Nonclinical and In Vivo Toxicology (Tox) Studies: Primary Safety and Toxicity Evaluation for your IND Submission

Toxicological or Toxicology (tox) Studies help determine drug safety by evaluating adverse effect profiles, organ and tissue exposures, and margins of efficacy vs. toxicity. Indeed, these toxicology studies in drug development often range doses encompassing the therapeutic index, defining the window between minimum efficacious and maximum tolerated (or feasible) doses. Typically, test articles selected for nonclinical toxicology assessment are optimized drug discovery leads evaluated previously for pharmacokinetics, potency, and efficacy in preclinical disease models. This preliminary data collection is often essential for designing initial toxicology studies, especially for selecting dose levels, routes, and regimens. Tox studies usually begin with dose range-finding (DRF), maximum tolerated dose (MTD), and single ascending dose or short-term (7-day) repeat dose nonclinical toxicology studies. The purpose of these toxicity studies is to ascertain an appropriate dosing regimen for the long term (≥28-day) repeat dose GLP toxicity study. Generally, the repeat dose studies encompass the drug effects on the entire body utilizing various toxicology services such as gross pathology, histology, and microscopy. Furthermore, additional focused studies are performed to evaluate safety on particular organ systems or anticipated risk factors.

Tox Studies: From Nonclinical Toxicology to Clinical Toxicological Analysis

Regulatory authorities mandate toxicological studies for all novel drug entities, their active metabolites, or metabolites demonstrating significant systemic exposure following drug administration. Before performing regulated repeated dose toxicity studies, pharmaceutical and biochemical researchers often perform single dose toxicity study, maximum tolerated dose (MTD) study, and dose range finding (DRF) study to establish appropriate dosing margins. A short term (typically 7 to 14 days) repeated dose toxicity study is often performed to evaluate any acute toxicity and determine whether dose accumulation occurs by performing toxicokinetic (TK) analysis on the first and last days of dosing. These results are then used to design definitive GLP repeat dose toxicology studies, typically dosing for at least 28 days, depending on the drug’s intended clinical administration. Afterward, TK analysis data are generated during these studies to interpret the dose-exposure relationships, whether saturable metabolism occurs with increasing doses or accumulation occurs with multiple doses, and to empirically demonstrate steady-state exposures. Additional evaluations and studies are performed to assess cardiac, pulmonary, or reproductive health effects and the drug’s potential for carcinogenicity or genetic mutations. Assuming the drug of interest demonstrates adequate safety for first in human (FIH) testing, results from the toxicological studies in drug development may be used to aid in the designs for initial single ascending dose (SAD) and subsequent multiple ascending dose (MAD) PK studies in clinical trials.

Toxicology (Tox) Analysis Services by NorthEast BioLab

NorthEast BioLab TK Assay and TK Analysis Services

NorthEast BioLab provides bioanalysis and pharmacokinetic/toxicokinetic analysis services from early drug discovery through clinical IND/BLA submission and beyond.

Bioanalysis: PK/TK analysis

We offer end-to-end PK/TK analysis services, such as method development, validation, and sample analysis of your formulation and biological samples for test articles, drugs, and metabolites. As needed, our veteran team performs all your preclinical and clinical bioanalytical services using GLP validated equipment, software, and methods. We provide detailed audited study reports for sample bioanalysis and Toxicokinetics as per sponsor requests.

Non-compartmental analysis (NCA): PK/TK parameter analysis

Furthermore, we have in-house expertise to perform your non-compartmental analysis (NCA) – pharmacokinetics or Toxicokinetics of small molecules, metabolites, or monoclonal antibodies during clinical and in vivo preclinical toxicology studies. We can put together Pharmacokinetic Concentration (PC) and Pharmacokinetic Parameter (PP) domains for your results in CDISC SEND or SDTM format for compliance with requirements for electronic submissions to the FDA and other global regulatory agencies.

In line with our solution provider philosophy, we are happy to further assist you with project and regulatory guidance, protocol design, study prosecution, and data interpretation at all project stages. NorthEast BioLab maintains the latest and fully validated software packages for your Toxicokinetic (TK) Study analysis, including Certara’s WinNonlin, Watson LIMS, Sciex Analyst, Spectramax, etc.

Complete Guide on IND Enabling Toxicology Studies

In pharmaceutical discovery and development, many drug substances and their formulations are generated. However, the vast majority of these compounds will not be suitable as final products for commercialization. …

Reliable Toxicokinetic Analysis from your GLP Tox Studies

At NorthEast BioLab, our veteran team of scientists has the necessary experience and expertise to assist with tox studies from planning and execution to TK analysis and data interpretation. Our expertise during toxicology study would empower you to get toxicokinetic studies right in the first go as an essential component of your drug development process. We perform toxicokinetic analysis to determine systemic exposure, steady-state exposure, and metabolic limitations for your compound. These TK parameters help scientists and clinicians decide the correct drug dosage and dosing regimens for early clinical trials. Hence, it is essential to perform reliable, efficient toxicological studies and analysis to aid compound characterization in drug development. Similarly, we carry out the GLP toxicity studies utilizing a fully validated and reliable bioanalytical and TK method to prepare for regulatory IND submissions. We offer formal and audited bioanalysis and toxicokinetics eCTD reports and present your pharmacokinetic concentration and non-compartmental TK parameter results in a compliant CDISC SEND format.

Related FAQs

Answers to additional Toxicology (Tox) Study questions popular among our potential clients.

What are GLP toxicology studies?

What is Toxicokinetics (TK) Study?

What are the various steps in a Toxicokinetics (TK) Study?

What process is involved in Toxicokinetics?

What are the different types of toxicology?

What is nonclinical toxicology?

How is Toxicology used?

How do you test for drug toxicity?

What is the difference between TK and PK?

How are pharmacokinetics and Toxicokinetics related?

What is SEND and which Tox Studies require data submission in SEND format?

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