Licensing Of Seasonal Influenza Vaccines
The Food and Drug Administration is responsible for regulating vaccines in the United States. Licensure of seasonal influenza vaccines follows the same general approach as licensure of other vaccines and has been described previously. Licensure may be obtained either through a traditional approval pathway or by the accelerated approval mechanism. Both pathways share similar requirements for demonstration of product safety and consistency of vaccine manufacturing. Traditional approval provides prelicensure evidence of efficacy from clinical trials in which influenza illness is assessed as the primary endpoint. Recent examples of influenza vaccines that have been approved by the traditional pathway include Flucelvax® in 2012, an inactivated trivalent vaccine produced in cell culture by Novartis Vaccines and Diagnostics, Inc. , and Flublok® in 2013, a recombinant protein vaccine manufactured by Protein Sciences Corporation.
Evaluation of the vaccineinduced immune response in the clinical disease endpoint efficacy studies is important to potentially extrapolate vaccine effectiveness to populations not included in the efficacy trial. For example, persons 659 months of age and those 65 years of age and older may not have been included in efficacy studies because of ethical concerns related to conducting placebocontrolled efficacy studies in populations for which influenza vaccines are recommended. In such populations, effectiveness can be based on immunogenicity endpoints.
Licensure Of Monovalent Seasonal Influenza Vaccines
Prior to 1978, inactivated seasonal influenza vaccines were monovalent and bivalent since 1978, most US licensed influenza vaccines have been trivalent incorporating two influenza A subtype viruses and an influenza B virus. More recently, quadrivalent inactivated influenza vaccines containing an additional influenza B virus antigen have been licensed. However, monovalent seasonal influenza vaccines have also been licensed as supplemental vaccines to a manufacturer’s existing influenza vaccine license. For example, in 1986, a newly emerged antigenic variant of influenza A H1N1, A/Taiwan/1/86, began to circulate among the human population, which had little prior immunity, and this virus was poorly inhibited by antibodies induced by previously circulating H1N1 strains. Because of the novel characteristics of this H1N1 virus, a monovalent influenza A/Taiwan/1/86 H1N1 was approved as a supplemental vaccine to each manufacturer’s license application and recommended for use. As discussed below, a similar regulatory approach was used in 2009 in response to the emergence of the 2009 H1N1 pandemic virus.
Influenza Vaccines And How They Are Made
Influenza 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 seasons 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.
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How Influenza Vaccines Are Made
For the United States there are three different influenza vaccine production technologies approved by the U.S. Food and Drug Administration external icon:
- egg-based flu vaccine,
- cell-based flu vaccine, and
- recombinant flu vaccine.
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 effectiveness requirements. Different vaccines have different indications. See Different Types of Flu Vaccines for more information.
Fda Approves Recombinant Flu Vaccine
The agency’s approval of the first seasonal flu vaccine made of recombinant proteins rather than inactivated or weakened virus comes as emergency rooms are clogged with victims of an early and severe flu season
The US Food and Drug Administration has approved the first seasonal flu vaccine comprised of recombinant proteins, rather than inactivated or weakened virus.
The 16 January approval of Flublok, developed by Protein Sciences Corporation in Meriden, Connecticut, arrives as US emergency rooms are clogged with victims of an early and severe flu season. Thirty states are reporting high levels of flu-like illness this season, and New York state and the city of Boston have declared public health emergencies. Vaccine supplies are dwindling.
Flublok is one of a new wave of flu vaccines intended to make production more nimble. The three influenza hemagglutinin proteins comprising Flublok are made in insect cells rather than in chicken eggs, the classical incubator for seasonal flu vaccine. It is the second egg-free vaccine to be approved by the FDA. In November, the agency approved Flucelvax, made by the Swiss pharmaceutical firm Novartis.
Flublok will be out on the market in full force in time for the 2013-2014 flu season, and limited supplies will be available to help out during the current season.
This article is reproduced with permission from the Nature News Blog. The article was first published on January 17, 2013.
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Whos Most At Risk Of Getting The Flu
Typically, children and older people are most at risk of getting sick with influenza. The best way to protect babies who are too young to be vaccinated is to make sure people around them are vaccinated. Occasionally, a flu virus will circulate that disproportionately affects young and middle-age adults.
You also can reduce the spread of the flu and its effects by taking such practical measures as washing your hands, covering coughs and sneezes, and staying home when youre sick.
The FDA has approved numerous vaccines for the prevention of influenza. But if you do get the flu, there are FDA-approved antiviral drugs, available by prescription, to treat your illness. There are several FDA-approved antiviral drugs recommended by the CDC for use against circulating influenza viruses. These drugs work best if started soon after the onset of symptoms .
How Flu Vaccine Virus Strains Are Selected
Every year, in late February or early March, before that years flu season ends, the FDA, the World Health Organization , the CDC, and other public health experts collaborate on collecting and reviewing data from around the world to identify the flu viruses likely to cause the most illnesses during the next flu season.
Following that process, the FDA convenes its vaccines advisory committee, consisting of outside experts, to discuss the WHO recommendations and to consider which flu viruses are expected to circulate in the U.S. The committee also reviews data about which flu viruses have caused illnesses in the past year, how the viruses are changing, and disease trends for the U.S. The FDA takes that information into account before it selects the virus strains for FDA-licensed manufacturers to include in their vaccines for use in the U.S.
The closer the match between the virus strains chosen for the vaccine and the circulating strains causing disease during flu season, the better the protection that the flu vaccine provides. Although the vaccine and viruses may not be an exact match in some years, that does not mean the vaccine is not benefiting people. Available data show that the vaccine can reduce the severity of illness in people who get vaccinated but still get sick.
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Seqirus Receives Fda Approval Of Its Cell
– Approval aligns with universal age recommendation for all eligible people six months and older to receive annual influenza vaccination
– Cell-based influenza vaccines are designed to produce an exact match to the World Health Organization -selected influenza virus strains,
– This approval reinforces the value of this innovative influenza vaccine technology as part of Seqirus’ mission to help protect as many eligible people as possible against influenza, especially in light of the ongoing COVID-19 pandemic
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Evergreen Flu Vaccine Ingredients: The Preservatives And Additives
Beyond the three to four viral components, a number of additives and preservatives are required to make vaccines effective and to keep them from going bad. These ingredients, sometimes covered as trade secrets by drug companies in less public drugs, have led to many a conspiracy theory that anti-vaxxers would have you latch onto. Its really much more boring than that.
Here are some of the ingredients you will find in the 2021-2022 flu vaccine and why theyre there.
The Ingredient: Aluminum Salts
Use: Boosts bodys response to the vaccine
The Ingredient: Sugar or gelatin
In: Most vaccines
In: Few flu vaccines only multi-dose vials
The CDC says: Thimerosal has a different form of mercury than the kind that causes mercury poisoning . Its safe to use ethylmercury in vaccines because its processed differently in the body and its less likely to build up in the body and because its used in tiny amounts. Even so, most vaccines do not have any thimerosal in them.
The Ingredient: Egg proteins
In: Some vaccines
Use: Growing the vaccine
The CDC says: Because influenza and yellow fever vaccines are both made in eggs, egg proteins are present in the final products. However, there are two new flu vaccines now available for people with egg allergies.
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A Closer Look At The Safety Data
Findings from vaccine safety monitoring systems and scientific studies have shown that the flu vaccines have an excellent safety profile. Hundreds of millions of Americans have safely received flu vaccines for more than 50 years and the body of scientific evidence overwhelmingly supports their safety.
The safety of flu vaccines is monitored by CDC and FDA. Certain safety outcomes are commonly evaluated, including Guillain-Barré Syndrome, maternal and infant safety, and febrile seizures.
The data on an association between seasonal inactivated influenza vaccine and GBS have been variable from season-to-season. When there has been an increased risk, it has been in the range of 1-2 additional GBS cases per million flu vaccine doses administered. The data also indicate that a person is more likely to get GBS after flu disease than after getting a flu vaccine. Learn more about Guillain-Barré Syndrome.
Maternal and Infant Safety
Pregnant women are considered at high risk for developing serious complications from flu. Several studies have shown that influenza vaccination can protect pregnant women during and after pregnancy and protect the baby from influenza infection for several months after birth. More information on flu vaccine effectiveness in pregnant women and their babies.
Northern Hemisphere Influenza Season
The composition of trivalent virus vaccines for use in the 2017â2018 Northern Hemisphere influenza season recommended by the Advisory Committee on Immunization Practices on August 25, 2017, was:
- an A/Michigan/45/2015 pdm09âlike virus
- an A/Hong Kong/4801/2014 -like virus
- a B/Brisbane/60/2008âlike virus
In addition to these components, quadrivalent vaccines will also include a B/Phuket/3073/2013âlike virus .
In California, some emergency systems were strained by a spike in H3N2 flu cases. In addition, some areas experienced local shortages of oseltamivir. The severity of the flu season seemed somewhat comparable to the 2009â10 swine flu outbreak. A February 2018 CDC interim report estimated the vaccine effectiveness to be 25% against H3N2, 67% against H1N1, and 42% against influenza B.
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Fda Approves First Flu Vaccine Grown In Insect Cells
Flublok, a trivalent vaccine developed by Protein Sciences Corp. of Meriden, Conn., was approved for adults ages 18 through 49. The only flu virus component it contains is hemagglutinin, the active ingredient, which is produced by infecting cultures of insect cells with a baculovirus that turns them into hemagglutinin factories.
Most flu vaccines use viruses grown in chicken eggs. However, in November the FDA approved Novartis’s Flucelvax, which uses flu viruses grown in mammalian cells, making it the first vaccine of its kind to gain US approval.
Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research, called Flublok a technological advance. “The new technology offers the potential for faster startup of the vaccine manufacturing process in the event of a pandemic, because it is not dependent on an egg supply or on availability of the influenza virus,” she said in an FDA press release.
But the vaccine is similar to other licensed flu vaccines in that it uses hemagglutinin as the active ingredient or immune system target, according to a recent major report on flu vaccines. A number of flu experts have said that new kinds of flu vaccines with novel antigens are needed in order to provide broader, more enduring protection than today’s vaccines, which must be reformulated each year to keep pace with viral mutations. Today’s vaccines are generally about 60% effective in working-age adults.
Regulatory Experience And Challenges With New And Novel Influenza Vaccines
As noted earlier, current influenza vaccines are neither rapidly produced, nor ideal in terms of protection. Consequently, significant effort has been expended toward developing and approving improved vaccines, for example, development of quadrivalent vaccines containing antigens from two influenza B virus lineages, cell cultureproduced vaccines, recombinant proteinbased vaccines, and adjuvanted vaccines.
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Table 1 Influenza Vaccines United States 202021 Influenza Season*
|Trade name||HA or virus count for each vaccine virus||Route|
|Standard dose, cell culture based|
|High dose, egg based|
|Fluzone High-Dose Quadrivalent|
|Standard dose, egg based with MF59 adjuvant|
|Standard dose, egg based with MF59 adjuvant|
|0.2-mL prefilled single-use intranasal sprayer||2 through 49 yrs||106.5-7.5 fluorescent focus units/0.2 mL||NAS|
Abbreviations: ACIP = Advisory Committee on Immunization Practices FDA = Food and Drug Administration HA = hemagglutinin IIV3 = inactivated influenza vaccine, trivalent IIV4 = inactivated influenza vaccine, quadrivalent IM = intramuscular LAIV4 = live attenuated influenza vaccine, quadrivalent MDV = multidose vial NAS = intranasal PFS = prefilled syringe RIV4 = recombinant influenza vaccine, quadrivalent SDV = single-dose vial.
* Vaccination providers should consult FDA-approved prescribing information for 202021 influenza vaccines for the most complete and updated information, including indications, contraindications, warnings, and precautions. Package inserts for U.S.-licensed vaccinesexternal icon. Availability and characteristics of specific products and presentations might change and/or differ from what is described in this table and in the text of the full report.
§ The dose volume for Afluria Quadrivalent is 0.25 mL for children aged 6 through 35 months and 0.5 mL for persons aged 3 years.
Influenza Vaccine News 2021
– A non-peer-reviewed study involving influenza-vaccinated people’s airway cells suggests that a unique H3N2 clade is circulating has differences from key antigenic sites on the hemagglutinin protein of the H3N2 vaccine strain.
– Emergent BioSolutions Inc. announced the first participant dosed in its phase 1 study, EBS-UFV-001, evaluating the safety, tolerability, and immunogenicity of the company’s investigational universal influenza vaccine candidate. This current version contains multiple components intended to induce broad and supra-seasonal immunity against influenza A viruses.
– The journal Cell Host and Microbe published an article: Human influenza virus challenge identifies cellular correlates of protection for oral vaccination. The study demonstrated that VXA-A1.1, an investigational oral tablet flu vaccine under development by Vaxart, Inc., had cellular correlates of protection against influenza infection.
– The Lancet published results of a Phase 4 study confirming that concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines.
– H. Keipp Talbot, M.D., MPH, Chair, ACIP, Influenza Work Group, presented a ‘Seasonal Influenza Vaccine’ overview. And, ‘Change in Age Indication for Flucelvax Quadrivalent’ was presented by Lisa Grohskopf, M.D., MPH.
– The WHO recommended influenza virus vaccine composition in the 2021 – 2022 northern hemisphere influenza season.
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Myth: The Fda Determines When A Manufacturer Applies For Approval
While the FDA determines if a vaccine qualifies for FDA approval and sets nonbinding guidelines for manufacturers to follow, its not entirely up to the organization to decide when. That timeline is first determined by the manufacturers of the products seeking FDA approval.
Manufacturers decide whether and when to submit a request for authorization or for approval, an FDA spokesperson said in a statement to HuffPost. Then the review process starts.
In the midst of the pandemic, the vaccine manufacturers chose to first apply for FDA emergency use authorization before applying for FDA approval. While an EUA is not usually a prerequisite before applying for approval, the FDA spokesperson said pharmaceutical companies did the right thing by applying for an EUA before applying for approval while the pandemic is still considered a public health emergency. In this case, authorization simply precedes approval, similar to how the FDA granted an EUA for the COVID-19 antiviral drug remdesivir six months before it gained FDA approval in October.
Latest Cold And Flu News
WEDNESDAY, Jan. 16 — The U.S. Food and Drug Administration has approved a novel type of flu vaccine, the agency announced Wednesday.
Flublok, as the vaccine is called, does not use the traditional method of the influenza virus or eggs in its production. Instead, it is made using an “insect virus expression system and recombinant DNA technology,” the FDA said in a news release. This will allow vaccine maker Protein Sciences Corp., of Meriden, Conn., to produce Flublok in large quantities, the agency added.
The vaccine is approved for use in those aged 18 to 49.
“This approval represents a technological advance in the manufacturing of an influenza vaccine,” said Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research. “The new technology offers the potential for faster start-up of the vaccine manufacturing process in the event of a pandemic, because it is not dependent on an egg supply or on availability of the influenza virus.”
While the technology is new to flu vaccine production, it has been employed in the making of vaccines that prevent other infectious diseases, the agency noted.
The new flu vaccine could not have come at a better time, with the flu season well under way and sporadic shortages of both the traditional flu vaccine and the flu treatment Tamiflu.
She said that people who already have the flu may also be experiencing local shortages of Tamiflu.
— Robert Preidt
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