A Precipitation-Based Process to Generate a Solid Formulation of a Therapeutic Monoclonal Antibody: An Alternative to Lyophilization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Monoclonal Antibody
2.2. Precipitation Process
2.3. Analytical Characterization
2.3.1. Critical Quality Attributes
2.3.2. Biological Characterization
2.3.3. Biophysical Characterization
3. Results and Discussion
3.1. Process Reproducibility and Formulation Characterization
3.2. Process Characterization
3.3. Stability of the Precipitated Formulations
4. Conclusions and Future Work
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample Number | Solvent Temperature | Mixing |
---|---|---|
1′ | −20 °C | Medium |
1 | 25 °C | None |
1 * | 25 °C | None |
2 | 25 °C | High |
3 | 0 °C | None |
4 | 0 °C | High |
5 | −20 °C | High |
5 * | −20 °C | High |
6 | 0 °C | Medium |
7 | 25 °C | Medium |
Assay | Sample Number | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
mAb X | 1′ | 1 | 1 * | 2 | 3 | 4 | 5 | 5 * | 6 | 7 | ||
UP-SEC | Monomer % | 99.1 | 98.6 | 98.2 | 99.0 | 99.6 | 96.8 | 98.9 | 97.9 | 94.2 | 99.3 | 99.4 |
HMW species % | 0.9 | 1.4 | 1.9 | 1.0 | 0.4 | 3.2 | 1.1 | 2.1 | 5.8 | 0.7 | 0.6 | |
HP-IEX | Acidic variants % | 15.8 | 18.6 | 16.5 | 17.5 | 18.1 | 17.6 | 18.1 | 18.3 | 16.9 | 18.0 | 17.9 |
Total main % | 51.9 | 51.5 | 53.6 | 52.7 | 52.7 | 51.3 | 52.0 | 51.3 | 51.8 | 52.5 | 52.6 | |
Basic variants % | 32.3 | 29.9 | 29.9 | 29.8 | 29.3 | 31.1 | 29.9 | 30.4 | 31.3 | 29.6 | 29.5 | |
Reduced CE-SDS | HC + LC % | 97.9 | 98.6 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 | 99.2 | 99.3 | 99.3 |
Total impurity % | 2.1 | 1.4 | 0.7 | 0.7 | 0.7 | 0.7 | 0.7 | 0.7 | 0.8 | 0.7 | 0.7 | |
Non-reduced CE-SDS | Intact IgG % | 98.6 | 97.7 | 98.3 | 98.3 | 98.0 | 98.3 | 98.2 | 98.3 | 97.9 | 98.2 | 98.4 |
Total LMW species % | 1.4 | 2.2 | 1.6 | 1.6 | 1.9 | 1.5 | 1.7 | 1.5 | 1.9 | 1.8 | 1.5 |
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Koynov, A.A.; Lin, W.; Bothe, J.R.; Schenck, L.; Parajuli, B.; Li, Z.; Ruzanski, R.; Hoffman, N.; Frank, D.; VanAernum, Z. A Precipitation-Based Process to Generate a Solid Formulation of a Therapeutic Monoclonal Antibody: An Alternative to Lyophilization. J. Pharm. BioTech Ind. 2025, 2, 2. https://doi.org/10.3390/jpbi2010002
Koynov AA, Lin W, Bothe JR, Schenck L, Parajuli B, Li Z, Ruzanski R, Hoffman N, Frank D, VanAernum Z. A Precipitation-Based Process to Generate a Solid Formulation of a Therapeutic Monoclonal Antibody: An Alternative to Lyophilization. Journal of Pharmaceutical and BioTech Industry. 2025; 2(1):2. https://doi.org/10.3390/jpbi2010002
Chicago/Turabian StyleKoynov, Athanas A., Wei Lin, Jameson R. Bothe, Luke Schenck, Bibek Parajuli, Zhao Li, Richard Ruzanski, Natalie Hoffman, Derek Frank, and Zachary VanAernum. 2025. "A Precipitation-Based Process to Generate a Solid Formulation of a Therapeutic Monoclonal Antibody: An Alternative to Lyophilization" Journal of Pharmaceutical and BioTech Industry 2, no. 1: 2. https://doi.org/10.3390/jpbi2010002
APA StyleKoynov, A. A., Lin, W., Bothe, J. R., Schenck, L., Parajuli, B., Li, Z., Ruzanski, R., Hoffman, N., Frank, D., & VanAernum, Z. (2025). A Precipitation-Based Process to Generate a Solid Formulation of a Therapeutic Monoclonal Antibody: An Alternative to Lyophilization. Journal of Pharmaceutical and BioTech Industry, 2(1), 2. https://doi.org/10.3390/jpbi2010002