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

    Process Development

    During process development, we quickly identify and optimize process conditions and parameters. Various formulations related process development can be conducted at Integrity Bio including:

    • Ultrafiltration/diafiltration (UF/DF)
    • Product concentration
    • Sterile filtration
    • Buffer characterization
    • Aseptic fill/finish process development
    • Temperature sensitive formulations
    • Process scale up
    • Engineering runs
    • Lyophilization cycle development

    A properly developed lyophilization cycle not only reduce the cost associated with the drying process but also can protect the drug product during drying process and subsequent storage.

    Lyophilization process development requires good understanding of the following parameters:

    • Product integrity during lyophilization: stability indicating assays, FTIR structural analysis
    • Physical properties of formulations under frozen condition, e.g., glass transition temperature or collapse temperature, re-crystallization or devitrification, and eutectic melting temperature of excipient in the unfrozen fraction
    • Presence of key stabilizers, e.g., surfactant, water-replacing glass formers
    • Potential pH change during freezing due to selective crystallization of buffer components
    • Phase separation of key ingredients during freezing
    • Desired final moisture content
    • Vapor pressure of ice at desired product temperature
    • Lyophilizer capacity and limitation
    • Scale up to GMP lyophilization
    • Validation of processes
    • Preparation of draft manufacturing protocols and templates of batch records

    Each of the following steps can be optimized to achieve the most efficient cycle with good product integrity:

    • Freezing and subsequent annealing
    • Primary drying
    • Transition to the secondary drying
    • Secondary drying

    Integrity Bio has two laboratory scale lyophilizers and one GMP lyophilizer for process development, scale up, engineering run, and GMP manufacturing of final drug products. Other supporting analytical equipment including subambient DSC and FTIR are crucial for proper cycle development.

    Deliverables

    • Clinical Manufacturing Process: develop a scalable formulation process to take the laboratory method to clinical production
    • Lyophilization Scale-Up: expertise to ensure the method piloted in the laboratory effectively scales to clinical manufacturing
    • Array Based Designs: investigate a broad parameter space for route selection and process development for catalytic and other organic transformations
    • Crystallization Development: identify key organic solvents and solvent systems which yield optimal solubility curves
    • Validation reports and draft manufacturing protocols