Abstract
The production sector is experiencing significant transformations driven by comprehensive digitalization, interconnection, and further automation advances. One sub-sector that can benefit significantly from these trends is the production of Advanced Therapy Medicinal Products (ATMPs). ATMPs show promise for treating different serious conditions, but they are very expensive—being patient tailored products whose production is a highly manual, minimally automated process. In a recent research project with an ATMP producer, we investigated how the degree of automation can be increased. It became apparent that in parallel to increasing automation across the actual production steps, quality assurance needs to be addressed in a similar way. This paper introduces a framework for automating (parts of) the quality assurance of ATMPs using two concepts: (a) digital shadows or twins and (b) assurance cases. We demonstrate its conceptual implementation along a case study for Car-T cell products used to treat certain forms of cancer.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Details of the asset administration shell - part 1. https://www.plattform-i40.de/PI40/Redaktion/DE/Downloads/Publikation/Details_of_the_Asset_Administration_Shell_Part1_V3.html
The development of a digital plant maturity model to aid transformation in biopharmaceutical manufacturing. https://pharmaceutical.report/whitepapers/the-development-of-a-digital-plant-maturity-model-to-aid-transformation-in-biopharmaceutical-manufacturing/1848
EudraLex The Rules Governing Medicinal Products in the European Union Volume 4 - Part 4 - Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf
Submodel templates of the asset administration shell - zvei digital nameplate for industrial equipment (version 1.0). https://www.plattform-i40.de/PI40/Redaktion/DE/Downloads/Publikation/Submodel_Templates-Asset_Administration_Shell-digital_nameplate.html
Bedenbender, H., et al.: Examples of the Asset Administration Shell for I4.0 Components. ZVEI White Paper (2017)
Chowdhury, T., Wassyng, A., Paige, R.F., Lawford, M.: Systematic evaluation of (safety) assurance cases. In: Casimiro, A., Ortmeier, F., Bitsch, F., Ferreira, P. (eds.) SAFECOMP 2020. LNCS, vol. 12234, pp. 18–33. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-54549-9_2
Grangel-González, I., Halilaj, L., Coskun, G., Auer, S., Collarana, D., Hoffmeister, M.: Towards a semantic administrative shell for industry 4.0 components. In: IEEE 10th Intlernation Conference on Semantic Computing (ICSC), pp. 230–237 (2016)
Holtmann, J., Steghöfer, J.P., Rath, M., Schmelter, D.: Cutting through the jungle: disambiguating model-based traceability terminology. In: IEEE 28th International Requirements Engineering Conference (RE), pp. 8–19 (2020)
Li, Y., Huo, Y., Yu, L., Wang, J.: Quality control and nonclinical research on car-t cell products: general principles and key issues. Engineering 5(1), 122–131 (2019)
Marshall, S., et al.: Model-informed drug discovery and development: current industry good practice and regulatory expectations and future perspectives. CPT Pharma. Syst. Pharmacol. 8(2), 87–96 (2019)
Mould, D.R., Upton, R.: Basic concepts in population modeling, simulation, and model-based drug development. CPT Pharma. Syst. Pharmacol. 1(9), 1–14 (2012)
Reich, J., Zeller, M., Schneider, D.: Automated evidence analysis of safety arguments using digital dependability identities. In: Romanovsky, A., Troubitsyna, E., Bitsch, F. (eds.) SAFECOMP 2019. LNCS, vol. 11698, pp. 254–268. Springer, Cham (2019). https://doi.org/10.1007/978-3-030-26601-1_18
Schneider, D., Trapp, M., Papadopoulos, Y., Armengaud, E., Zeller, M., Höfig, K.: Wap: digital dependability identities. In: 2015 IEEE 26th International Symposium on Software Reliability Engineering (ISSRE), pp. 324–329. IEEE (2015)
Spriggs, J.: GSN-the Goal Structuring Notation: A Structured Approach to Presenting Arguments. Springer Science & Business Media, London (2012)
Stembridge, K., Adkins, M.: Making the move to electronic batch records. Pharma. Technol. 42(4), 52–55 (2018)
Terzimehic, T., et al.: Towards an industry 4.0 compliant control software architecture using IEC 61499 & opc ua. In: 22nd IEEE Intl. Conference on Emerging Technologies and Factory Automation (ETFA), pp. 1–4 (2017)
Tyagarajan, S., Spencer, T., Smith, J.: Optimizing car-t cell manufacturing processes during pivotal clinical trials. Mol. Therapy Methods Clin. Dev. 16, 136–144 (2020)
Vormittag, P., Gunn, R., Ghorashian, S., Veraitch, F.S.: A guide to manufacturing car t cell therapies. Curr. Opin. Biotechnol. 53, 164–181 (2018)
Wagner, C., et al.: The role of the industry 4.0 asset administration shell and the digital twin during the life cycle of a plant. In: 22nd IEEE International Conference on Emerging Technologies and Factory Automation (ETFA), pp. 1–8 (2017)
Zhang, Y., Larson, B., Hatcliff, J.: Assurance case considerations for interoperable medical systems. In: Gallina, B., Skavhaug, A., Schoitsch, E., Bitsch, F. (eds.) SAFECOMP 2018. LNCS, vol. 11094, pp. 42–48. Springer, Cham (2018). https://doi.org/10.1007/978-3-319-99229-7_5
Zobel-Roos, S., et al.: Accelerating biologics manufacturing by modeling or: is approval under the GBD and pat approaches demanded by authorities acceptable without a digital-twin? Processes 7(2), 94 (2019)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this paper
Cite this paper
Schmidt, A. et al. (2021). A Framework for Automated Quality Assurance and Documentation for Pharma 4.0. In: Habli, I., Sujan, M., Bitsch, F. (eds) Computer Safety, Reliability, and Security. SAFECOMP 2021. Lecture Notes in Computer Science(), vol 12852. Springer, Cham. https://doi.org/10.1007/978-3-030-83903-1_15
Download citation
DOI: https://doi.org/10.1007/978-3-030-83903-1_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-83902-4
Online ISBN: 978-3-030-83903-1
eBook Packages: Computer ScienceComputer Science (R0)