Environmental Health and Biosafety Risk Assessment Guidance for Commercial-Scale Cell and Gene Therapy Manufacturing.

Abstract

This article aims to identify best practices, improve risk controls, and aid regulatory agencies in developing guidance for environmental and biosafety risk assessment for commercial-scale cell and gene therapy manufacturing. A cross-functional team should start with hazard classification and testing requirements for materials used or generated by the process and process hazard characterization. The team develops a safety profile of the process to mitigate risks, including: product biological contamination risk and process controls, including raw materials, facilities, operator and environmental controls, and method of detection;a technical review of the process to evaluate the operational and engineering controls;monitoring systems to mitigate the risk of failure and/or breach of the system, preventing the release of material to the facility or operator exposure;site sanitization strategy and facility containment measures, including engineering designs, air handling systems, spill containment measures, surface cleanability, waste flows, and decontamination practices;a review of site practices, including process, employee, material and waste flows, staff training, controlled access, operator gowning, and emergency response plans/measures. The cross-functional team should regularly reconvene to provide solutions for enhanced process control, process life-cycle management, monitor assumptions, and track performance. The plan must be revised following any relevant failure event or process change. A risk assessment template is shared to bring to the reader's attention the complexity of commercial-scale manufacturing, areas to assess, potential questions to ask, and other pertinent parties who may input to the risk assessment.