Process development and optimization for optimum process economics


Our microbial development service offering supports clinical development through to commercialization. We are able to optimize existing fermentation and purification processes to improve manufacturability and process economy no matter what your development stage or expression platform. Our scientists and engineers have the experience and expertise to help solve challenges such as solubility, productivity, product quality and stability. Our microbial development and manufacturing teams work in close collaboration to ensure seamless transition between project phases. Our analytical and regulatory services are integrated into programs to de-risk your path to the clinic or market.


  • Fermentation Recovery and Development

    Our fermentation specialists maximize yield while maintaining the highest quality product. Process optimization is key to reducing potential pitfalls, such as formation of product related impurities or improper folding, leading to insoluble aggregate. Our experience with upstream optimization techniques and materials allows us to produce the most functional protein or plasmid DNA candidate. The choice of expression system and product localization will then drive the primary recovery approach. The upstream development laboratory is equipped to deal with most unit operations.

    Scaling-up of traditional Pichia fermentation processes can be challenging due to complex steps and feed regimes. In addition, typical fermentation times require a long guaranteed sterility of the vessel and medium. To address these challenges, we have developed Pichia 2.0, a proprietary expression system and associated upstream process specifically designed for easy implementation in large-scale plants. This system delivers high titers in drastically-reduced fermentation times that approximate E.coli processes.

    The advantages of the new Pichia 2.0 system include a shorter screening process in strain development with upstream protocols which are based on easy-to-implement fermentation regimes that deliver high space-time yields (STYs) with shorter product retention time in the supernatant for improved product quality. This system also allows for easier transition into single-use bioreactors, as the Pichia 2.0 process demands much less oxygen and produces significantly less heat compared to AOX1 processes.

    Lonza’s fermentation expertise includes:

    • Fermentation development
    • Miniature bioreactor systems (15mL and 250mL)
    • Feed strategy optimization
    • Media optimization
    • Induction kinetics optimization
    • Recovery and separation development
    • Inclusion body expression and recovery optimization (E. coli)
    • High cell-density fermentation

  • High yield production of your lead biomolecule of choice is just the beginning to a successful final product. We continue our quest for excellence with superior downstream purification and refolding capabilities. We have worked with a variety of molecule types including recombinant proteins, DNA and polysaccharides. Building on many years of experience, we defined a modular workflow to develop the sequence of DSP unit operations. Successfully combining your knowledge of the target molecule, our expertise in biopharmaceutical manufacturing and our standardized high throughput approach will give you the best chance to speed up your development time while maintaining the highest standard of quality.
     

    Our downstream purification offering includes:

    • Filtration and chromatography development
    • High throughput chromatography resin screening
    • Tangential flow filtration for purification, concentration and buffer exchange
    • Impurity removal studies (endotoxin, residual DNA)
    • High throughput refolding development and optimization
    • PEGylation Development and Optimization
    • Buffer characterization
    • Evaluating alternatives to chromatography
  • As your product moves toward commercialization, the process development team can carry on process validation support activities (process parameter qualification, small scale chromatography resin reuse, process and host related clearance and many others). These studies increase the process understanding, identify critical process parameters and define operating ranges. 

    The microbial development team has gained extensive experience in recent process validation projects. The scope of the studies performed is dependent on your needs and the current regulatory guidelines. As some of the needed information can be collected during a typical program, we recommend an early meeting with the regulatory authority to discuss your regulatory needs, and to jointly develop an appropriate plan.

    Lonza’s validation services include:

    • Scale-down modeling
    • Fermentation characterization using miniature bioreactors
    • Critical process parameter studies
    • Range finding studies
    • Analytical method validation
    • Media & buffer stability
    • In-process hold studies
    • Resin & filter re-use studies
Our scientists and engineers have the experience and expertise required to help you solve challenges where others may struggle, specifically in areas of solubility, productivity, product quality and stability.

Technologies and products


Technology is at the core of our microbial offering. Our XS Technologies® platform includes Escherichia coli, Pichia pastoris and Bacillus subtilis expression systems. Our XS Technologies® are available for use in your own labs under appropriate commercial terms.