Source: Health Products and Food Branch (CA) Revision Year: 2021
ZONOVATE – Antihemophilic Factor (Recombinant, B-Domain Truncated) turoctocog alfa.
Lyophilized Powder 250, 500, 1000, 1500, 2000 and 3000 IU/vial.
Antihemophilic Factor (Recombinant, B-Domain Truncated), turoctocog alfa, is a purified protein that has 1445 amino acids with an approximate molecular mass of 166 kDa (calculated excluding post-translational modifications). The molecule has been designed as a polypeptide containing a heavy chain of 87 kDa and a light chain of 79 kDa, held together by non-covalent interactions. In wild type Factor VIII the heavy chain contains varying lengths of B-domain, which in turoctocog alfa is a truncated B-domain with 21 amino acid residues. Six potential sites for tyrosine sulfation have been shown to be sulfated in the turoctocog alfa molecule. The tyrosine sulfation site corresponding to Tyr1680 in the (endogenous full length) Factor VIII, which is important for the binding to von Willebrand Factor, has been found to be fully sulfated in the turoctocog alfa molecule.
ZONOVATE is synthesized by a genetically engineered Chinese hamster ovary (CHO) cell line. In culture, the CHO cell line expresses recombinant Factor VIII (rFVIII) into the cell culture medium. The cell culture and purification processes used in the manufacture of ZONOVATE employ no additives of human or animal origin. The rFVIII is purified from the cell culture medium using a series of chromatography steps. The purification process includes an immunoaffinity chromatography step in which a monoclonal antibody directed against Factor VIII is employed to selectively isolate the rFVIII from the medium. The process also includes a size exclusion chromatography step to separate High Molecular Weight Protein from rFVIII. The production process includes a detergent treatment step and a dedicated 20 nanometer virus filtration step. The rFVIII synthesized by the CHO cells has the same biological effects on clotting as native human Factor VIII.
ZONOVATE is formulated as a sterile, non-pyrogenic, white or slightly yellow powder for intravenous injection. Each vial of ZONOVATE is labeled with the rFVIII activity expressed in IU determined using the European Pharmacopoeia chromogenic assay, using a reference material calibrated against a World Health Organization (WHO) International Standard for Factor VIII Concentrates. One IU, as defined by the WHO standard for human FVIII, is approximately equal to the level of FVIII activity in 1 mL of fresh pooled human plasma.
To help ensure the traceability of biologic products, including biosimilars, health professionals should recognize the importance of recording both the brand name and the non-proprietary (active ingredient) name as well as other product-specific identifiers such as the Drug Identification Number (DIN) and the batch/lot number of the product supplied.
Table 1-5. Dosage Forms, Strengths, Composition and Packaging:
| Route of Administration | Dosage Form/Strength/Composition | Non-medicinal Ingredients |
|---|---|---|
| Intravenous injection | Lyophilized powder and solvent for solution for injection 250, 500, 1000, 1500, 2000 and 3000 IU/vial | Powder: Calcium chloride dihydrate, L-histidine, Lmethionine, polysorbate 80, sodium chloride, sucrose Solvent: Sodium chloride, water for injections |
ZONOVATE is supplied as a white, lyophilized powder in a single-use vial. ZONOVATE is available in strengths of 250, 500, 1000, 1500, 2000 or 3000 IU/vial.
The solvent for reconstitution of ZONOVATE is 0.9% sodium chloride solution and is supplied as a clear colorless solution in a prefilled syringe.
The ZONOVATE package contains 1 vial of ZONOVATE and 1 MixPro prefilled solvent syringe with sterile vial adapter, which serves as a needleless reconstitution system.
Each ZONOVATE package contains:
After reconstitution, ZONOVATE contains the following non-medicinal ingredients:
| Contents | Per vial | Function |
|---|---|---|
| Sodium chloride* | 18 mg/mL | Stabiliser |
| L-histidine | 1.5 mg/mL | Buffering agent |
| Sucrose | 3 mg/mL | Bulking agent |
| Polysorbate 80 | 0.1 mg/mL | Surfactant |
| L-methionine | 0.055 mg/mL | Antioxidant |
| Calcium chloride dihydrate | 0.25 mg/mL | Stabiliser |
* The amount of sodium chloride originates from the formulation and from the solvent (0.9% Sodium Chloride Solution) used for reconstitution.
| Marketing Informations | Authorization Dates |
|---|---|
|
Authorization holder:
Novo Nordisk Canada Inc., 101-2476 Argentia Road, Mississauga, Ontario, L5N 6M1 Canada 239150 |
Date of approval:
December 08, 2014 April 12, 2021 |
| Drug | Countries | |
|---|---|---|
| ZONOVATE | Brazil, Canada |
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