Repeat Administration Toxicity Assay Service
Repeat administration toxicity assay (long-term toxicity assay) is performed after the primary pharmacodynamics and acute toxicity assay of the new drug have been completed and further research value has been confirmed. This study looked at the long-term toxicity of the drug in animals. Long-term toxicity assay is to observe the changes of toxicity, hematology, blood biochemistry and pathology in experimental animals through continuous repeated administration over a period of time. This study can analyze the relationship between the dose toxicity effect, the main target organs, the nature and degree of the toxic reaction, the reversibility of the toxic reaction, the animal tolerance, the non-toxic reaction dose, the toxic reaction dose and the safe range. Repeat administration toxicity assay is one of the main contents of drug safety evaluation and is the main basis for the transition to clinical trial. It is of great significance to predict the initial dose and safe dose range of clinical trials. It is the key monitoring index of clinical trial and has important significance for detoxification of drug poisoning in clinical trial.
Creative Biolabs has international leading talent team and practical experience in repeat administration toxicity assay service, providing high-quality data and fast turnaround time to support various in vivo toxicological evaluation studies. Toxicological study can be carried out in accordance with national standards.
We provide but are not limited to:
- Subacute toxicity assay (2-4 weeks). The duration of repeat administration toxicity assay is usually related to the duration of phase I clinical trials, the observed indicators and the proposed cycle of administration. For some clinical indications, a 2-week trial is sufficient to support a phase I trial. However, for most drug candidates, clinical trials in which more than one dose is administered must be preceded by a 4-week toxicity assay to provide adequate safety information.
- Subchronic toxicity assay (13 weeks). For the 13-week subchronic toxicity assay, it contains specified number of rodents and the animals underwent additional toxicokinetic analysis. Toxicokinetic samples are collected at least at the beginning, middle and end of administration. The toxicological analysis animals can be assigned to the recovery phase to evaluate the reversibility of any adverse reactions found.
- Chronic toxicity assay (6-12 months). ICH S4 recommends that chronic toxicity assay should be reduced from 12 months to 6 months of rodent testing and 12 months to 9 months of non-rodent testing. In rodent and non-rodent experiments, the number and toxicological parameters used are approximately the same as in the 13-week toxicity assay.
Creative Biolabs is committed to providing in vivo toxicological evaluation services to support early drug development and lead compound selection/optimization. Creative Biolabs can provide rapid and high-quality long-term toxicity evaluation according to the process required by customers, so as to understand the toxicity reaction time, peak time and duration, delayed toxicity, accumulative toxicity and tolerance.
The targets of repeat administration toxicity assay service:
- To predict the clinical adverse reactions, including the nature, degree, dose-response relationship, time-response relationship and reversibility of adverse reactions.
- To determine the target organ and tissue of toxicity of repeated administration.
- To infer the starting dose and safe dose range of repeated administration for clinical trials.
- To give some suggestions for the indicators that need to be monitored in clinical trials.
- To provide reference for detoxification and rescue measures in clinical trials.
References
- Chovanec M, et al. Long-term toxicity of cisplatin in germ-cell tumor survivors [J]. Ann Oncol. 2017, 28(11):2670‐2679.
- López-Massaguer O, et al. Generating Modeling Data From Repeat-Dose Toxicity Reports [J]. Toxicol Sci. 2018, 162(1):287‐300.
*For Research Use Only. Not for use in diagnostic procedures.