Selecting the Strain
In February of each year, the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) review surveillance data on circulating influenza viruses and select three strains to include in influenza vaccine for the flu season, which begins in November. Next, according to the FDA, manufacturers licensed and approved by the FDA apply for reference strains of each of the influenza viruses from WHO Collaborating Centers. These references strains are used as "seed" to produce the vaccine.
Growing the Virus
According to the FDA, these "seed" strains are grown in fertilized chicken eggs. Antibiotics including kanamicin, gentamicin, neomycin and polymixin B are usually used to prevent bacterial contamination. Using antibiotics improves the yield of batches because there are no contaminated eggs to discard; however, many people are allergic to antibiotics. For the 2009-2010 vaccine, two manufacturers, Sanofi Pasteur (Fluzone) and ID Biomedical (Flulaval), did not use antibiotics.
Purification of Virus
After the virus has been allowed to replicate in the chicken eggs, it is recovered and purified from other components of the eggs. Manufacturers use detergents such as sodium taurodeoxycholate, a salt found in human bile, to solubilize the contents of the eggs. Then the solution is ultra-centrifuged using a technique known as a "sucrose density gradient" to separate the components of the solution by density. Viruses are composed of nucleic acids that are much denser than all other components of the eggs and settle out at their own level. Sometimes trace amounts of eggs, detergent, and sucrose can still be found in the final vaccine. Each manufacturer's product literature includes an overview of this process and information on the specific detergent as a warning for people with allergies.
Inactivation of Virus
Since injectible influenza vaccines use inactivated virus, the virus must be inactivated (rendered unable to cause infection). According to the manufacturers' literature, for the 2009-2010 seasonal flu vaccine manufacturers used either beta-propioloactone or formaldehyde for this purpose. Trace amounts of the compound are present in the final vaccine. Flu Mist, an intranasal vaccine, uses live virus and does not undergo this step.
Formulation of Vaccine
The FDA says purified virus is next diluted into standard doses using sterile phosphate-buffered salt solutions in a concentration similar to bodily fluids. It is then added to bottles, prefilled syringes and nasal spray containers. Thimerisol, a mercury-based compound, is added to all multidose containers as a preservative.
Quality Control and Lot Release
Each batch or "lot" undergoes rigorous quality control testing to ensure it meets FDA standards for safety, efficacy and stability prior to distribution. Lots are also carefully labeled in case problems are identified after the vaccine has been distributed. Lots cannot be shipped until they are formally released by the FDA; the FDA maintains an updated list of released lots by manufacturer on its website.
