Bioprocess research and development

Our researchers at the Human Health Therapeutics Research Centre work with clients and collaborators to help develop and perfect bioprocesses at small and pilot scales so the commercial scale production will be consistent, safe and cost-effective.

We offer support in all areas of biologics manufacturing:

  • Cell line engineering
  • Manufacturability assessment
  • Upstream and downstream process development
  • In-process and release assay development
  • Formulation development
  • Process robustness and scalability testing
  • Drug stability testing

At the research and development stage, starting with shakers and microreactors at the bench, our teams can produce thousands of protein variants per year for high-throughput screening. We develop custom clones and processes, scale them up in our mammalian cell culture pilot plant research facility or microbial fermentation pilot plant research facility, purify the material and use analytics for biologics and vaccines for preclinical proof-of-concept studies and provide documentation and quality assurance.

Once the product is robust and ready to generate clinical trial material, we can complete the technology transfer for both mammalian and microbial products from our R&D labs to a contract manufacturing organization (CMO).

In addition, leveraging our newest biomanufacturing capabilities, we will soon be able to complete the technology transfer of mammalian processes for production in our clinical trial material facility, which is expected to be operational in 2024.

Our expertise

Protein production in animal cells

  • Production of antibodies, proteins, growth factors, receptors and peptides in wave bags up to 25 L
  • Proprietary CHO expression platform and HEK293SF-3F6 and HEK293-6E expression platforms for transient and stable production
  • Cell line development: CHOBRI and CHO2353™:
    • CHOBRI parental cell line genome fully sequenced
    • Constitutive or cumate-inducible expression
    • CHO pool generation in 2 weeks
    • Selection of fully characterized stable clones within 5 months
    • ClonePix™ and CellCelector™ equipment
    • Animal-component-free process from transfection to final clones

Viral vector production in animal cells

Process intensification

  • High-throughput evaluation of clones and of medium and feeding strategies for process yield optimization under controlled environment conditions in ambr15, 48 parallel microbioreactor system (10 mL to 15 mL)
  • Integrated scalable process development from final clone selection to bench-scale bioreactors (1 L to 10 L) to facilitate transition between bench and large-scale production
  • Fed-batch and perfusion process optimization based on protein-free and animal-component–free media and feed development
  • Online monitoring tools

Small-scale production by microbial fermentation

  • Engineering and selection of bacterial hosts:
    • Gram negative: for example, Escherichia coli and Methylobacterium extorquens
    • Gram positive: for example, Corynebacterium glutamicum and Lactococcus lactis
  • Yeast cell engineering (Pichia pastoris, Saccharomyces cerevisiae) for production of recombinant peptides, proteins and VLPs
  • Expression system and fermentation process development for the production of peptides, proteins, VLPs, nutraceuticals, biomass, organic acids, polymers and probiotics
  • Production of peptides and proteins by cell-free protein synthesis (CFPS)
  • Bacterial whole genome analysis and gene hunting

Scale up at pilot plants

  • Expertise and equipment to rapidly convert laboratory results into industrial processes up to 500 L (animal cells) or 1,500 L (microbial):
    • Batch, fed-batch and perfusion
    • Custom media development
  • The mammalian cell culture pilot plant offers bioprocess development, optimization and scale-up under various production modes, using transient constitutive and inducible expression systems:
    • 0.5 L to 200 L in single-use systems
    • 3 L to 500 L in stainless steel bioreactors
  • The microbial fermentation pilot plant offers flexibility, versatility and a broad range of equipment to rapidly convert laboratory results into industrial processes up to the 1,500 L scale:
    • 1 L to 14 L in glass vessel fermenters
    • 20 L to 1,500 L in stainless steel fermenters
    • Medium optimization and process development for BSL-2 pathogenic microorganisms up to 150 L

Purification

  • Established purification platforms offer rapid purification of gram-level proteins suitable for in-vivo application without process development
  • Large-volume high-throughput platforms offer on-column purification of 48 x 1 L harvests simultaneously to produce a significant quantity of a drug candidate to support early-stage development
  • Expertise in robust downstream process development for therapeutic proteins, vaccines, VLPs, viruses, viral vectors and nucleic acids produced from mammalian, microbial or insect cell production platforms
  • Expertise in scale-up and pilot-scale capability to process up to 1,000 L harvest to produce several hundred grams of drug substance
  • Extensive experience in process troubleshooting, process improvement and technology transfer for drug candidates at any clinical stage

Glyco-engineering

  • Improved half-life and stability of target proteins
  • Optimized monoclonal antibodies effector functions: improved Fc sialylation (anti-inflammatory) and reduced Fc fucosylation (antibody-dependent cell-mediated cytotoxicity, ADCC)
  • Three stages of optimization:
    • Pre-production: glycan optimization on CHO cell lines, metabolic engineering and co-expression of glycosyltransferases
    • During production: medium additives for enhanced glycosylation and sialidase inhibitor
    • Post-production: enzymes to modify glycosylation patterns on target proteins
  • Production of enzymes and sialic acids as glycan remodelling tools
  • Toolbox of enzymes for chemo-enzymatic synthesis of immune modulators, pathogen adhesion inhibitors and vaccine antigens