Drug development is a time-consuming and costly procedure. However, in an emergency circumstance like COVID-19, progress can be significantly faster. Toxicology testing is required for all drugs and must be prioritized throughout the drug development process. Majority of toxicology testing occurs during nonclinical and clinical phases. Toxicology testing uses animal models to assess a drug’s safety in humans and find compounds that may cause harm. Toxicological studies performed to support the delivery of the potential new drug candidate to patients in Phase I clinical studies are summarized in the investigational new drug (IND) filing. During the nonclinical phase, four categories of data are required:

1. Acute toxicity studies help identify doses for long-term animal research.
2. Repeated-dose toxicity experiments involve administration of acute doses daily for a specified period up to the expected lifespan of the test species. These studies use multiple dosages to characterize potential chronic side effects.
3. Safety pharmacology investigations assess cardiovascular, pulmonary, and neurological system side effects.
4. Genetic toxicology testing examines potential DNA damage in animals and humans.

The results of the studies are reviewed to find a safe starting dose for Phase I clinical trials. Once the dose regimen and toxicity profile determined, the company files an IND application. Phase I clinical studies can begin if FDA reviewers agree with the drug’s assessment. Poor toxicity profile in the preclinical stage of therapeutic development is a common reason for drug failure. Several global regulatory authorities require sponsors to maintain toxicity testing and data collection throughout the clinical trial phases. Therefore, during clinical studies, the drug’s safety must be tested in nonclinical animal models. Typical nonclinical toxicological studies conducted during the clinical phase of development include:

1. Sub-chronic and chronic toxicology studies are conducted over a longer period (usually three, six, nine, or twelve months) and are used to examine the drug’s long-term effects on animal models.
2. Reproductive toxicology studies are performed to determine if the potential new drug has any effects on male and female reproductive organs, male and female fertility, or embryonic development.
3. Carcinogenicity studies are typically performed in rats and mice for two years and are used to determine if a lifetime exposure to the potential new drug can cause cancer or tumors.

If the data show a satisfactory risk-benefit assessment, the company submits an NDA to the FDA or a corresponding submission to other regulatory bodies. While nonclinical animal toxicology studies follow accepted designs, the following crucial points must be considered:

1. Animal species: Toxicology investigations typically involve two species: one rodent and one non-rodent.
2. Drug administration route: The drug administration route chosen for toxicity testing usually mirrors the route used in clinical trial.
3. Endpoints: Endpoints that are included in every study are clinical observations, blood chemistry, histopathology, food consumption measurement, and body weights. Depending on the drug type (chemical, antibody, protein, vaccine, RNA etc.), additional endpoints can be included such as immunogenicity, cytokines, enzyme activity, special cell types, and immune function.

To assure the validity, integrity, and reliability of nonclinical safety data submitted for regulatory examination and approval, most nonclinical toxicological studies must follow good laboratory principles (GLPs). Bio/pharma businesses must be prepared to move quickly through the drug development process while ensuring the drugs are safe. Some R&D programs were able to be completed in one year due to the joint efforts of pharmaceutical corporations, governments, and CROs.

Noble Life Sciences’ established experience in toxicology testing guarantees that you have comprehensive safety testing results to support the advancement of your program. Our team of experts is well-equipped to collaborate on the general principles and designs of your toxicology tests, including the species to be tested, the size of the treatment group, the duration of treatment, the frequency of administration, and the route of administration, as well as relevant in-life observations and terminal endpoints based on the properties of your test article and intended clinical use.

For more information, visit www.noblelifesci.com, or contact us at info@noblesci.com