Stable Cell Line Development (CLD) at Aragen – Accelerating speed to IND
Efficient CLD is critical in bringing biologics to market and requires a team of experienced scientists, a portfolio of well validated cell line platforms, and ultramodern facilities. Aragen, a well-established preclinical CRO, delivers this combination and has completed more than 200 CLD projects, with over 100 of those cell lines in the clinic after successful investigational new drug (IND) filings. More than four of Aragen’s cell lines are producing marketed products.
Support for a Broad Range of Host Cell Lines and Expression Vectors
Aragen’s researchers have expertise in a wide range of host cell lines (CHO-DG44, CHO-GS, SP2/0, and NS0) and expression vectors (DHFR, Glutamine Synthetase (GS), and antibiotics). Aragen offers the royalty-free RapTr2022 platform, supporting CHO-DG44 and CHO-GS cell lines, which accelerates the cell line engineering process and offers higher titers.
Cell line development is a process by which a large population of identical cells is created, containing the gene that, on translation, encodes the biologic (recombinant proteins, monoclonal antibodies, bi-specific monoclonal antibodies, fusion proteins, vaccines). Chinese Hamster Ovarian (CHO) cells and Human Embryonic Kidney (HEK) cells for example, are among the most effective and prolific biological factories, and their cultures are utilized to produce novel cell lines. Apart from biologic production stable cell lines are also used in drug screening and gene functional studies.
To ensure the successful insertion of the vector in the host cell line several transfections are performed. When the transfected cultures are pooled together, it is called bulk transfection. To identify the best transfected cells or hot spots the bulk transfection is divided into several tiny populations called minipools and the leftover is referred as the bulkpool. Minipools help identify the high producing cells. Bulkpool is used for a fed-batch production run to generate materials that is purified and analysed as an analytical standard or benchmark against the expected product quality.
Clone screening is a process by which the transfected pools is analyzed for the cells those carrying the desired genomic changes and expressing the target protein. clone screening is a complex process because the performance of the clones is unpredictable in different culture conditions therefore the higher the number of clones screened the greater are the chances of discovering the high producing clone. Once a few efficient clones have been identified, multiple assays should be carried out to build a thorough picture of the features of each before selecting the best performing clone.
Clonality is one of the most crucial steps in guaranteeing cell line quality and safety. The FDA currently require evidence that each cell line used in manufacturing has been generated from a single cell. Single cell cloning (SCC) is a method in which single cells are separated from the pool of transfected pool such that final MCB is generated from the single cell and produces identical product. SCC is currently achieved using two commonly used methods i.e., single cell sorting using FACS and limiting dilution.
Research cell bank is a small cell bank produced under research conditions used for the production of a biotherapeutic for research purpose only. A master cell bank (MCB) is generated from a research cell bank (RCB) when cell line development is completed. Cells from a RCB are thawed and expanded, and when cell counts reach the desired number, a MCB is prepared and stored in a LN2 freezer.
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