Munich/Martinsried, December, 2011
Protein drug formulation is particularly challenging due to structural complexity and instability. The biological activity of most recombinant proteins emanates specifically from their 3-dimensional structure which needs to remain unaltered throughout the shelf-life of the product. However, cleavage or aggregation incidents may not only reduce efficacy but also produce adverse immunologic effects.
The current industry standard for the formulation development of biopharmaceutical drugs is a time consuming, trial-and-error driven process which requires accelerated stability testing to identify the best out of many formulation alternatives. Occasionally, the large number of formulation options is tested by means of high throughput screening, yet accepting the potential drawback of a highly artificial testing environment.
Predictive Formulation Analytics from ProJect Pharmaceutics offers an innovative scientific approach for designing optimized protein formulations and reduces the need for extensive stability testing.
Plying state-of-the-art analytical methods to characterize the physicochemical state of proteins and analyze their response to certain excipients allows us to quickly and reliably identify promising formulation candidates.
The stability of proteins in solution is mainly determined by intramolecular and intermolecular interactions. Intramolecular stability is characterized by protein thermodynamics which are measured by means of nano differencial scanning calorimetry (nanoDSC). Intermolecular stability is represented by the attractive or repulsive interaction between protein molecules which is quantified via composition gradient static light scattering (2nd virial coefficient).
A systematic algorithm based on design of experiments (DOE) is used to determine the most favorable composition for the native structure of a given protein with regard to its intra- and intermolecular physicochemical properties. Beneficial effects resulting from pH value, ionic strength, ion types, detergents and other stabilizing agents can be identified and quantified without stability testing.
The data obtained from our research provide the basis for a drug product composition that is tailored to the protein, its packaging system and its application. A final stability test program, carried out on samples filled into the final packaging system under genuine pharmaceutical manufacturing conditions, serves to confirm the suitability and stability of the composition and provides trustworthy data for initiating clinical trials.
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