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Crowell LE, Lu AE, Love KR, et al. On-demand manufacturing of clinical-quality biopharmaceuticals. Nat Biotechnol. 2018;doi: 10.1038/nbt.4262.
Crowell, L. E., Lu, A. E., Love, K. R., Stockdale, A., Timmick, S. M., Wu, D., Wang, Y. A., Doherty, W., Bonnyman, A., Vecchiarello, N., Goodwine, C., Bradbury, L., Brady, J. R., Clark, J. J., Colant, N. A., Cvetkovic, A., Dalvie, N. C., Liu, D., Liu, Y., Mascarenhas, C. A., Matthews, C. B., Mozdzierz, N. J., Shah, K. A., Wu, S. L., Hancock, W. S., Braatz, R. D., Cramer, S. M., & Love, J. C. (2018). On-demand manufacturing of clinical-quality biopharmaceuticals. Nature biotechnology, . https://doi.org/10.1038/nbt.4262
Crowell, Laura E, et al. "On-demand manufacturing of clinical-quality biopharmaceuticals." Nature biotechnology vol. (2018). doi: https://doi.org/10.1038/nbt.4262
Crowell LE, Lu AE, Love KR, Stockdale A, Timmick SM, Wu D, Wang YA, Doherty W, Bonnyman A, Vecchiarello N, Goodwine C, Bradbury L, Brady JR, Clark JJ, Colant NA, Cvetkovic A, Dalvie NC, Liu D, Liu Y, Mascarenhas CA, Matthews CB, Mozdzierz NJ, Shah KA, Wu SL, Hancock WS, Braatz RD, Cramer SM, Love JC. On-demand manufacturing of clinical-quality biopharmaceuticals. Nat Biotechnol. 2018 Oct 01; doi: 10.1038/nbt.4262. Epub 2018 Oct 01. PMID: 30272677; PMCID: PMC6443493.
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Nat Biotechnol. 2018 Oct 01; doi: 10.1038/nbt.4262. Epub 2018 Oct 01.

On-demand manufacturing of clinical-quality biopharmaceuticals.

Nature biotechnology

Laura E Crowell, Amos E Lu, Kerry R Love, Alan Stockdale, Steven M Timmick, Di Wu, Yu Annie Wang, William Doherty, Alexandra Bonnyman, Nicholas Vecchiarello, Chaz Goodwine, Lisa Bradbury, Joseph R Brady, John J Clark, Noelle A Colant, Aleksandar Cvetkovic, Neil C Dalvie, Diana Liu, Yanjun Liu, Craig A Mascarenhas, Catherine B Matthews, Nicholas J Mozdzierz, Kartik A Shah, Shiaw-Lin Wu, William S Hancock, Richard D Braatz, Steven M Cramer, J Christopher Love

Affiliations

  1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  3. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.
  4. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
  5. GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
  6. Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
  7. Pall Life Sciences, Westborough, Massachusetts, USA.
  8. Biogen, Cambridge, Massachusetts, USA.
  9. Department of Biochemical Engineering, University College London, London, England.
  10. Sanofi, Framingham, Massachusetts, USA.
  11. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  12. BioAnalytix Inc., Cambridge, Massachusetts, USA.

PMID: 30272677 PMCID: PMC6443493 DOI: 10.1038/nbt.4262

Abstract

Conventional manufacturing of protein biopharmaceuticals in centralized, large-scale, single-product facilities is not well-suited to the agile production of drugs for small patient populations or individuals. Previous solutions for small-scale manufacturing are limited in both process reproducibility and product quality, owing to their complicated means of protein expression and purification. We describe an automated, benchtop, multiproduct manufacturing system, called Integrated Scalable Cyto-Technology (InSCyT), for the end-to-end production of hundreds to thousands of doses of clinical-quality protein biologics in about 3 d. Unlike previous systems, InSCyT includes fully integrated modules for sustained production, efficient purification without the use of affinity tags, and formulation to a final dosage form of recombinant biopharmaceuticals. We demonstrate that InSCyT can accelerate process development from sequence to purified drug in 12 weeks. We used integrated design to produce human growth hormone, interferon α-2b and granulocyte colony-stimulating factor with highly similar processes on this system and show that their purity and potency are comparable to those of marketed reference products.

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