What is Cell Line Development?
Cell line development (CLD) is the engineering of a cell line, often mammalian, to produce a therapeutic biomolecule or biologic. It allows scientists to tailor cultures depending on the applications and desired properties of the targeted product.
Creating a robust, stable cell line that can yield sufficient material for testing, optimization, and manufacturing at commercial scales is a crucial step in bioprocess development. The route taken during the early stages of your project will determine its future success or failure. The following outline presents an overview of the cell line development workflow:
There are various stages which problems can arise during the creation and optimization of robust cell lines. However, a heightened awareness of potential future challenges during early process development can help mitigate the risk of failure, reduce the expenses associated with repeating processes, and ensure that the cell line and biotherapeutic meet regulatory requirements.
Watch the Video: What is Cell Line Development?
Watch this video to learn more about the steps and overcoming challenges in a cell line development workflow.
- Rapid cloning and screening of mini-pools for product titer, cell health and growth
- Early identification of high productivity clones with optimal CQAs and target specificities
- Screen culture conditions and media formulations for optimal growth and protein production
- Characterize top clone for stability, productivity and quality attributes of the protein
- Preparation of a research cell bank (RCB), master cell bank (MCB) and working cell bank (WCB)
Frequently Asked Questions
Primarily consisting of therapeutic recombinant proteins, biopharmaceuticals have had considerable success in treating various diseases, particularly cancers and inflammatory disorders. Biopharmaceutical manufacturing uses living host cells as production centers. The development of a robust, high-yielding and stable that can yield sufficient material for testing, optimization, and manufacturing at commercial scales is a crucial step in bioprocess development.
The cell line development workflow consists of five key steps:
- Gene cloning and initial clone selection
- Clone selection and confirmatory analytics
- Cultivation and media optimization
- Cell line evaluation and characterization
- Cell banking
To learn more about each of these steps in details, explore our Custom Solutions for Cell Line Development
Critical quality attributes (CQAs) of cell lines include identity, microbiological sterility, genetic fidelity and stability, and viability. In terms of characterizing the biopharmaceutical product the CQAs are extended to potency, and biological activity. The later includes the glycosylation pattern, which has implications on the half-life, immunogenicity, and pharmacokinetics of the biologic, and must be closely monitored throughout drug development and manufacturing.
To learn more about simplifying the analysis of CQAs, view our eBook.
Are you tired of seeding thousands of cells in large stacks of cell culture plates only to find out they are either no single cells, viable or productive? Tired of screening hundreds of plates for the one clone that has it all and will fulfill your projects titer goal? Why leave your pharmaceutical cell line development to chance? With the CellCelector single cell and colony picking platform you can now effectively assess and verify your clones before deciding which ones to choose. Within under a week you will get from a pool of single cells to plates full of clones that have proven to be monoclonal, viable and productive. Instead of relying on large quantities of plates to produce a winner you can now use actual data reliably predicting the future of your clones. This saves consumable and media costs, incubator space but most of all valuable time to reach your project goals by avoiding missteps, a second cloning round and unnecessary procedures.
In a conventional single cell cloning workflow single cells are seeded in 96 well plates making reliable automated single cell detection in bright field difficult as cells are often settled at the very edge of the well. Thus the monoclonality status of a given clone at day 0 is usually checked manually or retroactively once the clone has grown. But why search a single cell within a well area that is more than 100 times larger than the surface occupied by a cell? With the CellCelector HT-NIC approach the cells are separated and clearly visible within 200 µm large nanowells and can therefore be identified reliably and automatically by software. Even just after seeding or when they touch the nanowell border.
