Monoclonal Antibody Reagent Stability and Expiry Recommendation Combining Experimental Data with Mathematical Modeling
| Autor: | Thorsten Verch, Mary Shank-Retzlaff, Richard R. Rustandi, Malorie Fink, Matthew C. Troutman, Carl Hofmann, Erin Marie Cannon, John W. Loughney, Cindy Pauley, Nisarg Patel |
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| Rok vydání: | 2020 |
| Předmět: |
Quality Control
Protein Denaturation medicine.drug_class Pharmaceutical Science Antibody Degradation Guidelines as Topic Monoclonal antibody 030226 pharmacology & pharmacy Models Biological 03 medical and health sciences 0302 clinical medicine Risk groups medicine Deamidation Chromatography Chemistry Arabidopsis Proteins Experimental data Antibodies Monoclonal Nuclear Proteins Biopharmaceutical 030220 oncology & carcinogenesis Reagent Forced degradation Proteolysis Biological Assay Indicators and Reagents Laboratories |
| Zdroj: | The AAPS journal. 22(6) |
| ISSN: | 1550-7416 |
| Popis: | Monoclonal antibodies (mAbs) are widely used as critical reagents in analytical assays. While regulatory guidelines exist for stability monitoring of biopharmaceutical antibodies, they do not apply directly to the stability of mAbs used as assay reagent. We investigated alternative approaches to real-time stability monitoring of assay reagents. We compared functional (ELISA and cell-based) and biochemical (aggregation, deamidation) assay results using temperature-stressed mAb reagents. Data from both assay groups were compared for indications of antibody degradation. Arrhenius model kinetics was used to further extrapolate stability trends. Changes detected by traditionally monitored biochemical changes were not directly predictive of assay function. Instead, monitoring of reportable results was a closer indication of changes in assay performance related to mAb degradation. Using Arrhenius kinetic modeling, we combined forced degradation of individual reagents with reportable assay results to classify reagents into risk groups with associated re-evaluation and monitoring plans. This combined approach mitigates risk by monitoring each mAb reagent individually under stressed conditions while streamlining expiry assignment through simplified Arrhenius kinetics with only limited real-time stability data. |
| Databáze: | OpenAIRE |
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