"The US Food and Drug Administration (FDA) today approved a drug for children and adults with hemophilia B called albutrepenonacog alfa (Idelvion, CSL Behring), which combines albumin with factor IX to reduce injection frequency."...
[C1 Esterase Inhibitor (Human)] Freeze-dried Powder
Berinert is a human plasma-derived, purified, pasteurized, lyophilized concentrate of C1 esterase inhibitor to be reconstituted for intravenous administration. Berinert is prepared from large pools of human plasma from US donors. The potency of C1 esterase inhibitor is expressed in International Units (IU), which is related to the current WHO Standard for C1 esterase inhibitor products.
C1 esterase inhibitor is a soluble, single-chain glycoprotein containing 478 amino acid residues organized into three beta-sheets and eight or nine alpha-helices.3 The heavily glycosylated molecule has an apparent molecular weight of 105 kD, of which the carbohydrate chains comprise 26% to 35%.4
Each 500 IU vial of reconstituted Berinert contains 400-625 IU C1 esterase inhibitor, 50 to 80 mg total protein, 85 to 115 mg glycine, 70 to 100 mg sodium chloride, and 25 to 35 mg sodium citrate. All plasma used in the manufacture of Berinert is obtained from US donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-½ and HCV. Additionally, the plasma is tested with Nucleic Acid Testing (NAT) for HBV, HCV, HIV-1 and HAV and found to be non-reactive (negative). In addition, the plasma is also tested by NAT for Human Parvovirus B19. Only plasma that has passed virus screening is used for production, and the limit for Parvovirus B19 in the fractionation pool is set not to exceed 104 IU of Parvovirus B19 DNA per mL.
The manufacturing process for Berinert includes multiple steps that reduce the risk of virus transmission. The virus inactivation/reduction capacity consists of three steps:
- Pasteurization in aqueous solution at 60°C for 10 hours
- Hydrophobic interaction chromatography
- Virus filtration (also called nanofiltration) by two filters, 20 nm and 15 nm, in series
This was evaluated in a series of in vitro spiking experiments. The total mean cumulative virus inactivation/reduction is shown in Table 5.
Table 5: Mean Virus Inactivation/Reductions in
|Virus Studied||Pasteurization [log10]||Hydrophobic Interaction Chromatography [log10]||Virus Filtration [log10]||Total Cumulative [log10]|
|HIV-1||≥ 6.6||≥ 4.5||≥ 5.1||≥ 16.2|
|BVDV||≥ 9.2||≥ 4.7||≥ 5.3||≥ 19.2|
|PRV||6.3||≥ 6.5||≥ 7.1||≥ 19.9|
|WNV||≥ 7.0||ND||≥ 8.0||≥ 15.0|
|HAV||≥ 6.4||2.8||≥ 5.3||≥ 14.5|
|CPV||1.4||6.4||≥ 7.2||≥ 15.0|
|HIV-1, Human immunodeficiency virus type 1, a model for
HIV-1 and HIV-2
BVDV, Bovine viral diarrhea virus, a model for HCV
PRV, Pseudorabies virus, a model for large enveloped DNA viruses
WNV, West Nile virus
HAV, Hepatitis A virus
CPV, Canine parvovirus
B19V, Human Parvovirus B19
ND, Not determined
NA, Not applicable
3. Carrell RW, Boswell DR. Serpins: the superfamily of plasma serine proteinase inhibitors. In: Barrett A, Salvesen G, eds. Proteinase Inhibitors. Amsterdam: Elsevier. 1986;12:403-420.
What are the possible side effects of complement C1 esterase inhibitor (Berinert, Cinryze)?
Stop your IV infusion and get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing or difficult breathing; feeling like you might pass out; or swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have any other serious side effect, such as:
- new or worsening pain;
- sudden numbness or weakness, especially on one side of the body;
- sudden severe headache, confusion, problems with vision, speech, or balance;
- stomach pain or swelling;
Last reviewed on RxList: 6/16/2016
This monograph has been modified to include the generic and brand name in many instances.
Additional Berinert Information
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