The purpose of this guidance is to assist sponsors in the design of nonclinical studies for the development of pharmaceuticals used to treat patients with severely debilitating or lifethreatening hematologic disorders (SDLTHDs). This guidance is intended to streamline the development of pharmaceuticals used to treat patients with SDLTHDs, other than cancer, while still protecting patients’ safety and avoiding unnecessary use of animals, in accordance with the 3R (reduce, refine, replace) principles. This guidance applies to pharmaceuticals used both to treat the active disease and to prevent the recurrence of a life-threatening or debilitating event.

This guidance does not address radiopharmaceuticals, vaccines, cellular and gene therapy products, or blood products. This guidance provides recommendations for nonclinical studies in support of trials in patients only. For nonclinical studies in support of studies in healthy volunteers, consult the ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (January 2010). This guidance is not for anticancer pharmaceuticals intended to treat hematologic malignancies. For oncology indications, consult the ICH guidances for industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals (March 2010) and S9 Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers (June 2018).

The draft guidances for industry titled Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings (October 2018) and Rare Diseases: Common Issues in Drug Development (August 2015) do not specifically facilitate the nonclinical development of pharmaceuticals for treatment of SDLTHDs. Because SDLTHDs are not all rare diseases, they can fall outside the scope of the draft guidances for rare diseases. The present document provides consistent guidance for all nononcology SDLTHDs, independent of disease incidence or prevalence.

Posted on the FDA website on 14 March 2019