Development of a Safety Surveillance Plan for The Academic Medicine Sponsor Performing First in Human Cellular Therapy Clinical Trials: A Report from the Consortium for Pediatric Cellular Immunotherapy

Pharmacovigilance (PV), also known as drug safety, is the science of risk management; involving the detection, assessment, understanding, and prevention of adverse effects related to a medication. This discipline has traditionally focused on the post-marketing period, with less attention to early phase clinical trials. However, within the immuno- and cellular therapy investigational stage, regulatory agencies are increasingly emphasizing the need to identify and characterize safety signals earlier in clinical development as part of a comprehensive safety surveillance plan. Compliance with PV and safety regulations are further heightened as cell and gene therapy (CGT) trials grow in complexity and scope due to ever-changing and increasingly rigorous regulatory mandates. Based upon this changing landscape, a critical piece of early phase trials of cellular products where significant safety events are anticipated is to ensure that every effort is made to protect clinical trial participants by maximizing attention to the risk versus benefit profile. This includes the development of robust plans for safety surveillance that provide a continual assessment of safety signals to enable safety reporting to regulatory bodies and the Food and Drug Administration (FDA), a regular analysis of aggregate safety data, and a plan to communicate safety findings. This report focuses on PV in early-phase clinical trials of first in human investigational products sponsored by academic centers where the availability of PV resources and subject matter experts is limited. To more fully understand the challenges of CGT PV oversight within pediatric academic medical centers conducting early phase clinical trials, a working group from institutions participating in the Consortium for Pediatric Cellular Immunotherapy (CPCI), composed of faculty and regulatory professionals, was initiated to compare experiences, identify best practices, and review published literature to identify commonalities and opportunities for alignment. Here we present guidelines on PV planning in early-phase CGT clinical trials occurring in academic medical centers and offer strategies to mitigate risk to trial participants. Standards to address regulatory requirements and governance for safety-signal identification and risk assessment are discussed.