On Aug. 27, 2004, Centers for Disease Control and Prevention Director Dr. Julie Gerberding held a press conference and made the following statement:
"Yesterday, Chiron announced that it would have a delay in the delivery of some doses of influenza vaccine because of some production problems related to sterility of a small number of doses in their manufacturing plant in Liverpool. … But it is a problem that we're staying on top of. And what we want to do today is help put this in context so people understand what they will need to do and what they can expect in October in terms of their flu vaccine. What we expect at this point in time is that actually we'll end up having more vaccine doses than we ever have had before."
Dr. Gerberding's meteoric rise within the CDC began when she came to the attention of Health and Human Services Secretary Tommy Thompson during the department's efforts in connection with the anthrax attack at the Capitol. Her failure to develop a realistic assessment of the magnitude of the flu vaccine problem, however, will have serious implications for millions of at-risk Americans, as will the ineptitude of the Food and Drug Administration in inspecting the troubled facility and taking the appropriate steps to ensure the manufacture of safe and usable doses of the vaccine.
Chiron Vaccine is a subsidiary of Chiron Corporation, an Emeryville, Calif., biotech research firm that has transformed itself into a vaccine producer in an attempt to raise its bottom line as the company waits for its biotech discoveries to work their way through the regulatory pipeline and on to the world market. Last year, Chiron completed the acquisition of PowderJect Ltd, a British vaccine manufacturing company with facilities in Liverpool. In June 2003, the U.S. Food and Drug Administration did a complete top to bottom inspection of the newly acquired Liverpool manufacturing facility.
The legal authority and responsibility of the FDA, the CDC, the Public Health Service and the secretary of Health and Human Services to ensure the safety and availability of vaccines is unequivocal. The surgeon general is empowered to "make and enforce such regulations as in his judgment are necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries…or from one state…into any other state." Further, the federal law requires that "any establishment within any foreign country engaged in the manufacture….of a drug or device register with the Secretary…" and empowers the secretary to block imports from such establishments if there is not adequate assurance of the safety and purity of the product. It was under that authority that the FDA entered the Liverpool plant in June 2003. Federal law also allows the secretary to stockpile a six-month supply of vaccine. The annual change required for preparation of an effective flu vaccine renders that authority useless in combating influenza and therefore makes the inspection authority all the more critical.
John Taylor, the FDA's associate commissioner for regulatory affairs, told the Wall Street Journal that the 2003 Liverpool inspection showed "systemic quality-control issues" at the Chiron facility. The Journal summarized Taylor's remarks by stating that FDA inspectors concluded, "Chiron wouldn't necessarily be able to discover problems, identify the root cause and take steps to prevent similar issues from arising again."
Remarkably, the FDA never returned to the plant and as a result had no first hand verification that its directives had been followed or that the facility could produce vaccine that would meet minimum safety standards. The FDA chose simply rely on the producer's assurances that adequate steps had been taken to correct the identified deficiencies. It was on that basis that enough vaccine to inoculate more than 46 million Americans went into production.
Even after Chiron announced on Aug. 27 that it had identified contamination issues in a portion of those doses, the FDA did not schedule an inspection. It was not until October, after Britain's Medicines and Healthcare Products Regulatory Agency (MHRA) inspected the plant and found systemic breakdown in quality control, that the true dimensions of the debacle began to emerge.
There is every reason to believe that regular reinspections by the FDA would have forced the needed changes and saved all of Chiron's 2004 flu vaccine production. But even if the FDA had not been able to meet that goal, it could at least have stayed on top of the problems inside the plant and been able to give public health authorities an early warning of the upcoming shortages.
While the failure of the FDA to request more than verbal or written assurances of safe practices from the producer raises serious questions as to the agency's due diligence, the lack of response following Chiron's announcement of the discovery of contaminated doses on Aug. 27 is even more extraordinary. Had the FDA responded quickly to that announcement, much of the potential risk we now face might have been averted.
Aventis Pasteur, the other producer of flu vaccine for the United States, manufactured a total of 55 million units for the 2004 flu season in the United States. By the time that the full dimensions of the Chiron problem were disclosed by British regulators on Oct. 5, almost 60 percent, or 30 million doses, had already been shipped. But the vast majority of those doses were not shipped before Aug. 27. Had either the FDA or the CDC taken the steps needed to get a complete and independent assessment of the potential magnitude of the problems in the Liverpool plant, perhaps as many as 20 to 25 million additional doses of vaccine could have been redirected to high-risk individuals, increasing the overall supply for such individuals from the current level of 22.4 million to somewhere between 40 and 50 million—enough to inoculate all high-risk persons expected to seek inoculation.
About two-thirds as many Americans die of influenza each year as die from all types of accidents. Three times as many die from influenza as the number who are victims of homicide. In 2001, the mortality rate from influenza was less than half the level that the nation experienced as recently as the 1960s. Influenza is too serious a problem to be treated in the lackadaisical manner in which the Public Health Service has dealt with it. Recently appointed senior leaders at the Food and Drug Administration have refocused the agency's energies toward giving pharmaceutical companies more latitude in the advertising claims they can make and helping them combat liability claims. It would have taken only a tiny portion of the resources put into those priorities to have permitted regular inspections of the troubled Chiron Liverpool plant.
Scott Lilly is a senior fellow at the Center for American Progress.