Technology Transfer and Scale-up

The transfer and scale-up of processes can be a costly endeavor laden with unforeseen risks. BPAI has a successful record of accomplishment in technology transfer and scaling microbial, yeast, insect and mammalian cell biologics processes from lab bench to manufacturing scale. Our team can provide effective assistance during technology transfer, ultimately ensuring your peace of mind. BPAI’s bioprocess consultants can provide critical technology transfer services to assist your program and ensure success, such as:

technology-transfer-and-scale-up

  • Inter-site transfers: lab to lab, non-cGMP to cGMP, cGMP to cGMP
  • Drafting, review and approval of technology transfer protocols
  • Assistance in developing bioprocessing scale-down models to demonstrate successful technology transfer
  • Bioprocessing assessments for cGMP readiness, robustness and scalability
  • Expert advice on process changes related to site transfers, scale-up and compliance
  • Process technology transfer oversight
  • Analytical methods implementation, development, qualification and/or validation

 

Development

Process Development

Critical to every biologics CMC program is the need to develop an effective, robust and scalable process that allows for the expression and purification of valuable protein products. BPAI can assist your organization with biologics process development and optimization of your biomanufacturing process through our knowledgeable and experienced bioprocess technology consultants. Applying Quality-by-Design (QbD) principles, our focus is on providing fully scalable, GMP compliant biomanufactuirng processes that are compatible with the latest equipment and infrastructure. Our goal is to work seamlessly with your team, providing leading edge guidance for protein and antibody biomanufacturing from microbial, yeast and mammalian cell lines.

Upstream Development

Upstream processes are aimed at the controlled propagation of production cells (microbial, yeast, insect or mammalian)with the aim of harnessing the cellular machinery for the production of crude native or recombinant protein products ready for harvest and purification. BPAI’s upstream biologics process development experience is extensive and crosses the array of host cell types and expression systems. Our bioprocess technology consultants can assist with development oversight in the following areas:

  • Cell line development, initial expression and stability studies
  • Raw material screening combined with media selection and optimization
  • Cell banking, cell line stability and pre-culture development
  • Development and optimization of batch, fed-batch and perfusion processes
  • Scale-Up and scale-down; laboratory to commercial biomanufacturing scale
  • PAT, DOE and bioprocessing models
  • Technical and quality auditing of established biologics processes
  • Process troubleshooting for quality, yield, robustness, etc.
  • Assistance in equipment selection

Midstream Development

The main focus of midstream development is on host organism and/or cellular debris separation while maximizing native or recombinant protein recovery and maintaining product activity, including:

  • Filtration unit operation optimization (NFF, MF, UF, DF)
  • Continuous centrifugation bioprocessing optimization and development
  • Cell rupture for recombinant protein release
  • Inclusion body recovery and processing
  • Flocculation development, optimization and scale-up

Downstream Development

Downstream biologics unit operations are focused on the capture of your important product amidst a sea of host cell related proteins, and cellular debris. Subsequent purification and polishing of the product are aimed at attaining purity and activity levels worthy of human clinical trials. Purification and polishing are achieved through orthogonal combinations of selective chromatography media and membrane unit operations. Purification programs for biologics inherently have complex issues around product heterogeneity; challenges which are not normally encountered during small molecule purification. As such, purification operations can very often become the largest bottleneck in a biomanufacturing process, which necessitates development of cost and time effective purification processes that are robust, scalable, efficient and transferrable. BPAI has the experience you need in developing and scaling purification processes for routine and ‘tricky’ recombinant protein and antibodies. Our downstream bioprocess technology consultants can assist you in numerous areas, including:

  • Development of robust and scalable downstream purification processes
  • Resin screening and cycle optimization
  • Chromatographic optimization for product recovery and contaminant loss
  • Membrane filtration development and optimization
  • Development and optimization of protein refolding operations
  • Management of viral clearance studies
  • Tangential Flow Filtration development and optimization
  • Optimization of chromatography operations
  • Cleaning and reuse studies for media and membranes
  • Downstream process troubleshooting
  • PAT, DOE and bioprocessing models
  • Technical and quality auditing of established biologics processes
  • Process troubleshooting for quality, yield, robustness, etc.
  • Assistance in equipment and column selection

Analytical Development

Of fundamental importance in any clinical trial development and biomanufacturing program are reliable and reproducible analytical methods to support process development, in-process monitoring, finished product testing and stability monitoring. BPAI has a wealth of experience in designing and implementing analytical support for biologics programs:

  • Assay recommendations based on process flow
  • Creation of analytical transfer protocols for inter-site studies
  • Creation of assay qualification and validation protocols to ensure reliable assays
  • Real-time monitoring and interaction with service providers during protocol execution
  • A280, SDS-PAGE, IEF, Western Blot, ELISAs, Bioassays, Endotoxin, USP Testing

Manufacturing – GLP & cGMP

Let’s face it, all biologics process development projects are for one purpose and one purpose alone – to create large batches of GMP compliant product ready for toxicology and human clinical trials. It’s the pinnacle of every biomanufacturing program, with substantial energy, resources, time and money poured into every single GMP biomanufacturing run. BPAI understands the uniqueness of biologics manufacturing based on our extensive, real-world experience managing complex scale-up, engineering and GMP biomanufacturing projects. We work hands-on, in the plant with your chosen service provider. Our biomanufacturing support services are tailored to your organizations specific needs. Just browse our list of support service offerings to find the perfect balance of oversight:

  • Creation and review of important quality related biomanufacturing documents:
    • Process Flow Diagrams & Bill of Materials
    • Batch Production Records & Analytical Control Plan
    • Standard Operating Procedures
    • Analytical Procedures
    • Material Specifications
    • Product Specifications
  • Person-In-Plant during critical unit operations and oversight during manufacturing
  • Technical oversight during biomanufacturing runs including troubleshooting and review and approval of quality documents such as planned changes, deviations and excursions
  • Post-run batch record audit, data analysis, trending and overall compilation
  • Participation in post-run debriefs with biologics service provider to prepare for next run(s)
  • Assistance with CMC compilation for regulatory submission
  • Creation and review of Bulk Drug Substance and Finished Product stability studies
  • Project knowledge technology transfer to client representatives
  • Development of customized manufacturing training programs geared towards complex unit operations through combination of classroom and hands on practice

Quality & Compliance

In addition to our extensive biologics process development and biomanufacturing experience, BPAI has a wealth of experience in the quality arena. From the development of GMP-based quality systems to the implementation of environmental and utility monitoring programs, BPAI can serve as a great sounding board for your organization with the following oversight service offerings:

  • Auditing of third party service providers and material vendors
  • Independent auditing of quality systems to Health Canada, TGA, EMEA and FDA regulations
  • Review of conceptual and detailed facility design drawings for compliance aspects
  • Development of comprehensive, intrinsically linked CAPA based quality systems including Change Control, Deviation, Out of Specification, Product Investigation, Preventative Maintenance & Calibration, Investigations, etc.
  • Creation and implementation of globally compliant environmental and utility monitoring programs
  • Quality Control laboratory design, equipment sourcing and fit-up, set-up and oversight
  • GMP introductory training including three modules:
    • Introduction to GMP
    • Compliant Documentation Principles and Practices
    • Contamination Control
  • Batch production record audit for batch release
  • Support of regulatory submissions through drafting and review of regulatory documents