Status: withdrawn from the market

Organizations involved:

Parkedale Pharmaceuticals, Inc. – Manuf.; Former

King Pharmaceuticals, Inc. – Parent co.; Former

Mylan Laboratories Inc – Parent

Monarch Pharmaceuticals – USA mark.; Former

Parke-Davis Div. – R&D; Tech.; Former

Warner-Lambert Co. – Parent co.; Former

Cross ref: See Influenza Vaccine Products (entry #470).

Description: Influenza Virus Vaccine, Trivalent, Types A and B or Fluogen was a conventional trivalent split or subvirion influenza virus vaccine formulation. manufacture and marketing of this vaccine was halted in late Sept. 2000, prior to the 2000-2001 influenza season. Like other influenza vaccines, the product was manufactured from influenza virus cultured in fertile chicken embryos (eggs). manufacture included splitting of the cultured influenza virus particles and ether separation of the hemagglutinin (HA) and neuraminidase (NA) virus surface antigens.

The vaccine was supplied as a sterile liquid in 5 mL multiple dose vials (Steri-Vial), and in packages of ten 0.5 mL prefilled disposable syringes (Steri-Dose). The product was stored at 2-8˚C (refrigerated). The vaccine contained thimerosal (entry #939), a mercury-based antimicrobial preservative at a concentration of 0.01%.

Nomenclature: Influenza Vaccine/King [BIO]; Fluogen [TR reg. to Warner-Lambert Co.]; Influenza Virus Vaccine, Trivalent, Types A and B [FDA]; Influenza Virus Vaccine, Trivalent, Types A and B Subvirion Vaccine/Immunizing Antigen, Ether Extracted [FDA full name on product insert/labeling]; Influenza Virus Strains, (inactivated) [SY used on Parkedale MSDS]; NDC 64029-4099-1; NDC 64029-4099-2 [NDC]

Companies.: Fluogen was originally manufactured and marketed under this trade name by Parke-Davis Div., Warner-Lambert Co. (at its Parkedale, MI facility). The product, technology, and facilities were acquired in 1997 by Parkedale Pharmaceuticals, subsidiary of King Pharmaceuticals, Inc., which was acquired by Mylan Laboratories Inc. in 2004.

Parkedale/King halted all influenza virus vaccine manufacture in late Sept. 2000. The FDA had informed the company in early 2000 of violations of current Good Manufacturing Practice (cGMP) regulations and the company halted manufacture of Fluogen. The company subsequently resumed vaccine manufacture, but failed to receive FDA lot release approvals allowing marketing of its 2000-2001 influenza season’s supply of vaccine. King decided to permanently halt manufacture and marketing of this product, which it considered to have low profit margin and low growth potential. The company wrote off a loss of about $45 million for related property, plant, equipment, vaccine inventory, employee severance, and intangible assets.

Manufacture: The influenza virus strains were independently cultured in embryonated chicken eggs using an inocu-lum containing approximately 1 mg/mL of strep--to-mycin sulfate (antibacterial antibiotic). The allantoic fluid from the eggs containing the virus was removed (harvested), clarified by filtration and concentrated and refined by ultracentrifugation and zonal (density gradient) centrifugation. Polysorbate 80, USP, was added to the refined concentrate, resulting in disruption of the virus. Portions of the disrupted split virus and miscellaneous proteins are removed by solvent extraction with ethyl ether. Solvent extraction removed a high proportion of pyrogenic/reacto-genic substances (e.g., egg proteins), while retaining the influenza virus HA and NA components. The extracted concentrate was inactivated with formaldehyde, and the vaccine diluted to its final volume with phosphate-buffered-saline solution. Thimerosal was added at a concentration of 0.01%. Streptomycin was undetectable in the final product.

FDA class: Biologic PLA

CBER class: Viral And Rickettsial Vaccines

Approvals: Date = 19451126; 1st approval, PLA, granted to Parke-Davis division of Warner-Lambert Co.

Date = 19980821; approval revoked and reissued to new owner, Parkedale/King, formulation improvements, etc.

Status: Warner-Lambert Co. did not produce Fluogen for the 1997-1998 flu season. Supplementary approval was granted on Aug. 21, 1998, for the new owner, Parkdale/King, and formulation improvements. The product license was subsequently voluntarily revoked after King abandoned the product.

Market: For the 1999 calendar year, King reported $32 million gross sales and $28.7 net sales of Fluogen, with gross profit from Fluogen of $6.9 million.