Manufacturing Technology

We work with most cell lines used for manufacturing, including CHO, NS/0, BHK, 293 as well as murine hybridomas, and all selection systems used with these lines. We have also worked with several different selection systems such as dhfr - /methotrexate CHO, mycophenolic acid/xanthine, and G418 systems. Our experience includes surface dependent as well as suspension culture types.

• Cell Line development

  GBI scientists have considerable experience in the development of cell lines for cGMP manufacturing for clinical studies through commercial manufacturing. In addition, working with our partner, Rafagen , we can develop cell lines from cDNA that you provide. Rafagen utilizes its own proprietary vector with CMV promoter to develop cell lines that can routinely produce approximately 1g/L in CHO cell lines. GBI offers a full range of mammalian cell culture development services including:

  • Cell line evaluation and stability

    At the earliest stage of development, it is essential to characterize the processes that will be used for manufacturing a potential new therapy and to determine whether a product can be manufactured in sufficient quantity, at a high level of quality in an appropriate dosage form and at a reasonable price.

  • Cell line characterization

    GBI offers evaluation and characterization services for your cell line. The characterization includes establishing and documenting the line's growth and product manufacturing dynamics. This data is crucial for determining whether the project is practical with the existing cell line capabilities and along with target product amounts, providing initial estimates for project costs.

  Cell line adaptation

  Timothy Riley, M.Sc. Manager, Cell Culture Process Development Tim has over 10 years of academic and industrial experience in designing and planning mammalian cell culture projects to produce recombinant proteins, monoclonal antibodies and enzymes from shake flask and bench-scale bioreactors to large scale tanks. He is well versed in all phases of process development and production which include smooth and efficient technology transfer, adapting cell lines to serum-free media, developing media and process optimization strategies, as well as scaling up and manufacturing under cGLP and cGMP conditions. In addition to his technical abilities, Tim authors Standard Operating Procedures and Batch Records for cGMP for pilot scale bioreactors, trains and leads lab personnel and supports cell and molecular technology bio-assay development. Tim also has previous experience in manufacturing vaccines. Tim has a M.Sc in Cell Biology and Biotechnology from the University of Sciences in Philadelphia. Click here to learn more…

  • Clone selection

    Another service offered to enhance the performance of your cell line is cloning. Cloning and screening for more productive clones may improve performance if your line has had limited cloning previously or has been exposed to conditions that would promote multiple cell performance populations.

GBI offers a full array cell banking services for research or manufacturing use. Manufacturing banks include seed, master, working, and post production. All of these banks are GMP compliant and are tested based on the current Points to Consider for cell bank testing. GBI works closely with our clients and with our qualified contract testing organizations to assure acceptability of all testing. Banks are prepared using a controlled freeze rate system and are stored in either liquid nitrogen or in -150°C mechanical freezer systems. All bank inventories are secured and controlled by GBI's Quality department. Short- or long-term storage of cell banks is provided.

• Research Cell Bank

  Research cell banks can be made at GBI to carry out non-GMP process development activities.

• GMP (Master and Working)

  GBI produces Master Cell Banks (MCBs) and Working Cell Banks (WCBs) in compliance with cGMP requirements.

GBI will develop a robust and reproducible cell culture process for the production of complex therapeutic protein drug candidates. GBI has experience with a number of cell cultivation technologies including stationary culture disposable flasks, spinners, WAVE disposable and stirred tank bioreactors. GBI offers cell culture production services for non-bioreactor projects. Spinner flasks up to eight liters in volume and roller bottles totaling up to 68,000 cm² are available for production.

• Media selection and development (both animal component and animal-free components)

  GBI offers medium evaluation and adaptation to commercial serum free formulations for your cell line. Our goal is to increase your line's productivity, growth performance, and/or compliance level.

• Development and optimization of robust and scalable processes

  GBI offers three different types of bioreactor systems for production and process development services for each. We work with clients to determine the optimum bioreactor type to use for their project based on their cell expression system and product quantities needed.

• Stirred tank batch or fed-batch bioreactor

  Stirred tank bioreactors up to 500L are available. With the possibility of achieving yields up to three grams per liter, our bioreactors could produce up to 1,500 grams per every 8 to 10 day run.

• Fibracell disk immobilized bed perfusion bioreactors

  Bioreactors with cartridge surface areas ranging from 2.1 to 25.2m² are available. The larger of these bioreactors can produce in excess of 150 grams during a six-week production run.

• Hollow fiber
• 6 X 5L Sartorius Bioreactors

  GBI has available small bioreactor systems of each type for the development of specific run parameters and scaling data for the larger production bioreactors. These small systems are also available for the production of non-GMP material for testing and toxicology studies.

GBI maintains a Class 100 filling suite that provides customized, economical, and compliant filling of client products. This operation is a semi-automated process that utilizes a programmable pump and manual fill nozzle manipulation to accomplish the fill. Fill checks are performed at predetermined intervals and this semi-automated process has consistently met all standards for acceptable fill volume variation. Our semi-automated process provides improved yields as compared to fully automated systems. Vials are manually stoppered immediately after filling by a second operator before removal from the fill room for sealing and fill checks. All fill operations are continuously observed and environmentally monitored by Quality personnel. Sealing and fill checks performed outside of the fill room are also monitored by Quality.

Specialized filling for difficult materials such as Aluminum Hydroxide adsorbed proteins is also available. The techniques for keeping these materials in suspension during filling operations have been developed and successfully used for multiple clients.

The fill operation is fully validated for fills up to 2000 vials and for fill volumes of 0.6 to 10.0mLs per vial. The validation includes fill operator sterile gowning, environmental control, and aseptic fill of all vials. The fill validation is repeated yearly.

Lyophilization capabilities
We even have a lyophilizer that is perfect for small runs.