Regulatory Strategy, Project Management, and IND Readiness in the Early Development of Ex Vivo CRISPR-Edited Autologous Cell Therapy for Hemoglobinopathies: A Case Analysis for Pre-IND Meetings and the IND Application for FDA

Abstract

This article examines early drug development through the lens of regulatory affairs and project management, with emphasis on readiness for Pre-IND meetings and the IND application for FDA. Sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) are inherited blood disorders that have long needed durable, disease-modifying options. This article examines the category of ex vivo, CRISPR-edited autologous hematopoietic stem cell therapies, using exagamglogene autotemcel as an illustrative example, to show how a defensible target and therapy selection rationale can be built. The analysis covers the biology of fetal hemoglobin reactivation through the erythroid-specific enhancer of the BCL11A gene, the mechanistic logic of editing a patient's own stem cells, the pivotal clinical evidence, and the regulatory lifecycle, including the expansion of the approved population to children aged 2 years and older in July 2026. It closes with recommendations for strengthening a rationale document and safeguarding it against legal and copyright exposure. The article is scoped to the U.S. Food and Drug Administration (FDA) biologics pathway; the underlying science is universal, but the regulatory framing is FDA-specific. It explains how the selection rationale supports Pre-IND meeting requests and the IND application for FDA, shows how project management tools such as stage gates, a risk register, and document control turn a regulatory plan into a schedule, and connects the case to professional pathways in regulatory affairs.