Development of A549 Cells as a Cell Substrate for Vaccine Production.

Many vaccines are still produced using archaic egg-based methods that limit vaccine supply and maintain high cost. Although several manufacturers have developed novel cell culture based methods, regulatory agencies have been resistant to approving them due to uncertainty about their risks for use in making vaccines, especially those employing live virus. Advances in biotechnology now allow for extensive genetic characterization and purity testing of candidate production cells and the US FDA and EMEA have issued a detailed set of guidelines for characterization of novel cell substrates. Two animal based cell substrates have undergone extensive characterization and are licensed ex-US (MDCK: Optaflu?; PER.C6?: Quinvaxem?). However, neither have received regulatory approval for manufacture of live vaccines. PaxVax has developed a human tumour cell line, A549, which is well suited for the production of its live, replication competent, Adenovirus Type 4 (Ad4) vaccine vector. A549 can be further optimized for high productivity of other viruses such as influenza thereby enhancing its general utility for vaccine manufacture. This proposal outlines two critical steps to finalize development of A549 as an acceptable cell substrate: 1) Complete the extensive characterisation needed to file a Master File with the US FDA 2) Adapt the A549 cells for large-scale serum free viral production.