Sources of Variability in Manufacturing of Cell Therapeutics

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.

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Fig. 1

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

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Acknowledgments

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). https://doi.org/10.1007/s40883-019-00130-5

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Keywords

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