Operationalizing Digital Twins in Biomanufacturing through Interoperable Process Analytical Technology

Published

July 16, 2026

Author(s)

Abhijeet Satwekar, Cyndell Gracieux-Singleton, Veerabhadraiah Palakollu, Monica Acerbi, Ryan Barton, Chris Cummings, Allie Horton, Sandeep Kedia, Thomas Cornish, Katharina Yandrofski, Roger Hart, Dannielle Berlinghieri, James Saylor, Kelvin H. Lee

Abstract

The integration of Process Analytical Technologies (PAT) within digital twin architectures represents a critical advancement in biopharmaceutical manufacturing. While existing literature has separately addressed digital twin dimensions, interoperability levels, and manufacturing standards, their systematic integration for real-time bioprocess control remains underexplored. Our work provides an operational framework that bridges established frameworks on digital twin dimensions with hierarchical interoperability levels. Our conceptual framework establishes an interoperability "triangle" wherein Data and Connection dimensions function as the central hub linking Physical/Virtual entities with Services to enable model-based predictive control (MPC) through PAT integration. We exemplify the practical application of our proposed approach using a galactosylation adaptive control case study, encompassing purpose-driven systematic technology assessment through operational deployment at the BTEC SPIDER testbed. Our work establishes both theoretical advancement in digital twin operationalization and a practical approach for implementing MPC-enabled PAT systems in highly regulated biopharmaceutical manufacturing, with potential for broader application across diverse bioprocess critical quality attributes, unit operations, and manufacturing scales.

Citation

Bioprocess and Biosystems Engineering

Volume

49

Pub Type

Journals

Download Paper

https://doi.org/10.1007/s00449-026-03369-9

Local Download

Keywords

Process Analytical Technologies, Digital Twins, Interoperability, Model-Based Predictive Control, Biomanufacturing

Citation

Satwekar, A. , Gracieux-Singleton, C. , Palakollu, V. , Acerbi, M. , Barton, R. , Cummings, C. , Horton, A. , Kedia, S. , Cornish, T. , Yandrofski, K. , Hart, R. , Berlinghieri, D. , Saylor, J. and Lee, K. (2026), Operationalizing Digital Twins in Biomanufacturing through Interoperable Process Analytical Technology, Bioprocess and Biosystems Engineering, [online], https://doi.org/10.1007/s00449-026-03369-9, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=961340 (Accessed August 12, 2026)

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