Managing Cell Line Instability and Its Impact During Cell Line Development - By considering stability as part of the cell line selection and cell banking paradigm, we can ensure that instability probl

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Managing Cell Line Instability and Its Impact During Cell Line Development
By considering stability as part of the cell line selection and cell banking paradigm, we can ensure that instability problems are not observed during clinical or commercial manufacturing.


BioPharm International Supplements


Conclusions

In conclusion, we have developed, and will continue to develop, tools to increase our understanding of, and continuously improve, our expression systems, our cell line development practices, and our outcomes. This manuscript has described how certain of these tools have enabled us to better understand, and specifically cope with, cell line instability. Using these tools has enabled the earlier identification of unstable clones, which is critical given our aggressive development timelines. In addition, given the industry-wide movement toward using more efficient practices during the development of protein therapeutics, our ability to predict cell line instability, and to invest time and resources on only those clones that are viable candidates, is beneficial. Finally, the information and learnings that result from using these tools and assays will continue to be key in eliminating instability altogether, thus enabling improved consistency and predictability of cell lines in our future projects.

ROBIN HELLER-HARRISON is the associate director and the corresponding author, KERSTIN CROWE is a research scientist II, CECILIA COOLEY is a research scientist I, MEGAN HONE is scientist II, KEVIN MCCARTHY is a principal scientist I, and MARK LEONARD is the director, all in the cell and molecular sciences group in the department of Drug Substance Development at Wyeth BioPharma, Andover, MA, 978.247.1406,

References

1. Herman J, Baylin S. Gene silencing in cancer in association with promoter methylation. N Engl J Med. 2003;349:2042–2054.

2. Ehrlich M. DNA Methylation and Cancer-Associated Genetic Instability. In: Nigg EA, editor. Genome Instability in Cancer Development. The Netherlands: Springer; 2005. p. 363–92.

3. Doerfler W. In pursuit of the first recognized epigenetic signal-DNA methylation: A 1976 to 2008 synopsis. Epigenetics. 2008;3:125–33.

4. Weber M, Davies J, Wittig D, Oakeley E, Haase M, Lam W, Schubeler D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37:853–62.


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