It seems hard to fix the nation's vaccine supply problems. The flu vaccine shortage of last fall turned into a surprising
surplus by January, as confusion and delays discouraged millions of Americans from lining up for a shot. Centers for Disease
Control and Prevention (CDC) director Julie Gerberding cited "unprecedented supply-and-demand mismatches" at the local level
as she encouraged broader distribution of more than five million unused vaccine doses before the flu season ends. The future
doesn't look very bright, though, as doctors and manufacturers remain uncertain about who will produce flu vaccine for next
year, what the supply will be, and who will want treatment.
Financial accounting rules are blocking manufacturers from providing vaccines for national stockpiles, while liability concerns
are discouraging investment in new products and manufacturing operations. Industry complains that increasingly stringent good
manufacturing practices (GMP) standards delay production and raise costs. Policy makers are weighing legislative proposals
to address some of these issues, but disagreement over legal and manufacturing issues may block speedy agreement on needed
In January of this year, CDC's National Vaccine Advisory Commission (NVAC) held a two-day workshop to examine perennial problems
jeopardizing the US vaccine supply. NVAC addressed many of these concerns three years ago and published a report in the Journal of the American Medical Association (JAMA, Dec. 17, 2003; 290: 3122-3128) outlining strategies to improve vaccine development and distribution. The report called
for policymakers to:
- expand vaccine stockpiles
- streamline the regulatory process
- increase support for the Food and Drug Administration
- strengthen liability protections
- improve communication and public information about vaccine benefits.
Unfortunately, not much has been done. CDC mounted a vigorous campaign to promote vaccine benefits, and manufacturers report
some success with a voluntary program to give FDA advance notice of plans to cease vaccine production. However, periodic vaccine
shortages continue, aggravated by steady industry consolidation: only four manufacturers produce routine childhood vaccines
in the US, with just one supplier per product.
Although regulators and manufacturers agree on the need for vaccine production facilities to meet rigorous quality standards,
industry executives complain that overly inflexible GMP requirements block innovation and expansion. At the workshop, Norman
Baylor of FDA's Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research (CBER), cited the
agency's two-year GMP modernization initiative for streamlining manufacturing regulatory processes, including the agency's
Team Biologics inspection program. He noted that CBER is encouraging fast-track and accelerated approval approaches to speed
innovative vaccines to market, but he also acknowledged that tight budgets are preventing the agency from doing much more
than meet required review goals and deal with the most pressing problems.
Manufacturers at the meeting agreed that CBER requires more resources to support a critical scientific base capable of dealing
with the technological advances that will shape future vaccine development. At the same time, they complained that regulatory
requirements aggravate supply problems and add to the cost and time needed to develop new products. Alan Shaw of Merck noted
that the agency is requiring larger and larger safety studies, which still are unlikely to reveal really rare adverse events.
Vax-Gen CEO Lance Gordon described how very costly it was to build a GMP-compliant plant to produce an anticipated 75 million
doses of its new recombinant anthrax vaccine. Escalating GMP requirements, Gordon observed, erect barriers to entry for smaller
biotech firms and make it hard to obtain clinical supplies for early studies.
Despite harmonization efforts, Peter Paradiso, vice president at Wyeth Vaccines, explained that US and EU manufacturing standards
still focus on different areas, prompting manufacturers to meet the most stringent requirements to avoid future problems.
He urged more balance between safety concerns and public health, with product specifications and requirements geared to enhancing