"The U.S. Food and Drug Administration today approved Octaplas, a pooled plasma (human) blood product for the replacement of clotting proteins (coagulation factors) in certain medical conditions where patients have insufficient levels. Clotting pr"...
(recombinant) Lyophilized powder for reconstitution
ATryn (recombinant lyophilized powder) for Injection 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 (recombinant lyophilized powder) 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 product contains 100 mg glycine, 79 mg sodium chloride, and 26 mg sodium citrate. When 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 (recombinant lyophilized powder) 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)
|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 (recombinant lyophilized powder) . Modern Biopharmaceuticals 2005;995-1016.
Last reviewed on RxList: 3/10/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Atryn Information
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