Antigen Neutralization

Human Immunoglobulin G

Immunologic Deficiency Syndromes

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-9"></a><h1>11 DESCRIPTION</h1>CUVITRU is a ready-for-use, sterile, liquid preparation of highly purified and concentrated immunoglobulin G (IgG) antibodies. The distribution of the IgG subclasses is similar to that of normal plasma. The Fc and Fab functions are maintained in CUVITRU.CUVITRU has a purity ≥98% IgG and a pH of 4.6 to 5.1. The osmolality is 280-292 milli-osmoles per kilogram. CUVITRU contains 200 milligram/mL protein. The average immunoglobulin A (IgA) concentration is 80 mcg/mL. CUVITRU contains a broad spectrum of IgG antibodies against bacterial and viral agents. Glycine (0.25M) serves as a stabilizing and buffering agent, and there are no added sugars, sodium or preservatives.CUVITRU is manufactured from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography.Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of CUVITRU is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found to be negative.To further improve the margin of safety, validated virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment13, 35 nm nanofiltration, and a low pH incubation at elevated temperature (30°C to 32°C). The S/D process includes treatment with an organic mixture of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80 at 18°C to 25°C for a minimum of 60 minutes. S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes13. The ethanol fractionation process provides an additional virus clearance capacity.In vitro virus spiking studies have been used to validate the capability of the manufacturing process to inactivate and remove viruses. To establish the minimum applicable virus clearance capacity of the manufacturing process, these virus clearance studies were performed under extreme conditions (e.g., at minimum S/D concentrations, incubation time and temperature for the S/D treatment).Virus clearance studies for CUVITRU performed in accordance with good laboratory practices are summarized in Table 7.<table width="75%"><caption>Table 7 Three Dedicated Independent Virus Inactivation/Removal Steps Mean Log10 Reduction Factors<a class="Sup" href="#footnote-13" name="footnote-reference-13">*</a> (RFs) For Each Virus and Manufacturing Step</caption><col align="center" valign="middle" width="14%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="12%"/><col align="center" valign="middle" width="14%"/><thead><tr class="Botrule First"><th align="center" class="Lrule Rrule" valign="bottom">Virus type</th><th align="center" class="Rrule" colspan="3" valign="bottom">Enveloped RNA</th><th align="center" class="Rrule" valign="bottom">Enveloped DNA</th><th align="center" class="Rrule" colspan="2" valign="bottom">Non-enveloped RNA</th><th align="center" class="Rrule" valign="bottom">Non-enveloped DNA</th></tr><tr class="Botrule"><th align="center" class="Lrule Rrule">Family</th><th align="center" class="Rrule">Retroviridae</th><th align="center" class="Rrule" colspan="2">Flaviviridae</th><th align="center" class="Rrule">Herpesviridae</th><th align="center" class="Rrule" colspan="2">Picornaviridae</th><th align="center" class="Rrule">Parvoviridae</th></tr><tr class="Botrule Last"><th align="center" class="Lrule Rrule">Virus</th><th align="center" class="Rrule">HIV-1</th><th align="center" class="Rrule">BVDV</th><th align="center" class="Rrule">WNV</th><th align="center" class="Rrule">PRV</th><th align="center" class="Rrule">HAV</th><th align="center" class="Rrule">EMCV</th><th align="center" class="Rrule">MMV</th></tr></thead><tfoot><tr class="First Last"><td align="left" colspan="8">Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudorabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); EMCV, Encephalomyocarditis Virus (model for non-lipid enveloped RNA viruses, including Hepatitis A virus [HAV]); MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]); n.d. (not done), n.a. (not applicable).</td></tr><tr><td align="left" colspan="8"><dl class="Footnote"><dt><a href="#footnote-reference-13" name="footnote-13">*</a></dt><dd>For the calculation of these RF data from virus clearance study reports, applicable manufacturing conditions were used. Log10 RFs on the order of 4 or more are considered effective for virus clearance in accordance with the Committee for Medicinal Products for Human Use (CHMP, formerly CPMP) guidelines.</dd><dt><a href="#footnote-reference-14" name="footnote-14">†</a></dt><dd>No RF obtained due to immediate neutralization of HAV by the anti-HAV antibodies present in the product.</dd></dl></td></tr></tfoot><tbody><tr class="Botrule First"><td align="center" class="Lrule Rrule">Fractionation</td><td align="center" class="Rrule">&gt;5.1</td><td align="center" class="Rrule">1.3</td><td align="center" class="Rrule">&gt;6.1</td><td align="center" class="Rrule">&gt;4.9</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">4.2</td><td align="center" class="Rrule">4.9</td></tr><tr class="Botrule"><td align="center" class="Lrule Rrule">SD treatment</td><td align="center" class="Rrule">&gt;4.5</td><td align="center" class="Rrule">&gt;6.2</td><td align="center" class="Rrule">n.a.</td><td align="center" class="Rrule">&gt;4.8</td><td align="center" class="Rrule">n.d.</td><td align="center" class="Rrule">n.d.</td><td align="center" class="Rrule">n.d</td></tr><tr class="Botrule"><td align="center" class="Lrule Rrule">35 nm nanofiltration</td><td align="center" class="Rrule">&gt;4.5</td><td align="center" class="Rrule">&gt;5.1</td><td align="center" class="Rrule">&gt;6.2</td><td align="center" class="Rrule">&gt;5.6</td><td align="center" class="Rrule">5.7</td><td align="center" class="Rrule">1.4</td><td align="center" class="Rrule">2.0</td></tr><tr class="Botrule"><td align="center" class="Lrule Rrule">Low pH treatment</td><td align="center" class="Rrule">&gt;5.8</td><td align="center" class="Rrule">&gt;5.5</td><td align="center" class="Rrule">&gt;6.0</td><td align="center" class="Rrule">&gt;6.5</td><td align="center" class="Rrule">n.d.<a class="Sup" href="#footnote-14" name="footnote-reference-14">†</a></td><td align="center" class="Rrule">&gt;6.3</td><td align="center" class="Rrule">3.1</td></tr><tr class="Last"><td align="center" class="Lrule Rrule">Overall log reduction factor (ORF)</td><td align="center" class="Rrule">&gt;19.9</td><td align="center" class="Rrule">&gt;18.1</td><td align="center" class="Rrule">&gt;18.3</td><td align="center" class="Rrule">&gt;21.8</td><td align="center" class="Rrule">9.6<a class="Sup" href="#footnote-14">†</a></td><td align="center" class="Rrule">&gt;11.9</td><td align="center" class="Rrule">10.1</td></tr></tbody></table></section>

CUVITRU

immunoglobulin G, human

50 ML immunoglobulin G, human 200 MG/ML Injection

20 ML immunoglobulin G, human 200 MG/ML Injection

10 ML immunoglobulin G, human 200 MG/ML Injection

5 ML immunoglobulin G, human 200 MG/ML Injection

Cuvitru

5 ML immunoglobulin G, human 200 MG/ML Injection [Cuvitru]

10 ML immunoglobulin G, human 200 MG/ML Injection [Cuvitru]

20 ML immunoglobulin G, human 200 MG/ML Injection [Cuvitru]

40 ML immunoglobulin G, human 200 MG/ML Injection

40 ML immunoglobulin G, human 200 MG/ML Injection [Cuvitru]

50 ML immunoglobulin G, human 200 MG/ML Injection [Cuvitru]

immunoglobulin G

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

Report Adverse Event 

Prescribing Information

Pharmacy List 

Billing & Coding Guide 

Coverage Authorization Request 

Coverage Authorization Appeals 

Cuvitru One Path Start Form 

HelloCuvitru Free Trial Program 

About Cuvitru

About Cuvitru (Pediatrics)

Side Effects

Doctor Discussion Guide

Getting Started With Cuvitru

Patient Stories 

Patient Resources

MyIgSource: Community and Resources

FAQs: Primary Humoral Immunodeficiency

Enroll in Patient Savings Program 

Instructions For Use: Primary Humoral Immunodeficiency (PI)

Instructions For Use (Spanish): Primary Humoral Immunideficiency 

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