Automated manufacturing of cell therapies
Alice Melocchi, Brigitte Schmittlein, Sudeshna Sadhu, Sunaina Nayak, Angela Lares, Marco Uboldi, Lucia Zema, Benedetta Nicolis di Robilant, Steven A. Feldman, Jonathan H. Esensten
Abstract
Advanced therapy medicinal products (ATMPs), particularly genetically engineered cell-based therapies, are a major class of drugs with several high-profile Food and Drug Administration (FDA) approvals in the past decade. However, the high cost and limited production capacity of these drugs remain a barrier to access. These costs are primarily due to the complex manufacturing processes (often a single batch for a single patient), which increases personnel and facility expenses, and the challenges associated with tech-transfer from research and development stages to clinical-stage production. In order to scale up and scale out in a cost-effective way, automated solutions capable of multi-step manufacturing have been developed in academia and industry. The aim of the present article is to summarize the design approaches and key features of current multi-step automated systems for cell therapy manufacturing. For each system described in the literature, we will discuss different aspects in detail such as cell specificity, modularity, processing models, manufacturing locations, and integrated quality control. Our analysis highlights that developers need to balance competing needs in an environment where the biological, business, and technological factors are constantly evolving. Thus, designing engineering solutions that align with the pharmaceutical end-user is essential. Adopting a risk-based approach grounded in published data is the most effective strategy to evaluate existing and emerging automated systems. • Automation in cell therapy manufacturing reduces costs, risk of errors, and risk of microbial contamination. • Automation increases scalability and improves quality. • Comparative analysis of various automated systems, highlighting their suitability for cell therapy applications. • Evaluation frameworks for cell therapy focus on hardware, consumables, software, and standards. • Our analysis provides a holistic approach to evaluate automated cell therapy manufacturing solutions.