Drug Formulation Development

formulation

Drug formulation development für proteins, peptides, antibody drug conjugates (ADCs) and cytotoxics

Rational design of formulations and drug delivery systems for all kinds of biopharmaceutics inluding proteins, peptides ADCs and other cytotoxics.

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.

We can look back at a wealth of experience from many successfully completed formulation developments, including highly concentrated monoclonal antibodies and antibody drug conjugates /ADCs), cytokines, growth factors and peptides.

ProJect Pharmaceutics´ Predictive Formulation Analytics offers an innovative scientific approach for designing optimized protein formulations and reduces the need for extensive stability testing.

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 differential 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).

Plying these 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.

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. Furthermore we explore the behavior of the protein under a variety of process relevant stress conditions such as freeze/thaw, temperature, shear stress, surface contact, among others, to identify mechanisms of degradation and define strategies for formulation and process technologies.

The data we obtained from Predictive Formulation Analytics provide the basis for a drug product composition that is tailored to the protein, its packaging system and its route of administration.

We explore all possible options to design a stable, liquid formulation of our client’s drug and evaluate the maximally possible concentration of the API, if so required for the specific route of administration.

In case stability in aqueous solution is generally limited by the sensitivity of the API we develop freeze dried formulations selecting suitable excipients which stabilize the protein drug effectively within a defined amorphous matrix, and enable a straight forward and cost-effective lyophilization process.

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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