Factor IX Complex, Vapor Heated - Bebulin VH -Immuno; Antihemophilic factor B
Status: approval withdrawn
Organizations involved:
Baxter AG – R&D; Tech.; Former
Baxter Healthcare Corp. – Parent; Former
Immuno-U.S. – Former
Cross ref: See the Factor IX Products entry (#727) and the entries for other Factor IX products.
Description: Factor IX Complex, Vapor Heated is a lyophilized (freeze-dried) formulation of Factor IX along with other clotting factors manufactured by cold ethanol fractionation of pooled human blood plasma [Plasma (Human)]. Manufacturing includes viral inactivation involving heating (pasteurizing) the bulk in steam vapor at 60˚C for 10 hours and at 80˚C for one hour.
Factor IX Complex contains a combination of vitamin K-dependent clotting factors normally found in plasma. Bebulin VH Immuno may contain varying amounts of Factor II (prothrombin), Factor X, and Factor VII. The final product when reconstituted with Sterile Water for Injection contains 200-1,200 IU Factor IX/20 mL vial and not more than 0.15 IU heparin/IU Factor IX. Each vial is labeled with the exact number of Factor IX content in IU. The dating period is 24 months from date of manufacture when stored at 2-8˚C (refrigerated). The date of manufacture is the date of the first sterile filtration of the bulk.
Nomenclature: Factor IX VH [BIO]; Bebulin VH Immuno [TR]; Factor IX Complex, Vapor Heated [FDA]; 9001-28-9 [CAS RN]; Antihemophilic factor B [SY]; Factor IX [SY]; Christmas factor [SY]; Blood coagulation factor IX [SY]; Immunine [SY]
Companies.: Bebulin VH was developed and manufactured by Immuno International (Immuno AG; Vienna, Austria; formerly Oester-reichisches Institut fur Haemo-derivate GmbH), FDA CBER est. no. 0258. Bebulin VH was marketed in the U.S. by Immuno-U.S., Inc., and marketed internationally by Immuno AG affiliates. Immuno was acquired by Baxter and is now Baxter AG.
Manufacture: Bebulin VH is prepared from the supernatant of cryoprecipitated pooled human plasma (Source Plasma or Plasma) with further purification by adsorption onto and elution from an unspecified ion exchange resin. The product is viral inactivated using a two-step process involving heating in steam vapor phase at 60˚C for 10 hours at 1190 mbar and at 80˚C for one hour at 1375 mbar.
FDA class: Biologic PLA
CBER class: Blood And Blood Derivatives
Approvals: Date = 19920819; approval of 2-step vapor heated product; granted to Oesterreichisches Institut fur Haemo---derivate GmbH, with orphan designation
Date = 20000207; approval revoked
Indications: [from product insert/labeling]:
for replacement treatment and prophylaxis of the hemorrhagic complications of hemophilia B
Status: The approval for Bebulin VH was withdrawn in recent years.
The approval of Bebulin VH involved FDA ruling regarding interpretation of Orphan Drug exclusivity as it applied to the product. Another product, Coagulation Factor IX (Human) or AlphaNine from Alpha Therapeutic (now Grifols Biological Inc.), similarly containing purified Factor IX had previously received approval for treatment of hemophilia B with Orphan Drug designation. This generally provides seven years of marketing exclusivity (keeping equivalent products for the same indications: from receiving approval). FDA concluded that the levels of some markers of coagulation after infusion of Bebulin VH were higher and remained elevated longer than in patients treated with AlphaNine (although the value of these surrogate markers as predictors of thrombosis was unclear). The AlphaNine marketed at that time included 20 hour, 60˚C heating in n-heptane suspension for viral inactivation (i.e. it was not the current product). This method had been shown to allow breakthrough transmission of hepatitis C virus (HCV). No cases of hepatitis C were associated with Bebulin VH or other products including its two-step heat viral inactivation. The FDA concluded that the risk for transmission of HCV was lower with Bebulin VH. In view of the uncertainty regarding thrombogenic potential of both products and the apparent improved safety of Bebulin VH, FDA concluded Bebulin VH to be a different product (according to the Orphan Drug Act) and approved the product with orphan designation.
Companies involvement:
Full monograph
734 Factor IX VH
Nomenclature:
Factor IX VH [BIO]
Bebulin VH Immuno [TR]
Factor IX Complex, Vapor Heated [FDA]
9001-28-9 [CAS RN]
Antihemophilic factor B [SY]
Blood coagulation factor IX [SY]
Christmas factor [SY]
Factor IX [SY]
Immunine [SY]
FDA Class: Biologic PLA
Year of approval (FDA) = 1992
Date of 1st FDA approval = 19920819
(in format YYYYMMDD)
Index Terms:
antihemophilic factors
biopharmaceutical products
blood products
human materials used<!-- humansource -->
Factor VII
Factor X
heat treatment (pasteurization)
heparin
lyophilized (freeze-dried)
Plasma (Human)
prothrombin, human
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
FDA application withdrawn
orphan status
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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