Kallikrein Inhibitors

Human C1 Esterase Inhibitor

Angioedemas, Hereditary

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-9"></a><p></p><h1>11 DESCRIPTION</h1><p class="First">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.</p><p>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.<span class="Sup">4</span> The heavily glycosylated molecule has an apparent molecular weight of 105 kD, of which the carbohydrate chains comprise 26% to 35%.<span class="Sup">5</span></p><p>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.</p><p>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-1/2 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 10<span class="Sup">4</span> IU of Parvovirus B19 DNA per mL.</p><p>The manufacturing process for BERINERT includes multiple steps that reduce the risk of virus transmission. The virus inactivation/reduction capacity consists of three steps:</p><ul class="Disc"><li>Pasteurization in aqueous solution at 60°C for 10 hours</li><li>Hydrophobic interaction chromatography</li><li>Virus filtration (also called nanofiltration) by two filters, 20 nm and 15 nm, in series</li></ul><p>This was evaluated in a series of in vitro spiking experiments. The total mean cumulative virus inactivation/reduction is shown in Table 2.</p><table width="90%"><caption><span>Table 2. Mean Virus Inactivation/Reductions in BERINERT</span></caption><col align="left" valign="middle" width="18%"/><col align="center" valign="middle" width="18%"/><col align="center" valign="middle" width="28%"/><col align="center" valign="middle" width="18%"/><col align="center" valign="middle" width="18%"/><thead><tr class="First Last"><th align="center" class="Lrule Rrule">Virus Studied</th><th align="center" class="Rrule" valign="bottom">Pasteurization<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Hydrophobic Interaction Chromatography<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Virus Filtration<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Total Cumulative<br/>[log<span class="Sub">10</span>]</th></tr></thead><tfoot><tr class="First"><td align="left" colspan="5">HIV-1, Human immunodeficiency virus type 1, a model for HIV-1 and HIV-2</td></tr><tr><td align="left" colspan="5">BVDV, Bovine viral diarrhea virus, a model for HCV</td></tr><tr><td align="left" colspan="5">PRV, Pseudorabies virus, a model for large enveloped DNA viruses</td></tr><tr><td align="left" colspan="5">WNV, West Nile virus</td></tr><tr><td align="left" colspan="5">HAV, Hepatitis A virus</td></tr><tr><td align="left" colspan="5">CPV, Canine parvovirus</td></tr><tr><td align="left" colspan="5">B19V, Human Parvovirus B19</td></tr><tr><td align="left" colspan="5">ND, Not determined</td></tr><tr class="Last"><td align="left" colspan="5">NA, Not applicable</td></tr></tfoot><tbody><tr class="Botrule First"><td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Enveloped Viruses</span></td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">HIV-1</td><td align="center" class="Rrule">≥6.6</td><td align="center" class="Rrule">≥4.5</td><td align="center" class="Rrule">≥5.1</td><td align="center" class="Rrule">≥16.2</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">BVDV</td><td align="center" class="Rrule">≥9.2</td><td align="center" class="Rrule">≥4.7</td><td align="center" class="Rrule">≥5.3</td><td align="center" class="Rrule">≥19.2</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">PRV</td><td align="center" class="Rrule">6.3</td><td align="center" class="Rrule">≥6.5</td><td align="center" class="Rrule">≥7.1</td><td align="center" class="Rrule">≥19.9</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">WNV</td><td align="center" class="Rrule">≥7.0</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">≥8.0</td><td align="center" class="Rrule">≥15.0</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Non-Enveloped Viruses</span></td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">HAV</td><td align="center" class="Rrule">≥6.4</td><td align="center" class="Rrule">2.8</td><td align="center" class="Rrule">≥5.3</td><td align="center" class="Rrule">≥14.5</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">CPV</td><td align="center" class="Rrule">1.4</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">7.1</td><td align="center" class="Rrule">12.4</td></tr><tr class="Last"><td align="left" class="Lrule Rrule">B19V</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">NA</td></tr></tbody></table></section>

Berinert

C1 esterase inhibitor

C1 esterase inhibitor (human) 500 UNT Injection

C1 esterase inhibitor (human)

C1 esterase inhibitor (human) 500 UNT Injection [Berinert]

Psoriasis (PsO)

Psoriatic Arthritis (PsA)

Ankylosing Spondylitis (AS)

Nonradiographic Axial Spondyloarthritis

Taltz

Juvenile Idiopathic Arthritis

Hidradenitis Suppurativa (HS)

Cosentyx

Siliq

Tremfya

Crohn's Disease (CD)

Ulcerative Colitis (UC)

Stelara

Skyrizi

Ilumya

Migraine

Cluster Headache

Migraine Prevention

Emgality

Qulipta

Acute Migraine

Ubrelvy

Nurtec ODT

Vyepti

Aimovig

Ajovy

Breast Cancer: HR+ (HER2-)

Verzenio

Ibrance

Kisqali

Atopic Dermatitis (Eczema)

Cibinqo

Eucrisa

Asthma (injectable)

Asthma OCS Dependent

Nasal Polyposis

Eosinophilic Esophagitis (EoE)

Prurigo Nodularis

Dupixent

Opzelura

Adbry

NSCLC ALK+ OR ROS1+ Disease

Lorbrena

Alecensa

Alunbrig

NSCLC cMET Mutation

Xalkori

Rheumatoid Arthritis (RA)

Xeljanz

Uveitis

Graft Versus Host Disease (GVHD)

Orencia

COVID-19 Treatment

Alopecia Areata

Olumiant

Multiple Sclerosis (MS)

Secondary Progressive Multiple Sclerosis

Zeposia

Rinvoq

Entyvio

Berinert is a synthetic version of a protein naturally found in the bloodstream, which plays a role in regulating swelling within the body. Individuals with hereditary angioedema lack an adequate amount of this protein, which can lead to episodes of swelling and accompanying symptoms like digestive issues or breathing difficulties.

Berinert is prescribed for individuals with hereditary angioedema.

It is employed to manage acute angioedema attacks.