Upstream Cell Culture
There are numerous technical considerations associated with developing and manufacturing your antibody or recombinant protein, from optimization of the DNA sequence and developability to cell line development (with strategic partners) to proof-of-concept and preclinical studies, through to subsequent early-stage and late-stage clinical trials. In fact about 90% of Goodwin’s projects involve monoclonal antibodies and recombinant proteins (many with drug/chelator conjugates) and proceed through upstream process development and cGMP manufacturing. It is this comprehensive experience and expertise that makes Goodwin uniquely qualified as a development and manufacturing partner that offers a Single Source Solution™ for you.
- Ensuring from the earliest stage that any upstream process development project is scalable, compliant, and economical for large-scale cGMP manufacturing
- Producing a product that meets quality and regulatory requirements relative to safety, purity, potency, identity, and immunogenicity through rigorous characterization.
- Meeting these criteria requires both methods and processes must be developed as well as qualified and/or validated, as appropriate, during preclinical, early-stage clinical, and late stage clinical product development.
Goodwin Biotechnology 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 a sequence or cDNA that you provide. Our collaborative partners offer their own proprietary vectors to develop cell lines that can routinely produce over 7g/L in CHO cell lines for an IgG1 antibody. Alternatively we can express different sequences or cDNA and evaluate the constructs for developability / manufacturability prior to selecting the best sequence to incorporate into the cell line development activities.
Our Approach to Cell Line Development
Goodwin Biotechnology 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 you.
- 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.
- After transfection of the cells, screening amplification, and subcloning will be performed. The Cell lines will utilize a commercially available media platform that is in a suspension culture that is serum-free and, chemically-defined. Also, note that per client request, a 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 purification step (i.e., protein A) of the harvest can be performed for each cell line for initial characterization of the protein structural (primary, secondary, tertiary and, quaternary) characteristics via methods such as mass spectrometry, glycosylation, potency, amino acid analysis, binding characteristics, and binding kinetics (Octet systems, Biacore) to better aid in selection of the optimal cell line along with subsequent generational stability and productivity data.
- For each project, we will prepare a project plan for review and approval by you
- 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.
- In parallel the three (3) to Five (5) candidate cell lines will be evaluated in 5L bioreactors using Goodwin standard procedures developed specifically for each partner’s platform cell line.
- Together with our client we will evaluate the data and choose the best performing clone for creation of the 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 Goodwin Biotechnology 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.
Upstream Process Development
Goodwin Biotechnology has robust and reproducible cell culture upstream process development for the production of complex therapeutic protein drug candidates. Goodwin Biotechnology has experience with a number of upstream cell cultivation technologies including stationary culture disposable flasks, spinners, WAVE disposable, stirred tank bioreactors, and perfusion processes. Goodwin offers cell culture production services for non-bioreactor projects.
- Media selection and development (animal-free components).
- Goodwin Biotechnology offers medium evaluation 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.
- Goodwin Biotechnology offers three different types of bioreactor systems for production and process development services for each. We work with you 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 in the Process Development Lab.
- Stirred tank bioreactors ranging from 250mL to 40L are available in the process development lab. Our Process Development lab will work closely with our manufacturing team to execute the GMPnization of the process. This ensures a seamless transfer to our larger scale bioreactors in Goodwin’s cGMP core facility. With the possibility of achieving yields of three grams per liter or more, our cGMP bioreactors could produce in excess of 6,000 grams per every 8 to 10 day run.
- Multiple 5L Stir Tank Bioreactors — Goodwin Biotechnology 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.
- Fibracell disk immobilized bed perfusion bioreactors are available in both the Process Development Lab (XCell™ ATF 2) and cGMP core (XCell™ ATF 6) for Perfusion and Continuous Processing.
Meet the Upstream Development Technical Leadership
Catherine Uitz, PhD
Head of Product Development
Catherine Uitz, PhD, was most recently the consultant of USAID Global Health Supply Chain Program-Procurement and Supply Management and was previously the Associate Director at Novavax, where she was accountable for process development and attribute characterization to defend the integrated control strategy of flu VLP. She has worked in US FDA and WHO approved drugs, Process Development, and Manufacturing Sciences on a variety of product types (ACTs, RDTs, LLINs, ARVs, NuThrax™, PreviThrax™, NicVax, NEISVAC-C® , novel semi-synthetic conjugate vaccines) and at small and large companies (Emergent, Nabi Biopharmaceuticals and Baxter Bioscience). Catherine possesses numerous patents, publications, and corporate technical team awards.
Catherine has a BSc and PhD in Organic Chemistry from University Paris XI – Institute Curie, Paris, France.
What Clients Say
We are very pleased with the highly skilled scientists at Goodwin Biotechnology, who met the challenge of developing and scaling up the process to manufacture a monoclonal antibody using their perfusion cell culture process, and utilizing their bioconjugation expertise to prepare the IgM‐ligand conjugate needed for purification of our Q‐Cells®, while overcoming the many process and product‐related challenges associated with an IgM antibody
Goodwin Delivers with a Technical and Project Approach
The Goodwin technical, project management, quality, and regulatory approach to your project is borne of nearly 30 years of overall experience and expertise with approximately 500 projects executed with 150 clients in the proof of concept, process development, scale-up, and subsequent cGMP manufacturing with fill and finish of biopharmaceuticals such as monoclonal antibodies, recombinant proteins, fusion proteins, and vaccines.
Goodwin will work to establish Quality Systems and GMP manufacturing capabilities to be ready for commercial manufacturing for BLA filing and commercial manufacturing approval from FDA. Goodwin will also create a GAP analysis to address all the issues in terms of facility, resources and QA systems for FDA approval.
Your cGMP manufacturing goals
Let’s discuss the optimal approach for your cGMP manufacturing goals and develop a solution that is most optimal to meet them.