How to Optimize your Non GLP Toxicology Studies
How to Design the Best Non GLP Toxicology Study for You
Designing the right Non GLP Toxicology study to evaluate the safety of your molecule or biologic should be crafted in such a way to ensure the results are accurate, reflect the clinical setting, and maximize your return on investment. This post provide some key factors to keep in mind when designing an optimal new safety study.
Make Sure you are Using an Appropriate Species
Typically, one rodent and one second species is required to evaluate the safety profile of your drug candidate. For biologics, you may be limited to only one species.
Prior to your first dose, preliminary studies identifying and confirming that the pharmacological activity is the same in humans should be completed. This includes similar metabolism, similar target binding, and functional activity.
In parallel, the drug exposures achieved in the test species should be sufficient to cover multiple doses to establish a safety margin.
Are You Choosing the Right Dose or Doses?
The science of toxicology is based on the principle that there is a relationship between a response and the amount of dose received. The question you should ask is: how is dose related to toxicity?
Toxicology studies are designed to investigate how animals react at doses from low to high levels. Then, at various intervals, the animals are examined for the presence or absence of effects. These effects may be clinically observed, behavioral changes, alterations in serum chemistries, or effects on organs or organ systems.
Go for a Similar Clinical Exposure if Defining NOAEL
If the intent of your study is to define the no observable adverse effect level or NOAEL, which is used to define the starting dose in clinical trials, you should choose a dose that results in similar exposure as the estimated clinically relevant dose. Your high dose, in general, should be a dose that produces a toxicity, keeping in mind that biologics, even high doses, may show no overt toxicity.
Non-GLP is Informative
The key objective of a toxicology study in to define a safe clinical dose. Non-GLP toxicology studies are preliminary and can be extremely informative. When designed appropriately, the results can answer whether a suspected toxic issue is mechanism-based and, if so, with the right choice of dosing, is there an acceptable safety margin to move my candidate forward.
Non-GLP toxicology studies should aim to mimic the clinical setting if reasonable, i.e. length of dosing, route of administration, frequency of dosing. Lastly, consider including means to monitor safety pharmacology; measuring blood pressure, imaging the liver, monitoring hyperglycemic/hypoglycemic events, to maximize the most of your non-GLP toxicology study.
More information and guidance on toxicology and pharmacology studies is available from the FDA website.