Antithrombin III (Human) – Thrombate III; AT-III
Status – approved; marketed
Organizations involved:
Talecris Biotherapeutics Inc. – Manuf.; R&D; Tech.; USA mark.
Instituto Grifols, S.A. – Parent
NPS Pharmaceuticals Inc. – Former
Bayer Corp. – R&D; Tech.; Former
Bayer Schering Pharma AG – Intl. mark.
Cross ref: See the Antithrombin III Products entry (#706) above and the other AT-III product entries below.
Description: Antithrombin III (Human) or Thrombate III is a lyophilized (freeze-dried) formulation of antithrombin III (AT-III) glycoprotein obtained from pooled fractionated Plasma, with manufacture including viral inactivation by wet heating (pasteurization) in solution at 60˚C for 10 hours.
The minimal potency assignment of 500 IU for Thrombate III is determined using a standard calibrated against a World Health Organization (WHO) Antithrombin III Reference Preparation. Each vial is labeled with its content of AT-III in International Units (IU). Thrombate III, after reconstitution with Sterile Water for Injection USP, contains not less than 40 IU/mL of antithrombin III; alanine 0.075-0.125 M; and not more than 0.004 units of heparin/IU of AT-III. The product contains no preservatives. The AT-III content is variable but should be sufficient to maintain plasma levels of AT-III between 80-120% of normal. The dating period is 24 months from the date of manufacture (the date of the first sterile filtration of the bulk).
Nomenclature: Antithrombin III/Talecris [BIO]; Thrombate III [TR]; Antithrombin III (Human) [FDA]; Antithrombin III [CAS INN BAN]; 52014-67-2 [CAS RN]; 90170-80-2 [CAS RN]; AT-III [SY]; Heparin cofactor B [SY]; heparin cofactor I [SY]; EINECS 232-568-2; EINECS 290-516-4 [EINECS]
Companies.: Thrombate II was developed and previously manufactured by Bayer Corp. (now Bayer Schering Corp.; formerly Miles Labs.; before that Cutter Labs.), CBER/FDA est. no. 0008; with manufacturing facilities in Clayton, NC, and Berkeley, CA. In April 2005, Talecris Biotherapeutics Inc., then a subsidiary or NPS Pharmaceuticals Inc , acquired the blood/plasma products business of Bayer, including manufacturing and U.S marketing, with Bayer AG, now Bayer Schering Pharma AG, retaining international marketing.
In Feb. 2011, Instituto Grifols acquired Talecris.
FDA class: Biologic PLA
CBER class: Blood And Blood Derivatives
Approvals: Date = 19911230, first approval; PLA/ELA ref. no. 87-081 and 87-0129 granted to Miles Inc.; orphan designation (granted 11/26/1984; expired 12/30/1998)
Date = 20060706; BLA supplement; Indication = addition of prior removal verification information to product insert/labeling; reaffirmation of the proven safety profile of Thrombate III, derived from 14 years of clinical experience.
Indications: for replacement therapy in congenital deficiency of AT-III for prevention and treatment of thrombosis and pulmonary emboli
Status: The July 2006 approval of new safety-related information arose from Talecris demonstrating that potential infection risk from pathogenic prions, including those associated with variant Creutzfeldt-Jakob Disease (vCJD, the human form of “Mad Cow”), is significantly reduced during the manufacturing process (in the unlikely event such prions are present in the plasma starting material). Studies conducted with an experimental agent of transmissible spongiform encephalopathy, considered to be a model for vCJD, showed that 6.0 log10 are removed (99.9999% of any pathogenic prions present). With this approval, Talecris reported, “Available since 1992, Thrombate III® has demonstrated a safety and efficacy record that includes infusion of more than 220,000 vials without a single documented case of infectious disease transmission.”
Tech. transfer: U.S. 4,386,025, “Method of Preparing Antithrombin,” May 31, 1983, assigned to Cutter Labs. (Bayer, now Talacris), describes use of a lectin-containing, water insoluble, gel affinity chromatography matrix to which polysaccharidic substances, e.g., AT-III glycoprotein, can reversibly bind; and use for fractionation and purification of AT-III.
U.S. 4,656,254, “Method of Preparing alpha-1-Proteinase and Antithrombin III,” April, 7, 1987, assigned to Cutter/Miles/Bayer (now Talacris) describes improvements in the separation and purification of AT-III from plasma.
Market: The 2007 Average Wholesale Price (AWP) is $2.27/IU for either the 500 or 1,000 IU vials (Red Book, 2007). Medicare reimbursement is set at $1.12/IU for inpatient and home care, and $1.01/IU outpatient care. Estimated Acquisition Costs (for hospitals, treatment centers) is $1.05/IU [from NHF].
In its March 22, 2006 price list, FFF Enterprises, a major biologics distributor, reported its price as $1.53/IU for all sizes ($1.49 in 2005 and 2004).
Companies involvement:
Full monograph
707 Antithrombin III/Talecris
Nomenclature:
Antithrombin III/Talecris [BIO]
Thrombate III [TR]
Antithrombin III (Human) [FDA]
Antithrombin III [CAS INN BAN]
52014-67-2 [CAS RN]
90170-80-2 [CAS RN]
AT-III [SY]
heparin cofactor B [SY]
heparin cofactor I [SY]
EINECS 232-568-2 [EINECS]
EINECS 290-516-4 [EINECS]
FDA Class: Biologic PLA
Year of approval (FDA) = 1991
Date of 1st FDA approval = 19911230
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
blood products
human materials used<!-- humansource -->
alanine
heat treatment (pasteurization)
heparin
Plasma (Human)
sodium chloride
Sterile Water for Injection
thrombin, human
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
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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