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Liquid formulations for stabilizing IgMs during physical stress and long-term storage
Monika Mueller1, Maybelle Q T Loh, Rupert Tscheliessnig
1Bioprocessing Technology Institute A*STAR (Agency for Science Technology and Research), 20 Biopolis Way, #03-01, Centros, 138668, Singapore, Singapore. monika_mueller@bti.a-star.edu.sg
Pharmaceutical Research
|November 13, 2012
Summary
A new liquid formulation using sorbitol and glycine at pH 5.0-5.5 stabilizes monoclonal immunoglobulin M (IgM) against physical stress and long-term storage. This formulation preserves structure and immunoreactivity for over 12 months.
Area of Science:
- Biochemistry
- Protein Chemistry
- Formulation Science
Background:
- Monoclonal immunoglobulin M (IgM) antibodies are crucial therapeutics but prone to instability.
- Physical stress and storage conditions can lead to aggregation and fragmentation, compromising efficacy.
- Developing stable liquid formulations is essential for effective IgM-based therapies.
Purpose of the Study:
- To develop a stable liquid formulation for monoclonal immunoglobulin M (IgM) antibodies.
- To ensure IgM stability under various physical stress and storage conditions.
- To identify optimal formulation components and pH for long-term IgM preservation.
Main Methods:
- Differential scanning calorimetry (DSC) was used to screen stabilizing excipients.
- Formulations were tested for stability against shear stress, freeze-thaw cycles, and accelerated storage.
- Size exclusion chromatography, fluorescence activated cell sorting, and small-angle X-ray scattering (SAXS) analyzed IgM integrity and structure.
Main Results:
- Optimal conformational stability for IgMs was achieved near their isoelectric point, enhanced by sorbitol, sucrose, and glycine.
- Lowering pH improved storage stability, particularly when conformational and storage optima differed.
- The optimized formulation prevented aggregation and fragmentation, maintaining immunoreactivity for 12 months at 4°C and -20°C.
- SAXS analysis indicated that stabilized IgM structures were closer to the native model and less prone to aggregation.
Conclusions:
- A stable liquid formulation containing 20% sorbitol and 1 M glycine at pH 5.0-5.5 was developed for 8 monoclonal IgMs.
- This formulation demonstrated broad utility, preventing degradation and preserving function during long-term storage.
- The formulation development approach using DSC and accelerated storage can be applied to other protein therapeutics.
