Abstract
Formulation development is an essential part of every biopharmaceutical development program and important for the therapeutic and commercial success of a protein drug product by assuring the quality, safety, and efficacy. The multiple phases of formulation development interact with other product development exercises as early as discovery research all the way until and beyond market approval. Every drug product demands a tailor-made formulation, due to the complexity of different degradation pathways potentially affecting product stability, the specific characteristics of the individual drug molecule, special patient needs, and even marketing considerations. Formulation development can be approached using various strategies, based on a rational design, relying on scientific knowledge in low or medium throughput, or high-throughput formulation screening of hundreds or even thousands of conditions employing miniaturized analytical methods. In this chapter, an introduction to the field of protein formulation development is given, the literature on current protein formulation development strategies is reviewed, and current challenges are summarized.
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Abbreviations
- AF4:
-
Asymmetrical flow field-flow fractionation
- API:
-
Active pharmaceutical ingredient
- AUC:
-
Analytical ultracentrifugation
- CTA:
-
Clinical trial authorization
- DLS:
-
Dynamic light scattering
- DNA:
-
Deoxyribonucleic acid
- DOE:
-
Design of experiment
- DP:
-
Drug product
- DS:
-
Drug substance
- DSC:
-
Differential scanning calorimetry
- DSF:
-
Differential scanning fluorimetry
- FTIR:
-
Fourier-transform infrared
- Glu:
-
Glutamic acid
- GMP:
-
Good manufacturing practice
- h:
-
Hour(s)
- H2O2:
-
Hydrogen peroxide
- His:
-
Histidine
- HPLC:
-
High-performance liquid chromatography
- HTF:
-
High-throughput formulation
- ICH:
-
International conference on harmonization
- LA:
-
License application
- LC-MS:
-
Liquid chromatography-coupled mass spectrometry
- mg/ml:
-
Milligram per milliliter
- mM:
-
Millimolar
- μm:
-
Micrometer
- nm:
-
Nanometer
- pH:
-
Potential of hydrogen
- pI:
-
Isoelectric point
- pKa:
-
Acid dissociation constant
- QC:
-
Quality control
- RH:
-
Relative humidity
- RNA:
-
Ribonucleic acid
- rpm:
-
Rounds per minute
- SEC:
-
Size exclusion chromatography
- SLS:
-
Static light scattering
- Tg’:
-
Glass transition temperature
- UPLC:
-
Ultrahigh-performance liquid chromatography
- USP:
-
United States Pharmacopeia
- UV:
-
Ultraviolet
- °C:
-
Degrees Celsius
- %:
-
Percent
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Further Reading
Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals. F. Jameel, S. Hershenson (Editors), 2010. Hoboken, NJ, USA: John Wiley & Sons. ISBN 978-0-470-111812-2.
Rationale Design of stable protein formulations-theory and practice. J.F. Carpenter, M.C. Manning (Editors), 2002. New York, NY, USA. Kluwer Academic/Plenum. ISBN 978-1-4615-0557-0.
Development and Manufacture of Protein Pharmaceuticals. S.L. Nail, M.J. Akers (Editors), 2002. New York, NY, USA. Kluwer Academic/Plenum. ISBN 978-1-4615-0549-5.
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Weinbuch, D., Hawe, A., Jiskoot, W., Friess, W. (2018). Introduction into Formulation Development of Biologics. In: Warne, N., Mahler, HC. (eds) Challenges in Protein Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 38. Springer, Cham. https://doi.org/10.1007/978-3-319-90603-4_1
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DOI: https://doi.org/10.1007/978-3-319-90603-4_1
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