Author(s): Farah Hamad Farah

Email(s): f.hamad@ajman.ac.ae

DOI: 10.5958/0974-360X.2020.00785.4   

Address: Farah Hamad Farah
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman P O Box 346, United Arab Emirates.
*Corresponding Author

Published In:   Volume - 13,      Issue - 9,     Year - 2020


ABSTRACT:
Protein-based biopharmaceuticals are prone to physical or chemical instabilities. Their major instability is the high tendency of their molecules to aggregate under a wide range of processing and improper storage conditions. Protein aggregation is classified into native protein conformations (colloidal instability) or partially denatured (non-native) protein aggregation. Both aggregation pathways may occur for the same protein. A clear knowledge of which route of aggregation dominates under particular formulation conditions is essential. In order to prevent protein aggregation, both aggregation pathways should be targeted in a systematic way. Certain formulation conditions, which reduce aggregation through one pathway, may lead to an increase in aggregation through the other pathway; therefore, in order to reduce protein aggregation due to both pathways, a balanced formulation procedure can be adopted. Long-term stability of protein-based biopharmaceuticals is attainable by two main strategies. The first is the designing of molecules that are aggregation-resistant and the second is the inclusion of formulation additives that prevent aggregation. The ideal way is to develop a rapid method of predicting stability at the early stage of the product development, with a reasonable level of confidence. Measurements probing conformational stability, such as protein melting temperature (Tm) and time-dependent rates of thermal unfolding, as well as measurements probing colloidal stability, such as second virial coefficients (B22) from static light scattering or protein precipitation by salting out technique, should be performed to give a clear picture of the mechanisms that may have an impact on long-term stability. The main clinical consequences of protein-based biopharmaceuticals is immunogenicity. The implications of an immune reaction to protein-based biopharmaceuticals, range from transient appearance of antibodies without clinical significance to severe life threatening complications such as anaphylaxis, neutralization of the effectiveness of lifesaving or highly effective therapies, or neutralization of endogenous proteins with non-redundant functions and decrease in efficacy and induction of autoimmunity, including antibodies to the endogenous form of the protein.


Cite this article:
Farah Hamad Farah. Stability and potential clinical Consequences of protein-based Biopharmaceuticals. Research J. Pharm. and Tech 2020; 13(9):4443-4452. doi: 10.5958/0974-360X.2020.00785.4


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