A multiscale simulation framework for the manufacturing facility and supply chain of autologous cell therapies

Kan Wang; Yi Liu; Junxuan Li; Ben Wang; Reid Bishop; Chip White; Amritava Das; Aaron D Levine; Linda Ho; Bruce L Levine; Andrew D Fesnak

doi:10.1016/j.jcyt.2019.07.002

A multiscale simulation framework for the manufacturing facility and supply chain of autologous cell therapies

Cytotherapy. 2019 Oct;21(10):1081-1093. doi: 10.1016/j.jcyt.2019.07.002. Epub 2019 Aug 21.

Authors

Kan Wang¹, Yi Liu², Junxuan Li³, Ben Wang⁴, Reid Bishop³, Chip White³, Amritava Das⁵, Aaron D Levine⁶, Linda Ho⁶, Bruce L Levine⁷, Andrew D Fesnak⁸

Affiliations

¹ Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, Georgia, USA. Electronic address: kan.wang@gatech.edu.
² Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, Georgia, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
³ H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
⁴ Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, Georgia, USA; H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
⁵ Morgridge Institutes of Research, Madison, Wisconsin, USA.
⁶ School of Public Policy, Georgia Institute of Technology, Atlanta, Georgia, USA.
⁷ Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 31445816
DOI: 10.1016/j.jcyt.2019.07.002

Abstract

Background aims: Autologous cell therapy (AuCT) is an emerging therapeutic treatment that is undergoing transformation from laboratory- to industry-scale manufacturing with recent regulatory approvals. Various challenges facing the complex AuCT manufacturing and supply chain process hinder the scale out and broader application of this highly potent treatment.

Methods: We present a multiscale logistics simulation framework, AuCT-Sim, that integrates novel supply chain system modeling algorithms, methods, and tools. AuCT-Sim includes a single facility model and a system-wide network model. Unique challenges of the AuCT industry are analyzed and addressed in AuCT-Sim. Decision-supporting tools can be developed based on this framework to explore "what-if" manufacturing and supply chain scenarios of importance to various cell therapy stakeholder groups.

Results: Two case studies demonstrate the decision-supporting capability of AuCT-Sim where one investigates the optimal reagent base stocking level, and the other one simulates a reagent supply disruption event. These case studies serve as guidelines for designing computational experiments with AuCT-Sim to solve specific problems in AuCT manufacturing and supply chain.

Discussion: This simulation framework will be useful in understanding the impact of possible manufacturing and supply chain strategies, policies, regulations, and standards informing strategies to increase patient access to AuCT.

Keywords: autologous cell therapy; cell manufacturing; multiscale simulation framework; supply chain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Cell- and Tissue-Based Therapy* / economics
Cell- and Tissue-Based Therapy* / methods
Cell- and Tissue-Based Therapy* / standards
Cell- and Tissue-Based Therapy* / statistics & numerical data
Commerce
Computer Simulation*
Drug Industry* / economics
Drug Industry* / organization & administration
Drug Industry* / standards
Drug Industry* / statistics & numerical data
Equipment and Supplies Utilization / statistics & numerical data
Humans
Manufactured Materials / economics
Manufactured Materials / statistics & numerical data
Manufactured Materials / supply & distribution*
Manufacturing and Industrial Facilities* / economics
Manufacturing and Industrial Facilities* / standards
Manufacturing and Industrial Facilities* / statistics & numerical data
Manufacturing and Industrial Facilities* / supply & distribution
Quality Control
Quality Indicators, Health Care
Transplantation, Autologous
United States / epidemiology