Upstream Development

Upstream Process Development

Following cell line development, we at ProBioGen establish and validate robust and economical production processes according to GMP guidelines. Certain Upstream Process Development (USP) parameters are already taken into account during clone selection in cell line development, in order to select the clones with the most suitable process properties.

The foundation of efficient therapeutic protein manufacturing is laid at the end of cell line development with an excellent producer cell clone, stringently developed for its use in a subsequent manufacturing process. Such a producer clone from our cell line development, together with our broad experience and state-of-the-art equipment, are the basis for subsequent process engineering, during which robust and economical upstream and downstream processes are developed.

At ProBioGen a significant portion of upstream process development is already an integral part during clone selection at the end of cell line development (e. g. by analyzing metabolic parameters). The first step of process development is a "Bioreactor Performance Analysis" (BPA), in which typically three final clones from cell line development are analyzed in a fully controlled multi-parallel small-scale bioreactor system. Based on cell growth, metabolic parameters and protein characterization data of the expressed product, the final producer clone is selected. This is then followed by cell banking and process development.

Cell Banking

Cell banking at ProBioGen begins with determining cell line specific cryopreservation parameters, followed by employing cryopreservation processes and subsequent storage in separate cryo tanks with optical and acoustic alarm systems. Our facility includes a separate GMP unit with qualified state-of-the-art equipment for cryo storage.

Upstream Process Development

The following steps are the main building blocks of our upstream development:

  • Determining cellular behavior under different growth conditions
    • Defining boundaries of constant cellular performance
  • Adaptation of a developed generic model-based process control towards a clone-specific process
  • Consistency runs for material supply at larger bioreactor scales (up to 500 L possible)

Pre-clinical and Clinical Manufacturing

We manufacture pre-clinical and clinical grade material in up to 500 L scales. The use of fully disposable manufacturing systems, including different bioreactor platforms (stir-tank, wave bioreactors) ensures highest flexibility and safety and enables processes to be run in parallel, while simultaneously guaranteeing highest slot flexibility. During all steps, we provide professional project management and regulatory support

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Key facts of ProBioGen's Upstream Process Development

  • Final Producer clone selection with optimal process parameters based on Bioreactor Performance Analyses
  • Cell banking and cell bank storage
  • Process Development up to 500 L working volume
  • Fully Disposable systems: Maximal safety and flexibility
  • Open source concept: All materials are commercially available
  • Process validation according to GMP guidelines