Wednesday, November 11, 2009

Full Speed Ahead For Cell-Based Vaccines?

By Marilyn Werber Serafini  

Eric Althoff

Director of global media relations for Novartis

As the American public tries to make sense of the swine flu vaccine shortage, policy makers and vaccine manufacturers are contemplating new ways to produce vaccine that don't rely on the old, unreliable process of growing it in chicken eggs.

The manufacturer Novartis already is making cell-based vaccine in Germany for seasonal flu, and is about to open a facility in North Carolina to do the same for the United States. Novartis put its new technology to the test in Germany, where it produced a cell-based H1N1 vaccine that was ready months before any egg-based vaccine was. Because the company didn't have to wait for a lab to make a seed virus, which is required when growing vaccine in eggs, that saved four to five weeks. And because it didn't face the additional delay that occurred when the seed virus didn't grow well in eggs for other companies, that saved another month.

Eric Althoff, director of global media relations for Novartis, talked to National Journal last week about the advantages of using the next-generation, cell-based process for making vaccine. The following are edited excerpts from the interview.

NJ: What are the problems with growing vaccine in chicken eggs?

Althoff: With H1N1, we still had an egg supply because we were at the end of our seasonal [flu vaccine] run. But usually for each seasonal campaign, production starts in January, and we order eggs in advance. Hens still have to lay the eggs, and we had to order more. If this had been in August, it could have taken longer.

NJ: How is cell-based production better?

Althoff: We could save considerable time getting a vaccine to market.

If you have a situation where you are really seeing increased demand in vaccine, you could extend the production cycle more easily than with eggs. You have a process that is more easily scalable at any point in time, so you can ramp up or ramp down. You also have a vaccine that people with egg allergies can use. There's no passage through eggs, so there's no residue of egg protein. There's less chance of contamination and ruining a whole batch.

NJ: How is vaccine made in cells?

Althoff: We use MDCK [Madin-Darby canine kidney] cells. They are an old cell line taken out of the kidney of a dog. We have the original cell line that we can replicate. It's been altered and purified.

NJ: Novartis produced a cell-based vaccine for H1N1 at its German plant by making the vaccine directly from the so-called wild-type virus that comes directly from an infected person, thereby skipping the usual method of first creating a seed virus that's used to grow the vaccine in eggs. How much faster was that?

Althoff: Novartis requested and received a wild-type virus in early May. Without having to modify it greatly, we could go into production, and we had a first batch [of vaccine] in early June. It was an experiment. So it took four to five weeks to get the first batch.

NJ: If the cell-based vaccine was ready in June, why did European regulators only approve it for use last week?

Althoff: One still needs to test it, because it's never been done. Our process still needs clinical studies to validate it. The cell facility in Germany was licensed by European regulators in 2007 [for seasonal flu vaccine]. We need to make sure the process is robust enough for a pandemic [flu] strain.

NJ: While Novartis' U.S. plant isn't ready, why can't the United States buy cell-based seasonal flu vaccine from the German plant in the meantime?

Althoff: We were preparing to file for licensure in the U.S. for seasonal flu vaccine, but then everything shifted to H1N1 when there was the pandemic.

NJ: When will the North Carolina facility be ready?

Althoff: It will be open later this month. We expect full validation by 2011 for the first cell-based vaccines.

NJ: Why hasn't the movement to cell-based vaccines come about more quickly?

Althoff: Until we had the shortfall in 2004 of seasonal vaccine, when Chiron couldn't deliver, more and more companies pulled out of the seasonal flu vaccine business because it's hard to even cover your costs. Prices became so low that you had barely covered cost, but there was no room for investment.

NJ: Is that changing?

Althoff: Since the '50s and '60s, we've improved on childhood vaccines, but not many new vaccines have come to market. Now there's a more viable product. We're also taking advantage of new technologies, allowing for reinvestment in discovery of new vaccines.

NJ: What kind of commitment is there from the U.S. government to take the next step to cell-based vaccines?

Althoff: The U.S. investment in [the Novartis facility in] North Carolina is a big help. These are long-term investments. It's a partnership.

NJ: What is the agreement between the U.S. government and Novartis?

Althoff: There are several contracts. The first is for the development of cell-cultured vaccine for the U.S. and to get a clinical and regulatory pathway. Part of the investment was to develop adjuvant [to stretch vaccine supply] for the U.S. market. Also, there was a bricks-and-mortar investment into the facility itself.