Protein Formulation Science

Formulation Science

Formulation development: Optimized pharmaceutical formulation strategies for liquid and freeze dried formulations to enhance drug product stability and efficacy for biologics, peptides and delicate small molecules.

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 fusion proteins, cytokines, growth factors and peptides.
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 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.

Protein bulk formulation
Freezing and thawing of bulk protein solutions is common practice in API and drug product manufacturing. However, freezing-induced aggregation and denaturation caused by cryo-concentration and ice water interface formation as well as degradation caused by pH shifting due to crystallization of buffer components may lead to a significant loss in protein activity. Based on an in-depth analysis of the impact of freezing on the protein we develop optimized systems of cryo-protectants and other stabilizing excipients, freezing process parameters and cryo-containers. Alternatives to bulk freezing of biologics drug substance are under evaluation in our R&D laboratories.

Drug product liquid formulation / freeze dried formulation
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 as deamidation, aggregation or oxidation we develop freeze dried formulations selecting suitable cryoprotectants and lyoprotectants which stabilize the protein drug effectively within a defined amorphous matrix, and enable a straight forward and cost-effective lyophilization process.

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