FDA recommendations for preclinical testing of gonadotropin releasing hormone (GnRH) analogues

Gonadotropin-releasing hormone (GnRH) agonists and antagonists are synthetic analogues synthesized by modifications of the naturally occurring hypothalamic decapeptide GnRH. These modifications significantly increase the biological potency and duration of action of GnRH agonists as well as the solubility, potency, and duration of action of GnRH antagonists while decreasing GnRH antagonists toxicity. The field of GnRH analogues has expanded significantly during the past few years in terms of the number of analogues, therapeutic indications, formulations, and mode of administration. This paper provides recommendations for nonclinical testing of GnRH analogues and reflects the type and degree of toxicity testing expected by the Division. However, these recommendations are not formal guidelines in that alternative testing methods will be considered. Furthermore, these recommendations should not be used as guidance for testing of other new drugs.