FDA Considers Safety of Using Tumorigenic Cells in Vaccines

[Tara]

FDA To Seek Input On Safety Of Flu Vaccine Produced In Tumorigenic Canine Cells

FDA ADVISORY COMMITTEE
Posted: Tuesday, November 15, 2005


FDA will solicit input from the Vaccines & Related Biological Products Advisory Committee at its Nov. 16 meeting on the agency's approach to evaluating the safety of highly tumorigenic cells in vaccine production.

The agency will raise the question as part of a discussion over the use of the Madin Darby canine kidney cell line for influenza vaccine production.

"While some lines of MDCK cells are not tumorigenic, others are highly tumorigenic," FDA briefing materials state. "Thus, one goal of this meeting is for the committee to comment on our modified [Defined Risks Approach] as applied to highly tumorigenic cell substrates."

The agency acknowledged that there is a perception that vaccines produced using tumorigenic cell substrates could pose a safety risk - articularly with regard to the potential for unrecognized oncogenic viruses - that increases with the tumorigenicity of the cells.

It is "not possible to determine whether the use of a cell substrate that is strongly tumorigenic poses more of a risk than one that is weakly tumorigenic," FDA said.

Consequently, "a key and unresolved scientific question is whether and how the degree of tumorigenicity of a cell substrate should influence the testing algorithm for the determination of its suitability for use in vaccine production."

HHS is trying to incentivize flu vaccine manufacturers to transition from the current egg-based production model to cell-based manufacturing.

The agency appears comfortable that potential risks associated with tumorigenic cell substrates can be mitigated.

"Although there is a perception that highly tumorigenic cells may carry greater risks than less tumorigenic cells, we are proposing that such risks can be mitigated by careful testing of the cells, validation of the production process for its capacity to remove adventitious agents, and limitation of residual DNA in the final product," FDA said.

FDA is also asking the committee to discuss whether the agency should take additional steps "to address issues associated with the use of MDCK cells or neoplastic cell substrates."

The committee will hear presentations from Chiron and Solvay about the development of their MDCK-based flu vaccines.

Solvay recently filed a Drug Master File for its MDCK-based flu vaccine and plans to file an IND, the company's briefing document states. Solvay received approval for Influvac TC in the Netherlands in 2001 based on clinical trials enrolling 1,023 vaccinated patients.

Chiron's briefing document states that the company expects to commence clinical studies of its MDCK-based flu vaccine in the U.S. this year. The company has vaccinated over 3,000 patients in trials in Europe and New Zealand and is seeking approval by the European Medicines Agency.