Abstract
Cellular immunotherapies are expected to greatly impact the future therapeutic landscape. Like other innovative and transformative fields, the industry is currently refining to keep pace with available technology. As a result, developers are employing more controls to minimize variability, and suppliers are addressing industry needs by addressing supply issues and characterizing material attributes with the careful awareness to the impact of the cost of the therapies. Process and analytical technologies are continuing to develop along with the components that are needed for them.
Lay Summary
Future efforts will focus in closing the gap in standardization of processes and materials. Creation of standards can mitigate risks associated with the variability intrinsic to cell therapy products. Increased characterization of processes, methods, products, and materials will also address variability within the cell therapy field.
Similar content being viewed by others
Abbreviations
- AM:
-
ancillary material
- ARMI:
-
Advanced Regenerative Manufacturing Institute
- ASTM:
-
American Society for Testing and Materials
- CAPA:
-
corrective action/preventative action
- CD:
-
cluster of differentiation
- CFR:
-
Code of Federal Regulations
- CMA:
-
critical material attribute
- CPP:
-
critical process parameter
- CQA:
-
critical quality attribute
- GMP:
-
good manufacturing practice
- ISO:
-
International Organization for Standardization
- TC:
-
Technical Committee
- NIIMBL:
-
National Institute for Innovation in Manufacturing Biopharmaceuticals
- NIST:
-
National Institute of Standards and Technology
- PDA:
-
Parenteral Drug Association
- SCB:
-
Standards Coordinating Body
- SDO:
-
Standards Development Organization
References
Haddock R, Lin-Gibson S, Lumelsky N, McFarland R, Roy K, Saha K, et al. Manufacturing cell therapies: the paradigm shift in health Care of this Century. NAM Perspectives. Discussion paper. Washington, DC: National Academy of Medicine; 2017.
Rosenberg S, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233(4770):1318–21.
Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86:10024–8.
Standards Coordinating Body Projects. https://www.standardscoordinatingbody.org/current-projects
International Organization for Standardization, ISO/TC 276. https://www.iso.org/committee/4514241/x/catalogue/p/1/u/0/w/0/d/0
Collins FS, Gottlieb S. The next phase of human gene-therapy oversight. N Engl J Med. 2018;379:1393–5. https://doi.org/10.1056/NEJMp1810628.
Bailey AM, Mendicino M, Au. P. An FDA perspective on preclinical development of cell-based regenerative medicine products. Nat Biotechnol. 2014;32(8):721–3.
European Biopharmaceutical Enterprises, “Management and control of raw materials used in the manufacture of biological medicinal products and ATMPs”, Dec 2018.
Bravery CA, Robinson S, Burger SR. Making the grade: untangling the myths of raw materials used for the manufacture of cell- and gene-based medicinal products. Cell Gene Ther Insights. 2018. https://doi.org/10.18609/cgti.2018.022.
National Institute of Standards and Technology - Cell Counting for Cell Therapies, https://www.nist.gov/programs-projects/cell-counting-cell-therapies
Standards Coordinating Body Project: Transportation Requirements for Cell Therapy Products, https://www.standardscoordinatingbody.org/project-transportation-requirements-of-cell-therapy-products
Harrison RP, Zylberberg E, Ellison S, Levine BL. Chimeric antigen receptor–T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy. 2019; (in press).
Stanton D.. Finding closure: lowering the costs of cell and gene therapies. 2019 https://bioprocessintl.com/bioprocess-insider/finding-closure-lowering-the-costs-of-cell-and-gene-therapies/?utm_source=hs_email&utm_medium=email&utm_content=69576800&_hsenc=p2ANqtz-85IW7DDak3ihv-7S4BV3sPK2ePB0esqo_U7Tz_meONuoFvqftCDrZa2gDMZ5B_kRcYAi8vUPFLbZ8G-IbdgV8vWC-xrtpRSbKXYG7AU-Nj_5bIiYU&_hsmi=69576800
Acknowledgments
Thanks to Chuck Felice, Hari Kamaraju, Don Powers, Kathleen Vermeersch, Cristy Dougherty, Ravi Bhatia, and Jean Stanton for their input and helpful discussions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Carl Burke is employed at Century Therapeutics, a cell therapy company. Claudia Zylberberg is Co-founder and CEO of Akron Biotech, a company that provides ancillary materials for cell and biological products, and sits on the Standards Coordinating Body. Both authors have no conflicts of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Burke, C.J., Zylberberg, C. Sources of Variability in Manufacturing of Cell Therapeutics. Regen. Eng. Transl. Med. 5, 332–340 (2019). https://doi.org/10.1007/s40883-019-00130-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40883-019-00130-5