Protein Formulation and Process Development along with GMP Fill Finish Services from a Single Experienced Source


    Preformulation Characterization

    Preformulation characterization studies generally include accelerated stability (stress) studies, stability-indicating analytical method development, and other physiochemical characterizations designed to pinpoint potential product candidate stability problems and enable formulation optimization. The following table shows examples of preformulation studies.

    The objectives of the pre-formulation research will include:

    • Understanding the pharmaceutically significant physicochemical properties
    • Estimating product’s stability when exposed to various common stresses
    • Developing stability-indicating assays for major degradation products
    • Deciding upon a lyophilized or liquid formulation for initial clinical studies
    • Finalizing a formulation development research protocol (matrix of buffer, pH, stabilizer, tonicity modifier; analytical methods; etc.)

    Example of Integrity Bio’s preformulation study Package (2-3 months)

    A preformulation study will perform systematic research designed to examine the physicochemical properties of product candidate that may be important in formulation development. During such a study, the product candidate will be exposed to various stresses, key degradation products will be identified, and appropriate stability-indicating assays will be developed. The product candidates will be prepared in well defined formulation matrix, exposed to relevant stresses, and analyzed by stability indicating assays.

    Stability indicating analytical methods, either developed by Integrity Bio or transferred from clients, will be used to determine the degradation products. We recommend using orthogonal methods to assess comprehensive stability profile of each product.

    Analytical Methods

    • Stability Indicating Assays and Stress Testing: orthogonal physical and chemical degradation products
    • Structural analysis: CD, FTIR, fluorescence, thermal denaturation
    • HPLC: size-exclusion, ion-exchange, reversed-phase, hydrophobic interaction
    • Electrophoresis: SDS-PAGE, Protein Analyzer, Capillary electrophoresis
    • Particle analysis: Microflow imaging (MFI), FlowCam, DLS, HIAC
    • Viscosity or syringeability: Instron
    • Biological activity

    Deliverables

    • Key product stability profile: stress, degradation products, stability indicating assays
    • Formulation sweet spot: pH, ionic strength, surfactant, other necessary stabilizer(s)
    • Liquid Formulation: refrigerated or frozen
    • Lyophilized formulation: refrigerated
    • Short term stability study result (both accelerated and real time)