Cell Culture Technology

GBI offers a full range of mammalian cell culture development and manufacturing services ranging from the creation of up and downstream processes sufficient for the manufacturing of proof of concept or toxicology product material to processes for licensed manufacturing. We do that with one goal in mind—to provide superior service to our clients that not only meets, but exceeds their expectations.

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.

Our clients have come from Eastern and Western Europe, North America and Asia, and have included biotechnology startup firms, research institutes, university laboratories, multinational biotechnology and pharmaceutical companies, and government institutes with projects that range from Translational Medicine and Proof of Concept projects to producing material for clinical trials.

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 partners, we can develop cell lines from cDNA that you provide. Our partners offer their own proprietary vectors to develop cell lines that can routinely produce up to 4g/L in CHO cell lines.

Our Approach to Cell Line Development

• GBI will work with one of our collaborative partners for molecular biology and cell line development activities.
• For each project, we will prepare a cell line development project plan (design input) for review and approval by the client.
• Cell line development can either begin with an existing vector as supplied by the client, or vector design and construction (gene synthesis) can be performed.
• Through our collaborative partnerships, we can take your gene sequence or cDNA for your recombinant protein, antibody, or hybridoma and engineer a highly productive, stable cell line in CHO, BHK, NS0, HEK-293, SP2/0 cells or proprietary third-party systems (GS, ACE, UCOE, PER.C6®, etc.). 
• After transfection of the cells, screening amplification and subcloning will be performed.  Cell lines will be adapted to suspension culture in serum-free, chemically-defined media. Also, note that per client request, stable pool of transfectants can be generated and characterized prior to the generation of a high producing single stable clone.
• Typically, cell line development activities will result in the identification of three (3) to five (5) high-producing candidate clones and ten (10) liquid nitrogen vials of each of three (3) to five (5) clones will be created.
• During cell line development at the shake flask stage, a small-scale, one (1) column protein A purification of the harvest can be performed for each cell line for initial characterization of the protein structural (primary, secondary, tertiary and quaternary) and binding characteristics via methods such as mass spectrometry, binding kinetics (ForteBio Blitz or Octet systems), glycosylation, potency, amino acid analysis, etc., to better aid in selection of the optimal cell line along with subsequent generational stability and productivity data.

For more information on our cell line development capabilities, please click here.

Generational Stability Studies of Cell Line and RCB Creation

• For each project, we will prepare a project plan for review and approval by the client.
• The stability of the three (3) to five (5) candidate cell lines will be evaluated in shake flask culture for up to fifty (50) generations, for example. Cell growth kinetics and productivity will be evaluated at regular intervals, e.g., every five (5) generations.
• Together with our client we will evaluate the data and choose the best performing clone for creation of Research Cell Bank (RCB).
• At least forty (40) vials of the RCB will be produced.
• The RCB will be tested for mycoplasma, sterility, and adventitious viruses, and then shipped to GBI for process development work and creation of a GMP MCB.
• A final report for cell line development will be prepared for review and approval by the client for each project.

To learn more on our approach to cell line development, click here.

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 -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.

• 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.