GSK gives to WHO bird flu vaccine stockpile; cell-based seasonal flu vaccine approved in EU

Some influenza-related goings-on this week:

• Yesterday, GSK announced via press release its plan to donate to WHO 50 million doses of its pre-pandemic avian influenza vaccine. WHO responded with a press release of its own, noting some of the many, many still-to-be-answered questions regarding if, when, and how such a stockpile would be used. Here's the AP story on the announcement. While a nice corporate gesture, vaccine doses for 25 million people -- delivered over 3 years, no less -- seems like a drop-in-the-bucket in the event that anything even resembling the estimates of policy-makers comes to fruition. Also, we've discussed the many uncertainties regarding the value of pre-pandemic vaccines previously, but suffice it to say, the benefit of such vaccines is uncertain today, much less three years from now in light of the viral mutation that would precede a pandemic in humans. All that said, this news can be seen as a good start, one could say, but by no means a major step in preparedness.

• In seasonal flu news, the EU approved a cell-based vaccine by Novartis, likely to be the first marketed flu vaccine produced without the use of eggs. Here's the AP story, courtesy of the Washington Post, and the Novartis press release. The story notes that the vaccine will not be available throughout the EU until the 2008-09 flu season and that U.S. approval will be sought next year. In light of the well-rehearsed problems with egg-based flu vaccine production (most notably the 2004 shortage), this may prove to be a major moment in flu vaccine development.

Potency concerns for pandemic flu vaccine stockpiles; HHS planning update; more contracts awarded

For months, we've been discussing some of the many challenges and potential problems associated with the "pre-pandemic" avian flu vaccines currently being developed, tested, and stockpiled. More reason for concern came late last week, when this CIDRAP News story reported that a significant percentage of the stockpile has lost potency, resulting in a one-million-person decrease in the number of people who could potentially be protected by vaccine doses currently on hand (3 million, down from 4 million in an HHS document released in July). Here's an excerpt from the story, quoting an HHS spokesman:

"'All vaccines have shelf lives,' Hall told CIDRAP News. 'The early vaccine that was purchased, the first lots, have begun to lose their potency.'

He said the potency has begun to decrease for 'the majority' of doses in the stockpile, adding, 'That doesn't mean it goes from 100 percent to zero percent' or that the doses would be unusable."

On Friday, a day after the story above appeared, the same HHS spokesman seemed to walk back his earlier comments in this CIDRAP follow-up, explaining that only 20% of the current doses on hand are losing potency, not "a majority," as he previously said. Either way, it should come as a surprise to no one that these vaccines have a limited shelf life, an issue avoided by seasonal flu vaccines on account of their annual reformulations. Even with full potency, the vaccine doses in question are from "clade 1" virus samples from 2004. Since early this year, vaccine development has been based on a 2005 sample, working toward "clade 2" vaccines expected to be a closer fit to a possible pandemic strain.

All of this news came as a result of the release last week of the latest HHS Pandemic Planning Update. Not a lot of news in the 13-page report (and, thus, virtually no news coverage about its release), but it provides a good overview of the current status of U.S. planning and spending.

Finally, HHS announced today that another $200 million in contracts have been awarded to Sanofi Pasteur, Novartis, and GlaxoSmithKline for an additional 5.3 million doses of "clade 2" pre-pandemic vaccines, enough to vaccinate roughly 2.7 million people. (Here's the story from Reuters.) This would double the current stockpile (notwithstanding further decreases in potency of older vaccines), but still represent only a bit more than 1/4 of the goal of having enough vaccine stockpiled for 20 million Americans.

FDA approves 2006-2007 flu vaccines

News from Washington yesterday that the FDA approved the vaccines to be used for the upcoming flu season. Here's the FDA press release and AP story regarding the announcement.

These approvals are an annual occurrence, as manufacturers produce flu vaccines including the specific strains of the virus recommended by WHO and FDA. There are four vaccines available:

• Fluvirin (Novartis Vaccines, formerly Chiron)
• Fluarix (GSK)
• Fluzone (Sanofi Pasteur)
• FluMist (Medimmune)

FluMist is the increasingly popular nasally-administered vaccine, the other three are injected (and few patients know which of the three they receive). In total, the FDA estimates a supply of approximately 100 million doses in the U.S. for the season.

Novartis to build first U.S. cell-culture flu vaccine plant

Using $220 million awarded in May by HHS as part of the government's pandemic flu plan, Novartis announced plans yesterday to build the first U.S. manufacturing plant for cell-culture derived flu vaccines. The plant, to be built in Holly Springs, NC, has a total bill of $600 million, according to this Novartis press release. Here is a news report on the announcement from Reuters and a lengthier story from the U. of Minnesota's CIDRAP.

Once complete, the plant will be able to produce 50 million doses of seasonal flu vaccine annually and as many as 150 million doses of a possible pandemic flu vaccine. It marks another step away from reliance on an egg-based flu vaccine production method, with its many shortcomings. We'll still be using eggs for many years to come, however. Novartis estimates the plant won't be fully functional until 2012.

More problems for Chiron vaccines

News today that Chiron has recalled and withdrawn one of its measles, mumps, and rubella vaccines, Morupar, due to concerns over rates of adverse events. Here's the Chiron press release. The AP story, courtesy of the Washington Post site, explains...

"Italy determined five patients immunized with Morupar suffered adverse reactions, including fever and swelling of the glands, commonly associated with the vaccine, Marquiss said.

The same pattern hasn't been cropping up with MMR vaccines made by two other manufacturers, prompting the Italian Medicine Agency to order a withdrawal of Chiron's product from the market to protect the public's health."

It should be noted that this news has no direct impact on vaccination in the U.S., where the recalled vaccine is not licensed. (The only MMR vaccine available in the U.S. is this one from Merck. Whether it's wise to have only a single manufacturer for a universal vaccine is a topic for another post.)

Indirectly, however, today's news -- the sequel to their flu vaccine debacle in 2004 -- should raise alarms worldwide over Chiron's overall competence. At this point, it may be worth taking a closer look at how greatly Chiron should be relied upon to meet future vaccine needs, particularly with respect to avian flu. Just last month, in fact, Chiron received an extension from the U.S. government to deliver the (1st generation) avian flu vaccine for which they received a $62.5 million contract last October.