Status: approved; marketed

Organizations involved:

CSL Bioplasma Inc. – Manuf.; R&D; Tech.; USA mark.

CSL Bioplasma AG – Intl. mark.; Parent

CSL Ltd. – Parent

Cross ref: See the Immune Globulin Products entry (#743) and the entries for other IGIV products.

Description: Gammar-P I.V. is a lyophilized (freeze-dried) formulation of highly refined Immune Globulin Intravenous (Human) obtained from pooled fractionated Plasma. manufacture includes heat treatment (pasteurization) for viral inactivation at 60˚C for 10 hours.

Gammar-P-IV is packaged in 1, 2.5, 5, and 10 gram vials. After reconstitution with 100 ml of Sterile Water for Injection, USP (not supplied), Gammar-P contains 5% IgG, 3% Albumin (Human), 5% sucrose, and 0.5% sodium chloride. The product also contains citric acid and/or sodium carbonate to adjust the pH to 6.8. Gammar-P I.V., contains primarily intact unmodified (unpolymerized) IgG, stabilized with Albumin (Human) and sucrose. The distribution of IgG subclasses in the product is similar to that present in normal plasma. IgG content is ≥ 98%, with monomeric IgG ≥ 96%. IgG subclass content includes IgG1 69%, IgG2 23%, IgG3 6% and IgG4 2%. IgA content is 25-50 µg/ml. The product contains no preservatives. Gammar-P may be stored at room temperature (≤ 25˚C) with a shelf life of two years.

Nomenclature: Immune Globulin (IGIV)/CSL [BIO]; Gammar-P I.V. [TR]; Immune Globulin Intravenous (Human) [FDA]; intravenous immune globulin (IVIG) [SY]; gamma globulin [SY]; IVIG [SY]; immune globulin, intravenous [SY]; NDC 0053-7486-01; NDC 0053-7486-02; NDC 0053-7486-05; NDC 0053-7486-10; NDC 0053-7486-06 [NDC]

Companies.: Gammar-P I.V. was manufactured and marketed in the U.S. by Aventis Behring LLC (King of Prussia, PA), FDA CBER est. no. 1281 (fromerly Centeon LLC); now by CSL Bioplasma Inc., CBER/FDA est. no. 1639. It is marketed internationally by CSL Bioplasma Inc.’s parent company, CSL Bioplasma AG, which is a subsidiary of CSL Ltd.

Manufacture: Gammar-P-IV is manufactured at the company’s Kankakee, IL facility. The product is derived from Plasma obtained from paid donors, presumably from paid donors at the company’s own plasmapheresis facilities. Pooled human plasma is fractionated using the Cohn-Oncley cold-ethanol process (methods 6 and 9) at a neutral pH with repeated ethanol treatments. The product is then subjected to ultrafiltration, Albumin (Human) is added, it is subjected to diafil-tra-tion, sucrose is added, and the bulk product is pasteurized (wet heat) viral inactivation at 60˚C (140˚F) for ten hours. The product is sterile filtered (ultrafiltered) and lyophilized (freeze-dried). The resulting IgG is not chemically modified or enzymatically degraded. The total viral reduction capacity of the manufacturing procedure, including fractionation and heat treatment, has been shown to reduce HIV by ≥ 12.1 log and murine encephalomyocarditis virus (EMC; a non-lipid enveloped virus) by ≥ 12.8 log.

Aventis Behring, now CSL Bioplasma, was the first company (May 2000) in North America to manufacture plasma products exclusively from plasma released after proprietary investigational polymerase chain reaction (PCR; Nucleic Acid Testing or NAT) screening for HIV-1, hepatitis B virus, and hepatitis C virus. In Sept. 2000, Aventis Behring further added PCR/NAT screening for parvovirus B19 and hepatitis A viruses, making it the first company in the world to screen plasma using proprietary investigational PCR for five viruses (HIV-1, hepatitis B, hepatitis C, parvovirus B19, and hepatitis A).

FDA class: Biologic PLA BLA

CBER class: Blood And Blood Derivatives

Approvals: Date = 19891214; first approval, PLA

Date = 19950000; PLA supplement; addition of heat pasteurization viral inactivation step (Gammar-P I.V.)

Date = 20000317; approval revoked from Centeon LLC and granted (reissued) to new owner, Aventis Behring LLC

Date = 20000328; supplemental approval; Indication = for the treatment of Primary Immune Deficiency (PID) in adolescents and children who are at an increased risk of infection

Date = 20000511; BLA supplement (indicating PLA/ELA converted to BLA); Indication = addition of statement, “The plasma used in the manufacture of this product has been tested and found negative for HBV [hepatitis B virus], HCV [hepatitis C virus], and HIV-1 by an investigational test procedure referred to as Nucleic Acid Testing (NAT) using Polymerase Chain Reaction (PCR) technology. Investigational testing is being performed to determine the effectiveness of NAT to detect low levels of viral material. The significance of a negative result is unknown since the effectiveness of the test has not been established.”

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

Gammar -P I.V. is indicated for patients with primary defective antibody synthesis such as agammaglobulinemia or hypogammaglobulinemia, who are at increased risk for infection. When high levels or rapid elevation of circulating gamma globulins are desired, intravenous administration is more desirable than intramuscular therapy.

Market: The 2007 Average Wholesale Price (AWP) is $500.00/5 g and $1,000/10 g (Red Book, 2007). These prices are unchanged from 2004.

In June 2003, Aventis Behring launched the Gammar-P I.V. Assurance Program. This was the first such program in the U.S. Enrolled patients earn one Certificate for every three consecutive months they use one Gammar-P I.V.. Each Certificate can be redeemed for one month’s worth of free product, based on the average monthly usage by the patient, in the event of a lapse in insurance. Patients can earn up to four months of free product after a year in the Program, and up to a full year after three years.