Biotech Capabilities

The proper development of formulations for protein and peptide biologics is paramount to maintaining potency and reducing the potential for immunogenicity of a biopharmaceutical product. Typical factors resulting in therapeutic failure or toxicity are directly related to degradation pathways. Appropriate characterization and formulation development of protein and peptide biologics are key to preventing chemical or physical instability. Many biotechnology companies initially skip this phase of development under the misconception that “what worked on the benchtop will be adequate for development and commercialization”. Often, this decision can result in significant unanticipated late stage delays, which are usually more costly and time consuming to overcome than developing a robust formulation for clinical evaluation.

Degradation Pathways

  1. Deamidation
  2. Oxidation
  3. Aggregation
  4. Disulfide Exchange or Scrambling
  5. Secondary structure
  6. Tertiary structure

Characterization (pre-formulation) Capabilities for Biologics

  • Isoelectric Point (pI)
  • Denaturation temperature by differential scanning calorimetry (DSC)
    • including excipient compatability
  • pH – solubility
  • Stress degradation
    • Acid
    • Base
    • Thermal
    • Oxidation
    • Disulfide exchange (cysteine)

Formulation Capabilities for Biologics

  • pH-rate profile
  • Buffer selection
  • Optimization to manage issues with:
    • Hydrolysis
    • Aggregarion
    • Oxidation
    • Adsorption
  • Stability
    • See available storage conditions below
    • Freeze-thaw
    • Mechanical shaking
    • Light
  • Lyophilization
    • Cryoprotectant
    • Lyoprotectant
    • Cycle conditions assessment by DSC

Analytical Capabilities for Biologics

  • UV-obscuration
  • SEC
  • RP-HPLC
  • Particle Size Analysis
  • DSC
  • SDS-PAGE
  • Native-PAGE
  • IEF
  • IEX
  • Shared Capabilities:
    • HIC
    • Far-/Near-UV CD
    • Fluorescence
    • Peptide mapping

Stability of Biologics

  • 25C/60%RH
  • 30C/65%RH
  • 40C/75%RH
  • 5C (2C-8C)
  • -20C
  • -70C
  • Freeze-thaw
  • ICH Photostability