FDA Finalizes Guidance on Nonclinical Drug Development for Serious Hematologic Disorders

Regulatory NewsRegulatory News | 14 March 2019 |  By 

The US Food and Drug Administration (FDA) on Thursday finalized guidance on the nonclinical studies drugmakers should conduct when developing products to treat severely debilitating or life-threatening hematologic disorders (SDLTHDs).
FDA classifies SDLTHDs as hematologic conditions that cause shorter life expectancy or greatly diminished quality of life even with available treatments.
FDA notes that the guidance does not apply to hematologic cancers and covers drugs that either treat the active disease or prevent the recurrence of symptoms.
“The guidance is intended to streamline the development of pharmaceuticals used to treat patients with SDLTHDs, other than cancer, while protecting the patients’ safety and avoiding unnecessary use of animals, in accordance with the 3R (reduce, refine, replace) principles,” FDA writes.
The 12-page guidance comes nearly a year after the agency released the draft version for comment in April 2018.
While the final guidance largely mirrors the recommendations made in the draft version, FDA has expanded its explanation for what conditions qualify as SDLTHDs, saying that a condition can be considered severely debilitating or life-threatening “despite available therapies, depending on how the patient population is defined (e.g., refractory), the effectiveness of available therapies and whether available therapies include medications or procedures associated with undesirable health outcomes (e.g., complications associated with organ transplant).”
Examples of conditions the agency considers SDLTHDs include multicentric Castleman’s disease, amyloidosis, sickle cell disease and hemophilia.
The final guidance makes other clarifications from the draft guidance, including a recommendation for sponsors to provide data from secondary pharmacology assessments with their initial investigational new drug (IND) submission and a note that stand-alone safety pharmacology studies “will not be called for” unless there are specific safety concerns that would warrant such studies.
FDA also added a sub-section to the general toxicology recommendations in the final guidance explaining steps sponsors should take when considering a change in the clinical schedule for an investigational drug.
“When considering a change in the clinical schedule, the sponsor should conduct an evaluation of the existing clinical data to justify such change,” FDA writes, noting that if previous toxicology data and other available information do not support a change in clinical schedules that an additional one-month toxicology study in a single species “is usually sufficient to support the new clinical schedule.”
The guidance also includes more detailed recommendations for studying drug combinations to treat SDLTHDs and adds a caveat for when juvenile animal toxicology studies, while not typically necessary before initiating pediatric clinical trials, may be required to answer specific questions not addressed in other clinical and nonclinical data.
Guidance, Federal Register Notice


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