FDA's Critical Role in Ensuring Supply of Influenza Vaccine

The flu vaccine you get at your doctor’s office or pharmacy is the year-round work of highly skilled microbiologists, epidemiologists, physicians and other public health experts.

Sound complicated? It is.

The U.S. Food and Drug Administration (FDA) and the U.S. Department of Health and Human Services (HHS) are working toward developing new and better technologies for producing flu vaccines. As new strains of flu viruses emerge, the FDA works in close coordination with sister agencies, such as the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), encouraging manufacturers to develop vaccines that will successfully protect us from influenza disease, which can be a very serious illness.

The more diverse the influenza vaccine supply, the better we can respond to flu public health emergencies in a timely manner. All U.S. licensed flu vaccines have been evaluated and determined to be safe and effective by the FDA.

There is often more than one type of influenza virus circulating each season, so influenza vaccines are formulated to target three or four of the most likely influenza viruses of the season: two influenza A types (H1N1 and H3N2) and one (trivalent vaccine formulation) or two (quadrivalent vaccine formulation) types of influenza B.

Influenza Vaccines and How They Are Made

Influenza (flu) vaccine works by triggering your immune system to produce antibodies that help the body prevent the flu.

Most of the U.S. influenza vaccine supply is made using an egg-based production process. In this method of making influenza vaccines, manufacturers use fertilized eggs to grow flu viruses. After about six months of laboratory work and manufacturing, those viruses are incorporated into that season’s flu vaccine. While this method produces safe and effective vaccines, FDA, HHS, and manufacturers have been working on different technologies to increase the influenza vaccine supply, making sure to still maintain safety and effectiveness. Some technologies have the potential to produce these vaccines faster and less labor-intensively.

For example, more recent approvals include influenza vaccines that do not use an egg-based production process for manufacturing. In addition, quadrivalent vaccines, which protect against two influenza A strains and two influenza B strains, have been available for several years. Quadrivalent vaccines provide protection against the two lineages of influenza B strains, both of which circulate each flu season. This is important, particularly for preschool and school-age children who get Influenza B more often than adults do. Influenza B also causes more complications and fatalities in children than adults.

In addition, the FDA has approved a high-dose and an adjuvanted vaccine specifically for people ages 65 and older, who typically bear the greatest burden of severe influenza disease and account for most of influenza-related hospitalizations and deaths. Adjuvants are incorporated into some vaccine formulations to enhance the immune response of the vaccinated individual.

Making the Flu Vaccine: A Year-Round Effort

The job of producing a new vaccine for the next flu season starts well before the current flu season ends. For the FDA, it’s a year-round initiative.

The composition of vaccines for the prevention of other infectious diseases stays the same year after year. In contrast, flu viruses are constantly evolving. And the flu viruses that circulate causing disease in people, often change from one year to another. So, every year, there is a need for a new flu vaccine. To that end, FDA, World Health Organization (WHO), CDC, and other partners collaborate by collecting and reviewing data on the circulating strains of influenza from around the world to identify those likely to cause the most illness in the upcoming flu season.

In late February/early March — well before the new flu season begins — an FDA advisory committee reviews data about which flu viruses have caused disease in the past year, how the viruses are changing, and disease trends so they can recommend the three or four flu strains to include in the trivalent and quadrivalent influenza vaccines for the U.S in the upcoming flu season.

Once the strains are selected, vaccine manufacturers begin the manufacturing process to include the newly selected flu strains in their FDA-approved vaccines. The different flu virus strains are combined to formulate the vaccine into standard dosages. The vaccine is then filled into vials, syringes and, for the nasal vaccine, sprayers. Both egg-based and non-egg-based manufacturing methods for FDA-approved flu vaccines require high-tech processes and manufacturing facilities that have been inspected by the FDA. Vaccine manufacturers must submit applications to the FDA to include the new flu strains in their FDA-approved vaccines.

In its own laboratories, the FDA also produces materials that are critical for making the vaccine. These include generating candidate vaccine virus strains suitable for further vaccine manufacture and producing the critical potency reagents, which are materials needed to test the vaccines for potency and identity (to ensure standardization) before the FDA approves the new formulation of the approved seasonal influenza vaccines for U.S. distribution.

The FDA is also responsible for ensuring that released lots of influenza vaccines meet appropriate standards. Each vaccine undergoes quality control tests, including testing for sterility. Manufacturers submit the results of their testing, along with sample vials from each lot to the FDA for “lot release.” The FDA typically begins releasing lots of flu vaccines in late summer. Lot release can continue into early fall. Once lots are released, manufacturers distribute the vaccine throughout the United States for use by the public.

Flu seasons and severity are unpredictable. Annual vaccination is the best way to prevent the flu for people ages 6 months and older.

An annual immunization with flu vaccine is the most effective and safest way for most of us to reduce our risk of getting the flu and spreading it to others. When more people get vaccinated, it is less likely that the flu viruses will spread through a community, making us all healthier.

Updated: March 1, 2019