Mechanistic models are being constructed for all unit operations for the end-to-end continuous manufacturing of mRNA biotherapeutics. The dynamic models are integrated with models for constraints, uncertainties, and disturbances to form a digital twin for automated, integrated manufacturing. The digital twin is suitable for (1) evaluation and validation of mechanistic hypotheses to gain mechanistic understanding, (2) comparison of multiple process flowsheet options, (3) optimization of individual unit operations and their control systems, (4) the design of end-to-end operations, and (5) the real-time operation alongside plant operations. Experimentally validated results are presented for multiple unit operations.