Factor IX Complex Solvent Detergent Treated - Profilnine SD; Antihemophilic factor B
Status: approved; marketed
Organizations involved:
Grifols Biological Inc. – Manuf.; Tech.; USA mark.
Istituto Grifols S.A. – Intl. mark
Probitas S.A. – Parent
Alpha Therapeutic Corp. – R&D; Tech.; Former
Green Cross Corp. – Former inv.
Yoshitomi Pharmaceutical Industries, Ltd. – Former
Mitsubishi Chemical Corp. – Former inv.
New York Blood Center, Inc. – Tech.
Cross ref: See the Factor IX Products entry (#727).
Description: Profilnine SD is a lyophilized (freeze-dried) formulation of non-activated Factor IX Complex containing purified Factor IX (antihemophilic factor B), Factor II (prothrombin), Factor X (Stuart-Prower Factor), and low levels of Factor VII (proconvertin) prepared from cold ethanol fractionated Plasma (Human). Manufacturing includes ion exchange chromatography (DEAE cellulose), dual affinity chromatography, and viral inactivation using solvent/detergent [SD; using tri-n-butyl phosphate (TNBP) and poly-sorbate 80] and heat (pasteurization) methods, and virus removal by nanofiltration.
Profilnine SD is supplied in single dose vials along with diluent (Sterile Water for Injection, USP), a double-ended needle, and a microaggregate filter for intravenous administration only. Each vial of Profilnine SD is labeled with the number of plasma equivalents of Factor IX per vial, expressed as International Units referenced to the WHO International Standard. One unit is defined as the activity contained in one mL of pooled normal human plasma. The final reconstituted product contains a minimum of 150 IU Factor IX per mg of protein (generally 230 IU/mg) for intravenous administration only. The final reconstituted product also contains not more than (NMT) 150 Units of Factor II per 100 Factor IX Units, Factor X is NMT 100 Units per 100 Factor IX Units, and Factor VII is NMT 35 Units per 100 Factor IX Units. After reconstitution with the appropriate volume of Sterile Water for Injection, USP, Profilnine SD contains not more than 2.5 µg polysorbate 80 and 0.40 µg tri(n-butyl)phosphate per IU of Factor IX. Profilnine SD does not contain heparin, contains low levels of activated coagulation factors, and contains no preservatives. Profilnine SD should be stored at 2-8˚C (refrigerated), and may be stored at room temperature not to exceed 30˚C for up to three months.
Nomenclature: Factor IX/Grifols [BIO]; Profilnine SD [TR]; Factor IX Complex Solvent Detergent Treated [FDA]; Antihemophilic factor B [SY]
Companies.: Profilnine SD is manufactured by Grifols Biological Inc., CBER/FDA est. no. 1694, previously Alpha Therapeutic Corp. (originally independent, later a subsidiary of Green Cross Corp., a subsidiary of Yoshitomi Pharmaceutical Industries, Ltd.; later acquired by Mitsubishi Chemical), CBER/FDA lic. no. 0744. Alpha was acquired by Probitas Pharma S.A. in July 2003, and merged into its Instituto Grifols subsidiary.
Profilnine SD is marketed in the U.S. by Grifols Biological Inc., and internationally by Istituto Grifols S.A. and affiliates (previously by Alpha Therapeutic Corp. and affiliates, including Green Cross and Yoshitomi).
Manufacture: The solvent detergent process used in the manufacture of Profilnine SD has been shown to inactivate greater than 12.2 logs (1012.2) of HIV-1 when the retrovirus was intentionally added (as measured by virus antigen capture and reverse transcriptase assays). The process has also been shown to inactivate 6.0 logs of HIV-2 (as measured by reverse transcriptase assays), 5.3 logs of Sindbis virus, and a minimum of 4.9 logs of vesicular stomatitis virus (VSV) after 180 minutes of incubation with solvent detergent (compared to an untreated control). The actual incubation time for the Profilnine SD process is twice (360 minutes total) that used in the model virus studies. Viruses are also removed by physical partitioning (separation) during fractionation and purification. Addition of Sindbis virus prior to Factor IX Complex adsorption by DEAE chromatography showed that this step to eliminated 1.4 logs of added virus.
FDA class: Biologic PLA
Approvals: Date = 19901231; PLA, first approval
Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling]:
Factor IX Complex, Profilnine SD is indicated for the prevention and control of bleeding in patients with Factor IX deficiency due to hemophilia B.
This product contains non-therapeutic levels of Factor VII, and is not indicated for use in the treatment of Factor VII deficiency.
Tech. transfer: Solvent detergent virus inactivation was developed by and nonexclusively licensed from the New York Blood Center. For example, see U.S. patent 4,820,805. See the entry for Pooled Plasma, Solvent Detergent Treated (SD Plasma) (#799) for further information about solvent detergent viral inactivation, used primarily for inactivation of enveloped viruses (e.g., HIV, hepatitis B and C viruses).
Market: The 2007 Average Wholesale Price (AWP) is $0.90/IU for 500 and 1000-1500 IU vials, with a Direct Price (discount price) of $.75/IU (Red Book, 2007).
Medicare reimbursement is set at $0.71/IU for inpatient and home care, and at $0.51/IU for outpatient care. Estimated Acquisition Costs (for hospitals, treatment centers) is $0.35-0.46/IU [from NHF].
In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported its price as $0.49/IU ($0.38 in 2005; $0.35/IU in 2004).
Companies involvement:
Full monograph
730 Factor IX Complex/Grifols
Nomenclature:
Factor IX/Grifols [BIO]
Profilnine SD [TR]
Factor IX Complex Solvent Detergent Treated [FDA]
Antihemophilic factor B [SY]
FDA Class: Biologic PLA
Year of approval (FDA) = 1990
Date of 1st FDA approval = 19901231
(in format YYYYMMDD)
Index Terms:
antihemophilic factors
biopharmaceutical products
blood products
human materials used<!-- humansource -->
DEAE cellulose
Factor IX WHO International Standard
Factor VII
Factor X
heat treatment (pasteurization)
heptane
lyophilized (freeze-dried)
Plasma (Human)
polysorbate 80 (Tween 80)
prothrombin, human
Sterile Water for Injection
tri-n-butyl phosphate (TNBP)
viral inactivation, solvent detergent
WHO Intl. Standard, Factor IX
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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