Still, the vaccine business carries considerable risks. Pfizer has run into delays gaining FDA approval of its improved Prevnar
13 vaccine for pneumococcal disease in children, despite its priority-review status and strong recommendation for approval
by an advisory committee last November. Merck has found it hard to sell its shingles vaccine Zostavax largely due to Medicare
reimbursement complications (see sidebar, "Coverage matters").
The H1N1 swine-flu vaccine shortage in October and November brought home the perils involved in influenza vaccine development
and production. Last July, US government officials predicted that vaccine makers would produce 80–120 million doses by mid-October
2009, and public health agencies ramped up for a major vaccination drive. The government, along with vaccine producers, lost
considerable credibility when only 40 million doses were available in September, and some 20 million Americans had already
been hit by the new flu.
Health and Human Services (HHS) Secretary Kathleen Sebelius said she relied on industry predictions that turned out to be
wildly overly optimistic. Meanwhile, vaccine makers claimed they kept health officials informed of technical problems and
resulting delays at various steps in the manufacturing process.
The 2009 pandemic flu was supposed to demonstrate the viability of US government plans for responding to health emergencies.
The 2004 closure of a Chiron vaccine-manufacturing plant in Liverpool, England, which cut off half of the US flu vaccine supply
that year, had ignited concerns about the nation's ability to ramp up its emergency response to biological attacks and global
pandemics, resulting in multiple programs to deal with such crises.
Speedy production of the H1N1 vaccine, however, was hampered by a very tight development timeline. Manufacturers first had
to complete production of millions of doses of seasonal flu vaccine for the regular 2009 flu season. Even though scientists
had plenty of eggs to inject with the H1N1 seed virus in late May, vaccine production took longer than expected because the
yield in each egg was much lower than with the seasonal influenza viral strain, a problem not immediately recognized due to
difficulties developing a suitable potency test for the new product.
FDA received some of the blame for delays in providing an effective H1N1 vaccine, and Commissioner Margaret Hamburg admitted
to being disappointed and frustrated that the production process was not smoother. But she told the author in November that
she prefers to regard the response from FDA and industry as "quite remarkable in terms of how much has been mobilized in response
to a previously unrecognized strain of flu virus." Some of the disappointment may stem from over-optimism in predicting how
much vaccine would be available when. "Sadly, we know that it's the nature of manufacturing vaccines to have some unexpected
delays, and it's the nature of science to have unanticipated problems emerge."
One initial unknown was whether one dose would provide sufficient protection to patients, or if re-vaccination would be necessary.
Clinical-trial results indicated that the new H1N1 vaccine was sufficiently potent to support a single dose in adults and
two doses in young children. But low potency remained a problem for vaccine makers: AstraZeneca's (London) MedImmune had
to recall nearly 5 million doses of its nasal-spray vaccine in December 2009, while sanofi-aventis pulled 800,000 doses in
pre-filled syringes for young children.
By then, the flu plague was ebbing, and manufacturers faced a new problem: more vaccine than anyone wanted. Last month, the
French government moved to sell millions of doses to countries in the Middle East and Latin America and to cancel sizeable
orders from sanofi, GSK, Novartis (Basel, Switzerland), and Baxter (Deerfield, IL). Germany and other European countries quickly