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 purification1,2,3,4. 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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This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) and SPAWAR System Center Pacific (SSC Pacific) under contract no. N66001-13-C-4025. This work was also supported in part by the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute and funding from the Department of Chemical Engineering, School of Engineering, Massachusetts Institute of Technology. J.R.B., N.C.D. and N.J.M. were supported by a NIGMS/MIT Biotechnology Training Program Fellowship under NIH contract no. 2T32GM008334-26. K.A.S. was supported by a Mazumdar Shaw International Fellowship. J.C.L. is a Camille Dreyfus Teacher-Scholar. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, NIH, DARPA or SSC Pacific.

Author information

Author notes

    • Laura E Crowell
    • , Amos E Lu
    •  & Kerry R Love

    These authors contributed equally to this work.


  1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Laura E Crowell
    • , Kerry R Love
    • , Alan Stockdale
    • , William Doherty
    • , Alexandra Bonnyman
    • , Joseph R Brady
    • , John J Clark
    • , Noelle A Colant
    • , Neil C Dalvie
    • , Diana Liu
    • , Craig A Mascarenhas
    • , Catherine B Matthews
    • , Nicholas J Mozdzierz
    • , Kartik A Shah
    •  & J Christopher Love
  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Laura E Crowell
    • , Amos E Lu
    • , Joseph R Brady
    • , Noelle A Colant
    • , Neil C Dalvie
    • , Catherine B Matthews
    • , Nicholas J Mozdzierz
    • , Richard D Braatz
    •  & J Christopher Love
  3. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.

    • Steven M Timmick
    • , Nicholas Vecchiarello
    • , Chaz Goodwine
    •  & Steven M Cramer
  4. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.

    • Steven M Timmick
    • , Nicholas Vecchiarello
    • , Chaz Goodwine
    •  & Steven M Cramer
  5. GlaxoSmithKline, King of Prussia, Pennsylvania, USA.

    • Steven M Timmick
  6. Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.

    • Di Wu
    • , Yu (Annie) Wang
    • , Yanjun Liu
    •  & William S Hancock
  7. Pall Life Sciences, Westborough, Massachusetts, USA.

    • Lisa Bradbury
    •  & Aleksandar Cvetkovic
  8. Biogen, Cambridge, Massachusetts, USA.

    • John J Clark
  9. Department of Biochemical Engineering, University College London, London, England.

    • Noelle A Colant
  10. Sanofi, Framingham, Massachusetts, USA.

    • Aleksandar Cvetkovic
  11. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Craig A Mascarenhas
  12. BioAnalytix Inc., Cambridge, Massachusetts, USA.

    • Shiaw-Lin Wu


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L.E.C., A.E.L. and K.R.L. designed experiments, analyzed data and wrote the manuscript. J.C.L., K.R.L., R.D.B., A.S., A.E.L., N.J.M. and L.E.C. designed and built the InSCyT system. A.E.L. and R.D.B. developed controls for the InSCyT system. L.E.C., W.D. and A.B. performed experiments on the InSCyT system and performed quality assessments. D.W., Y.A.W., Y.L., S.-L.W. and W.S.H. assessed quality by mass spectrometry and isoelectric focusing. S.M.T., N.V., C.G. and S.M.C. developed the purification processess and assessed quality by RPLC, size exclusion chromatography and CD. J.R.B., N.C.D. and K.R.L. developed and performed product-specific ELISAs. K.R.L., K.A.S., N.J.M. and J.R.B. engineered the strains used in production. J.J.C., N.A.C., D.L., C.A.M., C.B.M., N.J.M. and K.R.L. contributed to development of upstream processes. A.C. and L.B. developed the purification process for hGH. J.C.L., S.M.C., R.D.B. and W.S.H. designed the experimental strategy, supervised analysis and wrote the manuscript. All authors reviewed the manuscript.

Competing interests

The authors have filed patents related to this work.

Corresponding author

Correspondence to J Christopher Love.

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