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Published on: August 14, 2018
Controlling the Size and Shape of Monoclonal Antibody Particles through Crystallization Process Design.
L Codan1, P Larpent2, R Kalapos-Dobszay1
1Process Research and Development, MSD Werthenstein BioPharma, Industrie Nord 1, CH-6105 Schachen LU, Switzerland.
Molecular Pharmaceutics
|May 12, 2026
Summary
Developing robust crystallization and filtration strategies for monoclonal antibodies (mAbs) is crucial. This study demonstrates successful crystallization and isolation of mAb particles, maintaining crystal form through filtration and washing cycles.
Area of Science:
- Biopharmaceutical Manufacturing
- Protein Crystallization
- Antibody Engineering
Background:
- Monoclonal antibodies (mAbs) present crystallization challenges due to size and flexibility.
- mAb crystals often lose integrity upon air exposure, complicating downstream processing like filtration.
Purpose of the Study:
- To develop crystallization design strategies for mAbs using pembrolizumab caffeine cocrystal as a model.
- To optimize crystallization and filtration processes by minimizing cycle times and improving particle attributes.
- To establish methods for retaining crystal form during isolation and processing.
Main Methods:
- Utilized pembrolizumab caffeine cocrystal-1 for crystallization studies with poly(ethylene glycol) 3350 (PEG) and dextran sodium sulfate (DSS).
- Investigated seeding strategies to shorten crystallization cycle times and enhance process robustness.
- Developed conservative filtration techniques, including partial deliquoring and supernatant submersion, to prevent particle amorphization.
- Performed seeded semicontinuous crystallizations for improved supersaturation control.
Main Results:
- Identified optimal crystallization conditions and developed metrics to rank filtration performance.
- Demonstrated successful seeding of mAb crystallization, leading to shorter cycle times and improved robustness.
- Showcased the ability to retain crystal form through multiple filtration, dilution, and wash cycles.
- Confirmed particle resistance to solvent composition changes, enabling matrix swapping for product delivery.
Conclusions:
- Established feasible crystallization and isolation strategies for monoclonal antibodies.
- Demonstrated that seeded crystallization and conservative filtration techniques can overcome common challenges in mAb processing.
- The developed methods allow for robust isolation and solvent exchange while maintaining the desired crystal form.
