The use of such high-concentration formulations introduces new challenges in the form of solubility constraints, high viscosity, aggregates, and phase separation that could make subcutaneous delivery unsuitable for a given product [ 21, 54].
It wasn't until Pronova patented its high-concentration formulation in 1992 that a pharmaceutical market emerged.
In addition, new potential inhibitors should be robust to handle in order to facilitate their evaluation in different model systems and to facilitate high-concentration formulation development for clinical applications.
Importantly, in addition to good specificity and strong affinity, the generated DARPins exhibit a very high robustness including high thermal and thermodynamic stability and high solubility, which allows for straight-forward high-concentration formulation development and the evaluation and use of new application routes.
High protein concentration formulations are required for low-volume administration of therapeutic antibodies targeted for subcutaneous, self-administration by patients.
The reconstitution strategy of reduced diluent volume, however, has enabled significant decrease in reconstitution time (4 7-fold) of lyophilized high protein concentration formulations.
Due to the injection volume limitation (<1.5 mL) associated with sc administration, high protein concentration formulations at or exceeding 100 mg/mL are required to achieve the dose.
Higher protein concentration formulations often have higher viscosities (17).
In this paper, a systematic approach is presented to develop a lyophilized high concentration protein formulation.
Development of a high concentration protein formulation can be challenging due to increased aggregation at higher concentration and/or chemical instability, which necessitates the development of lyophilized formulation for high protein concentration drug products.
Our results show that currently available technologies, while allowing comparisons between samples of a given protein at a fixed concentration, may be unable to measure particle numbers accurately in a variety of protein formulations, e.g., at high concentration in sugar-based formulations.
