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Sources of Variability in Manufacturing of Cell Therapeutics


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.

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ancillary material


Advanced Regenerative Manufacturing Institute


American Society for Testing and Materials


corrective action/preventative action


cluster of differentiation


Code of Federal Regulations


critical material attribute


critical process parameter


critical quality attribute


good manufacturing practice


International Organization for Standardization


Technical Committee


National Institute for Innovation in Manufacturing Biopharmaceuticals


National Institute of Standards and Technology


Parenteral Drug Association


Standards Coordinating Body


Standards Development Organization


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Thanks to Chuck Felice, Hari Kamaraju, Don Powers, Kathleen Vermeersch, Cristy Dougherty, Ravi Bhatia, and Jean Stanton for their input and helpful discussions.

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Correspondence to Carl J. Burke.

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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.

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Burke, C.J., Zylberberg, C. Sources of Variability in Manufacturing of Cell Therapeutics. Regen. Eng. Transl. Med. 5, 332–340 (2019).

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  • Cell therapy
  • CAR-T
  • Manufacturing
  • Autologous
  • Allogeneic
  • Ancillary material