Assessing Pre-Clinical Data
All FDA-approved drugs have undergone some preclinical
safety testing. However, the scope of the testing was dependent
on the proposed/intended use. For example, a drug approved for short
term or single-use administration would not necessarily have undergone
any long-term safety or carcinogenicity studies.
To get an idea of what the implications of insufficient preclinical
testing, compare your intended use with the FDA-approved uses of
the study drug, considering whether the following potential pre-clinical
studies may have been conducted:
- Drug Absorption/Distribution/Metabolism studies
- Chronic/Long-term safety studies
You may conclude that it would be unsafe to use the study drug
as you intended without first conducting pre-clinical safety studies.
Examples to consider
If a drug was indicated exclusively
for use in men over the age of 65, would embryotoxicity and teratogenicity
studies be important?
Yes. For example, Propecia®, which was originally developed
as a treatment for benign prostatic hypertrophy and therefore only
intended for men, was found to distribute in many body fluids, including
semen. The drug was also found to be highly teratogenic (caused
malformations in external genitalia of male offpsring in rats).
Had these preclinical studies NOT be done, pregnancies of female
sexual partners of treated males may have been put at risk.
This risk is so high that the drug labeling includes warning against
women coming in contact with crushed or broken tablets.
developed as an oral tablet, can be taken rectally. Since
the rectal mucosa has markedly different absorptive properties than
the gastrointestinal tract, it was important to study pharmacokinetic
properties in animals prior to introducing this route of administration
to humans. It was found that a markedly different formulation
of Tylenol® was necessary to achieve the same pharmacokinetic
and therapeutic profile as the oral formulation.