STABILITY

ProteinMentor can be implemented to assess the relative stability for drug substance and determine lot-to-lot variation. The approach is also amenable to the comparability assessment of drug substance to drug product or standard reference to predict the shelf-life of the drug product for release testing. In addition, this approach may be implemented to evaluate stability comparability between a Biosimilar candidate with the Biologic. 

Measurements of protein secondary structure changes help to elucidate the mechanisms that underpin the stability of a therapeutic protein. Different assessments can be made for comparative stability analysis such as:

* evaluating the molecular events that occur prior to the onset temperature transition under varying formulation conditions; 

* monitoring weak-interactions associated with significant instability of the therapeutic protein;

* generating thermal dependence plots that provide the onset and temperature during which the specific event of interest occurs. 

The cumulative comparative evaluation of the above events during thermal stress provides valuable insight into understanding the relationship between secondary structure, associated weak interactions and stability. 

The therapeutic activity of a protein drug is directly related to its 3-dimensional structure, which is derived from the interaction of amino acids within the protein sequence.

ProteinMentor is uniquely positioned to investigate the contributions of weak interactions, asparagine/glutamine deamidation, and/or aggregation that led to the conformational changes. These changes in-turn impact domain stability, and the sequential molecular order of events that define cooperativity can be determined. A rank order based on stability can also be performed through the comparative assessment for an array of proteins in solution.