Aches and pains: Learning lessons from the influenza vaccine shortage

IAVIReportOnline.org article by Sheri Fink, MD, PhD

“As the US supply of influenza vaccine see-sawed from shortage to surplus this past year and flu experts again confronted warning signs of the next flu pandemic, AIDS vaccine experts might have considered taking notes. Experts say these unfortunate episodes provide valuable case studies highlighting the precarious nature of vaccine manufacturing, the difficulty of forecasting demand for biological products, and the challenges of ensuring an adequate supply. Many of the lessons flu experts are learning and the solutions they are proposing could apply to HIV/AIDS should an efficacious vaccine be developed……….

“From 1966 to 1977, half of all commercial vaccine manufacturers left the market. Now, only five manufacturers—GlaxoSmithKline, Merck, Sanofi Pasteur, Wyeth and Chiron—produce all vaccines for the US market that are recommended for routine child and adult immunizations. As of 2003, eight important vaccines for US consumers were each made by a single company—measles/mumps/rubella, tetanus toxoid, tetanus/diphtheria, inactivated poliovirus, varicella, pneumococcal conjugate (PCV-7), meningococcal, and pneumococcal polysaccharide (adult). The reason companies are either leaving or reluctant to enter the vaccine market is no secret: vaccines are seen as a risky business…….

“According to results of a National Health Interview Survey, only 43 million vaccine doses would have been required in 2004-5 to vaccinate high-risk patients at the same rate these groups were vaccinated in the 2002-3 season. That year, a mere 64% of the over-65 population was vaccinated (compared with a target rate of 90%), and rates for other high-risk groups were even lower. While the CDC recommended that 185 million Americans in at-risk populations and other target groups get vaccinated in 2004-5, the US had planned for a supply of only 100 million vaccine doses……….

“At three eggs per influenza vaccine dose, producing for the US market requires hundreds of millions of eggs per year. In order to secure adequate supplies of eggs, manufacturers need to forecast yearly vaccine demand six to nine months in advance of each flu season. This makes it impossible to respond to emergencies.

“New influenza vaccines must be produced each year because the influenza virus, like HIV, quickly changes its genetic stripes. The influenza surface proteins hemagglutinin (HA) and neuraminidase (NA)—antigens targeted by traditional influenza vaccines—are constantly changing, a process known as antigenic drift. More marked and sudden genetic reassortment leads to new virus subtypes and the risk of pandemics and is known as antigenic shift……….

“For influenza, the emergence of a pandemic strain is considered inevitable and overdue. Avian H5N1 influenza virus first emerged in 1997 but has re-emerged in recent years and made its way through large regions of Asia. This viral strain is able sometimes to infect humans in contact with birds and cause a high mortality rate and, most worryingly, it seems to have been transmitted on rare occasion from human to human. Only the inefficiency of this transmission between humans seems to have prevented it from becoming a full-blown pandemic virus.

“In November 2004, the World Health Organization convened a two-day meeting of all major vaccine manufacturers to assess the status of vaccine preparedness for an influenza pandemic. The troubling conclusion was that should a pandemic strain emerge, companies wouldn’t be able to quickly produce vaccine for the commercial market. Even at full production levels, worldwide influenza vaccine manufacturing capacity totals only an estimated 300 million doses per year. “A new pandemic would show up the inadequacy of current facilities to produce enough vaccine for billions of people, and poor countries would be the first to suffer,” says Plotkin. Experts predict a flu pandemic could cause in excess of 200,000 deaths in the US alone.”

300 million doses won't go far distributed among six billion plus people. But, of course, the limited supply will be used primarily to protect high-risk people in rich countries, not to interrupt the pandemic! And so it goes!