The recommendations come after more than a year of public comment following the issue of two draft guidance documents by the FDA in March last year - one for seasonal and one for pandemic influenza vaccines.

The draft documents outlined specific approaches for manufacturers to develop new vaccines that were safe, pure and potent.

The final guidances reflect public input from vaccine companies and public health officials, with the goal of outlining the regulatory pathways for the rapid development and approval of these products.

In the light of a shortfall of available vaccines for seasonal influenza, and the impending threat of a bird flu pandemic, the administration encouraged ongoing investigations in improving the efficiency of vaccines and making a little go a long way.

Of note, the FDA recommended using recent technologies such as cell culture and recombinant manufacturing to enhance the development and evaluation of vaccines.

The administration also recommended the use of additional substances, such as novel adjuvants, that would improve the immune response and require a lower dose of the antigen.

The document stated: "An effective adjuvant might reduce the amount of antigen needed to elicit protective immune responses and may have other desirable properties such as cross protection against evolving strains and priming the immune system in a prepandemic setting. Data supporting the safety of the adjuvanted formulation must be submitted in the BLA (Biologics License Application) as well as clinical value of adding the adjuvant."

The documents also encouraged the investigation of alternative drug delivery systems which may reduce the amount of antigen while potentially expanding the available vaccination supply or increasing the ease and speed of programs.

The guidances described the approval pathways to vaccine licensure.

Companies seeking approval through the conventional pathway must provide clinical evidence that the vaccine prevents influenza.

Meanwhile, accelerated vaccine approval can be obtained by noting a clinical trial or using a biological indicator, such as an immune response to the vaccine, which would predict its effectiveness. Ongoing clinical studies would be required to verify the vaccines clinical benefit.

Manufacturers should submit a new BLA for the initial licensure of a pandemic or seasonal influenza vaccine to ensure that each pandemic and seasonal vaccine has its own trade name and labeling.

FDA Center for Biologics Evaluation and Research (CBER) director Jesse Goodman said in a statement: "FDA continues it commitment to help increase the supply of influenza vaccines and support the development of new approaches to vaccine production.

"Having additional manufacturers of licensed influenza vaccines will enhance the capacity to produce more doses of seasonal influenza vaccines, as well as contribute to the nation's pandemic preparedness, one of our top priorities."

The World Health Organization (WHO) estimates global flu vaccine capacity is at fewer than 400 million doses a year, and current demand hitting 300 million doses a year. WHO claims the industry is woefully under-prepared for a pandemic that could shoot demand up by 20 times.

About 200,000 people are hospitalized in the US every year with influenza. An additional 36,000 people die annually from the disease.

If a pandemic occurred without a vaccine, the WHO estimates that at least 50 million people could die. In the 1918-1919 Spanish flu outbreak, 50 million people died.

Currently, GlaxoSmithKline (GSK), Sanofi-Aventis, Novartis and MedImmune manufacture seasonal influenza vaccines for the US.

In April, Sanofi-Aventis won US approval for a vaccine against the H5N1 avian virus strain. GSK and Novartis are working on their own vaccines for the strain.