Status: approved; marketed

Organizations involved:

Abbvie – Manuf.; R&D; World mark.

Abbott Laboratories – Former

Mitsubishi-Tokyo Pharm. Co. - R&D; Tech.

ONY, Inc. – Patent dispute

Forest Pharmaceuticals, Inc. – Patent dispute

Cross ref.: See Lung Surfactant Products (entry #940).

Description: Beractant Intratracheal Suspension or Survanta is an aqueous formulation of organic solvent-extracted post-mortem bovine (calf) lung surfactants containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins to which colfosceril palmitate (dipalmitoylphosphati-dyl-choline; DPPC), palmitic acid, and tripalmitin are added to standardize the composition and better mimic the surface-tension lowering properties of natural human lung surfactant. Survanta’s active protein content consists of two hydrophobic, low molecular weight, surfactant-associated proteins commonly known as SP-B and SP-C. Survanta does not contain the hydrophilic, large molecular weight surfactant-associated protein known as SP-A. The product contains 25 mg/mL phospholipids (including 11.0-15.5 mg/mL disaturated phosphatidylcholine), 0.5-1.75 mg/mL triglycerides, 1.4-3.5 mg/mL free fatty acids, and less than 1.0 mg/mL protein. These components are suspended in 0.9% sodium chloride solution, and heat sterilized (pasteurization).

Survanta is packaged in single-use vials containing 8 mL. Each milliliter contains 25 mg of phospholipids (200 mg phospholipids/8 mL) suspended in 0.9% sodium chloride solution. Survanta contains no preservatives. Vials are stored at 2-8˚C (refrigerated).

Note, derived from dead tissue, with no live organisms or bioprocessing involved, Beractant is not considered by this author to be a biopharmaceutical.

Nomenclature: Survanta [TR]; Beractant [FDA]; bovine lung surfactants [SY]

Companies.: Survanta was developed and is manufactured and marketed by the Ross Products Div., Abbott Laboratories. On Jan. 1, 2013, Abbott Labs. spun off its innovative pharmaceuticals business to Abbvie.

FDA class: Drug NDA

Approvals: Date = 19910701; NDA, first approval, orphan designation (expired)

Indications: [full text of the "INDICATIONS AND USAGE” section from product insert/labeling]:

SURVANTA is indicated for prevention and treatment (“rescue”) of Respiratory Distress Syndrome (RDS) (hyaline membrane disease) in premature infants. SURVANTA significantly reduces the incidence of RDS, mortality due to RDS and air leak complications.

Prevention: In premature infants less than 1250 g birth weight or with evidence of surfactant deficiency, give SURVANTA as soon as possible, preferably within 15 minutes of birth.

Rescue To treat infants with RDS confirmed by x-ray and requiring mechanical ventilation, give SURVANTA as soon as possible, preferably by 8 hours of age.

Tech. transfer: U.S. patents covering aspects of Survanta were exclusively licensed by Abbott from Mitsubishi-Tokyo Pharmaceuticals Co. (formerly Tokyo Tanabe Co.). These include U.S. 4,338,301, “Lung tissue extract useful for treating hyaline-membrane disease and method for producing the extract,” July 6, 1982; 4,397,839; and 4,603,124 (and also 5,827,825) concerning bovine-derived lung surfactant-based compositions (including Survanta). Claim 1 of 4,338,301 states, “Surface active material containing phospholipid, neutral lipid, total cholesterol, carbohydrate, protein and water, which material is obtained from lung tissue of a mammal with or without further phospholipid, characterized in that the phospholipid content is 75.0-95.5%, the neutral lipid content is 1.8-14.0%, the total cholesterol content is 0.0-3.0%, the carbohydrate content is 0.1-1.5%, the protein content is 0.5-5.0% and water content is 1.7-6.0%, all based on the dried weight of said material, the minimum and maximum surface tension ranges of the material estimated by Wilhelmy’s method wherein the material is added dropwise to the surface of physiological saline in an amount of 0.3-0.8 µg per square centimeter of surface area thereof being 2.1-8.6 dynes/cm and 48.2-58.0 dynes/cm when surface areas are 21.0 cm2 and 45.6 cm2 respectively.”

Based on time in clinical trials and FDA regulatory review (under 35 USC §156), the expiration date of U.S. 4,397,839 was extended 215 days to July 5, 2001.

Medical: Survanta restores partial lung surfactant activity and is not as potent in terms of lowering surface tension and assisting respiration as Infasurf, which fully restores surfactant activity. Despite the differences between Survanta and Infasurf, only a modest difference in efficacy in the acute phase of RDS was observed in a comparative clinical trial.

Market: Since its introduction in 1991, more than 350,000 children have been treated with Survanta, and it been the standard surfactant therapy in the U.S. for most of this period.

The 2007 Average Wholesale Price (AWP) is $459.60/4 mL vial, with a Direct Price (Manufacturer’s discount price) of $383.00/vial; and the AWP is $813.46/8 mL vial, with a Direct Price of $677.88 (unchanged since 2004) (Red Book, 2007).