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">CINRYZE (C1 esterase inhibitor [human]) (Freeze-Dried Powder for Reconstitution) is a sterile, stable, lyophilized preparation of C1 esterase inhibitor derived from human plasma. CINRYZE is manufactured from human plasma purified by a combination of filtration and chromatographic procedures. CINRYZE potency is expressed by its C1 esterase inhibitor activity measured with a validated chromogenic assay. 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. One International Unit (IU) corresponds to the amount of C1 esterase inhibitor present in 1 mL of normal plasma.</p><p>The specific activity of CINRYZE is 4.0 to 9.0 U/mg protein. The purity is ≥ 90% human C1 esterase inhibitor. Following reconstitution with 5 mL of Sterile Water for Injection, USP, each vial contains approximately 500 IU of functionally active C1 esterase inhibitor, pH 6.6 to 7.4, and an osmolality between 200 to 400 mosmol/kg.</p><p>CINRYZE, when reconstituted with 5 mL of Sterile Water for Injection, USP contains the following excipients: 4.1 mg/mL sodium chloride, 21 mg/mL sucrose, 2.6 mg/mL trisodium citrate, 2.0 mg/mL L-Valine, 1.2 mg/mL L-Alanine, and 4.5 mg/mL L-Threonine.</p><p>The following manufacturing steps are designed to reduce the risk of viral transmission:</p><ul class="Disc"><li>Screening donors at U.S. licensed blood collection centers to rule out infection with Human Immunodeficiency Virus (HIV-1/HIV-2), Hepatitis B Virus, or Hepatitis C Virus.</li><li>Testing plasma pools by in-process NAT for parvovirus B19 via minipool testing and the limit of B19 in the manufacturing pool is set not to exceed 10<span class="Sup">4</span> IU of B19 DNA per mL.</li><li>Use of two independent viral reduction steps in the manufacture of CINRYZE: pasteurization (heat treatment at 60°C for 10 hours in solution with stabilizers) and nano filtration through two sequential 15 nm filters.</li></ul><p>These viral reduction steps, along with a step in the manufacturing process, PEG precipitation, have been validated in a series of <span class="Italics">in vitro</span> experiments for their capacity to inactivate/remove a wide range of viruses of diverse physicochemical characteristics including: Human Immunodeficiency Virus (HIV), Hepatitis A Virus (HAV), and the following model viruses: Bovine Viral Diarrhea Virus (BVDV) as a model virus for HCV, Canine Parvovirus (CPV) as a model virus for Parvovirus B19, Pseudorabies Virus (PRV) as a model virus for large enveloped DNA viruses (e.g. herpes virus). Total mean log<span class="Sub">10</span> reductions are shown in <span class="Bold">Table 4.</span></p><table width="75%"><caption><span>Table 4 Log<span class="Sub">10</span> Virus Reduction Factor for Selected Viruses.</span></caption><col align="left" valign="top" width="16%"/><col align="left" valign="top" width="16%"/><col align="left" valign="top" width="17%"/><col align="left" valign="top" width="17%"/><col align="left" valign="top" width="17%"/><col align="left" valign="top" width="17%"/><thead><tr class="First Last"><th align="left" class="Lrule Rrule">Process Step</th><th align="left" class="Rrule">Enveloped Viruses - HIV</th><th align="left" class="Rrule">Enveloped Viruses - BVDV</th><th align="left" class="Rrule">Enveloped Viruses - PRV</th><th align="left" class="Rrule">Non-enveloped Viruses - HAV</th><th align="left" class="Rrule">Non-enveloped Viruses - CPV</th></tr></thead><tbody><tr class="Botrule First"><td align="left" class="Lrule Rrule"><span class="Bold">PEG precipitation</span></td><td align="left" class="Rrule">5.1 ± 0.2</td><td align="left" class="Rrule">4.5 ± 0.3</td><td align="left" class="Rrule">6.0 ± 0.3</td><td align="left" class="Rrule">2.8 ± 0.2</td><td align="left" class="Rrule">4.2 ± 0.2</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule"><span class="Bold">Pasteurization</span></td><td align="left" class="Rrule">&gt; 6.1 ± 0.2</td><td align="left" class="Rrule">&gt; 6.7 ± 0.3</td><td align="left" class="Rrule">&gt; 6.7 ± 0.2</td><td align="left" class="Rrule">2.8 ± 0.3</td><td align="left" class="Rrule">0.1 ± 0.3</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule"><span class="Bold">Nano filtration</span></td><td align="left" class="Rrule">&gt; 5.6 ± 0.2</td><td align="left" class="Rrule">&gt; 5.5 ± 0.2</td><td align="left" class="Rrule">&gt; 6.4 ± 0.3</td><td align="left" class="Rrule">&gt; 4.9 ± 0.2</td><td align="left" class="Rrule">&gt; 4.5 ± 0.3</td></tr><tr class="Last"><td align="left" class="Lrule Rrule"><span class="Bold">Total reduction</span></td><td align="left" class="Rrule">&gt; 16.8</td><td align="left" class="Rrule">&gt; 16.7</td><td align="left" class="Rrule">&gt; 19.1</td><td align="left" class="Rrule">&gt; 10.5</td><td align="left" class="Rrule">&gt; 8.7</td></tr></tbody></table></section>

Cinryze

C1 esterase inhibitor

C1 esterase inhibitor (human) 500 UNT Injection

C1 esterase inhibitor (human)

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

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

Cinryze is a synthetic version of a protein found naturally in the bloodstream, which plays a vital role in regulating inflammation in the body. Individuals with a condition known as hereditary angioedema lack an adequate amount of this protein, leading to episodes of swelling and associated symptoms like digestive issues or breathing difficulties.

Cinryze is employed to proactively safeguard against angioedema attacks.