Nov 21, 2012 (CIDRAP News) – The US Food and Drug Administration (FDA) yesterday approved the nation's first cell-based flu vaccine, a product from Novartis that uses technology that could help vaccinate more Americans in a pandemic but still has many of the same limitations of older egg-based flu vaccines.
The approval marks a milestone in federal efforts to improve vaccine technology, because cell-based production is thought to be more flexible and faster than the decades-old method of growing flu vaccine in chicken eggs.
The development of Flucelvax involved major federal investments in not only the vaccine itself, but also in the facility the company will soon use to produce future doses for the US market.
In a press release yesterday, the FDA said the vaccine, an inactivated product, is grown in mammalian cells and that cell-culture technology has already been used for decades to produce other US-licensed vaccines, such those against polio and rubella. The agency said Flucelvax is approved to prevent seasonal flu in people ages 18 and older.
Andrin Oswald, divisional head of Novartis Vaccines in Diagnostics, said in a statement from the company yesterday, "the approval of Flucelvax is an important milestone for our influenza franchise and brings an innovative vaccine to the US."
A flu vaccine expert from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, however, called it an incremental improvement and not the dramatic novel-antigen vaccine the country needs. CIDRAP publishes CIDRAP News.
In developing the vaccine, Novartis partnered with the Biomedical Advanced Research and Development Authority (BARDA), which is part of the US Department of Health and Human Services (HHS).
Novartis put the total price tag of the public-private investment in the vaccine's development and construction of the Holly Springs, N.C., facility that will make it at more than $1 billion. The HHS contributed $487 million toward the construction and certification of the facility, according to the agency.
The facility opened in late 2011 and produces prepandemic H5N1 vaccine. Federal officials have said the plant is designed to make 150 million doses of monovalent vaccine within 6 months of a pandemic.
The US has poured its development support into a host of other cell-based flu vaccine development projects, but some projects have been sidelined, and so far Novartis' vaccine is the only one to make it to the marketplace. The vaccine has been under development since 2006, when Novartis was awarded a $220 million contract from the HHS.
In August 2010, a report from President Obama's science advisors that explored factors that led to the late delivery of the 2009 H1N1 vaccine said cell-culture vaccines would shave some time off the process needed to produce the first dose, but the bigger benefit would be providing enough doses needed to immunize the entire population.
In a statement yesterday, HHS Secretary Kathleen Sebelius said the vaccine's approval demonstrates what can be accomplished through public-private partnerships that are designed to bolster national pandemic preparedness. "The goal is simple: provide additional and better influenza vaccines sooner to combat public health threats including pandemics," she said.
Elizabeth Power, a spokeswoman for Novartis, said Flucelvax is currently made in Marburg, Germany, and that the company plans to file for approval to produce it at the Holly Springs facility next year. She said a small number of doses will be available for this year's US flu season. The company filed its biologics license application for the vaccine to the FDA in November 2011.
The FDA's approval was based on large clinical trials that were conducted in the United States, Finland, and Poland. A randomized, blinded, placebo-controlled trial conducted during the 2007-08 season showed that the vaccine efficacy for Flucelvax was 83.8% against matched strains compared with placebo. A separate study in adults ages 65 and older found that the immunogenicity of Flucelvax was similar to Agriflu, an egg-based flu vaccine also made by Novartis.
The clinical trials suggested that Flucelvax was well tolerated in the study groups, with the most common adverse reaction being pain and redness at the injection site within 7 days of vaccination.
Last month, CIDRAP's Comprehensive Influenza Vaccine Initiative (CCIVI) published a report that said while cell-based flu vaccine platforms might have the potential to reduce the time needed to make flu vaccines, their efficacy profiles don't show benefits over currently licensed vaccines that target the head of the hemagglutinin (HA) protein on the surface of the flu virus. They also observed that a cell-based vaccine used in Europe during the 2009 H1N1 pandemic didn't appear to speed up the delivery of the vaccine.
The main thrust of the CCIVI report was that the world needs "game-changing" flu vaccines, but misperceptions about the modest effectiveness of existing vaccines are a barrier to developing more potent versions.
Nick Kelley, PhD, one of the report's authors and a research associate at CIDRAP, said the 83.8% Flucelvax efficacy against matched strains shows the best possible effect, but the clinical study showed that the efficacy against all circulating strains was 69.5%, which is the most relevant measure for public health purposes.
He noted that vaccine efficacy was 58.7% against the unmatched strains and that there was an influenza B mismatch during the year of the clinical study.
Kelley said the arrival of cell-based flu vaccine is an incremental improvement that could speed production by a week or two and boost the production volume over the long term. He said, however, that the new vaccine will encounter many of the same stiff headwinds that traditional egg-based vaccine face: modest efficacy with an even lower impact on people over age 65 and lukewarm uptake among the public in a pandemic situation if the bulk of the product is available after the peak, like we saw in 2009.
Kelley also said the time span between BARDA's investment in the vaccine's development and its approval was lengthy and shows how difficult it is to bring new flu vaccines to the marketplace.
Nov 20 FDA press release
Nov 20 Novartis press release
Nov 20 HHS press release
Nov 21 University of Minnesota interview with Kelley on Flucelvax
Aug 19, 2010, CIDRAP News story "Obama's science advisers outline plan for faster flu vaccine"
Full CCIVI report