Formulations for clinical trials and beyond

Budget is often scarce for pharmaceutical development projects before the drug has even shown proof of concept in first clinical trials. In that early stage, many drug developing companies are hesitant to spend the money for a fully-fledged pharmaceutical development of the formulation.

Thus, quite often formulations in preclinical studies and clinical stages I and II are far from being rationally designed. Particularly when it comes to therapeutic proteins, where formulation development is highly challenging due to the structural complexity and instability of the compound, pharmaceutical quality issues are the likely consequence.

Once proof of concept has been established with the rudimentary formulation, pharmaceutical companies are reluctant to change this formulation due to concerns of jeopardizing the data obtained so far in preclinical and early clinical testing.

As a result, formulations reflecting an early preclinical development status often find their way into pharmaceutical dossiers, and authorities frequently deny approval of numerous drug applications due to the lack of pharmaceutically sound data documenting state-of-the-art formulation and process development.

The key to overcome this dilemma is Predictive Formulation Analytics offered by ProJect Pharmaceutics: Plying state-of-the-art analytical methods permits us to characterize the protein molecule and analyze its response to certain excipients with regard to its intra and intermolecular physicochemical properties. This allows us to quickly and reliably identify those combinations of pH value, ionic strength, ion types, detergents and other stabilizing agents, which preserve the active 3 dimensional structure of the protein in an ideal manner.

Costs, timelines and the amount of API required for this highly efficient approach towards a rational and reliable formulation for clinics and beyond is surprisingly low.

Our deliverable will be a science-based formulation for a freeze dried product of your drug, and a conventional lyophilization cycle, ready for tech transfer to GMP manufacturing.

Once your drug has mastered critical milestones in early clinical development, call on us to carefully work out the final formulation of your drug, by means of an in-depth experimental program, to verify or optimize the quantitative composition of the drug product tailored to the route of application, the delivery system and the pharmaceutical manufacturing process.

ProJect Pharmaceutics introduces Predictive Formulation Analytics for a rational design of optimized biopharmaceutical formulations.

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.

For more information please visit: www.project-pharmaceutics.com or contact:

ProJect Pharmaceutics GmbH
Fraunhoferstraße 22
D-82152 Martinsried
+49 (0) 89 452289700

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