Status: approved; marketed

Organizations involved:

Baxter Hyland Immuno – Manuf.; R&D; Tech.; World mark.

Baxter Healthcare Corp. – Parent

Cross ref: See the Factor IX Products entry (#727) and the entries for other Factor IX products.

Description: Factor IX Complex, Heat Treated or Proplex T is a sterile, lyophilized (freeze-dried) fraction derived by Cohn cold ethanol fractionation from human plasma containing a mixture of coagulation factors – Factor IX (antihemophilic factor B); Factor II (prothrombin), Factor VII (proconvertin), and Factor X (Stuart-Prower factor). manufacture includes heat treatment (pasteurization) for 144 hours at 60˚C for viral inactivation. Other proteins are also present in minimal amounts. Proplex T also contains a small amount of heparin, 1.5 units or less per mL of reconstituted material, as a stabilizing agent. This amount does not affect the clinical usefulness of the complex in moderate dosage. Previous versions of this product were marketed as Proplex SX-T and, prior to that, Proplex SX.

Proplex T is prepared by cryoprecipitation involving calcium phosphate absorption of cold ethanol precipitates from Plasma (Human). Proplex T contains higher ratios of Factor VII and Factor X to Factor IX than other products prepared using Sephadex-type (ion-exchange) chromatography.

Factor IX Complex, Proplex T, is packaged in vials with Sterile Water for Injection, USP, a double-ended needle, and a filter needle. Each vial is labeled with both the Factor IX and Factor VII content. The Factor IX content is expressed in International Units per bottle and is traceable to the World Health Organization International Standard through a secondary concentrate standard. The Factor VII content is expressed in units per bottle and is traceable to pooled normal plasma through a secondary standard. The product should be stored at 2 to 8°C (refrigerated).

In vitro virus inhibition studies performed in association with the 1986 approval of dry heat viral inactivation (Proplex T) report 5.5 log reduction for Sindbis virus, no detectable cytomegalovirus (CMV), 6.6 log reduction for vesicular stomatitis virus (VSV), and 4.75 log reduction for pseudorabies virus. Recent product insert/labeling reports viral reductions of 10.5 log for Sindbis virus, 5.6 log for vesicular stomatitis virus (VSV), and 1.4 log for pseudorabies virus. The combination of Cohn cold ethanol fractionation and heat treatment can be presumed to substantially lower the titer of viable HIV.

Nomenclature: Factor IX Complex/Baxter [BIO]; Proplex T [TR]; Factor IX Complex [FDA]; Factor IX Complex, Heat Treated [FDA used on product insert/labeling]; 9001-28-9 [CAS RN]; Factor VII [SY for component]; Antihemophilic factor B [SY]; Factor IX [SY]; Christmas factor [SY]; Blood coagulation factor IX [SY]; Proplex-SX [TR former]; Factors II, VII, IX and SX, Dried [SY]

Companies.: Proplex T is manufactured by Baxter Hyland Immuno (Glendale, CA), CBER/FDA lic. no. 0140. It is marketed in the U.S. by and internationally by Baxter.

FDA class: Biologic PLA

CBER class: Blood And Blood Derivatives

Approvals: Date = 19700821; PLA (for Proplex SX)

Date = 19841029; PLA supplement 83-470 (for Proplex SX-T); Indication = an optional wet solvent heat treatment viral inactivation (60˚C for 144 hours in heptane)

Date = 19860128; PLA supplement 83-131 (for Proplex T); Indication = inclusion of a dry heat treatment of the final container product [heat treatment of product manufactured from Fraction IV precipitate (60˚C for 144 hours; dry)]

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

Factor IX Complex, Proplex T, is indicated for:

1. Factor IX deficiency (hemophilia B, Christmas disease). The intravenous administration of Factor IX Complex, Proplex T, is intended to prevent or control bleeding episodes in patients with this deficiency. Factor IX Complex should not be used in patients with mild Factor IX deficiency for whom fresh frozen plasma is effective.

2. Bleeding episodes in patients with inhibitors to Factor VIII. Lusher et al, [12] have described the use of Factor IX Complex in hemarthroses occurring in hemophiliacs with inhibitors to Factor VIII.

3. Factor VII deficiency. The Factor VII content present in Factor IX Complex, Proplex T, has been shown to be effective in prevention or control of bleeding episodes in patients with Factor VII deficiency.

Tech. transfer: U.S. patent 4,495,278 is listed on the product insert/labeling. This patent, “Process for making novel blood clotting enzyme compositions,” assigned to Baxter Travenol Labs., Inc., Jan. 22, 1985, covers aspects of the dry heat viral inactivation of Proplex T.

Market: The 2007 Average Wholesale Price (AWP) is $0.60/IU (unchanged since 2005) (Red Book, 2007).