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Introduction
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FDA vs. OHRP
What FDA Regulates
FDA Authorities
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Clarifying the "new" in IND
Assessing Preclinical Data
Properties of the Study Drug
How the Data is Used
IND Submission
IND Holder Reponsibilities

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:

  • Carcinogenicity studies
  • Mutagenicity studies
  • Teratogenicity studies
  • Embryotoxic studies
  • Drug Absorption/Distribution/Metabolism studies
  • Pharmacokinetic/ Pharmacodynamic 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.

Tylenol®, originally 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.