High throughput screening of protein formulation stability: practical considerations.
The formulation of protein drugs is a difficult and time-consuming process, mainly due to the complexity of protein structure and the very specific physical and chemical properties involved. Understanding protein degradation pathways is essential for the success of a biopharmaceutical drug. The present review concerns the application of high throughput screening techniques in protein formulation development. A protein high throughput formulation (HTF) platform is based on the use of microplates. Basically, the HTF platform consists of two parts: (i) sample preparation and (ii) sample analysis. Sample preparation involves automated systems for dispensing the drug and the formulation ingredients in both liquid and powder form. The sample analysis involves specific methods developed for each protein to investigate physical and chemical properties of the formulations in microplates. Examples are presented of the use of protein intrinsic fluorescence for the analysis of protein aqueous properties (e.g., conformation and aggregation). Different techniques suitable for HTF analysis are discussed and some of the issues concerning implementation are presented with reference to the use of microplates.
Capelle
Martinus A H
MA
Department of Pharmaceutics and Biopharmaceutics, University of Geneva, University of Lausanne, CH-1211 Geneva 4, Switzerland.
Gurny
Robert
R
Arvinte
Tudor
T
D002151:Calorimetry; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D002942:Circular Dichroism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004355:Drug Stability; D004586:Electrophoresis; D005454:Fluorescence Polarization; D031541:Fluorescence Resonance Energy Transfer; D006863:Hydrogen-Ion Concentration; D008027:Light; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
D004364:Pharmaceutical Preparations; D011506:Proteins