Toxicology Study Design Considerations
Key points to note when designing a pre-clinical GLP toxicology study includes:
- The study objective is to evaluate the toxicity of a new molecule in the test system using the intended clinical route of delivery and dosing regimen.
- Safety assessment or toxicity in healthy animals with varying doses ranging from a minimum efficacious dose to a maximum tolerated (or feasible) dose.
- Regulations require preclinical toxicology studies to be conducted under 21 CFR part 58, GLP.
- Animal welfare compliance must be addressed, and protocols must be approved before execution by an Institution Animal Care and Use Committee (IACUC).
- The test article should be clearly characterized and defined, with a viable certificate of analysis (COA).
- Dosing vehicles and compound preparation should be clearly defined, and dosing excipients should be approved for the test model species.
- Test model species should be justified. These include comparisons (similarities and differences) between various species and humans for target receptor expression, homology, distribution and sub-types, metabolic profile, pharmacokinetic (PK) profile, plasma protein binding, and whether the pharmacology and physiology represent the expected effect in humans, to demonstrate relevance.
- Experimental design should include all intended doses, dose levels, routes of administration, and frequency and duration of administrations.
- A clear definition of animal observations is required, including detailed clinical observations, body weights, ophthalmic observations, food consumption, and dermal observations.
- Hematology, clinical chemistry, coagulation assays, urinalysis, electrocardiograms, and other relevant safety measures with clearly defined endpoints.
- Pathology and histopathology as needed to evaluate target organ toxicities. Pathological findings for both target and non-target tissues to determine scheduled and unscheduled deaths; comprehensive gross pathology, histopathology, and organ weights; pathologists blinded to treatment.
- Toxicokinetic (TK) analysis typically following a single-dose collected on the first day of dosing and multiple-doses collected on the last day of dosing. Known metabolites of the NME should be evaluated as well if they demonstrate significant in vivo exposures or therapeutic or toxicologic activities. TK parameters are necessary to describe compound exposures, multiple-dose accumulation or steady-state exposures, dose linearity, saturable metabolism, gender or population differences, formulation comparisons, etc. depending on the compound properties and study objectives.
Noble Life Sciences has an in-house experienced toxicology team 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, contact us at email@example.com