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Related Experiment Video

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Pembrolizumab microgravity crystallization experimentation.

Paul Reichert1, Winifred Prosise1, Thierry O Fischmann1

  • 11Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, NJ USA.

NPJ Microgravity
|December 10, 2019
PubMed
Summary

Crystallization of biologics like pembrolizumab was achieved in microgravity, yielding uniform particle sizes. These findings enabled improved earth-based methods for creating injectable drug formulations.

Keywords:
BiochemistryBiophysical chemistry

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Area of Science:

  • Biopharmaceutical manufacturing
  • Protein crystallization
  • Drug delivery systems

Background:

  • Crystallization is vital for pharmaceutical manufacturing but challenging for large biologics like monoclonal antibodies.
  • Developing crystallization processes for biologics offers significant therapeutic and delivery benefits.

Purpose of the Study:

  • To investigate the crystallization of pembrolizumab (Keytruda®) using microgravity conditions on the International Space Station (ISS).
  • To compare microgravity-induced crystallization with ground-based control experiments.
  • To apply findings to develop improved earth-based crystallization techniques for injectable formulations.

Main Methods:

  • Crystallization experiments with pembrolizumab conducted on the ISS via SpaceX-CRS-10 mission.
  • Utilized microgravity to minimize sedimentation and convection.
  • Ground control experiments performed for comparison.
  • Applied findings to develop earth-based rotational mixing and controlled temperature gradient techniques.

Main Results:

  • Microgravity yielded homogeneous, monomodal crystalline suspensions (39 μm) with high yield.
  • Ground controls produced heterogeneous, bimodal suspensions (13 μm and 102 μm).
  • Flight suspensions exhibited lower viscosity and more uniform sedimentation.
  • Earth-based methods produced uniform crystalline suspensions (1-5 μm) with suitable properties for injection.

Conclusions:

  • Microgravity facilitates uniform crystallization of biologics, overcoming challenges associated with size and flexibility.
  • Earth-based techniques inspired by space experiments enable production of high-quality crystalline suspensions for injectable formulations.
  • These advancements may expand drug delivery options, enhancing patient care.