PANDEMIC SHORTAGE

Amidst all this progress, the initial H1N1 vaccine shortage in October brought home the perils involved in vaccine development and production. Last July, US government officials predicted that vaccine makers would produce 80–120 million doses by mid-October, and public health agencies ramped up for a major vaccination drive. Government leaders and vaccine producers suffered a sharp loss of credibility when it appeared that only 16 million doses would be available early in the fall. Health and Human Services (HHS) secretary Kathleen Sebelius said she relied on industry predictions that turned out to be wildly overoptimistic, while manufacturers claimed they kept health officials informed of technical problems and anticipated delays at every step in the production process.

The crisis prompted broad re-examination of vaccine manufacturing and product formulation. One culprit is the continued reliance of US manufacturers on chicken eggs to grow the influenza vaccine. The process took longer than expected with the H1N1 vaccine, and the yield was much lower than with seasonal flu vaccine, a problem not quickly recognized because of difficulties developing a suitable potency test for the new product.

European manufacturers overcame some of these problems by authorizing vaccines with adjuvants that require less antigen for each dose. Novartis and GSK have licensed pandemic flu vaccines with adjuvant in the EU, but these products still are being tested in the US. Former FDA official Scott Gottlieb, now with the American Enterprise Institute, would like the FDA to do more to make adjuvants more readily available as components for new vaccines and to spur development of new assays that can better detect impurities in vaccine batches and speed up the release of final products.

SPURRING INNOVATION

However the pandemic plays out, it is spurring more investment in vaccine manufacturing, testing, and regulatory initiatives. Novartis has received considerable government funding to establish a new facility to grow a flu vaccine in animal cells. Several small biotech firms such as Protein Sciences, Novavax, and FluGen are developing flu vaccines that use cell-based production systems.

The need to quickly develop and produce a vaccine to meet global health needs also is focusing attention on the vaccine regulatory process in the US and abroad. Although FDA officials garnered praise for being proactive in streamlining testing and data requirements for H1N1 vaccine candidates, vaccine makers would like to see a more coordinated international approval process. The WHO vaccine prequalification process takes approximately 18 months, in addition to all the work involved in licensing a product with the FDA or European authorities.

FDA officials are taking steps to encourage industry development of vaccines to counter global infectious diseases. The guidance issued in 2008 explains regulatory processes that can speed up the review of important treatments and clarifies that the FDA can and will license vaccines for use outside the US. The FDA recently was designated a WHO "reference" national regulatory authority, which enables it to facilitate WHO prequalification of vaccines for distribution to developing countries by United Nations agencies.

In this capacity, the Center for Biologics Evaluation and Research (CBER) can help manufacturers develop and license vaccines to protect against infectious diseases, including those not endemic in the US, explained CBER Acting Director Karen Midthun at a November conference on global vaccine development sponsored by the Drug Information Association. The FDA is working with the WHO to help build regulatory capacity in developing countries and participates in a number of advisory committees on vaccine development and safety, noted Marion Gruber, deputy director of the CBER's Office of Vaccines Research and Review. The agency further supports vaccine development by providing advice to manufacturers and regulatory authorities on assay validation, clinical trial design, statistical issues, and manufacturing challenges.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com