Regulatory Beat: Manufacturers Struggle with Vaccine Production and Supply

Regulatory standards, liability concerns, and accounting policies aggravate shortages and undermine innovation.
Mar 01, 2005
Volume 18, Issue 3

Jill Wechsler
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 changes.

SEEKING STRATEGIES 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.

MANUFACTURING HURDLES 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 product quality.

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