PT  - JOURNAL ARTICLE
AU  - Paul Shabram
AU  - John L. Kolman
TI  - Evaluation of A549 as a New Vaccine Cell Substrate: Digging Deeper with Massively Parallel Sequencing
AID  - 10.5731/pdajpst.2014.01027
DP  - 2014 Nov 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 639--650
VI  - 68
IP  - 6
4099  - http://journal.pda.org/content/68/6/639.short
4100  - http://journal.pda.org/content/68/6/639.full
SO  - PDA J Pharm Sci Technol2014 Nov 01; 68
AB  - In the past three decades, the use of tumorigenic cell substrates has been the topic of five Vaccine and Related Biological Products Advisory Committee (VRBPAC) meetings, including a review of the A549 cell line in September 2012. Over that period of time, major technological advances in biotechnology have improved our ability to assess the risk associated with using a tumorigenic cell line. As part of the September 2012 review, we assessed the history of A549 cells and evaluated the probable transforming event based on patterns of mutations to cancer genes. In addition, massively parallel sequencing was used to first screen then augment the characterization of A549 cells by searching for the presence of hidden viral threats using sequencing of the entire cellular transcriptome and comparing sequences to a curated viral sequence database. Based upon the combined results of next-generation sequencing technology along with standard cell characterization as outlined in published regulatory guidances, we believe that A549 cells pose no more risk than any other cell substrate for the manufacture of vaccines.