How Influenza (Flu) Vaccines Are Made
There are three different influenza vaccine production technologies approved by the U.S. Food and Drug Administration (FDA):
All commercially available flu vaccines in the United States are made by private sector manufacturers. Different manufacturers use different production technologies, but all flu vaccines meet FDA safety and efficacy requirements. The different vaccines are approved with different indications. See Influenza Vaccines — United States, 2013–14 Influenza Season for specific indications.
The most common way that flu vaccines are made is using an egg-based manufacturing process that has been in existence for more than 70 years. Egg-based vaccine manufacturing is used to make both inactivated (killed) vaccine (usually called the “flu shot”) and live attenuated (weakened) vaccine (usually called the “nasal spray”).
The egg-based production process begins with CDC or another Influenza Collaborating Center providing private sector manufacturers with vaccine viruses grown in eggs per current FDA regulatory requirements. These vaccine viruses are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate. The virus-containing fluid is harvested from the eggs. For flu shots, the influenza viruses for the vaccine are then inactivated (killed), and virus antigen is purified. The manufacturing process continues with purification and testing. For the attenuated nasal spray vaccine, the viruses are weakened rather than killed and go through a slightly different production process. The manufacturers then put doses into vials, syringes, or nasal sprayers while waiting for FDA testing and approval to release lots. Each lot must be approved separately for release by the FDA prior to shipment.
There are many different manufacturers that use this production technology to make flu vaccines for use in the United States. This production method requires large numbers of chicken eggs to produce vaccine and usually takes the longest period of time to produce vaccine.
There also is a cell-based production process for flu vaccines, which was approved by FDA in 2012. This production process also begins with egg-grown vaccine viruses per FDA regulations. Manufacturers mix the vaccine viruses with cultured mammalian cells (instead of incubating them in eggs) and leave them to replicate for a few days. Then the virus-containing fluid is collected from the cells and the virus antigen is purified. The manufacturing process continues with purification and testing. Next the manufacturers put doses into vials or syringes, while waiting for FDA testing and approval to release lots.
Right now, there is just one FDA-approved cell-based flu vaccine in the United States. Cell-based flu vaccine production does not require large numbers of chicken eggs because the vaccine viruses used to make vaccine are grown in animal cells. This method takes slightly less time to manufacture vaccine than egg-based technology.
There is a third production technology for flu vaccines that was approved for use in the U.S. market in 2013 and that involves using recombinant technology. This production method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. Instead, manufacturers isolate a certain protein from a naturally occurring ("wild type") recommended vaccine virus (the HA protein, which induces an immune response in people). These proteins are then combined with portions of another virus that grows well in insect cells. This “recombinant” vaccine virus is then mixed with insect cells and allowed to replicate. The flu HA protein is then harvested from these cells and purified. The purified protein is packaged while waiting for FDA testing and approval to release lots. Recombinant flu vaccine is the only 100% egg-free vaccine on the U.S. market.
There are other vaccines on the U.S. market that use similar recombinant manufacturing processes. This process can produce vaccine in the shortest amount of time because it is not dependent on an egg supply or limited by the selection of vaccine viruses that are adapted for growth in eggs. There is one influenza vaccine produced using recombinant technology approved by the FDA for use in the United States at this time.
CDC and FDA monitor the safety of all vaccines licensed in the United States, including seasonal influenza vaccines. More information about the safety of egg-based, cell-based and recombinant influenza, including adverse events, contraindications and precautions, screening, and safe vaccine administration is available at Seasonal Influenza Vaccine Safety: A Summary for Clinicians.