As a protein-based drug transitions through the pipeline from discovery to development, it is important to achieve an optimal, robust formulation. This must be appropriate and effective for the molecule’s intended therapeutic use, and maintain its stability, conformation and efficacy during production, shipping and storage, for the whole of the desired shelf life.
The nature of biological materials means that their formulation as biopharmaceuticals presents specific challenges. Malvern Panalytical’s biophysical characterization tools are used to monitor protein conformation, predict thermal stability, and measure aggregate formation in response to formulation and storage conditions. They provide information that is critical to understanding the stability of biological molecules and accelerating biopharmaceutical formulation development.
Formulation stability
In biological formulation development, the main objective is to find the solution conditions that offer the greatest level of stabilization to support a molecule’s higher-order structure and which will therefore enable the highest proportion of bioactive, native protein to be delivered. Denatured proteins tend to be more susceptible to irreversible chemical processes such as proteolysis, oxidation, and deamidation, which in turn can lead to inactivation and the risk of aggregation, which may result in undesired immunogenic effects.
During formulation development, the biomolecule is exposed to a range of conditions, including:
- Different buffers, temperatures, shears, pH levels, and salt concentrations
- Various excipients that are used to help stabilize the protein, or aid in manufacturing or drug delivery
- High concentrations, to determine how far a drug candidate may be concentrated, in a range of buffers and additives, before protein aggregation occurs
Biophysical characterization techniques are used to determine the optimal formulation conditions and to select the best formulations for further development.
Biophysical characterization systems for formulation development
Zetasizer range
How Size Exclusion Chromatography can improve processes and quality in biopharmaceutical development
Application of Dynamic Light Scattering (DLS) to Protein Therapeutic Formulations: Principles, Measurements and Analysis - 2. Concentration Effects and Particle Interactions
Solve stability problems in preformulation and process development using DSC
Long-term stability studies
Once a drug formulation enters clinical trials, it is subjected to long-term stability testing, including accelerated (forced) degradation studies. Extended submicron and subvisible particle characterization have important roles here in monitoring the constituents of the formulation over time. It is important to understand the origin and nature of particles and to determine whether they are inherent, intrinsic or extrinsic.
Biophysical characterization tools are used to monitor protein conformation, predict thermal stability, and measure aggregate formation in response to formulation and storage conditions. These tools include Differential Scanning Calorimetry (DSC), Dynamic Light Scattering (DLS), Size Exclusion Chromatography (SEC), and Nanoparticle Tracking Analysis (NTA).
Analytical solutions to support long-term stability studies
Zetasizer Ultra
NanoSight range
How investing in Malvern Instruments helped KBI Biopharma find a clear commercial advantage
Differential scanning calorimetry: Robust and powerful physical characterization of therapeutic protein products
