Rational design of formulations and drug delivery systems for all kinds of biologics including recombinant proteins and protein conjugates, antibodies, fusion proteins, peptides, ADCs and other cytotoxics, small molecules, generics, as well as viral therapeutics, GMOs, ATMPs, VLPs and CGT products.
Protein drug formulation
Protein drug formulation is particularly challenging due to structural complexity and instability of the molecules. The biological activity of most recombinant proteins and protein conjugates emanates specifically from their complex 3-dimensional structure which needs to remain unaltered throughout the shelf-life of the product. However, cleavage, aggregation, or other post-translational modifications may not only reduce efficacy but also produce adverse immunologic effects.
We, as a formulation development company, can look back at a wealth of experience from many successfully completed drug product formulation developments for i.v. injection, s.c. injection, i.m. injection or other, including formulation services such as
hysico-chemical characterization: ProJect Pharmaceutics´ Predictive Formulation Analytics offers an innovative scientific approach to design optimized protein formulations and reduces the need for extensive stability testing (advantage: accelerated formulation development, faster to clinic and market).
Plying state-of-the-art analytical methods to characterize the physicochemical state of proteins and analyse their response to certain excipients allows us to quickly and reliably identify promising formulation candidates for injectable formulations.
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, light, oxygen, shear stress and surface interactions to identify mechanisms of degradation and define strategies for formulation and process technologies.
The data we obtain 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.
Lyo formulation development: 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 testing program (accelerated stability studies), 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.
ProJect Pharmaceutics is a credited contract laboratory for Wyatt Technology in Europe.