Influenza Virus Vaccine Package Insert

In my previous post, I discussed the strains of influenza virus that are targeted by this flu season’s vaccine, as well as an overview of the nomenclature behind those strains. Although I like to ask for a physical copy of the package insert to see what strains are included in each year’s vaccine, one can find the exact same information on DailyMed which is the official provider of FDA label information and leverages the Structured Product Labeling (SPL) document markup standard to display drug information.

Since October 31, 2005, the U.S. Food and Drug Administration (FDA) has required drug manufacturers to submit documentation about their products in SPL format. Before that, most people looked up drug information in annual hardcopy editions of the Physicians’ Desk Reference (which I have more recently repurposed as a monitor stand). DailyMed also launched in 2005 and displays the contents of SPL documents. Here is the package insert for the flu shot that I received yesterday: FLULAVAL QUADRIVALENT 2020/2021- influenza virus vaccine suspension.

Using this flu vaccine as an example, a structured product label includes standard document sections for Indications and Usage, Dosage and Administration, Dosage Forms and Strengths, and many other categories. If you look closely, you’ll notice that the information on DailyMed is exactly the same as what is printed on the hardcopy of the package insert. The Description section is where I found the 4 strains of influenza virus that are targeted by the 2020/2021 vaccine. Note that this pertains only to the flu vaccine made by this particular manufacturer, and different vaccine manufacturers may put different antigens into their vaccines. Here’s an overview of the flu vaccines and their manufacturers for this season.

The Clinical Studies section describes clinical trials that examined the efficacy and safety of the vaccine. It describes study designs, control groups, infection rates across groups, adverse effects, immunological responses, and much more. This is the scientific evidence showing us that the vaccine works, and just as importantly, that it is safe to administer. Safety is particularly important because unlike most other drugs that are used to treat illnesses, vaccines are given to large populations of healthy individuals to prevent disease, so to ensure that there is a net benefit, the safety profile must be extremely favorable.

Note that there are options to view printer-friendly versions, patient-friendly versions, and versions in PDF and XML. If interested, you can also download the entire set of package insert data for all drugs.

If you want to explore the package insert information for any other drug, just enter the drug name in the search. It understands generic and brand names. Just be aware that the package inserts are based not on ingredients but rather a combination of ingredient and other characteristics such as the dosage (the strength of each unit) and dosage form (e.g., tablet, extended release capsule, rectal suppository) depending on the drug, as this may impact the prescribing information that is contained on each label. Perhaps this will be the topic of a future post.

Influenza Viruses and Vaccines: What’s in a Name?

Yesterday our family got our annual flu shots. Since influenza virus constantly mutates, the influenza virus vaccine varies from year to year. Scientists try to predict which strains of influenza virus will result in the greatest number of cases, and they create vaccines to target those strains.

Out of curiosity, I usually ask the nurse to give me a copy of the package insert. Also referred to as a “drug label” or “FDA label” or other names, the package insert is the document that is created by the drug manufacturer and describes indications, contraindications, dosing, side effects, and other information relevant to the drug. Sometimes nurses refuse to give me the package insert, sometimes they make up excuses (e.g., “We don’t have it”), and sometimes they gladly give me a copy. Yesterday I was given a copy of the package insert for the 2020/2021 influenza virus vaccine:

As you can see, this package insert is quite lengthy, as are most package inserts. And as you could guess, most people don’t read them. But I am not like most people—I do uncommon things like write blog posts (that most people don’t read).

In any case, the reason for my interest in reading the package insert is to find out which strains of influenza virus the vaccine is designed to combat this year. For the 2020-2021 flu season, we are targeting the following 4 influenza virus strains (2 A strains and 2 B strains):

• A/Guangdong-Maonan/SWL1536/2019 (H1N1) CNIC-1909
• A/Hong Kong/2671/2019 (H3N2) NIB-121
• B/Washington/02/2019 (B-Victoria lineage)
• B/Phuket/3073/2013 (B-Yamagata lineage)

I’ll try to explain some of the nomenclature. The “A” and “B” refer to one of the 4 types of influenza virus. Influenza virus A and B viruses are the most common causes of seasonal influenza in humans, and some strains are included in the vaccine as described above. Influenza virus A (but not B) can cause flu pandemics, depending on viral characteristics. Influenza virus C also causes flu in humans, but illnesses are generally mild. Influenza virus D infects cattle but is not thought to cause human illnesses.

Influenza A viruses have 2 surface proteins that are important to characterize: hemagglutinin (H) and neuraminidase (N). There are 18 H subtypes (H1 to H18) and 11 N subtypes (N1 to N11), yielding 198 permutations of H and N proteins, of which 131 combinations have been found in nature.

Influenza B viruses also have H and N surface proteins, but for classification purposes, they are subdivided into one of 2 antigenically distinct lineages: Victoria and Yamagata.

Both influenza A and B viruses can be further subdivided into clades (groups) and sub-clades (sub-groups) based on the genetic codes behind the H surface proteins, and this sub-classification allows us to track which specific viruses are in circulation.

As you can see from the names of the virus strains, there are city names that indicate where the virus was isolate, and there are numbers that indicate the strain of the virus and the year they were isolated. For more information about the nomenclature of influenza viruses, check out this memorandum from the World Health Organization, and click on the free full text link if you want to see a PDF version of the full memorandum.

Because the H1N1 and H3N2 strains of influenza virus A are prevalent, the influenza virus vaccine usually contains antigens that resemble their structures. The vaccine also contains one or two influenza B virus antigens. I hope this sheds some light on what’s in this year’s flu vaccine.

In my next post, I’ll continue this discussion by focusing on the package insert of the influenza virus vaccine.