FDA approves first seasonal influenza vaccine containing an adjuvant

November 24, 2015

The U.S. Food and Drug Administration approved Fluad, the first seasonal influenza vaccine containing an adjuvant. Fluad, a trivalent vaccine produced from three influenza virus strains (two subtype A and one type B), is approved for the prevention of seasonal influenza in people 65 years of age and older.

Description

FLUAD* is presented as a sterile, milky-white suspension for intramuscular injection in a prefilled syringe. It has been formulated to contain a total of at least 45 mcg hemagglutinin (HA) per 0.5 mL dose in the recommended ratio of 15 mcg HA of each of the following three influenza strains recommended for the 2012/2013 influenza season:

  • A/California/7/2009 (H1N1)pdm09-like virus (H1N1);
  • A/Victoria/361/2011 (H3N2)-like virus (H3N2); and
  • B/Wisconsin/1/2010-like virus,

as recommended annually for immunization by the World Health Organisation (WHO) and the National Advisory Committee on Immunization (NACI)

FLUAD* is a trivalent, surface antigen, inactivated influenza vaccine adjuvanted with MF59C.

The influenza virus strains are individually grown in the allantoic cavity of embryonated hens’ eggs inoculated with a specific type of influenza virus suspension containing kanamycin and neomycin sulphate. Each of the influenza virus strains is harvested and clarified separately by centrifugation and filtration prior to inactivation with formaldehyde. The inactivated virus is concentrated and purified by zonal centrifugation. The surface antigens, hemagglutinin and neuraminidase, are obtained from the influenza virus particle by further centrifugation in the presence of cetyltrimethylammonium bromide (CTAB), a process which removes most of the internal proteins. The CTAB is removed from the surface antigen preparation.

The MF59C.1 adjuvant contained in FLUAD* is an oil-in-water emulsion composed of squalene as the oil phase, stabilised with the surfactants polysorbate 80 and sorbitan trioleate, in citrate buffer.

Duration of Effect

The duration of post-vaccination immunity to homologous strains or to strains closely related to the vaccine strains varies, but it is usually 6-12 months.

STORAGE AND STABILITY

  • Store between 2 degree C and 8 degree C.
  • Do not freeze.
  • Do not use if vaccine has been frozen.
  • Protect from light.
  • Do not use vaccine after expiration date.

DOSAGE FORMS

Dosage Forms FLUAD* is a sterile milky-white suspension for intramuscular injection in 1 mL prefilled syringes containing a 0.5 mL dose.

Safety & Efficacy

Fluad was evaluated in a multicenter clinical trial conducted in the United States and internationally that compared the safety and immunogenicity (ability to generate an antibody response) of Fluad to Agriflu, an FDA-approved unadjuvanted trivalent seasonal influenza vaccine, in individuals 65 years of age and older. In that trial, 7,082 participants received either Fluad or Agriflu. The study showed that Fluad induced antibody levels that were comparable to the levels induced by Agriflu.

Safety was also evaluated in approximately 27,000 additional individuals 65 years of age and older. No safety concerns were identified with Fluad.

WARNINGS AND PRECAUTIONS

General FLUAD* should under no circumstances be administered by any other route than intramuscularly.

Immunization with FLUAD* should be postponed in patients with febrile illness or acute infections.

Hematologic:  careful consideration in patients with clinically significant bleeding disorders.

Immune: The immune response to FLUAD* in immunocompromised persons, including individuals receiving immunosuppressive therapy, may be lower than in immunocompetent individuals. Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.

Neurologic:  If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give FLUAD* should be based on careful consideration of the potential benefits and risks.

ADRs

The most common adverse events reported include injection site pain and tenderness, muscle aches, headache and fatigue. 

Fluad was approved using the accelerated approval regulatory pathway, which allows the FDA to approve products for serious or life-threatening diseases based on evidence that the product has an effect on an outcome that is reasonably likely to predict clinical benefit. In the case of Fluad, the antibody response to the vaccine provided this evidence. Under the accelerated approval requirements, a confirmatory study is required to verify and describe the clinical benefit of Fluad.

Fluad was first approved for use in Italy in 1997 and is currently approved in 38 countries, including Canada and 15 European countries. Fluad and Agriflu are manufactured by Novartis Vaccines and Diagnostics Limited, an affiliate of Novartis Vaccines and Diagnostics, Inc., based in Cambridge, Massachusetts.

Reference:

FDA News

Prescribing Information