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Monoclonal Antibody Reagent Stability and Expiry Recommendation Combining Experimental Data with Mathematical
Malorie Fink1, Erin Marie Cannon1, Carl Hofmann1
1Analytical Research & Development, Merck & Co., Inc., Kenilworth, New Jersey, USA.
The AAPS Journal
|November 8, 2020
Summary
Stability monitoring for monoclonal antibodies (mAbs) as assay reagents differs from biopharmaceuticals. Reportable results, not biochemical changes, better predict assay function, enabling risk-based expiry assignment.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Immunology
Background:
- Monoclonal antibodies (mAbs) are essential reagents in analytical assays.
- Existing regulatory guidelines for biopharmaceutical antibody stability do not directly address mAbs as assay reagents.
Purpose of the Study:
- To investigate alternative approaches for real-time stability monitoring of mAbs used as assay reagents.
- To compare functional and biochemical methods for detecting mAb degradation in assay reagents.
Main Methods:
- Temperature-stressed monoclonal antibody (mAb) reagents were analyzed using functional assays (ELISA, cell-based) and biochemical assays (aggregation, deamidation).
- Arrhenius kinetic modeling was applied to extrapolate stability trends.
- Reportable assay results were monitored alongside traditional biochemical indicators.
Main Results:
- Biochemical changes (aggregation, deamidation) did not directly predict functional assay performance.
- Monitoring of reportable assay results more accurately indicated changes in assay performance due to mAb degradation.
- Arrhenius modeling combined with forced degradation and reportable results allowed risk-based classification of reagents.
Conclusions:
- Reportable assay results are a more reliable indicator of mAb reagent stability than traditional biochemical markers.
- A combined approach using forced degradation, Arrhenius kinetics, and reportable results streamlines expiry assignment and mitigates risk for mAb assay reagents.
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