Abstract:The biopharmaceutical industry is increasingly developing digital twins to digitalize and automate the manufacturing process in response to the growing market demands. However, this shift presents significant challenges for human operators, as the complexity and volume of information can overwhelm their ability to manage the process effectively. These issues are compounded when digital twins are designed without considering interaction and collaboration with operators, who are responsible for monitoring processes and assessing situations, particularly during abnormalities. Our review of current trends in biopharma digital twin development reveals a predominant focus on technology and often overlooks the critical role of human operators. To bridge this gap, this article proposes a collaborative intelligence framework that emphasizes the integration of operators with digital twins. Approaches to system design that can enhance operator trust and human-machine interface usability are presented. Moreover, innovative training programs for preparing operators to understand and utilize digital twins are discussed. The framework outlined in this article aims to enhance collaboration between operators and digital twins effectively by using their full capabilities to boost resilience and productivity in biopharmaceutical manufacturing.