first thing that researchers must decide is the sample type. An appropriate study sample must be decided. It must be followed by a suitable processing protocol. Finally, storage systems must be in place to handle biological samples during experiments.
Researchers must thoughtfully plan and execute these actions with systems to track the developments. Besides, researchers must have standard operating procedures and quality management systems to ensure reliable and accurate bioanalysis.
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Toxicological analysis
Toxicological studies are a crucial component of IND enabling studies. Only after demonstrating safety and efficacy in animal models, the FDA authorizes the use of a potential drug candidate in human trials. The following section discusses crucial FDA guidelines for clinical toxicological analysis.
- Generally, toxicity analysis uses the Maximum Tolerated Dose (MTD) study to find the maximum tolerated dose and deduce potentially clinically relevant insights. However, it is not necessary to demonstrate MTD in all studies.
- Toxicology services employ both in vitro and in vivo toxicology studies to assess the toxic properties of a drug product. Often studies move forward without in vitro analysis, but FDA needs in vivo toxicology data to support IND applications.
- Researchers generally obtain acute toxicity data from single-dose toxicity studies. They must conduct acute toxicity studies in two mammalian species through both parenteral and clinical routes of administration. However, acute toxicity information can also be derived from short-duration dose-ranging studies or dose-escalation studies that determine the MTD in the test species. Dose range-finding studies are clinical trials that test different doses of the drug candidate to determine the best drug doses with the highest therapeutic effect but with the least toxicity.
- The duration of repeated-dose toxicity studies generally depends on the duration, scope, and therapeutic indication of the clinical trial. In principle, repeated dose toxicity studies must consist of two mammalian species (one nonrodent) and should not exceed or must be equal to the duration of clinical studies in humans.
