"The U.S. Food and Drug Administration yesterday approved Obizur [Antihemophilic Factor (Recombinant), Porcine Sequence] for the treatment of bleeding episodes in adults with acquired hemophilia A (acquired Factor VIII [FVII] deficiency).
[Antithrombin (Recombinant)] Reconstitution for Intravenous Use Only
ATryn is a nanofiltered, sterile, terminally heat treated, lyophilized dosage form. Antithrombin (Recombinant), active ingredient of ATryn, is a recombinant human antithrombin. It is a 432 amino acid glycoprotein with a molecular weight of approximately 57,215 Daltons. The molecular formula is: C2191H3457N583O656S18. Antithrombin (Recombinant) is produced by recombinant DNA technology using genetically engineered goats into which the DNA coding sequence for human antithrombin has been introduced along with a mammary gland specific DNA sequence, which directs the expression of the antithrombin into the milk. The goats in which antithrombin (Recombinant) is produced are USDA certified scrapie-free, and controlled for specific pathogens.
The amino acid sequence of antithrombin (Recombinant) is identical to that of human plasma-derived antithrombin.
Antithrombin (Recombinant) and plasma-derived antithrombin both contain six cysteine residues forming three disulphide bridges and 3-4 N-linked carbohydrate moieties. The glycosylation profile of antithrombin (Recombinant) is different from plasma-derived antithrombin, which results in an increased heparin affinity. When assayed in the presence of excess of heparin the potency of the recombinant product is not different from that of plasma-derived product.
Each vial of ATryn is tested for potency stated on the product label using a reference standard calibrated against the World Health Organization international standard for antithrombin concentrate. In addition to antithrombin (Recombinant), each vial of the 525 IU package strength contains 30 mg glycine, 23.7 mg sodium chloride, and 7.8 mg sodium citrate. Each vial of the 1750 IU package strength contains 100 mg glycine, 79 mg sodium chloride, and 26 mg sodium citrate. When the 525 IU vial is reconstituted with 3.2 mL Sterile Water for Injection or the 1750 IU vial is reconstituted with 10 mL Sterile Water for Injection, the pH is approximately 7.0. Following reconstitution, the solution may be further diluted into 0.9% sodium chloride for injection.
ATryn does not contain any preservatives nor is it formulated with human plasma proteins. Antithrombin (Recombinant) is affinity purified using a heparin immobilized resin and contains no detectable heparin ( < 0.0002 IU heparin per IU antithrombin) in the final product.
The purification and drug product manufacturing processes have been validated to demonstrate its capacity for removal and/or inactivation of viruses4. Results of removal and/or inactivation for each of the steps are shown in Table 4.
Table 4: Viral Clearance Results (log10 reductions)
|Process Step||Pseudo- rabies Virus||Xenotropic Murine Retrovims||Human Adeno- virus||Porcine Parvovims|
|Tangential Flow Filtration||≥ 5.1|
|Nanofiltration||≥ 3.8||≥ 6.3||≥ 3.7|
|Ion Exchange Chromatography||3.6||1.0||≥ 7.1||NA|
|Hydrophobic Interaction Chromatography||≥ 5.6||≥ 4.4||≥ 4.8||≥ 5.7|
|Heat Treatment||2.8||≥ 5.0||≥ 1.8||2.4|
|Total Reduction||≥ 18.7||≥ 15.4||≥ 20.0||≥ 13.2|
|NA = Not Applicable since log10 reduction was less than 1.0.|
In addition, although the goats are from a closed, USDA certified scrapie-free herd, the purification process was challenged to remove prions. The manufacturing steps were shown capable of achieving the following log10 reductions: 2.0 (tangential filtration), 2.2 (affinity column), ≥ 3.3 (ion exchange column), ≥ 3.8 (hydrophobic interaction column).
(4) Echelard Y, Meade H, Ziomek C. The first biopharmaceutical from transgenic animals: ATryn. Modern Biopharmaceuticals 2005;995-1016.
Last reviewed on RxList: 5/25/2016
This monograph has been modified to include the generic and brand name in many instances.
Additional Atryn Information
- Atryn Drug Interactions Center: antithrombin iii, hum recom iv
- Atryn Side Effects Center
- Atryn FDA Approved Prescribing Information including Dosage
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